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  • 1980-1984  (826)
  • 1965-1969
  • 1980  (826)
  • Life and Medical Sciences  (768)
  • pharmacokinetics
  • Nuclear reactions
  • 1
    Electronic Resource
    Electronic Resource
    Melatonin administration to dogs (1980)
    Springer
    Journal of neural transmission 49 (1980), S. 281-285 
    Details
    ISSN: 1435-1463
    Keywords: Melatonin administration ; diurnal rhythm ; dog ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Melatonin concentrations in serum and urine were examined following oral administration of melatonin to dogs. Four different doses of melatonin ranging from 10 to 80 mg per kg of body weight were given. Melatonin was rapidly absorbed and reached a maximum serum level after 20–30 min, with a distribution phase of 3.5 hours and elimination half life (t1/2) of 5 hours. The fraction excreted in the urine was 0.25% of the administrated dose during the first 5 hours. These results as well as the diurnal rhythm of serum melatonin in the dog are similar to corresponding data reported in the human.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01252131
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  • 2
    Electronic Resource
    Electronic Resource
    Metabolic effects and pharmacokinetics of intravenously administered dichloroacetate in humans (1980)
    Springer
    Diabetologia 19 (1980), S. 109-113 
    Details
    ISSN: 1432-0428
    Keywords: Dichloroacetate ; pharmacokinetics ; lactate ; lactic acidosis ; alanine ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1–50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p〈0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 μg/ml, elimination was monoexponential with a half-life of 32±11 min (mean±SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421855
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sodium valproate in epileptic patients: Prediction of maintenance dosage by single-dose study (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 71-77 
    Details
    ISSN: 1432-1041
    Keywords: sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic analysis of the plasma valproic acid concentration-time course, following a single oral dose (600 mg) of sodium valproate, was performed in 20 epileptic patients as an aid to the prediction of a proper chronic dosage regimen. A simple one-compartment model was found inadequate to describe the drug concentration-time course in 15 of the 20 patients studied. The average elimination (β phase) half-life of 9 h was shorter than that previously reported in healthy subjects. The latter observation and the wide variation in plasma valproic acid clearance observed between patients (0.09–0.53 ml/kg/min) may have been related to its altered disposition by concomitant anticonvulsant therapy. Sodium valproate maintenance therapy, determined by single-dose pharmacokinetic prediction of steady-state plasma valproic acid levels, did not require dosage adjustment because of unwanted effects. However, the occurrence of drug-related adverse events led to dosage reduction in 4 of 9 patients whose chronic therapy was not pharmacokinetically predicted. Moreover, the pharmacokinetic variability demonstrated for sodium valproate by patients on multiple therapy, whose chronic sodium valproate therapy was pharmacokinetically predicted, indicates the value of monitoring plasma valproic acid levels for the regulation of anticonvulsant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561679
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  • 4
    Electronic Resource
    Electronic Resource
    Metabolic and haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 81-86 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562614
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 6
    Electronic Resource
    Electronic Resource
    Plasma and salivary pharmacokinetics of dapsone estimated by a thin layer chromatographic method (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 129-133 
    Details
    ISSN: 1432-1041
    Keywords: dapsone ; salivary drug elimination ; pharmacokinetics ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high performance thin layer chromatographic assay for dapsone is described with a minimum level of detection of 20 ng ml−1 which is suitable for the study of dapsone pharmacokinetics in plasma and saliva. 100 mg dapsone was administered orally to seven normal adult volunteers, the mean plasma pharmacokinetic parameters were: α=0.23 h−1; β=0.0236 h−1, and t1/2β=30.2 h. Dapsone is also eliminated into the saliva and the t1/2 may be determined via its estimation in saliva. It is 73% bound to plasma protein and the saliva/plasma concentration ratio was found to be 27%. In two subjects the free plasma dapsone concentration was identical to the simultaneous salivary dapsone concentration. Therefore the salivary dapsone concentration is a measure of the free plasma fraction of dapsone. Saliva/plasma dapsone concentration ratios show no time or concentration dependence and little inter-individual variation but are unsuitable for acetylator phenotype determination because monoacetyldapsone is not eliminated in the saliva.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562621
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sotalol after chronic administration to patients with renal insufficiency (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561389
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  • 8
    Electronic Resource
    Electronic Resource
    Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    Details
    ISSN: 1432-1041
    Keywords: desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874666
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  • 9
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of alcuronium chloride in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    Details
    ISSN: 1432-1041
    Keywords: alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t1/2β), apparent volume of distribution (Vdβ), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 µg/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 µg/ml.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570163
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  • 10
    Electronic Resource
    Electronic Resource
    Paracetamol pharmacokinetics in thyroid disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 269-273 
    Details
    ISSN: 1432-1041
    Keywords: paracetamol ; thyrotoxicosis ; hypothyroidism ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n=7) and hypothyroidism (n=4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563010
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  • 11
    Electronic Resource
    Electronic Resource
    Pharmacokinetic of 2-(p-methylallylaminophenyl) propionic acid, alminoprofene, in man after single and multiple oral doses (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 419-422 
    Details
    ISSN: 1432-1041
    Keywords: alminoprofene ; antalgic ; pharmacokinetics ; single dose ; multiple doses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-(p-methylallylaminophenyl) propionic acid, alminoprofene (INN), a new antalgic drug, was administered orally to men as a single (300 mg) and multiple doses (300 mg three times daily). Plasma and urine concentrations of alminoprofene were determined by gas-liquid chromatography. After the single oral dose, the peak plasma level (36.2 to 41.5 mg/l) was reached within 0.5–1.5 h. The biological half-life ranged from 2.5 to 3.2 h. During chronic administration of alminoprofene, steady-state equilibrium quilibrium was etablished within 24 h. The urinary excretion of alminoprofene as unchanged product and as glucuronide was very important.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636796
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and oral bioavailability of pyridostigmine in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    Details
    ISSN: 1432-1041
    Keywords: pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636797
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  • 13
    Electronic Resource
    Electronic Resource
    Rapid prediction of steady-state serum theophylline concentration in patients treated with intravenous aminophylline (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    Details
    ISSN: 1432-1041
    Keywords: aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration)=−0.22±1.97 mg/l (mean ± SD); r=0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error=0.58±3.88, r=0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error=3.62±13.36, r=0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874658
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  • 14
    Electronic Resource
    Electronic Resource
    Lack of pharmacokinetic interaction of colestipol and fenofibrate in volunteers (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 459-463 
    Details
    ISSN: 1432-1041
    Keywords: colestipol ; fenofibrate ; fenofibric acid ; pharmacokinetics ; interaction ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of a pharmacokinetic interaction between two hypolipidemic drugs, colestipol, an ion exchange resin, and fenofibrate, a phenoxyacid derivative, was studied in 6 male volunteers. The investigation followed a four-step protocol during 18 days, and relied on determination of plasma and urinary levels of fenofibric acid, the active metabolite of fenofibrate. The kinetics of a single dose of fenofibrate 300 mg was established over 3 days. Thereafter, from Days 4 to 9 fenofibrate was given daily as 200 mg in the morning and 100 mg in the evening; the plasma fenofibric acid level reached about 10 µg/ml. From Days 9 to 15 the same dose of fenofibrate was administered together with colestipol 10 g in the morning and 5 g in the evening. Plasma fenofibric acid concentrations remained unchanged and the 24 h urinary excretion of fenofibric acid did not fall. On Day 15, a last single dose of fenofibrate 300 mg was given with colestipol 15 g. The pharmacokinetic pattern of fenofibric acid on Days 15 to 18 did not differ significantly from that found previously (Days 1 to 3). From these results, it is likely that there is no pharmacokinetic interaction between the two hypolipidemic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570164
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and clinical response (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 51-53 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; phenobarbital ; aminoglycoside antibiotics ; pharmacokinetics ; clinical response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561478
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  • 16
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diuretics and methylxanthines in the neonate (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 55-63 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; furosemide ; caffeine ; theophylline ; neonate ; pharmacokinetics ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of diuretics and methylxanthines is considerably slower in the neonate than in the adult. Dose guidelines, especially during long term maintenance, must be adjusted to account for this slower drug elimination. Pharmacokinetic studies and the requisite pharmacologic evaluation on diuretics such as hydrochlorothiazide, spironolactone, ethacrynic acid and others should be done. Furosemide undergoes biotransformation in the newborn producing an acid metabolite and a glucuronide conjugate. Methylxanthines are effective in the treatment of neonatal apnea. Plasma elimination of theophylline is exceedingly slow, more so with caffeine. Decreased elimination is partly explained by decreased oxidative biotransformation. Caffeine is excreted in the urine of the newborn mainly unchanged (85%) in contrast to the adult where caffeine is a minor portion of urinary excretion (2%). Theophylline is methylated to caffeine and may possibly exert additive pharmacologic effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561479
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  • 17
    Electronic Resource
    Electronic Resource
    Absorption and disposition of ampicillin in the elderly (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 195-198 
    Details
    ISSN: 1432-1041
    Keywords: ampicillin ; age ; oral dose ; i. v. dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ampicillin (500 mg) was administered intravenously (i. v.) and orally to a small panel of young and elderly subjects in a cross-over fashion. Plasma concentrations of ampicillin were measured by a fluorimetric technique for 8 h following dosage. A two compartment-open model was used to characterise the plasma concentration-time data for the intravenous study, and a one compartment-open model incorporating an absorption lag time and a first-order absorption rate constant for the oral data. Plasma clearance after i. v. ampicillin was found to be significantly decreased in the elderly (P〈0.05, 0.08 1 h−1kg−1 versus 0.18 1 h−1kg−1), and half life and area under the plasma level-time curve were significantly increased (P〈0.05, 6.70 h versus 1.68 h, t1/2β; p〈0.01, 176.51 µg·h ml−1 versus 37.88 µg·h ml−1, AUC o ∞ ) as compared to the young. No sigificant differences were observed between the age groups for the volume of distribution terms and the changes in drug handling noted in the elderly were attributed to a decrease in the renal elimination of ampicillin. Following oral administration a significant increase in t1/2β, AUC o ∞ and the maximum plasma concentration (Cpmax P〈0.01, 6.59 µg ml−1 versus 3.42 µg ml−1) of ampicillin was found in the elderly subjects. These findings were similarly attributed to a decrease in drug elimination in the aged, since no apparent age differences were noted in the pharmacokinetic parameters governing both rate and extent of ampicillin absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561590
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  • 18
