Demeclocycline in the treatment of the syndrome of inappropriate antidiuretic hormone release: with measurement of plasma ADH.
A patient with the syndrome of inappropriate antidiuretic hormone release (SIADH) following head injury and meningitis was studied during treatment with demeclocycline, a drug known to produce a reversible nephrogenic diabetes insipidus. No changes were observed during six days of demeclocycline 1200 mg/24 hr but urine output increased significantly, with the production of a dilute urine, when the dose was increased to 2400 mg/24 hr. The patient lost weight, and all biochemical features of the syndrome were rapidly corrected despite an unchanged fluid intake and despite the persistence of high plasma levels of ADH. The rise in serum sodium was accompanied by mild sodium retention, as measured by external balance and exchangeable sodium. A complication of treatment was the development of acute renal failure possibly induced by a nephrotoxic effect of high circulating levels of demeclocyline. On stopping demeclocyline renal function returned to normal and, after some delay, SIADH returned, and was still present 9 months after initial presentation. This confirms earlier reports of the efficacy of demeclocycline in SIADH; but the authors advise caution against increasing the dose above 1200 mg/24 hr. (+info)
Osmoregulation of vasopressin secretion in patients with the syndrome of inappropriate antidiuresis associated with central nervous system disorders.
To clarify the characteristics of vasopressin (AVP) secretion in patients with the syndrome of inappropriate antidiuresis (SIAD) related to central nervous system disorders, we examined the response of AVP secretion to osmotic stimulus by hypertonic saline infusion and analyzed the possible causative factors in six patients with SIAD associated with head trauma or cerebral infarction. Hyponatremia developed after head trauma in four patients and cerebral infarction in two patients. In all patients the clinical state and laboratory findings fulfilled the criteria for SIAD, which was supported by either nonsuppressible plasma AVP levels or effectiveness of treatments with water restriction, demeclocycline, nonpeptide V2 AVP antagonist or diphenylhydantoin. Although patterns of plasma AVP response to the osmotic stimulus varied, plasma AVP concentrations neither increased nor decreased to undetectable levels with a rise in plasma osmolality. In one patient, plasma AVP levels responded to increasing plasma osmolality when plasma osmolality normalized; in which the threshold and the sensitivity of osmostat were normal. In two other patients, AVP secretion responded to plasma osmolality after the treatment. The changes in AVP secretion were not due to nonosmotic stimuli for AVP release. In conclusion, this study shows that patients with SIAD and central nervous system disorders may have persistent AVP secretion with a loss of hypotonic suppression such as found in patients with adrenal insufficiency or depletional hyponatremia in central nervous system disorders, indicating that careful evaluation is necessary to determine the relationship between persistent AVP secretion and the pathogenesis of hyponatremic disorders. (+info)
Mechanism of the incidental production of a melanin-like pigment during 6-demethylchlortetracycline production in Streptomyces aureofaciens.
The secondary metabolite 6-demethylchlortetracycline (6-DCT), which is produced by Streptomyces aureofaciens, is used as a precursor of semisynthetic tetracyclines. Strains that produce 6-DCT also produce a melanin-like pigment (MP). The correlation between MP production and 6-DCT production was investigated by using S. aureofaciens NRRL 3203. Production of both MP and 6-DCT was repressed by phosphate or ammonium ions, suggesting that syntheses of these compounds are controlled by the same regulators. Ten chlortetracycline-producing recombinants were derived from 6-DCT-producing mutant NRRL 3203 by gene replacement. All of the recombinants produced chlortetracycline but not MP, indicating that MP production is the results of a defect in the 6-methylation step and suggesting that the polyketide nonaketideamide is a common intermediate leading to MP as well as 6-DCT. To further examine the possibility that MP might be synthesized via the 6-DCT-biosynthetic pathway, mutants defective in 6-DCT biosynthesis were derived from a 6-DCT producer. Some of these mutants were able to produce MP, while others, including mutants with mutations in the gene encoding anhydrotetracycline oxygenase, an enzyme catalyzing the penultimate step in the pathway, produced neither 6-DCT nor MP. Production of 6-DCT and production of MP were restored simultaneously by integrative transformation with the corresponding 6-DCT-biosynthetic genes, indicating that some of 6-DCT-biosynthetic enzymes are indispensable for MP production. These findings suggest that a defect in the 6-methylation step results in redirection of carbon flux from a certain intermediate in the 6-DCT-biosynthetic pathway to a shunt pathway and results in MP production. (+info)
Re-evaluation of a randomized controlled trial of antibiotics for minor respiratory illness in general practice.
