Search PubMed⌕ Search

Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 415 records · Page 23Linked to original sources

Three-period crossover trial with ambulatory blood pressure monitoring for evaluating antihypertensive therapy.

A double-blind, three-period, crossover trial used 24-hour ambulatory blood pressure monitoring to compare diltiazem controlled diffusion (CD) 300 mg with placebo. Patients with hypertension (N = 43) were randomly assigned to one of four crossover treatment sequences of three treatment periods each. Ambulatory blood pressure was obtained at the end of each 4-week treatment period. Diltiazem CD significantly decreased diastolic and systolic blood pressure at bihourly ambulatory blood pressure evaluations (p < 0.05, all). However, when all ambulatory blood pressure monitoring data were combined into one statistical model, blood pressure reductions were quantifiably similar to those in the overall bihourly analysis, but with a consistent 24-hour antihypertensive effect for both diastolic and systolic blood pressure relative to that with placebo (i.e., parallel blood pressure profiles) and with increased precision. Mean +/- SE changes in diastolic and systolic blood pressure across the 24-hour dosing interval were -5.6 +/- 0.4 mm Hg and -7.6 +/- 0.5 mm Hg, respectively (p < 0.001, both). Therefore, by using a crossover design with ambulatory blood pressure monitoring, we showed diltiazem CD to reduce blood pressure consistently throughout a 24-hour dosing interval in comparison with placebo in patients with hypertension.

Adult↗

High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest.

This trial compared blinded 10 mg aliquots of adrenaline with placebo in 194 cardiac arrest patients treated in hospital using American Heart Association guidelines. In-hospital and out-of-hospital arrests were included. Of the 339 eligible patients a large proportion (145 (45%)) were not randomised and received open 1 mg aliquots of adrenaline. This group is also analysed. Supervising physicians gave significant preference for males, patients with no previous cardiac history and without multiple organ disease to be given open 1 mg adrenaline. Patients in asystole at the time of consideration for entry were preferentially placed in the trial group (114 (69%) vs. 170 (88%)) and patients in ventricular fibrillation were preferentially given open 1 mg adrenaline (31 (21%) vs. 24 (12%) P < 0.03). The most beneficial rhythm changes which led to survival were sinus rhythm and ventricular tachycardia. Analysis of rhythm changes resulting from the dosing showed a significant (P = 0.01) change to a beneficial rhythm with 10 mg adrenaline but not for 1 mg adrenaline or placebo. This was not reflected by an improvement in immediate survival. No significant differences in immediate survival (IS) or hospital discharge (HD) exists between open 1 mg adrenaline (IS 14 (9.7%), HD 3 (2%)) or the 10 mg adrenaline (IS 9 (9.6%), HD 0) vs. placebo (IS 7 (7%), HD 0) trial arms. Patients reaching the point of use of adrenaline have a uniformly poor immediate survival (8.8%) and hospital discharge rate (0.9%). Dosing with 10 mg or 1 mg adrenaline does not influence outcome compared with placebo.

Aged↗

Evaluation of the Duke criteria versus the Beth Israel criteria for the diagnosis of infective endocarditis.

New diagnostic criteria for infective endocarditis (IE) have been proposed by the Duke University Endocarditis Service (Durham, NC) to update the widely used Beth Israel (Boston) criteria. We compared the Duke criteria with the Beth Israel criteria in a series of 115 consecutive patients with suspected IE who were hospitalized in a referral center. The diagnosis of IE was histologically and/or bacteriologically confirmed for 27 operated patients. If surgery had not been performed on these 27 patients, 22 vs. 12 would have been classified as having ¿clinically definite¿ and ¿probable¿ IE by the Duke vs. the Beth Israel criteria, respectively, whereas 0 vs. 5 would have been ¿rejected¿ by the Duke vs. the Beth Israel criteria, respectively. The improvement in sensitivity of the criteria from 44% (Beth Israel) to 82% (Duke) was statistically significant (P < .01). We confirm that the Duke criteria improve the sensitivity of diagnosis of IE. The specificity of these criteria should be further evaluated.

Adult↗

Acyclovir-resistant chronic cutaneous herpes simplex in Wiskott-Aldrich syndrome.