    Electronic Resource
    Electronic Resource
    Effects and pharmacokinetics of isosorbide dinitrate in normal man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 237-244 
    Details
    ISSN: 1432-1041
    Keywords: isosorbide dinitrate ; 2-isosorbide mononitrate ; 5-isosorbide mononitrate ; digital plethysmography ; hypotension ; bradycardia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 18 subjects were given isosorbide dinitrate (ISDN) 5 mg sublingually and serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) were measured, as well as changes in digital plethysmographic amplitude, heart rate, ECG, blood pressure and Schellong's test. ISDN was rapidly absorbed and metabolized, having an elimination half-life of 29 min. Its metabolites 2-ISMN and 5-ISMN had longer half-lives of 1.75 and 7.6 h respectively. The amplitude of the α-wave of the digital plethysmograph did not change significantly either in the predrug period or after placebo administration. It increased within 4 min of administration of ISDN, and reached a maximum after 14 min; the effect lasted for about 2 h. ISDN lowers blood pressure and increases heart rate in most volunteers, but in 3 of the 18 subjects severe hypotension occurred, accompanied by severe, reversible bradycardia, which was probably due to vagal reflexes initiated by the markedly diminished ventricular enddiastolic volume (LVEDV) and pressure (LVEDP). No correlation could be demonstrated between the serum concentration of ISDN and/or its vasoactive metabolites and changes in plethysmographic amplitude.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563005
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  • 19
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics and oral bioavailability of ketobemidone (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    Details
    ISSN: 1432-1041
    Keywords: ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The basic pharmacokinetics and oral bioavailability of ketobemidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin® 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin®, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemidone was 34%±16% (SD, n=6). The mean plasma half-life of elimination (t1/2β) was about the same following oral (2.45±0.73 h; SD, n=5) as after intravenous administration (2.25±0.35 h; SD, n=6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin® (ketobemidone 5–10 mg every 6–7 h) in patients with severe pain is too low.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561676
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  • 20
    Electronic Resource
    Electronic Resource
    A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metoprolol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 87-92 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562615
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  • 21
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    Details
    ISSN: 1432-1041
    Keywords: flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were no changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10–15 ng/ml after the first and 15–20 ng/ml after the last dose. The β-half-life was found to be between 20 and 36 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561899
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  • 22
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    Details
    ISSN: 1432-1041
    Keywords: chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625801
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  • 23
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of naproxen in subjects with normal and impaired renal function (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 263-268 
    Details
    ISSN: 1432-1041
    Keywords: naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7± 3.0 h (mean±SD) and it was not significantly prolonged in patients with renal failure (18.1±5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6± 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563009
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  • 24
    Electronic Resource
    Electronic Resource
    Pharmacokinetic studies in volunteers of intravenous and oral cis (Z)-flupentixol and intramuscular cis (Z)-flupentixol decanoate in viscoleo® (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 355-360 
    Details
    ISSN: 1432-1041
    Keywords: cis (Z)-flupentixol ; cis (Z)-flupentixol decanoate ; serum concentration ; biological half-life ; pharmacokinetics ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations of cis (Z)-flupentixol have been estimated in three male human volunteers who received cis (Z)-flupentixol by intravenous infusion, flupentixol (cis (Z)/trans (E) mixture, 1:1) orally as single and repeated doses, and i. m. cis (Z)-flupentixol decanoate in Viscoleo®. The intravenous data show that cis (Z)-flupentixol followed a multicompartment model, but it was not possible to fit the data to a two or three compartment model. The concentration curves after oral administration indicated relatively slow absorption with a peak concentration at 3–6 h, except for one case with peak at 1 h. The variation in the dosage interval after one daily oral administration was relatively limited (1.7–3.0 times), which indicates that 24 h is a reasonable dosage interval. Biological half-lives were estimated in different ways and showed some intra-individual variation; the half-life was of medium length (19–39 h). The serum concentrations after intramuscular injection of cis (Z)-flupentixol decanoate clearly demonstrated a depot effect, with a maximal concentration at 3–5 days after injection. The descending part of the serum curves allowed an approximate estimation of half-life of 3–8 days. This was not the elimination half-life, but in all probability the half-life of release of drug from the oil depot which was the rate-limiting step. From the areas under the serum concentration curves the fraction of orally administered cis (Z)-flupentixol available to the organism was calculated to be 55% (range 48–60%). The loss of drug might have been due to imcomplete absorption, but it is more likely that cis (Z)-flupentixol underwent first-pass metabolism in the gut wall and the liver. As the tablets contained about 50% cis (Z)-flupentixol, while the depot preparation contained 74% cis (Z)-flupentixol, the pharmacokinetically equivalent doses are: 10 mg tablet daily corresponds to 25 mg depot weekly. Calculation of systemic clearance gave values of 0.44–0.49 l/min, and an apparent volume of distribution was 12.5–17.2 l/kg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561395
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  • 25
    Electronic Resource
    Electronic Resource
    Time-course of the anti-hypertensive action of atenolol: Comparison of response to first dose and to maintained oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 365-374 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636787
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  • 26
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of acebutolol in patients with all grades of renal failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 339-348 
    Details
    ISSN: 1432-1041
    Keywords: acebutolol ; renal failure ; dialysis ; pharmacokinetics ; N-acetylmetabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acebutolol was studied in 10 healthy subjects with normal renal function (RN), in 13 patients with various degrees of renal failure (RI) and in 8 patients undergoing repeated haemodialysis (RD). A highly specific method was used to measure acebutolol (A) and N-acetylmetabolite (NAM). In RN the decrease in plasma levels was biexponential with an apparent plasma half lives in the slow phase of A: 8.8±2.3 h and NAM: 11.4±2.2 h. The percentage of the dose excreted unchanged was 13.9% and as NAM 25.8%. Renal clearances were A: 167±20 ml/min and NAM: 150±18 ml/min. The apparent plasma half life of acebutolol does not change according to the degree of renal insufficiency (RI: 7.0±2.7 h, RD: 7.5±2.7 h), while that of NAM is increased (RI: 21.5±10.1 h, RD: 32.3±16.8 h). There is a linear relationship between the apparent elimination rate constant of NAM and creatinine clearance (r=0.832,p〈0.001). In RI 21.7% of the dose is excreted in urine (A 5.0%, NAM 16.7%). When renal function is impaired, the renal clearance of A and NAM decrease in parallel with the creatinine clearance (A: r=0.874,p〈0.001; NAM: r=0.954,p〈0.001). During dialysis the plasma half life fell (A=3.4±0.9 h, NAM=7.4±2.6 h). The dialytic clearance was A: 42.6±12.7 ml/min and NAM: 40.4±16.3 ml/min, for a blood flow of 238±35 ml/min through a dialyser with a cuprophane membrane (Ultraflo II Travenol). Acebutolol is taken up by erythrocytes (λbc=0.50±0.04). The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558446
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  • 27
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of microcrystalline theophylline (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558452
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  • 28
    Electronic Resource
    Electronic Resource
    Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636790
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  • 29
    Electronic Resource
    Electronic Resource
    Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 279-283 
    Details
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563012
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  • 30
    Electronic Resource
    Electronic Resource
    Disposition of dibekacin in patients undergoing haemodialysis (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 347-350 
    Details
    ISSN: 1432-1041
    Keywords: dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance 〈5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determined microbiologically by a plate diffusion method usingB. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561393
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  • 31
    Electronic Resource
    Electronic Resource
    Haemodynamic effects, plasma concentrations and tolerance of orally administered prenalterol in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 383-390 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was studied in six healthy volunteers given single oral doses of 2.5, 5 and 10 mg and placebo. It displayed a distinct positive inotropic action, manifested as a dose-related reduction of 16.5–27.2 msec in the pre-ejection period (PEPc; systolic time-intervals), and an increase of 4.2–5.9 Ω/sec2 in the Heather index (impedance cardiography). There was also a dose-related increase of 17.6–34.0 mmHg in systolic blood pressure, whereas diastolic pressure showed a slight, transient decrease, not related to the dose given. Heart rate rose by 5–12 beats/min. Stroke volume, as determined by impedance cardiography, increased by 24.2–28.5 ml at all three dose-levels. The effects of the drug developed rapidly, reaching their maximum within 30–60 min and lasting for about 4 h. The time-course of the effects corresponded to the plasma concentrations of the drug. The increases in systolic pressure and contractility were linearly correlated with the plasma concentrations (r=0.8−0.9,p〈0.001). The activity of prenalterol was also tested in the same volunteers after blockade of β-receptors with oxprenolol 80 mg. Under these conditions, oral doses of 25, 50 and 100 mg produced effects similar to or slightly less marked than those recorded after doses ten times lower in the absence of β-blockade. In a further 10 healthy volunteers, in whom tolerance to prenalterol was studied by repeated administration for 10 days of 5 mg four times daily, no change in blood chemistry, haematological parameters or urine values was found. The positive inotropic effect of a single oral dose of prenalterol 5 mg was also demonstrated by reference to the systolic time-intervals and the echocardiogram, in six patients with chronic heart failure, five of whom were digitalized. Prenalterol did not give rise to premature concentrations or other arrhythmias. The only untoward effect definitely attributable to the drug was palpitation, which was dose-related and as a rule was not unduly distressing; in one volunteer, however, the palpitations were unbearable. Prenalterol is a cardiostimulant agent with no direct effect on the peripheral circulation. On the basis of its pharmacological activity, it might well be of therapeutic benefit in all conditions in which an improvement in the pumping efficiency of the heart is required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636789
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  • 32
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636794
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  • 33
    Electronic Resource
    Electronic Resource
    Inhibition by idrocilamide of the disposition of caffeine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 37-43 
    Details
    ISSN: 1432-1041
    Keywords: caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561675
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  • 34
    Electronic Resource
    Electronic Resource
    Altered prazosin pharmacokinetics in congestive heart failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prazosin (Minipress®) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double in the patients in comparison to the control group. Reduction in hepatic blood flow, altered gastrointestinal absorption of the drug or diminished intrinsic hepatic metabolic activity in the patient group may have contributed to the observed changes in prazosin disposition. The finding of higher prazosin plasma concentrations in patients with refractory heart failure demonstrates the need for close monitoring of these individuals following administration of the drug in the treatment of chronic congestive heart failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570159
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  • 35
