OVERHEATING IN BED AS AN IMPORTANT FACTOR IN MANY COMMON DERMATOSES

Background. Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. Methods. In order to test the hypothesis, 12 “clean-skinned” subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. Results. All the subjects were too hot by 3 to 4°C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the “heat-sink” area. Conclusions. The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. “Lifestyle” modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive.     

Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 3. 7-(3,5-Disubstituted [1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives

The syntheses of a series of 7-(3,5-disubstituted [1,1'-bephenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported. Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl moiety is substituted by chloro or methyl groups at positions 3 and 5 and a fluoro group at position 4'. These substitutions, followed by resolution, provided compounds 100(+) and 110(+) with 2.8 times the intrinsic inhibitory activity of compactin. Compound 100(+) was shown to possess the same chirality in the lactone ring as compactin by single-crystal X-ray crystallography.     

A phase II study of 5-fluorouracil and leucovorin in advanced carcinoma of the esophagus.

Thirty-five patients with advanced epidermoid carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin 20 mg/m2, day 1-5 every 28 days. Six patients had a partial response (95% confidence limit, 7-35%) with a median response duration of 32 weeks. The median survival time of the patients on study was 14 weeks. The toxicity was acceptable, with only two patients experiencing severe hematologic toxicity and one patient experiencing severe nausea and vomiting. The addition of leucovorin at this dose level in this population of patients with advanced disease does not appear to enhance the activity of 5-FU for patients with squamous cell cancer of the esophagus. Since only a small percentage of patients experienced significant toxicity, a higher response rate could be achieved in patients treated with the maximally tolerated dose.     

Subtype classification of the presynaptic alpha-adrenoceptors which regulate [3H]-noradrenaline secretion in guinea-pig isolated urethra.

1. The following experiments were carried out to investigate the presence and type of functional presynaptic receptors in adrenergic nerves of the guinea-pig urethra. 2. The urethra from male guinea-pigs was incubated with [3H]-noradrenaline and superfused with Tyrode solution in vitro. The fractional secretion of [3H]-noradrenaline evoked by 300 electrical pulses was measured. 3. The [3H]-noradrenaline secretion was positively frequency-dependent, yielding a half-maximal secretion at 8 +/- 5 Hz. Stimulation was usually applied at 5 Hz. 4. The [3H]-noradrenaline secretion was not altered by noradrenaline (1 or 100 microM), norephedrine (1 microM), isoprenaline (0.1 microM), 5-hydroxytryptamine (10 microM), oxotremorine (10 microM), adenosine (0.2 mM), propranolol (1 microM), atropine (1 microM) or 8-phenyltheophylline (10 microM). 5. The [3H]-noradrenaline secretion was enhanced by clonidine (3 microM), chlorpromazine (10 microM), metitepine (1 microM), 4-aminopyridine (0.5 mM), tetraethylammonium (2 mM), 3-isobutyl-1-methylxanthine (4 mM), 8-bromo cyclic AMP (1 mM) and forskolin (25 microM). 6. The alpha-adrenoceptor antagonists rauwolscine, yohimbine, phentolamine, prazosin and AR-C 239 maximally enhanced the [3H]-noradrenaline secretion to about 300% of control. The partial alpha-adrenoceptor agonist oxymetazoline maximally enhanced the secretion to about 200% of control. The order of apparent EC50 values was rauwolscine less than yohimbine less than phentolamine less than oxymetazoline less than prazosin less than AR-C 239.(ABSTRACT TRUNCATED AT 250 WORDS)