A 28-year-old man with Wiskott-Aldrich syndrome presented with ulcerative-proliferative lesions on his face from which herpes simplex type 1 (HSV-1) was isolated. He was initially treated with 10 mg/kg of acyclovir (Zovirax) intravenously every 8 h, but his skin lesions worsened. Clinical resistance to acyclovir was suspected, and therapy with this drug was intensified. The dosage of acyclovir was increased to 45 mg/kg, administered by continuous infusion, and the lesions subsequently resolved. The strain of HSV recovered from the patient showed acyclovir-resistance in vitro, using the colorimetric method with neutral red. Herpes simplex virus resistance to acyclovir is rare. It is more common in immunocompromised patients if subtherapeutic doses are administered in the treatment of chronic persistent forms of infection. Whenever clinical resistance to acyclovir is suspected, the dosage should be increased to 2 mg/kg per h administered via an infusion pump. If no improvement is observed in the patient's condition with this regimen, a phosphorylated medication whose mechanism of action is not dependent on viral thymidine kinase, such as foscarnet (phosphonoformic acid), should be substituted.

Acyclovir↗

Use of cryomicrotomy to study gastric diffusion of amoxicillin in guinea pigs.

Cryomicrotomy has been used as a new technique for removing gastric mucosae from adult guinea pigs for the study of amoxicillin secretion across gastric mucosae. This method allowed a very regular thickness of the removed surface layer of mucosa to be obtained with good reproducibility. Gastric superficial mucosa concentrations and gastric juice concentrations of amoxicillin were determined 1, 2, and 4 h after intramuscular administration (50 mg/kg) in 21 guinea pigs by a microbiological method. No antibiotic was detected in gastric samples at 4 h, except for a low-level mucosal concentration in one animal, thus indicating the short time that amoxicillin is present in gastric samples.

Amoxicillin↗

Protective immunity induced by Bacillus anthracis toxin-deficient strains.

The two toxins secreted by Bacillus anthracis are composed of binary combinations of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). Six mutant strains that are deficient in the production of one or two of these toxin components have been previously constructed and characterized (C. Pezard, E. Duflot, and M. Mock, J. Gen. Microbiol. 139:2459-2463, 1993). In this work, we examined the antibody response to the in vivo production of PA, LF, and EF in mice immunized with spores of strains producing these proteins. High titers of antibody to PA were observed after immunization with all strains producing PA, while titers of antibodies to EF and LF were weak in animals immunized with strains producing only EF or LF. In contrast, immunization with strains producing either PA and EF or PA and LF resulted in an increased antibody response to EF or LF, respectively. The differing levels of protection from a lethal anthrax challenge afforded to mice immunized with spores of the mutant strains not only confirm the role of PA as the major protective antigen in the humoral response but also indicate a significant contribution of LF and EF to immunoprotection. We observed, however, that PA-deficient strains were also able to provide some protection, thereby suggesting that immune mechanisms other than the humoral response may be involved in immunity to anthrax. Finally, a control strain lacking the toxin-encoding plasmid was unable to provide protection or elicit an antibody response against bacterial antigens, indicating a possible role for pXO1 in the survival of B. anthracis in a host.

Animals↗

Ultrastructural and histochemical mesangial alterations in Callitrichid IgM nephropathy (primates: platyrrhina).

The ultrastructural and histochemical alterations during different stages of spontaneously occurring IgM nephropathy in Callitrichidae were determined. Callitrichid IgM nephropathy was classified according to the light microscopic sequence of the mesangial lesions in the individual glomeruli. In minimal disease and axial proliferation mesangial cells and mesangial matrix were symmetrically increased, whereas in panmesangial disease matrix deposition exceeded the cellular responses. However, ultrastructural matrix changes such as deposition of electron-dense particles, dilatation of the matrix channel system, and slightly increased collagen fiber expression were present also in minimal disease and axial proliferation. Histochemically collagen I and III phenotypes could only be verified in glomerular sclerosis, at that time accompanied by diminution of collagen IV. The mesangial cellular lesions, in contrast, were very limited. The numerical increase in mesangial cells was associated with increased bleb formation and increased heterolysosome contents, whereas the amount of microfilaments was never increased.

Animals↗

In vitro growth inhibition of growth factor-stimulated meningioma cells by calcium channel antagonists.