    Electronic Resource
    Electronic Resource
    Placental transfer of pethidine and norpethidine and their pharmacokinetics in the newborn (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The literature data available on pethidine and norpethidine kinetics in women in labour and in their newborns is reviewed and compared with recent personal observations. In pregnant women the apparent blood half-life of pethidine is not different from that in healthy controls, however, apparent volume of distribution and total body clearance are reduced. Norpethidine blood levels are measurable after 10–20 min and tend to increase with time. The amount of drug transferred to the foetus is clearly linked to the dose administered to the mother, the dosing-delivery interval and to the metabolic capability of the mother. An equilibrium between maternal and umbilical venous blood is reached 2–3 h after dosing for pethidine and later for norpethidine. In the neonate, the apparent pethidine half-life is 2 to 7 times longer than in adults with values ranging from 7 to 32 h. Norpethidine is actively formed in the newborn with peak blood levels at 12–36 h and an apparent blood half-life of 20–36 h. At the doses usually recommended blood concentrations at birth are frequently higher than those required for analgesia and close to or within toxic ranges. An effort toward a more individualized dosage as well as toward a better understanding of the possible role of norpethidine with regard to adverse effects is needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561475
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  • 36
    Electronic Resource
    Electronic Resource
    Disposition and pharmacodynamics of diuretics and antihypertensive agents in renal disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methyldopa, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561487
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  • 37
    Electronic Resource
    Electronic Resource
    Bromocriptine concentration in saliva and plasma after long-term treatment of patients with Parkinson's disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 171-174 
    Details
    ISSN: 1432-1041
    Keywords: bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561586
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  • 38
    Electronic Resource
    Electronic Resource
    Comparative in vitro effects and in vivo kinetics of antithyroid drugs (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    Details
    ISSN: 1432-1041
    Keywords: propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625803
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  • 39
    Electronic Resource
    Electronic Resource
    Time course of blood pressure, pulse rate, plasma renin and metoprolol during treatment of hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558443
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  • 40
    Electronic Resource
    Electronic Resource
    Influence of dose on the pharmacokinetics of Cefadroxil (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
    Details
    ISSN: 1432-1041
    Keywords: cefadroxil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Cefadroxil have been studied in a crossover study involving 20 experiments in four healthy volunteers (19–24 years), after oral administration of five individual doses of 250, 500, 750, 1000 and 1500 mg of the antibiotic in capsules to each person. Plasma and urine concentrations of the antibiotic were determined microbiologically by a plate diffusion method. The antibiotic followed an open, single-compartment kinetic model. The plasma half-life was not significantly influenced by dose; the average was 1.438±0.220 h. The percentage of the antibiotic excreted in urine, too, was not significantly affected by the dose, being close to 80% of the quantity originally administered within 24 h. The values of Cmax and (AUC) increased linearly with the administered dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874664
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  • 41
    Electronic Resource
    Electronic Resource
    Comparative bioavailability of disopyramide after multiple dosing with standard capsules and controlled-release tablets (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561902
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  • 42
    Electronic Resource
    Electronic Resource
    Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    Details
    ISSN: 1432-1041
    Keywords: L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561903
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  • 43
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    Details
    ISSN: 1432-1041
    Keywords: sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558453
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  • 44
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and dosage of digoxin in neonates and infants (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (〉1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients. The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561481
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  • 45
    Electronic Resource
    Electronic Resource
    Effectiveness and pharmacokinetics of indomethacin in premature newborns with patent ductus arteriosus (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
    Details
    ISSN: 1432-1041
    Keywords: patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A review of the published data on pharmacological closure of PDA in premature newborns shows that doses of 0.2 mg/kg indomethacin are less successful when given enterally (18 to 85% closure) than when given intravenously (88 to 90% closure). The elimination half-life is markedly prolonged in premature newborns compared to adults but there are wide differences between the patients and some discrepancies between mean values reported by various authors. The present study compares clinical and pharmacological results obtained in two groups of low birth weight infants with symptomatic PDA and treated with 0.2 mg/kg indomethacin: 7 patients treated enterally (group A) and 11 patients treated intravenously (group B). Permanent closure of the ductus was observed in 4 cases in group A and in 9 cases in group B. Transient closure was observed twice in each group. Of a total of 18 infants, 15 were saved (83%). One baby treated with indomethacin in spite of preexisting oliguria died from persistent anuria. Indomethacin plasma levels were measured by gas chromatography. The mean elimination half-life of the drug in group A (40.3±12.2 h) did not differ from that in group B (33.9±11.7 h). The apparent plasma half-life appears to be inversely correlated with gestational age (r=0.66,p〈0.05). No relationship between peak plasma levels and ductal closure was established, but a significant difference was found for area under the curve (0 to 24 h) between patients in whom a permanent closure was obtained and those in whom the closure was either transient or absent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561483
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  • 46
    Electronic Resource
    Electronic Resource
    Nortriptyline therapy in elderly patients: Dosage prediction after single dose pharmacokinetic study (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
    Details
    ISSN: 1432-1041
    Keywords: antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p〈0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561582
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  • 47
    Electronic Resource
    Electronic Resource
    Effect of posture and sleep on pharmacokinetics (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
    Details
    ISSN: 1432-1041
    Keywords: amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561587
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  • 48
    Electronic Resource
    Electronic Resource
    Use of an (n, α) nuclear reaction to study the long-distance transport of boron in trifolium repens after foliar application (1980)
    Springer
    Planta 150 (1980), S. 197-205 
    Details
    ISSN: 1432-2048
    Keywords: Boron ; Foliar nutrition ; Nuclear reactions ; Transport (boron) ; Trifolium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The growth of white clover (Trifolium repens L.) is severely inhibited by boron starvation, but a foliar treatment with boric acid can transitorily alleviate the deficiency symptoms. The 10B(n ,α)7 Li nuclear reaction has been used to study boron transport in the plant after foliar application. More than 98% of the boron supplied remained at the point where it was applied to the leaves, and less than 2% was useful to the growth of the treated plant. This small “efficient” portion of boron was quite mobile. It was distributed to the different parts of the plant, then was transferred from the oldest parts to the newly formed leaves. Physiological and agronomical implications of these data are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00390826
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  • 49
    Electronic Resource
    Electronic Resource
    Symbols in pharmacokinetics (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 497-507 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; symbols ; notation ; nomenclature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To encourage uniformity in the presentation of pharmacokinetic data, a general nomenclature has been developed. The system has wide application. Flexibility is achieved through the use of general variables, constants, qualifying terms, and subscripts. Yet, through the use of implied terms, the symbols describing many common variables and constants are simple.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059548
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  • 50
    Electronic Resource
    Electronic Resource
    Identifiable pharmacokinetic models: The role of extra inputs and measurements (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
    Details
    ISSN: 1573-8744
    Keywords: compartmental analysis ; dynamic response ; identification ; linear systems ; modeling ; parameter estimation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Single input, single output experiments can result in nonunique solutions for the rate constants of a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is an infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtain a unique solution for the others. This paper considers such experiments and determines whether either the addition of an extra input (simultaneously with the first input) or the taking of an extra measurement would result in a unique solution. It is found that perturbing a second input can be useful, but only if the perturbation is of different shape from the first input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, though, the second measurement (for example, by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060058
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  • 51
    Electronic Resource
    Electronic Resource
    Accumulation in the peripheral compartment of a linear two-compartment open model (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacological effects ; two-compartment model ; tissue accumulation ; aminoglycoside antibiotics ; gentamicin ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Accumulation factors for the peripheral compartment in a two-compartment open model are derived. These expressions are contrasted with some previously published statements concerning drug accumulation. The utility of the new indices of accumulation is illustrated by reference to studies of gentamicin tissue uptake and its proposed relation to nephrotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059451
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  • 52
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    Electronic Resource
    Pharmacokinetics of intravenously administered bumetanide in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
    Details
    ISSN: 1573-8744
    Keywords: bumetanide ; diuretics ; pharmacokinetics ; three-compartment model ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disposition of [ 14C] bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059643
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  • 53
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bretylium in man after intravenous administration (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
    Details
    ISSN: 1573-8744
    Keywords: bretylium ; pharmacokinetics ; healthy subjects ; antiarrhythmic ; twocompartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2β)of 7.8 hr and apparent volume of distribution (Vd,β)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059384
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  • 54
    Electronic Resource
    Electronic Resource
    Influence of renal failure on the hepatic clearance of bufuralol in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
    Details
    ISSN: 1573-8744
    Keywords: bufuralol ; renal failure ; pharmacokinetics ; metabolites ; renal clearance ; hepatic clearance ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1′-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Bufuralol was given orally to all subjects (20 mg); some of the healthy volunteers also received the drug intravenously (5 mg). Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its halflife of elimination was not markedly influenced. The behavior of 1′-hydroxy-bufuralol was consistent with a decreased renal clearance. The behavior of bufuralol in patients with renal failure was analyzed using the clearance approach. From this analysis it appears that the presystemic biotransformation of bufuralol is decreased in renal failure and that changes in systemic clearance are compensated in our patients by modifications of the volume of distribution, resulting in little net change in the halflife of elimination.