BACKGROUND: A systematic review examining the efficacy of antibiotics in acute respiratory illness concluded that antibiotics are of little benefit. However, that review was based on analysis of only six randomized controlled trials, one of which was excluded because its analysis included patients with multiple episodes of illness; treatment group, either antibiotic or placebo, might have confounded the likelihood of suffering a subsequent episode of illness. METHODS: This previously excluded randomized controlled trial of 301 patients with symptoms of minor respiratory illness was re-analysed to examine the efficacy of antibiotic versus placebo in terms of resolution of symptoms, most particularly cough. RESULTS: Antibiotic had no impact on the resolution of symptoms of cough at 1 and 2 weeks, respectively; adjusted odds ratio 1.2 [95% confidence interval (CI) 0.7--2.1] and 0.8 (95% CI 0.4--1.6). In those 220 (73%) individuals who suffered a cough, 48 (44%) and 19 (17%) of patients taking placebo were still coughing after 1 and 2 weeks, respectively. CONCLUSION: It appears that an antibiotic is likely to have, at best, a marginal impact on resolution of symptoms for most patients with minor respiratory illness in the community. (+info)
Demeclocycline in the treatment of the syndrome of inappropriate secretion of antidiuretic hormone.
Fourteen patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been treated with demethylchlortetracycline (demeclocycline) 1200 mg daily. In 12 patients the underlying lesion was malignant. The serum sodium returned to normal (greater than 135 mmol/l) in all patients after a mean of 8.6 days (SD +/- 5.3 days). Blood urea rose significantly from the pretreatment level of 4.2 +/- 2.3 mmol/l to 10.1 +/- 5.1 mmol/l at ten days (P less than 0.001). The average maximum blood urea was 13.4 +/- 6.8 mmol/l. In four patients the urea rose above 20 mmol/l, and in two of these demecyocycline was discontinued because of thie rise. The azotaemia could be attributed to a combination of increased urea producation and a mild specific drug-induced nephrotoxicity. Discontinuation of demeclocycline in six patients led to a fall in serum sodium, in one case precipitously, and return of the urea towards normal levels. Demeclocycline appears therefore to be an effective maintenance treatment of SIADH, and the azotaemia that occurs is reversible and probably dose dependent. (+info)
Double-blind comparison of two regimens in the treatment of nongonococcal urethritis. Seven-day vs 21-day course of triple tetracyclinc (Deteclo).
In a double-blind comparison of two regimens of triple tetracycline (Deteclo, Lederle) in the treatment of nongonococcal urethritis, 68 (88.6%) of 70 patients treated with one tablet twice for 21 days and seen four weeks after starting therapy had satisfactory results. This was significantly better than the findings among the 73 patients treated with one tablet twice daily for seven days and followed for four weeks, among whom only 47 (64.4%) had satisfactory results. Results were also better for the group treated with the 21-day regimen at three months afer the start of treatment. When analysed individually at four and 12 weeks, urethral discharge, urethral Gram-stained smears, and first-glass urine test all gave similar results, which were markedly better than those before treatment. It appears that the longer course of treatment it indicated where any regular partner may not be treated. Slightly fewer patients had satisfactory results among those who admitted consuming alcohol than among those who did not. Chlamydiae-negative patients, treated for seven days, had fewer clinically satisfactory results than other sub-groups. (+info)
Microbiological degradation of tetracyclines.
Meyers, Edward (Squibb Institute for Medical Research, New Brunswick, N.J.) and Dorothy A. Smith. Microbiological degradation of tetracyclines. J. Bacteriol. 84:797-802. 1962-The degradation of tetracyclines by an ascomycete, Xylaria digitata, was demonstrated. Washedcell suspensions were capable of degrading tetracycline, 5-hydroxytetracycline, 7-chlortetracycline, 7-chlor-6-demethyltetracycline, 2-acetyl-2-decarboxamido-5-hydroxytetracycline, and 12-alpha-deoxytetracycline. The influence of environmental conditions upon the degradation of tetracycline was investigated. A nonantibacterial, nonfluorescent product was located from the degradation of (14)C 5-hydroxytetracycline. Evidence indicated that neither the A nor D ring of 5-hydroxytetracycline is attacked. Acetone powders, lyophilized powders, and cell-free extracts exhibited a relatively limited substrate specificity compared to the washed cells. (+info)
BRUCELLOSIS IN A VETERAN'S HOSPITAL, 1963.
In Canada, about 100 sporadically occurring cases of brucellosis are reported yearly. Three patients were admitted to one Montreal hospital in the first seven months of 1963; all were employed in or around a packing plant. One had pain and electrocardiographic changes suggestive of Brucella myocarditis; he recovered promptly. Symptoms of neurasthenia and anxiety are common and were observed in two of these three cases. Two had positive blood cultures; the third showed conclusive agglutination to Br. abortus (1:10,240). In some patients with frequent previous exposures to infection the agglutination response may be equivocal and difficult to interpret. All three patients responded well to tetracycline; streptomycin and corticosteroids also have a role in the therapy of some cases. There may also be some place for combined antibiotic and vaccine therapy. The program of control of the disease in cattle in Canada is aimed at eradication by 1967. (+info)