Megestrol acetate-induced adrenal suppression.
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Biomedical subjects
Publications and source records attributed to R Fonseca.
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Chondrosarcoma of the larynx is a rare, slow-growing malignant tumor. One hundred and fifty cases of this entity have been reported in the literature. In 75% of cases the site of involvement was the cricoid cartilage, while 20% have involved the thyroid cartilage. The tumor presents as a space-occupying lesion in the subglottic region, or as a neck mass. An insidious, slowly progressing disease course associated with hoarseness and dyspnea accounts for usual delays in arriving at a diagnosis. We report our experiences with six cases of this entity and discuss a diagnostic and therapeutic approach. Whenever possible a conservative surgical management should be attempted.
Systemic vasculitis are an heterogeneous group of diseases characterized by inflammatory infiltration and necrosis of blood vessel walls. Antineutrophil cytoplasmic antibodies (ANCA) with different immunofluorescent patterns (C or P) have been described as serological markers of some of these diseases and some types of glomerulonephritis. The presence of ANCA by immunofluorescence on normal fixed polymorphonuclear neutrophils was investigated in 182 patients. Results are depicted in Table 1. ANCA was present in 16/17 (94%) patients with Wegener Granulomatosis (W.G.) (ACR criteria) (p < 0.001). In 14 out of the 16 (82%), the pattern was ANCA-C (associated in 10 with ANCA-P) and only ANCA-P was observed in the remaining two. The presence of ANCA was associated with active disease: 15/16 samples of active patients and 3/9 of inactive patients were ANCA positive (p < 0.01). Among the other groups, ANCA-C was detected in only one patient with isolated subglottal stenosis. The specificity of ANCA-C for W.G. was 99%. ANCA-P was also detected in 3/49 (6%) patients with connective tissue disorders and in 3/63 (5%) patients in chronic hemodialysis with exclusive or predominant renal disease of unknown etiology. Three additional ANCA positive patients with known diagnosis (2 W.G. and 1 Systemic Lupus Erythematosus) were also in hemodialysis in the same unit. Thus, an ANCA related mechanism may be involved in the pathogenesis of approximately 10% of cases undergoing this procedure. None of 45 sera submitted for the detection of antinuclear antibodies were ANCA positive. Detection of ANCA (especially C pattern) may be of help in the diagnosis of W.G. and in monitoring clinical activity of the disease.
This Latin American study assessed in the general practice setting the efficacy and tolerance of once-daily doxazosin in the treatment of mild or moderate essential hypertension (sitting diastolic blood pressure, 95 to 115 mm Hg). Patients (n = 220) were treated with doxazosin for 12 weeks as monotherapy or in combination with other antihypertensive agents. At the final visit, doxazosin produced a mean change in sitting systolic/diastolic blood pressure of -18.4/-14.4 mm Hg, at a mean daily dose of 4.3 mg. One hundred sixty-three (77.6%) of the 210 evaluable patients were considered a therapeutic success. Lipid analyses identified a statistically significant (p = 0.02) reduction in total serum cholesterol (4.85%) and an overall decrease in triglyceride levels (5.12%). According to the Framingham Heart Study equation, doxazosin produced a highly significant (p less than 0.001) 20% reduction in the calculated probability of developing coronary heart disease in 10 years. Of the 220 patients evaluated, 54 (24.5%) reported side effects that were considered related to treatment. Ten (4.5%) patients reported side effects unrelated to treatment and 37 (16.8%) reported events of unknown relationship. Most side effects were mild or moderate and were tolerated or disappeared with continued treatment. Nine patients (4.1%) were discontinued from therapy and in 13 (5.9%) the dose was reduced. The most prevalent side effects were headache and dizziness. The investigator's overall assessment of antihypertensive efficacy was excellent or good for 176 patients (80.4%); tolerance was considered excellent or good in 193 patients (88.5%).(ABSTRACT TRUNCATED AT 250 WORDS)
A single daily dose of doxazosin taken during a 12-week period produced a significant reduction in blood pressure and left ventricular mass index in patients with mild or moderate hypertension. The systolic shortening coefficient was also increased and a trend in the improvement of ejection fraction, rate of circumferential fiber shortening, systolic contraction time, and preejective/ejective ratio was observed. No change in heart rate was recorded and no patients had side effects. The serum lipid profile was modified favorably, particularly with regard to the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio. By producing a reduction in blood pressure and left ventricular mass while favorably modifying the serum lipid profile, doxazosin produced a beneficial change in the overall coronary heart disease risk profile.