    Type of Medium: Electronic Resource
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    Lithium pharmacokinetics: Single-dose experiments and analysis using a physiological model (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 439-461 
    Details
    ISSN: 1573-8744
    Keywords: lithium ; pharmacokinetics ; physiological parameters ; cellular transport ; three-compartment model ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of lithium (Li +) distribution after a single dose was studied in healthy human subjects. Experiments were performed by simultaneously following changes of Li+ concentration in plasma, erythrocytes (RBC), and urine. The data were fitted by a simple but physiologically realistic model, so that extracted rate constants could be assigned to real body compartments and compared with independent measurements of cellular transport characteristics. The extracted rate constants were used to calculate steady-state cell-to-plasma Li+ ratios for RBC and for inaccessible cells (mainly muscle). In both cell types, the intracellular Li+ concentration is far below electrochemical equilibrium. This finding suggests that the Li+ countertransport efflux mechanism of RBC may be shared with muscle. We also present evidence for a circadian rhythm in Li+ excretion that parallels the daily cycle of Na+ and K+ excretion.
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    A pharmacokinetic model-independent approach for estimating dose required to give desired steady-state trough concentrations of drug in plasma (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 105-110 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; maintenance dose ; dose estimation ; multiple dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A maintenance dose designed to give a desired minimum concentration of drug in plasma at steady-state can be determined in a model-independent manner assuming that concentration-time data needed for the calculation are obtained after absorption and distribution are complete. Using a few concentration-time points obtained after the first dose, numerical values of β and Z, a parameter consisting of different pharmacokinetic parameters for different models, can be obtained. An administration interval (τ) can be chosen based on β. Using the values of β, Z, and τ, a maintenance dose is calculated. This approach will allow calculation of a maintenance dose when drug is present in plasma at the time the first monitored dose is given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059452
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    Heuristic modeling of drug delivery to malignant brain tumors (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    Details
    ISSN: 1573-8744
    Keywords: chemotherapy ; pharmacokinetics ; brain tumors ; modeling ; solid tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the “breakdown” in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059646
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    Visceral anatomy of the amphisbaenia (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 99-133 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Study of the visceral anatomy of 41 specimens of amphisbaenians representing 13 genera shows that they share a very distinct structure which differs from that found in either snakes or typical lizards. The left lung is large while the right is rudimentary or absent (unique); the kidneys are freely suspended in the coelom by a mesentery (unique); the spleen is usually embedded in the anterior end of the pancreas (as in snakes); the gall bladder lies in a notch in the liver, and the kidneys lie opposite each other (as in lizards). The distinctness of this pattern supports the recognition of the Amphisbaenia as a separate suborder of the Squamata.
    Additional Material: 28 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051630202
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    Cytodifferentiation and vitellogenesis during oogenesis in arachnida: Cytological studies on developing oocytes of a harvestman (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 175-190 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Light and electron microscope studies were made on harvestman oocytes during the course of their origin, differentiation, and vitellogenesis. The germ cells appear to originate from the ovarian epithelium. They subsequently migrate to the outer surface of the epithelium, where they remain attached often by means of stalk cells which suspend them in the hemocoel during oogenesis. The “Balbiani bodies,” “yolk nuclei,” or “nuage” constitute a prominent feature of young, previtellogenic oocytes, and take the form of large, but variable sizes of electron-dense cytoplasmic aggregates with small fibrogranular components. The cytoplasmic aggregates fragment and disperse, and cannot be detected in vitellogenic oocytes. The young oocytes become surrounded by a vitelline envelope that appears to represent a secretory product of the oocyte. The previtellogenic oocytes are impermeable to horseradish peroxidase under both in vivo and in vitro conditions. In addition to mitochondria, dictyosomes, and abundant ribosomes, the ooplasm of the previtellogenic oocyte acquires both vesicular and lamellar forms of the rough-surfaced endoplasmic reticulum. In many areas, a dense homogeneous product appears within the cisternae of the endoplasmic reticulum and represents nascent yolk protein synthesized by the oocyte during early stages of vitellogenesis. Later in vitellogenesis, the oocyte becomes permeable to horseradish peroxidase under both in vivo and in vitro conditions. This change is associated with a massive process of micropinocytosis which is reflected in the presence of large numbers of vesicles of variable form and structure in the cortical ooplasm. Both spherical and tubular vesicles are present, as are coated and uncoated vesicles. Stages in the fusion of the vesicles with each other and with developing yolk platelets are illustrated. In the harvester oocytes, vitellogenesis is a process that involves both autosynthetic and heterosynthetic mechanisms.
    Additional Material: 32 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051630206
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    Ultrastructural study on cocoon formation in the freshwater oligochaete, Tubifex hattai (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 25-38 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The clitellar epithelium of the freshwater oligochaete, Tubifex hattai, is composed of four types of gland cells (Type I, II, III, and IV), in addition to the cells generally found in the epidermis of this worm. The possible function of these gland cells in cocoon formation was studied with the electron microscope.Type I cells discharge their secretory granules by means of compound exocytosis and provide the materials for the future cocoon membrane. Immediately after completion of the discharge from Type I cells, Type II and III cells simultaneously discharge their secretory granules by means of compound exocytosis. The secretions from Type II cells constitute a colloid in the cocoon lumen and probably cause structural modifications in the future cocoon membrane. The secretory products from Type III cells form the cocoon plug. Although the process of discharge of secretory granules from Type IV cells was not observed, the contribution of these cells to the cocoon formation, producing hoops on the outer surface of the future cocoon membrane and fixing its anterior ends on the clitellum, is inferred from a morphological comparison of the hoop and the structure of the secretory granules.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051640103
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    The distribution of monoamine oxidase and biogenic monoamines in the central nervous system of spiders (Arachnida: Araneida) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 69-81 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The distribution and activity patterns of monoamine oxidase and monoaminergic (formaldehyde-induced) fluorescence in the central nervous system of web-building and hunting spiders have been studied using histochemical methods. Enzyme activity occurred in the neuronal perikarya and in varying intensity in the structures of the neuropile mass, but only when dopamine, adrenaline, and noradrenaline were used as substrates. The optic centres of the spider brain normally exhibited relatively strong enzyme reactions when compared with the staining intensity of the rest of the nervous system.The neuronal cell bodies contained numerous granules of yellow-green fluorescence. Monoaminergic fluorescence of the neuropile was generally a weak green. The optic mases of the hunting spiders, the anterior bridge, several commissures of the ventral cord, and the neural lamellae showed a slightly higher fluorescence intensity and single fluorescing granules.The results obtained indicate the presence of catecholamines in the spider nervous system.
