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Notes: A 28-year-old man presented with his first leg ulcer at the age of 10 years. With regard to the family history, there was no consanguinity between the parents, and the patient had a brother with similar findings. He had frequent infections in childhood, such as otitis media, tuberculosis, and septic arthritis. At the age of 11 years, he showed photosensitivity, malar erythema, and positive antinuclear antibody test (1 : 40), and systemic lupus erythematosus was diagnosed (〈link href="#f1"〉Fig. 1). This disease was later ruled out because diagnostic criteria were not present.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2411:IJD_2411_f1"/〉Photosensitivity and malar erythema at the age of 11 years (Case 1)At the age of 12 years, the ulcers worsened and did not respond to different treatments (antimicrobials, prednisone), and a diagnosis of pyoderma gangrenosum was suggested. Nevertheless, histopathology rejected such a diagnosis. The disease progressed until the patient presented again to our department.On examination, the ulcers were located on both legs and thighs, had a polygonal form, elevated borders, and necrotic base (〈link href="#f2"〉Fig. 2). They showed edema and induration with multiple scars. Dystrophic nails, saddle nose, hypertelorism, syndactyly, obesity, and deformity of the auricle were observed. Laboratory analysis revealed iron deficiency anemia (hematocrit, 30%), an erythrocyte sedimentation rate of 120 mm/h, an elevated gammaglobulin level (3.79 g%), and an elevated immunoglobulin E (IgE) (3285 U/L). Skin cultures were negative. The rest of the laboratory studies were normal (creatinine, glucose, C3, C4, negative HIV, and normal abdominal examination). The evaluation of cellular and humoral immunity showed normal results; chromosome studies disclosed no abnormalities.〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2411:IJD_2411_f2"/〉Polygonal and deep ulcers on the left thigh (Case 1)A skin biopsy showed no specific abnormalities, except fibroblastic proliferation, inflammation, and ulcers that infiltrated the hypodermis. No signs of vasculitis were found. Multiple histologic analyses had been performed throughout the patient's life without any different findings.Aliquots of urine from the patient and controls were analyzed by capillary zone electrophoresis (CZE) according to the method proposed by Zanaboni et al. (Zanaboni G, Grimm KM, Dyne KM, et al. Use of capillary zone electrophoresis for analysis of iminodipeptides in urine of prolidase-deficient patients. J Chromatogr B 1996; 683: 97–107.) The presence of a large amount of dipeptides, normally absent from control samples, was detected in the patient.There is no specific or effective treatment for prolidase deficiency, but the patient received oral and topical antimicrobials, oral prednisone, 1 mg/kg/day, and thalidomide, 200 mg/day, for 8 months in order to decrease the size of the ulcers and to improve his life quality. Unfortunately, treatment failed.〈section xml:id="abs1-2"〉〈title type="main"〉Case 2The 23-year-old younger brother showed his first lesion at the age of 8 years. He had smaller leg ulcers than his brother, but they were pruriginous (〈link href="#f3"〉Fig. 3). The round ulcers of 2–3 cm in diameter were on the inner part of the thighs. Laboratory analysis revealed hypergammaglobulinemia (26.3 g%), an erythrocyte sedimentation rate of 58 mm/h, splenomegaly, and elevated iminodipeptides in the urine. The evaluation of humoral and cellular immunity showed normal results. Skin biopsy showed no specific abnormalities, but fibrosis and perivascular inflammatory changes were present.〈figure xml:id="f3"〉3〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2411:IJD_2411_f3"/〉Rounded ulcers on the left thigh of the younger brother (Case 2)He was treated with topical antimicrobials, cortisone, and thalidomide, 200 mg/day, for 8 months without response.

Notes: Abstract: Melatonin (0.3 to 0.4 mg/kg) dissolved in 0.5 ml dimethylsulphoxide (DMSO) was injected i.v. into six baboons, and their cardiovascular parameters were monitored. Left ventricular end-diastolic and end-systolic volumes, stroke volume, cardiac output, and left ventricular ejection fraction were measured, using conventional radionuclide ventriculography, and compared to normal values previously established. These parameters were also measured after an i.v. administration of only DMSO. The only statistical significant change due to melatonin was the increase in the cardiac output and left ventricular ejection fraction. With the reduced heart rate the increase in cardiac output implies a positive inotropic action on the heart by melatonin. There are indications that DMSO possibly suppresses cardiovascular actions of melatonin.

Notes: Abstract The baboon under general anaesthesia as a model to assess drug-induced cerebral blood flow changes (Δ CBF) using single-photon emission tomography (SPET) offers great in vivo possibilities but has to comply with demands on control of anaesthesia-related influencing factors, such as P aCO2 changes. The model sought in this study and described here allows control of P aCO2, in the baboon under thiopentone anaesthesia by ventilation, and was evaluated for the functional dependence of Δ CBF vs Δ P aCO2, using SPET technetium-99m hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with controlled ventilation. During the experiment the model was validated for normal reactivity to P aCO2 changes, and subsequently applied to investigate the mechanisms (still uncertain) of CBF increase known to follow administration of the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine intravenously. CBF was measured between two consecutive SPET acquisitions (split-dose method) respectively relating to HM-PAO distributions in the brain before and after the injection of lidocaine. Meanwhile the animals were maintained at constant respiratory rate and volume. The results indicate that the correlation between Δ CBF and the ensuing fall in PaCO2 deviated from the baseline pattern from the model and confirmed a cerebrovascular contribution to the lidocaine-induced CBF increase. This agreed well with mean and systolic blood pressure changes and heart rate.

Notes: Abstract Technetium-99m-labelled immunoglobulin G (99mTc-IgG) is a convenient and useful radio-pharmaceutical for the scintigraphic detection of inflammatory foci. However, unfavourable physiological biodistribution patterns such as high activities in the liver and especially in the kidneys impede the efficacy of this agent. This report describes biodistribution studies in the baboon model of various thiol reduction-mediated 99mTc-labelled immunoglobulins, including human IgG preparations (Sandoglobulin and Sigma: γ-globulins prepared from Cohn fractions II and III) as well as baboon IgG preparations (Sigma: γ-globulins prepared from Cohn fractions II and III and IgG isolated from the serum obtained from specific animals). The biodistribution studies demonstrated differences in kidney concentration, i.e. human IgG (Sandoglobulin) 〉 baboon IgG (cross-over animal experiments with IgG isolated from the serum of the different animals) 〉 human IgG (Sigma)≈ baboon IgG (Sigma)≈baboon IgG (own IgG isolated from the serum of a specific animal, labelled with 99mTc and reinjected). Differences in liver concentration were also observed: human IgG (Sandoglobulin)〈human IgG(Sigma)≈baboon IgG (Sigma)≈baboon IgG (own IgG)≈IgG (cross-over). Characteristic were the relatively high activities in the liver and kidneys compared to those in other organs with high blood supply, and a relatively high retention in the blood pool. The results indicate that the effect of the heterologous antibody system is insignificant. These studies also demonstrate the suitability of the baboon model for evaluation of 99mTc-IgG preparations for scintigraphic purposes and suggest that damage to the Fc portion of the IgG molecule during Sandoglobulin preparation may be the cause of the high kidney accumulation of 99mTc-Sandoglobulin.