Studies have shown that a majority of meningiomas contain receptors for platelet-derived growth factor and epidermal growth factor and that these growth factors promote the proliferation of meningioma cells in culture. Although the mechanism of action has not been elucidated, intracellular calcium appears to be part of the signal transduction mechanism. Because alterations in intracellular calcium could interrupt this pathway and decrease cellular proliferation, we investigated the effects of calcium channel-blocking agents on the growth of meningioma cells in vitro. Primary meningioma cell cultures were established, and the cells were characterized by light and electron microscopy and by immunohistochemical studies. Then, the cultures were given growth factors and/or various calcium channel antagonists, and growth rates were measured. A dose-response decrease in cell growth was seen when verapamil, nifedipine, or diltiazem (voltage-dependent calcium channel-blocking agents) was added to serum-containing media. Also, these drugs blocked the growth stimulation of epidermal growth factor and platelet-derived growth factor in a similar fashion. Dantrolene, which inhibits the release of sequestered intracellular calcium, was also an effective blocker of the mitogenic stimulation of these growth factors.

Adult↗

Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome.

Antiglomerular basement membrane (GBM) antibodies can cause glomerulonephritis or pulmonary hemorrhage by themselves or Goodpasture syndrome when they occur together. It is unknown if variations in antibody reactivity contribute to the different patterns of organ involvement seen in this disease. This study examines the reactivity of the alpha 1-alpha 6 NC1 domains of Type IV collagen, the putative autoantigen, in sera from patients with anti-GBM antibodies after various clinical presentations of lung hemorrhage and renal injury. Serum or plasma containing anti-GBM antibodies from 35 patients with combined glomerulonephritis and pulmonary hemorrhage, 19 with glomerulonephritis alone, and 4 with pulmonary hemorrhage alone were compared with samples from 19 normal controls and 32 patients with other kidney diseases. Four different immunologic assays were performed with bovine alpha 1-alpha 6(IV) and recombinant human type alpha 1-alpha 5(IV) collagen NC1 domains. The study found that the anti-GBM antibodies from all patients reacted with the alpha 3(IV) NC1 (85% exclusively). Additional limited reactivity with the alpha 1(IV) NC1 and alpha 4(IV) NC1 was found in 15 and 3%, respectively. This non-alpha 3(IV) NC1 reactivity was most frequent in the patients with anti-GBM antibodies and glomerulonephritis alone. None of the patients had reactivity to other basement membrane components like laminin, fibronectin, heparan sulfate proteoglycan, entactin, or the 7S and triple helical fragments of Type IV collagen. The observed alpha-chain NC1 reactivity was confined to patients with anti-GBM antibodies with no additional reactivities detected among a large number of other kidney diseases controls. The correlation of alpha 1-alpha 6(IV) NC1 reactivity in a large number of patients with anti-GBM antibodies defined by classic assays definitively establishes that reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease directed to the NC1 domain of Type IV collagen. On the basis of the evidence, the classification of antibasement membrane disease and Goodpasture syndrome as anti-Type IV collagen disease is proposed.

Animals↗

[Chronic recurrent meningoencephalitis simulating limbic encephalitis].

We report on a woman patient who since 1976 has suffered eight episodes of a meningoencephalitis with features of limbic encephalitis. The duration of the individual episodes has varied from 3 weeks to 2 months. Each time recovery has always been complete. Despite numerous cultural and serological examinations of blood and cerebral spinal fluid (CSF), no infectious agent has been detected. The etiology and entity of this illness are still unclear. To our knowledge such a clinical course has never been reported.

Adult↗

[Right ventricular metastasis of renal cell carcinoma 10 years after kidney transplantation].

In a 61-year-old man, renal cell carcinoma of the right kidney was diagnosed 10 years after renal transplantation. Echocardiography revealed a right ventricular mass 5.5 x 3.5 m in size. The patient died suddenly 10 weeks later, post-mortem examination confirmed diagnosis of right ventricular metastasis of renal cell carcinoma. This case underlines the importance of echocardiographic examination in tumor patients if signs of heart failure, angina pectoris, embolism, or rhythm disturbances arise; or if cardiac murmur becomes audible, or heart size increases.

Carcinoma, Renal Cell↗