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051640106
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    Formation of the pits with taste buds at the lingual root in the striped dolphin, Stenella coeruleoalba (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 107-119 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The tongue of the striped dolphin, Stenella coeruleoalba, shows a V-shaped row of pits on its posterior dorsum. Their development is described on the basis of macroscopic and light microscopic observations on fetal, young, and adult stages. Four to eight pits occur, most often five in the adult. Anlagen of the pits first protrude as round epithelial thickenings which later increase in diameter and become thin. The circular primordia then sink, and grooves oriented both circularly and radially develop in the walls of the shallow pits thus formed. Pits and grooves deepen with development so that older pits become lined with conical projections. As pits grow further, they become elongated anterolaterally, retaining slit-like openings. Each pit in the adult is 2-8 mm long and about 1 mm wide. The pits are not derived from lingual gland ducts but develop independently. Taste buds resembling those of other mammalian tongues can be found in young dolphins but are few in number and limited to the thin epithelium of the pit projections and to that of the side wall of the pits. They first appear in the late prenatal period but degenerate in the adult. A rich nerve supply is observable in the lamina propria below taste buds in the calf. The pits and their projections in the dolphin correspond to the vallate papillae of other mammals, but whether each projection or a whole pit corresponds to a single vallate papilla is undecided.
    Additional Material: 22 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051640202
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    Fine structure and distribution of epidermal projections associated with taste buds on the oral papillae in some loricariid catfishes (Siluroidei: Loricariidae) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 139-159 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Two morphologically distinct structures occur on the surfaces of the oral papillae in several loricariid catfish species; namely, (1) typical vertebrate taste buds composed of receptor and sustentacular cells and (2) brushlike projections, termed epidermal brushes, that represent specialized epidermal cells containing keratin. Both of these structures were studied with the combined use of light microscopy and scanning and transmission electron microscopy. The general body surface, fins, and rostral cutaneous processes of some loricariid catfishes are covered with taste or terminal buds but lack the epidermal brushes. It is suggested that the epidermal brushes found on the oral papillae serve as protective devices for the taste buds and as abrasive surfaces for substrate scraping during feeding. The taste buds on the oral papillae may detect any gustatory stimuli from the resulting substrate disturbance. Comparative studies reveal many differences in the number and spatial arrangement of these two structures on the oral papillae among the several species of the Loricariidae examined. These differences may represent functional adaptations to the various modes of life in the Loricariidae.
    Additional Material: 36 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051640204
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    Identification of the Y-organ in the larval stages of the crab, Cancer anthonyi Rathbun (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 83-88 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The Y-organ has been histologically identified in all six larval stages of the crab, Cancer anthonyi. The paired glands are located anterior to the branchial chamber and ventral to the base of the antennules. In the first zoeal stage the gland consists of a cord of 6 to 10 epidermal cells with dark staining nuclei, sparse cytoplasm, and indistinct cell boundaries. As development progresses the glands become more complex through extensive folding and intertwining of the cellular cords. The glands in all larval stages show cyclical activity which corresponds to the molt cycle. Immediately following a molt the gland is dense and compact with little cytoplasm. At approximately day four in the molt cycle, the glands become greatly hyperthropied due to an increase in the number and size of the cytoplasmic vacuoles. These histological changes suggests a cyclical production and presumably the release of some product most likely ecdysone.
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    URL: http://dx.doi.org/10.1002/jmor.1051640107
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    The morphology of a harpacticoid copepod gut: A review and synthesis (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 89-105 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The digestive tract of a harpacticoid copepod, Tigriopus californicus (Baker), was studied by using techniques of light and electron microscopy. Four cell types could be distinguished: type 1, an embryonic cell which will replace cells worn away or lost during secretion; type 2, a cell which synthesizes and secretes proteins and also plays a role in lipid absorption; and types 3 and 4, two cell types which absorb lipids. From the abundance of each cell type, the length of microvilli, the development of basal plasma membrane (PM), and luminal projections, the following conclusions were made. (1) The midgut caecum absorbs digested nutrients. (2) The anterior midgut absorbs nutrients and more importantly functions in merocrine and exocrine secretion. The presence of concretions in cell types 2 and 3 in the anterior midgut suggests that these tissues contribute in excretion, and in water and/or ion regulation. (3) The posterior midgut absorbs nutrients and contributes some holocrine secretion.
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    URL: http://dx.doi.org/10.1002/jmor.1051640108
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    Sense organs on the antennal flagellum of the human louse, Pediculus humanus (Anoplura) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 161-166 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Tactile hairs are present on all three subsegments of the antennal flagellum of the human louse. There is, in addition, a single chemoreceptor (tuft organ) on subsegment 2 and 12 or 13 chemoreceptors (one tuft organ, two pore organs and nine or ten pegs) on subsegment 3. The cuticle surrounding the bases of the pegs at the tip of the antenna is unusual in that parts of it are perforated by many fine pores. This cuticle is underlain by a thin layer of dendrites. This region may also have a chemoreceptor function.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051640205
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    An electron microscopic study of hemoglobin synthesis in the marine annelid, Amphitrite ornata (Polychaeta: Terebellidae) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 121-138 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The heart-body of the marine worm Amphitrite, located within the supraesophageal dorsal vessel, is in the form of a cylinder the thin wall of which is deeply corrugated by luminal projections and folds along its entire length. It is anchored in places to the luminal surface of the dorsal vessel by an extracellular matrix containing collagen fibers. The luminal surfaces of both the heart-body and the dorsal vessel are covered by a basement membrane-like vascular lamina which in turn supports a discontinuous pseudoendothelium of littoral hemocytes.The cells of the heart-body constitute a pseudostratified, high columnar epithelium. They possess extensive rough endoplasmic reticulum (RER), a well developed Golgi zone, ferritin particles and granules, and several types of membrane-bound inclusions. Hemoglobin molecules identical to those in the circulation lie within cytoplasmic, membrane-bound vesicles. Analysis of our electron micrographs suggests the following sequence of hemoglobin production and secretion: Large quantities of a moderately dense flocculent material, probably globin, are synthesized in RER and move to the Golgi zone within partly rough- and partly smooth-surfaced transitional cisternae; small transport vesicles, formed from Golgi cisternae that have fused with transitional cisternae, convey the flocculent material from the convex to the concave face of the Golgi complex; a similar flocculent material and an amorphous, highly dense material are processed in the Golgi complex and are transferred to condensing vacuoles in which clearly identifiable hemoglobin molecules are first observed. Mature secretory vesicles containing only hemoglobin migrate to the cell periphery and discharge their contents by exocytosis. Hemoglobin molecules then cross the vascular lamina to reach the circulation.
    Additional Material: 14 Ill.
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    The auditory region of dermoptera: Morphology and function relative to other living mammals (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 167-211 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The dermopteran basicranium combines a primitively constructed and oriented auditory bulla formed by ectotympanic, rostral entotympanic, and tubal cartilage with derived features of the middle ear transformer and internal carotid circulation. Living dermopterans possess a primitive eutherian auditory region that has been structurally modified to perceive a lower frequency sound spectrum than probably was utilized by ancestral Mesozoic therians. Perception of the low to midfrequency range is enhanced in Dermoptera by reducing stiffness in the mechanical transformer while maintaining low mass of the component parts. Stiffness has been reduced by (1) development of an epitympanic sinus about four times the volume of the middle ear cavity proper, (2) detachment of the anterior process of the malleus from the ectotympanic, and (3) by delicate suspension of the ear ossicles within the middle ear.We apply to dermopterans a measure of hearing efficiency derived from recent functional studies of the mammalian middle ear that regards the middle ear mechanism as an impedance matching transformer. Calculation of the impedance transformer ratio for Dermoptera suggests that these mammals are relatively efficient in comparison to other eutherians in their ability to match the impedance of cochlear fluids to that of air at the eardrum. Dermopterans theoretically are capable of using over 90% of incident sound energy striking the eardrum at the resonant or natural frequency. Mechanical impedance of the middle ear transformer exerts a minimal influence on hearing efficiency due to low mass, little stiffness, and little frictional resistance.Analysis of measurements of the middle ear transformer published by Gerald Fleischer and integration of these data with current theory on the peripheral hearing mechanism in mammals allow us to propose a model that describes the structural and functional evolution of the mammalian middle ear transformer. Structural changes appear to be correlated with alteration in function from primitive small mammals with stiff middle ear transformers and high frequency dominated hearing to mammals with a wider range in body size with more mobile middle ear transformers and a greater range of frequency perception, often including improved sensitivity to lower frequencies.Mammals employ different anatomical strategies in attainment of increased hearing efficiency and sensitivity. Efficiency is improved by adjustment of lever and areal ratios of the middle ear transformer to achieve an optimum impedance match of external air and cochlear fluids. Sensitivity over a broad frequency spectrum is attained by minimizing mass, stiffness, and frictional resistance of the transformer. The morphology of the auditory region of both living and fossil mammals seems explicable in terms of selection pressure directed toward these ends.
