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Notes: The effect of γ-hydroxybutyric acid on extracellular glutamate levels in the hippocampus was studied by microdialysis in freely moving rats and in isolated hippocampal synaptosomes. Intra-hippocampal (CA1) perfusion with γ-hydroxybutyric acid (10 nm–1 mm) concentration-dependently influenced glutamate levels: γ-hydroxybutyric acid (100 and 500 nm) increased glutamate levels; 100 and 300 µm concentrations were ineffective; whereas the highest 1 mm concentration reduced local glutamate levels. The stimulant effect of γ-hydroxybutyric acid (100 nm) was suppressed by the locally co-perfused γ-hydroxybutyric acid receptor antagonist NCS-382 (10 µm) but not by the GABAB receptor antagonist CGP-35348 (500 µm). Furthermore, the γ-hydroxybutyric acid (1 mm)-induced reduction in CA1 glutamate levels was counteracted by NCS-382 (10 µm), and it was also reversed into an increase by CGP-35348. Given alone, neither NCS-382 nor CGP-35348 modified glutamate levels. In hippocampal synaptosomes, γ-hydroxybutyric acid (50 and 100 nm) enhanced both the spontaneous and K+-evoked glutamate efflux, respectively, both effects being counteracted by NCS-382 (100 nm), but not by CGP-35348 (100 µm). These findings indicate that γ-hydroxybutyric acid exerts a concentration-dependent regulation of hippocampal glutamate transmission via two opposing mechanisms, whereby a direct γ-hydroxybutyric acid receptor mediated facilitation is observed at nanomolar γ-hydroxybutyric acid concentrations, and an indirect GABAB receptor mediated inhibition predominates at millimolar concentrations.

Notes: A 26-year-old woman presented with a high-grade fever and chills of 2 days’ duration. She complained of associated joint pain, especially in the wrists and knees. One day before admission, tender skin lesions began to develop on the fingers, and subsequently spread to the more proximal extremities. The patient recalled having a sore throat and a nonproductive cough before the onset of the fever and eruption.The past medical history was significant for Gardnerella vaginitis and several urinary tract infections. The patient was taking oral contraceptive pills; her most recent menstruation was 3 weeks before admission. She reported having sexual intercourse with her boyfriend 2 weeks before admission.The patient's temperature was 40 °C. Dermatologic examination revealed a 6-mm, hemorrhagic pustule on an ill-defined pink base, overlying the volar aspect of the left second proximal interphalangeal joint (〈link href="#f1"〉Fig. 1a). Scattered on the upper and lower extremities were occasional round, ill-defined pink macules with central pinpoint vesiculation (〈link href="#f1"〉Fig. 1b). A skin biopsy of the digit revealed a dense neutrophilic infiltrate with leukocytoclasis and marked fibrin deposition in the superficial and deep dermal vessels (〈link href="#f2"〉Fig. 2a). Gram stains demonstrated the presence of Gram-negative diplococci (〈link href="#f2"〉Fig. 2b).〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1720:IJD_1720_f1"/〉Dermatologic appearance. (a) Tender, hemorrhagic pustule overlying the volar aspect of the second proximal interphalangeal joint. (b) Round, ill-defined, pink macule with central pinpoint vesiculation on the forearm〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1720:IJD_1720_f2"/〉Results of skin biopsy. (a) Neutrophilic infiltrate with leukocytoclasis and marked fibrin deposition in a deep dermal vessel (hematoxylin and eosin stain; original magnification, × 100). (b) Gram-negative diplococci within and surrounding a dermal blood vessel (Gram stain; original magnification, × 600)Laboratory findings included leukocytosis (leukocyte count of 20 × 109/L, with 81% neutrophils). Analysis of an endocervical specimen by polymerase chain reaction was positive for Neisseria gonorrhoeae and negative for Chlamydia trachomatis. Throat and blood cultures grew N. gonorrhoeae. Specimen cultures obtained by skin biopsy yielded no growth. Results of serologic analysis for human immunodeficiency virus, hepatitis, syphilis, and pregnancy were negative.Beginning on admission, intravenous ceftriaxone, 2 g, was administered every 24 h for 6 days, followed by oral cefixime, 400 mg twice daily for 4 days. Oral azithromycin, 1 g, was administered to treat possible coinfection with C. trachomatis. By treatment day 4, the patient was afebrile, with the resolution of leukocytosis and symptomatic improvement of arthralgias.

Notes: A 66-year-old woman was referred for evaluation of a rash on the leg. She had a 1-year history of stage IV bronchogenic adenocarcinoma with previous metastases to the right first metatarsal-phalangeal (MTP) joint and a left supraclavicular lymph node. She underwent six cycles of chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ, USA) and carboplatin (Paraplatin; Bristol-Myers Squibb Company, Princeton, NJ, USA) as well as palliative radiation therapy to the metastasis sites. One month after completing radiation therapy, the patient developed a nonpainful rash on the right thigh. This eruption was treated as a herpes zoster infection by her internist with 3 weeks of valcyclovir (Valtrex; Catalytica Pharmaceuticals, Greenville, NC, USA), but without improvement. One month later the leg became painful and swollen and the rash spread up the thigh to involve the groin and vulva. The patient was referred to the dermatology department. Physical examination revealed multiple red, indurated, crusted papules and nodules involving the medial, anterior, and lateral right thigh, labia majora, and suprapubic area. The lesions were grouped and arranged in a dermatomal zosteriform distribution (〈link href="#f1"〉Fig. 1). There was a visible peau d’orange appearance of the right leg with pitting edema. A punch biopsy showed irregular islands of atypical glandular epithelial cells infiltrating the superficial and deep dermis, consistent with metastatic adenocarcinoma (〈link href="#f2"〉Fig. 2a). Immunohistochemistry showed positive staining to thyroid transcription factor (TTF) and cytokeratin 7 (〈link href="#f2"〉Fig. 2b and c). The tissue did not stain with progesterone receptor, estrogen receptor, or gross cystic disease fluid protein (BRST-2). This immunostaining pattern was identical to previous biopsies of the right first MTP joint and left supraclavicular lymph node metastases and is consistent with adenocarcinoma of the lung.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2112:IJD_2112_f1"/〉Eruption on the right thigh with grouped papules and nodules arranged in a zosteriform pattern〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2112:IJD_2112_f2"/〉(a) Punch biopsy showing irregular islands of atypical glandular epithelial cells within the dermis (hematoxylin and eosin; original magnification × 100). (b) Positive staining with thyroid transcription factor (original magnification × 40). (c) Positive staining with cytokeratin 7 (original magnification × 40)