A double-blind, parallel, comparative study of the antihypertensive efficacy and safety of once-daily oral doses of amlodipine (5-10 mg/day) vs. twice-daily oral doses of captopril (25-50 mg twice daily) in adult patients with mild or moderate essential hypertension (supine diastolic blood pressure of 95-115 mm Hg) was undertaken in two hospital centers. Interim analysis of data from 40 patients shows that amlodipine and captopril both significantly (p < 0.05) reduced blood pressure compared with baseline. Nineteen of 21 (90.5%) amlodipine-treated patients and 15 of 19 (78.9%) captopril-treated patients had their diastolic blood pressure "normalized" (< 90 mm Hg) with mean final doses of 8.2 and 76.7 mg/day, respectively. At the final visit, there were no statistically significant differences between the two treatment groups in either mean supine or standing blood pressure. Minor nonsignificant changes in standing heart rate were observed in both treatment groups. Seven of the 21 amlodipine-treated patients and 3 of the 19 captopril-treated patients reported adverse experiences. No patients in either treatment group discontinued due to adverse events; one patient in the amlodipine group required a dose reduction. These interim data indicate that the overall efficacy and safety profiles of these two drugs are comparable.
The gene encoding a heat-stable enterotoxin of Escherichia coli was cloned as a 960-bp fragment from a plasmid isolated from a Mexican strain of human origin. Deoxyribonucleotide sequencing unveiled a 216-bp open reading frame similar to that of a previously sequenced ST-toxin gene. The gene is preceded by a proposed binding site for the cAMP-mediated positive regulator (CAP) that is part of a 23-bp inverted repeat. The proposed CAP site is followed by a 6A, 1T, and 6A deoxyribonucleotides. Minicells containing the toxin gene, which were isolated from Ficoll gradients, shown to preserve the localization of intracellular and periplasmic enzymes, allowed the detection of a biosynthetically radiolabeled polypeptide with an apparent Mr 8400. The data suggest that the enterotoxin genes estA2, estA3, and estA4 are very similar, even in clinical strains isolated from distinct geographical locations; that the transcription of heat-stable enterotoxin genes is controlled by the cAMP-mediated positive regulatory system, and that the heat-stable enterotoxins are initially synthesized as 72 amino acid precursors to yield the extracellular active 18-19 amino acid polypeptides.
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Chromogranin polypeptides of Mr 100,000, Mr 85,000, Mr 75,000, and Mr 65,000 have been detected in adrenal medulla chromaffin granules using anti-chromogranin antiserum. Monoclonal antibodies to this protein also detect the multiple molecular weight chromogranin polypeptides. Analysis of phosphorylated amino acids gives a value of 5 phosphoserine residues/mol of Mr 75,000 chromogranin polypeptide. Immunological analysis of dephosphorylated chromogranin shows that the anti-chromogranin serum reacts with both the phosphorylated and unphosphorylated forms of the protein. Each of the chromogranin polypeptides has been isolated using a combination of DEAE-cellulose chromatography and reverse phase high pressure liquid chromatography. Sequencer analysis of each protein revealed a high degree of amino acid identities at the amino terminal of these proteins. Amino-terminal Sequencer analysis of chromogranin fragments also provides evidence for a gene duplication event. Preliminary studies also show that chromogranin may be degraded in the chromaffin granules by a calcium-dependent mechanism.
A monoclonal antibody to dopamine beta-monooxygenase (DBH) has been produced by an in vitro immunization technique. This antibody has been found to react with an epitope common to both soluble DBH (SDBH) and membrane-bound DBH (MDBH). A single CNBr fragment contains this antigenic site. Examination of electrophoretograms of chromaffin granule membrane and lysate by the immunoblot procedure revealed additional complexity. A 58-KDa polypeptide in low abundance was stained which could not be detected with the polyclonal antiserum. Chemical deglycosylation of SDBH produces two new polypeptides of 67 and 58 KDa. The entirety of this data suggests that the 58-KDa band is an unglycosylated form of DBH, proteolytically cleaved after biosynthesis.
Strains of Escherichia coli that host a plasmid that codes for the heat-stable (ST) enterotoxin showed 160 times more extracellular enterotoxin than intracellular activity. However, when washed bacteria were sonicated and incubated at between 50 and 85 degrees C, an activity similar to that of the ST enterotoxin was detected. No such effect was present in strains lacking the plasmid, in a plasmid ST- mutant, or in chromosomal mutants that lack a cyclic AMP-linked positive regulatory system which previously were shown to yield an ST- phenotype. The thermoactivation was inhibited by iodoacetamide and N-ethylmaleimide; chloramphenicol did not affect the phenomenon. The heat-activated ST-like enterotoxin was localized in the periplasmic space. The results are discussed in relation to the export of the toxin from the periplasm to the outside of the cell.
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In an Escherichia coli strain of human origin, ampicillin resistance and heat-stable enterotoxin activity were shown by EcoRI restriction endonuclease and genetic analysis to be in an 80-megadalton plasmid.
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