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    Announcement (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 311-311 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051640307
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    Gross structure and function of the quadriceps femoris in Lemur fulvus: An analysis based on telemetered ElectromyographyForce plate data on a wide variety of nonhuman primates (Kimura et al., '79) indicate that, in comparison to other mammalian quadrupeds (e.g., cats), virtually all primates are somewhat hindlimb dominated; i.e., the vertical and propelling peak component of force is consistently larger in the hindlimb than in the forelimb. The forelimbs of those species examined tend to act primarily to brake the body. (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 287-299 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Analysis based on telemetered electromyography from the quadriceps femoris of Lemur fulvus, a Malagasy prosimian, during walking, galloping, leaping, and a variety of postural behaviors partially confirms and partially contradicts earlier hypothesized functions of this musculoskeletal complex. As predicted on the basis of morphological criteria (large physiological cross-section and long parallel fibers), the vastus lateralis is of special functional significance in leaping. This relatively large muscle consistently initiates the leap and frequently undergoes a very long period of force enhancement via active stretch. By contrast, the vastus intermedius fails to exhibit increased electrical activity and undergoes little or no active stretch during jumps. The myological details of vastus intermedius (short fibers, no fusion with other components), therefore, cannot be accounted for as adaptations to leaping. Rather, a primary postural role is indicated for the vastus intermedius, because in normal resting postures, with the knee quite flexed, it alone is continuously active. The existence of a fibrocartilaginous superior patella in the tendon of vastus intermedius, however, is most plausibly related to the complex tensile and compressive stresses generated in the tendon during the completely hyperflexed phase of leaping.The phasic patterning of the quadriceps femoris of Lemur fulvus does not point to any special role of the vastus lateralis or vastus intermedius during walking and galloping; it does indicate very different patterns of muscle recruitment in comparison to those in nonprimate mammals and some anthropoid primates. The forward cross walk (diagonal sequence, diagonal couplets) of primates versus the backward cross gait (lateral sequence) of most other mammals probably accounts for some of these differences. Lemur fulvus lacks the degree of elastic storage and release of kinetic energy in the quadriceps femoris that characterizes the gallop of dogs, cats, and Erythrocebus patas.
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    URL: http://dx.doi.org/10.1002/jmor.1051640305
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    Time-lapse cinemicrographic studies of cell motility during morphogenesis of the embryonic yolk sac of Fundulus heteroclitus (Pisces: Teleosti) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 13-29 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The active motility of the cells of the yolk sac of the living Fundulus embryo was studied by time-lapse cinemicrography with phase contrast optics. In the teleost, the yolk sac lies peripheral to the body of the embryo proper and consists of a fluid-filled space bounded above by a superficial epithelium, the enveloping layer (EVL), and below by the yolk syncytial layer (YSL). The cell types treated in the present study are the enveloping layer epithelial cell, the stellate cell which lies in a layer flattened on the inner surface of the EVL, the epithelioid deep cell, the yolk sac amoebocyte, the yolk sac endothelial cell and the yolk sac melanoblast. The most actively motile cells examined in the present study are the yolk sac amebocyte and the melanoblast, which emigrates from the embryo proper at stages 19-21. The amoebocytes are compact rounded cells that move very rapidly by the extension of lamellipods with scalloped margins. The amoebocytes wander over the yolk sac in an apparently undirected fashion and invade the embryo proper when they happen to encounter it, moving between cells of the lateral mesoderm. The melanoblasts migrate by the gradual extension of elongated branching processes. Cells are sometimes monopodial, with movement being parallel to the long axis of the cell. Alternatively, movement may be perpendicular to the predominant long axis, with processes being extended alternatively from opposite ends of the cell obliquely forward, so the path described is a zig-zag to either side of the overall direction of movement. Although the melanoblasts show irregularity in their movement, the predominant direction of initial movement is away from the embryo proper. The major yolk sac blood vessels form in situ by the collective activities of presumptive endothelial cells that enclose volumes of the yolk sac space with sheet-like processes from the cell body and from the extensions that connect cells into networks.
    Additional Material: 17 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051650103
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051650201
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    Morphometrics of the skeleton of Dermophis mexicanus (Amphibia: Gymnophiona). Part I. The vertebrae, with comparisons to other species (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 117-130 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Morphometric analysis of vertebral structure in caecilians (Amphibia: Gymnophiona) is presented. Ontogenetic variation in Dermophis mexicanus is analyzed through the 100+ vertebrae composing the column. Vertebral structure in adult D. mexicanus is compared with that in Ichthyophis glutinosus and Typhlonectes compressicauda. Centra of the atlas, second, tenth, 20th, and 50th vertebrae grow at allometrically different rates in D. mexicanus, though the 20th and 50th are not significantly different, Growth appears significantly slower in several dimensions of anterior and posterior vertebrae relative to midtrunk vertebrae in all three species. Mensural patterns throughout the entire column are similar in the terrestrial burrowers D. mexicanus and I. glutinosus; patterns in the aquatic T. compressicauda differ substantially from those of the burrowing species and are strongly influenced by allometry. Of the 112 D. mexicanus examined, 13.4% had vertebral anomalies, usually fusions.
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  • 74
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    Comparative studies on the statoblasts of higher phylactolaemate bryozoans (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 131-155 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Statoblasts of five higher phylactolaemates were compared morphologically. As a result, they were divided into two groups: Group I comprising Lophopus crystallinus, Lophopodella carteri, and Pectinatella gelatinosa, and Group II comprising Pectinatella magnifica and Cristatella mucedo. These two groups are thought to represent independent evolutionary series. In Group I and in P. magnifica, the statoblasts are curved to varying degrees after the manner of a saddle. When the dorsal and ventral valves are flattened, therefore, the contour is different between the two. In Group I, the outermost layer of a mature statoblast is hard-gelatinous and basophilic; it remains intact after the statoblast is set free. The statoblast does not float until it is dry, and the float is similar in size on both valves. In Group II, a mature statoblast is covered by a softgelatinous basophilic layer, which decays after the statoblast is released. The statoblast floats without drying, and the float is better developed on the dorsal valve than on the ventral. Moreover, in the members of Group II, large yolk granules are first formed, followed by much smaller yolk granules. When their statoblasts are treated with KOH, the shell is separated completely into two valves. These characters are common to many lower phylactolaemates. By contrast, in L. carteri and P. gelatinosa, the yolk granules are uniformly small and the capsule proper resists KOH treatment. On these points, L. crystallinus is somewhat different from these two species, suggesting its primitive nature.
    Additional Material: 62 Ill.
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  • 75
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    Fetal tooth development and adult replacement in Dermophis mexicanus (Amphibia: Gymnophiona): Fields versus clones (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 203-216 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Teeth of fetuses of a caecilian, Dermophis mexicanus (Amphibia: Gymnophiona), show ontogenetic variation in crown structure from small, multidenticulate, and non-pedicellate to larger, spoon-shaped, pedicellate teeth with a single apical spike. Number of denticles decreases as enamel-secreting cells mature. Numbers of teeth and of tooth rows increase ontogenetically. A fetal vomeropalatine set of teeth is present in D. mexicanus but absent in species previously examined. Teeth transitional to the adult shape and arrangement appear shortly before birth. The transition is correlated with birth, not fetal size. There is relatively little increase in numbers of teeth during the juvenile period. The pattern of development does not fully agree with either morphogenetic field theory or with clone theory, both as defined by Osborn ('78). Sequence of initiation is appropriate to either. Tooth shape changes agree with aspects of clone theory. Multiple rows of fetal teeth and the transition to adult follow field theory. Clone theory holds that patterns of development and shape are self-regulated, field theory that they are controlled extrinsically. I suggest that substances regulating differentiation mediate early development, and hormones later development, including inception of adult teeth, and are comparable to “field substances” influencing primordia that originate according to clone theory. Components of both theories are appropriate to analyzing tooth development phenomena.
    Additional Material: 9 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051660207
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  • 76
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051660301
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    Pheromone glands of microcaddisflies, (Trichoptera: Hydroptilidae)Journal paper no. 925. Montana Agricultural Experimental Station. (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 9-12 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Previously unreported structures found on the head and thorax of several species of microcaddisflies (Trichoptera: Hydroptilidae) are described. Depending on the species, these presumptive pheromone-producing glands are found either (1) on the basal segment of the antenna, (2) on movable and immovable occipital sclerites, (3) as eversible organs from the occipital area of the head, or (4) on structures which are attached near the bases of the front wings.
    Additional Material: 11 Ill.
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  • 78
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    The morphology of dermal chromatophores in the infrared-reflecting glass-frog Centrolenella fleischmanni (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 37-44 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology and organization of chromatophores in the neotropical glass-frog, Centrolenella fleischmanni (family Centrolenidae), were studied with both light and electron microscopes. Four types of pigment cells are described in the dorsal skin. The fine structure of two chromatophores corresponds to the typical amphibian xanthophore and iridophore; one is similar to the unusual melanophore found in phyllomedusine hylids; the fourth cell type is unlike any chromatophore previously described. Pigment granules in the unusual chromatophore are moderately electron-dense and have an irregular shape, suggesting a fluid composition. This pigment appears to be laid down in organelles similar in appearance to pterinosomes. The organization of pigment cells in this species differs from that of other green, leaf-sitting frogs in that there are few discrete groups resembling “dermal chromatophore units.” It is suggested that the unusual new pigment cell contributes significantly to the overall green color of C. fleischmanni.
    Additional Material: 11 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051630106
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  • 79
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051630201
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  • 80
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    Intralamellar neurohemal complexes in the cerebral commissure of the leech Macrobdella decora (Say, 1824): An electron microscope study (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 157-165 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Electron microscopy of the cerebral ganglionic commissure of the leech Macrobdella decora (Say, 1824) revealed numerous neurosecretory axons terminating in the neural lamella of both the inner and outer capsules, and in the neural lamella deep within the neuropile. The proximal protions of the terminals, with an investment of glial tissue, contain either numerous large homogeneously electron dense granules, or numerous large granules of varying electron density. The distal portions, often devoid of glia, display numerous infoldings, omega profiles, and electron dense focal sites, and contain numerous neurosecretory granules, small lucent vesicles, and, occasionally, acanthosomes. Statistical analysis of the size distribution and morphology of the neurosecretory granules showed that in many individual terminals the granules are not significantly different from those seen within four groups of neurosecretory cells found in the cerebral ganglion. These terminals, because of their diffuse nature, probably represent a neurohemal complex of a primitive nature. The term “intralamellar complexes” is proposed to describe the form and location of these neurosecretory terminals.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051630204
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  • 81
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051630301
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    The secretory response in dissociated acini from the rat submandibular gland (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 219-230 
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    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Rat submandibular gland was dissociated by enzymatic digestion with collagenase and hyaluronidase, followed by mild mechanical shearing and filtration through a nylon mesh. The dissociated cell populations contained predominantly groups of acinar cells which maintained their acinar arrangement. The morphological and functional viability of the cells was confirmed by electron microscopic examination and a normal secretory response to β-adrenergic or cholinergic stimulation was observed. Both isoproterenol (IPR) and carbachol caused the fusion of secretory granules into large vacuoles which were also continuous with the lumen, and into which the secretory product was released. Secretion was assessed quantitatively from the incorporation of 14C-glucosamine into the acinar cells and its subsequent release into the culture medium as labelled glycoprotein. IPR stimulated secretion to 125% of untreated controls in the concentration range 5 × 10-5 to 5 × 10-7 M, and to 110% of controls at 5 × 10-8 M, after 40 min incubation. Carbachol stimulated secretion to 131% of controls at 5 × 10-5 M and to 115% at 5 × 10-6 M but had no effect at 5 × 10-7 or 5 × 10-8 M. The secretory response was blocked by the respective β-adrenergic and cholinergic antagonists, propranolol and atropine. These findings show that dissociated rat submandibular acinar cells provide a useful in vitro model for the study of mucus synthesis and secretion.
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    A scanning electron microscope study of the mesothoracic and metathoracic scolopophorous organs of Lethocerus (Belostomatidae-heteroptera) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 27-35 
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    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The presence of scolopophorous organs in aquatic Heteroptera has been reported in a number of species. This study presents a morphological investigation of these sensory structures of Lethocerus (Belostomatidae) as observed with the scanning electron microscope (SEM). Paired mesothoracic and metathoracic organs are present. Externally, each sensory structure consists of a raised sensory membrane. The distal-most portion consists of thickenings of this sensory membrane (sclerite). The receptor neurons of the mesothoracic organ are of two types - one discolopidial sensillum and 12 monoscolopidial sensilla. The former is attached to the internal wall and distal thickening of the sensory membrane, while the latter are dispersed throughout the interior and attached to the internal wall of the sensory membrane. The structure of the organs suggest that an effective stimulus could be a compression of the membrane. A discussion of possible functions (pressure reception and hearing) is included.
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  • 84
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    Scanning electron microscopy and distribution of specialized mechanoreceptors in the texas rat snake, Elaphe obsoleta lindheimeri (Baird and Girard) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 163 (1980), S. 59-67 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Scanning electron microscopy (SEM) of the surface tubercles of a specialized mechanoreceptor found within the head of Elaphe obsoleta lindheimeri indicates that the tubercle consists of a craterlike structure with a peg emerging from its center. After removal of the outer keratinized layers of the epidermis, the SEM discloses a replicate tubercle on the underlying alpha keratin layer. Over 6000 tubercles were found within a single snake. The mechanoreceptors were more densely concentrated on anterior scales, and their number appears to be species specific so that they are more concentrated in snakes with smaller heads than in those with larger ones.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051630108
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  • 85
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051640301
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  • 86
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    Hopping locomotion in a nematode: Functional anatomy of the caudal gland apparatus of Theristus caudasaliens sp. n. (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 164 (1980), S. 265-285 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The interstitial nematode Theristus caudasaliens n. sp. normally locomotes by hopping on the left side of its tail tip, a mode of locomotion that is unique among nematodes. The animal uses its caudal glands and caudal musculature to perform the hops, attaching itself momentarily between hops with the glands and executing the hops by straightening and curling the posterior part of its body.The caudal gland apparatus can be seen by electron microscopy to consist of five gland cells of two different types. Three of these cells, termed viscid glands, are involved in adhesion of the animal to substrates and produce ovoid granules with a central dense band. The other two cells are characterized by smaller, lessdense granules and presumably function in releasing the animal from substrates. The ducts of both gland types extend to the tail tip where they terminate in a common crescent-shaped space. Their secretions are released to the outside through two pores on the left side of the tail tip. There is no spinneret valve in this nematode. The muscles of the tail and of the mid-body region are developed to the same extent.The caudal gland apparatus can be compared with the duo-gland adhesive organs of other interstitial animals, but its homology with either these organs or the caudal glands of other nematodes is uncertain. Theristus caudasaliens is described as a new species.
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    URL: http://dx.doi.org/10.1002/jmor.1051640304
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  • 87
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    Bifurcate sensilla on the tarsi of female black flies, Simulium venustum (Diptera: Simuliidae): Contact chemosensilla adapted for olfaction? (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 1-11 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The ventral surface of the most proximal tarsomere of each mesothoracic leg of the female black fly, Simulium venustum Say, bears approximately 60 bifurcate sensilla. Externally, a sensillum appears as a hair set into an asymmetric socket and with the distal tip flattened into two flared lobes. A single pore opens into a short groove at the base of the lobes. The hair shaft is divided into two lumina, one of which contains the dendrites. Each sensillum is innervated by four neurons, the dendrites of which extend unbranched to the pore. Sensillum liquor bathes the dendritic tips and extends through the pore into the adjacent groove and across part of the lobes. A sieve-like structure exists in the pore region of many if not all sensilla. At least two sheath cells are associated with each sensillum.It is suggested that, although the bifurcate sensilla have the internal structure associated with known contact chemosensilla, they have secondarily acquired an olfactory function which is facilitated by the flattened lobes which increase the adsorptive surface area.Along each side of the bifurcate sensilla is a row of sturdy spines, each innervated by a neuron with a tubular body, a characteristic of cuticular mechanoreceptors. These spines are likely tactile sensilla.
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    URL: http://dx.doi.org/10.1002/jmor.1051650102
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  • 88
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    Structure of the dermal scales in gymnophiona (Amphibia) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 41-54 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Histology and cytology of dermal scales of the gymnophionans Ichthyophis kohtaoensis and Hypogeophis rostratus reveal their structure and the nature of their mineralization.Dermal scales are small flat disks set in pockets in the transverse ridges of the skin. Each pocket contains several scales of various sizes. A ring of “hypomineralization” of varying diameter may occur on scales of a particular dermal pocket but bears no relation to the diameter of these scales.Three different layers form the scales and are seen on sections perpendicular to the surface. The cells of the basal layer lie deepest. Each of the two or three more superficial fibrous layers is composed of bundles of fibres that are oriented in parallel. The orientation varies among layers. The striation of the fiber scales has a periodicity comparable to that of the surrounding dermal fibers. Squamulae form a discontinuous layer on the scale surface and are the only mineralized part of the scale. The minerals are deposited both on the collagen fibers passing from the fibrous layers into the squamulae, and in the interfibrillar spaces. Spherical concretions, either isolated or coalescent, reaching up to 1 μm, are found on the surface of the squamulae.The dermal scales of Gymnophiona present some analogies with those of evolved bony fishes. Their characteristics could make them an original model for the study of mineralization.
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    Light and electron microscopic studies of crayfish hemocytes (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 67-83 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Using light and electron microscopy, three hemocyte types are described in the hemolymph of the crayfish. The coagulocyte comprises 65% of the total hemocyte number and contains medium-sized cytoplasmic granules, abundant dilated rough endoplasmic reticulum, and a highly developed Golgi complex. It rapidly undergoes cytolysis in vitro and participates in coagulation by releasing the contents of its granules to the hemolymph. The granulocyte comprises 31% of the total hemocyte number and is capable of phagocytosis. It contains large, irregularly shaped cytoplasmic granules, a moderately developed Golgi complex, and moderate amounts of non-dilated rough endoplasmic reticulum. During coagulation in vitro, the cell attaches and spreads onto the substratum; this is followed by a slow intracellular granule breakdown and cytolysis. The amebocyte comprises 4% of the total hemocyte number and it is also capable of phagocytosis. It possesses small cytoplasmic granules, many vacuoles, a moderately developed Golgi complex, and large amounts of smooth endoplasmic reticulum. It is distinguished from the other two cell types by being stable and motile in vitro.
    Additional Material: 35 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1051650107
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    Intrinsic organization of snake lateral cortex (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 85-116 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Lateral cortex is the most laterally placed of the four cortical areas in snakes. Earlier studies suggest that it is composed of several subdivisions but provide no information on their organization. This paper first investigates the structure of lateral cortex in boa constrictors (Constrictor constrictor), garter snakes (Thamnophis sirtalis), and banded water snakes (Natrix sipedon) using Nissl and Golgi preparations; and secondly examines the relation of main olfactory bulb projections to the subdivisions of lateral cortex using Fink-Heimer and electron microscopic preparations.Lateral cortex is divided on cytoarchitectonic grounds into two major parts called rostral and caudal lateral cortex. Each part is further divided into dorsal and ventral subdivisions so that lateral cortex has a total of four subdivisions: dorsal rostral lateral cortex (drL), ventral rostral lateral cortex (vrL), dorsal caudal lateral cortex (dcL) and ventral caudal lateral cortex (vcL). Systematic analyses of Golgi preparations indicate that the rostral and caudal parts each contain distinct populations of neurons. Rostral lateral cortex contains bowl cells whose dendrites arborize widely in the outer cortical layer (layer 1). The axons of some bowl cells can be traced medially into dorsal cortex, dorsomedial cortex and medial cortex. Caudal lateral cortex contains pyramidal cells whose somata occur in layers 2 and 3 and whose dendrites extend radially up to the pial surface. In addition, three populations of neurons occur in both rostral and caudal lateral cortex. Stellate cells occur in all three layers and have dendrites which arborize in all directions. Double pyramidal cells occur primarily in layer 2 and have dendrites which form two conical fields whose long axes are oriented radially. Horizontal cells occur in layer 3 and have dendrites oriented concentric with the ependyma. Fink-Heimer preparations of snakes which underwent lesions of the main olfactory bulb show that the primary olfactory projections to cortex are bilateral and restricted precisely to rostral lateral cortex. Electron microscopic degeneration experiments indicate that the olfactory bulb fibers end as terminals which have clear, spherical vesicles and asymmetric active zones. The majority are presynaptic to dendritic spines in outer layer 1.These studies establish that lateral cortex in snakes is heterogeneous and contains two major parts, each containing two subdivisions. The rostral and caudal parts have characteristic neuronal populations. Primary olfactory input is restricted to rostral lateral cortex and seems to terminate heavily on the distal dendrites of bowl cells. Axons of some of these cells leave lateral cortex, so that the rostral lateral cortex forms a direct route by which olfactory information reaches other cortical areas. The functional role of caudal lateral cortex is not clear.
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    The caudal neurosecretory system of Poecilia sphenops (Poeciliidae) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 157-165 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The caudal neurosecretory system of the molly, Poecilia sphenops (Poeciliidae) was studied by light and electron microscopy. In this species the cell bodies form a focal nuclear group in the caudal spinal cord. The neurosecretory cells are in contact with glial elements, axon terminals, and the lumen of the central canal. The axons of the neurosecretory cells form a definitive tract, which leaves the spinal cord proper to penetrate a well defined neurohemal organ, the urophysis. The urophysis contains an abundance of neurosecretory granules within the neurosecretory axonal processes. This study is the first ultrastructural study of the caudal neurosecretory system in this family of fishes, which has been used as a neuroendocrine model. This species acclimates easily to the laboratory aquarium and may be most suitable for further studies on the effects of changes in external salinity on the caudal neurosecretory system.
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    URL: http://dx.doi.org/10.1002/jmor.1051650204
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    Scaling of subunit structures in book lungs of spiders (Araneae) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 167-174 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The relationships between dimensions of book lung subunits were measured and analyzed as a function of body size in diverse spiders over a body mass range of 3.4 to 3,190 mg. Book lungs are the characteristic respiratory gas exchange organs in these arachnids. Actual gas exchange occurs across numerous air-filled cuticular plates, which invaginate hemolymph sinuses within the abdomens of these animals. Characteristic linear dimensions of these air-filled compartments reflecting diffusion paths scaled to the 0.2 power of body mass and showed only a fourfold increase over the size range in the sample. This deviation from isometric scaling in the direction obtained and its numerical similarity to scaling of alveolar dimensions to body size in vertebrates was interpreted as an adaptation to reduce diffusion distances between these compartments and vascular fluids. Conversely, lengths and widths of these plates scaled to the one-third power of body mass, isometric scaling, and increased between six-and eightfold over the size range. This result is consistent with the hypothesis that respiratory gas distribution within spider lungs is achieved by convective mixing as has been recently hypothesized.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051650205
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  • 93
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    Erratum (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 223-223 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051650209
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  • 94
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    Fine structure of the midgut posterior caeca in the crustacean Orchestia in intermolt: Recognition of two distinct segments (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 261-284 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This study carried out on the posterior caeca of Orchestia in intermolt by means of light and electron microscopy shows that the diverticula of the midgut consist of two segments which are different from an anatomical point of view. The distal segment is in close relationship to the dorsal blood vessel, whereas the proximal segment, twice as long as the distal one, only touches the haemocoel. The cells of the distal segment are characterized by a brush border, some apical extrusions, a great number of ribosomes, rough endoplasmic reticulum, often associated with the mitochondria, the matrix of which is clear, high activity of the Golgi complexes, and a great development of extracellular channels. All these features indicate an activity in synthesizing proteins and transport. In the proximal segment, the cells are characterized by a striated border, reduced intercellular space, and especially by a great development of the smooth endoplasmic reticulum sometimes associated with mitochondria having a dense matrix. These diverse features indicate absorption ion and water transport. From an ultrastructural point of view, the posterior caeca of Orchestia cannot be considered homologous to the Malpighian tubules. Whereas during molting the posterior caeca of Orchestia are sites of calcium storage, during intermolt they are probably involved in the processes of water and mineral regulation and excretion.
    Additional Material: 22 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051650305
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  • 95
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    Spermathecal ultrastructure of the insect Rhodnius prolixus stal (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 1-25 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The paired spermathecae of Rhodnius are simple tubular out-pocketings of the common oviduct. Each consists of a short muscular proximal duct and the distal glandular region with a blind tapering end. The spermathecal wall has a cuticular intima, slender columnar epithelial cells and ensheathing longitudinal striated muscle, connective tissue, tracheoles, and nerves. Glandular epithelial cells possess an elaborate apical secretion-filled tubular inpocketing with an extensively folded plasma membrane. Laterally, cells interact by desmosomes, septate desmosomes, and extensive interdigitations. The cytoplasm is rich in longitudinally oriented microtubules associating with membrane densities along the invagination, lateral, and basal plasmalemmae. Apical concentration of mitochondria suggests their role in secretion or ion transport. The possible role of the spermathecae in maintaining the stored luminal sperm and its role in transmitting the mating stimulus is considered in light of the epithelial ultrastructure. The ultrastructure of the spermathecae of Rhodnius differs significantly from that of other insects.
    Additional Material: 35 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051660102
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  • 96
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    Innervation of the parathyroid in the european starling (Sturnus vulgaris) (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 65-80 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Anatomical studies were conducted to characterize the source, type, and distribution of parathyroid gland innervation in European starlings. Denervation experiments demonstrated that the parathyroid glands and adjacent carotid bodies are innervated by nerve fibers originating in the nodose ganglion of the vagus nerve. In the parathyroid parenchyma, these fibers terminate adjacent to chief cells or near vascular smooth muscle. Vagal fibers also form synapses with catecholamine-containing glomus cells of the carotid body. Blood that first perfuses the carotid body subsequently perfuses the parathyroid parenchyma. These observations suggest that vagal innervation may influence parathyroid function in starlings either through direct chief cell innervation or through alteration of vascular perfusion. A neurohemal relationship also may exist between the carotid body and parathyroids.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051660106
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  • 97
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    Functional morphology of the masticatory musculature of the rodent subfamily microtinae (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980), S. 205-222 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Voles and lemmings are the most successful group of graminivorous rodents, but the adaptations allowing them to enter this niche are not fully known. Dissections of the masticatory musculature of the 12 genera and subgenera of North American microtines show an increase in the potential anterior vector component and in the potential vertical vector component of these muscles relative to the molar tooth row. The result is a separation of the compressive and propulsive functions of the masticatory muscles during the power stroke of mastication. This has led to the formulation of a propalinal “swing” hypothesis which is supported by vector analyses of the musculature.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051650208
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  • 98
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    Masthead (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 165 (1980) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051650301
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  • 99
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    Cytodiffrentiation in the accessory glands of Tenebrio molitor. VI. A congruent map of cells and their secretions in the layered elastic product of the male bean-shaped gland (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 289-322 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology of the bean-shaped accessory glands (BAGs) of males of Tenebrio molitor is described. All cells in the secretory epithelium are long and narrow (300-400 mμ × 5 mμ). The seven types of secretory cells are distinguished from one another by the morphology of their secretory granules. Granule substructure varies from simple spheres with homogeneous electrondense contents to complex forms with thickened exterior walls or with crystalline and membranous contents. Individual cell types were mapped by staining whole glands with Oil Red O, and the cell distributions were confirmed by wax histology and ultramicroscopy. The secretions of all seven cell types form a secretory plug composed of seven layers. During mating, the secretory plug from each BAG is forced into the ejaculatory duct by contractions of a sheath of circular muscle. The mirror image plugs from symmetrical BAGs fuse and are transformed into the wall of the spermatophore.
    Additional Material: 69 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051660304
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  • 100
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    Announcement and call for papers. International conference on factors and mechanisms influencing bone growth (1980)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 166 (1980), S. 387-387 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1051660307
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