Search PubMed⌕ Search

Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 955 records · Page 53Linked to original sources
PubMedDate not supplied

Preclinical safety studies with recombinant human interleukin 6 (rhIL-6) in the primate Callithrix jacchus (marmoset): comparison with studies in rats.

The haemopoietic and immunostimulatory properties of recombinant human interleukin 6 (rhIL-6) might be used clinically in cancer patients. For the preclinical assessment of the safety of such a therapy, we chose the primate marmoset (Callithrix jacchus) and Wistar rats. Recombinant hIL-6 given to marmosets at doses of up to 1000 micrograms kg-1 day-1 over 4 and 9 weeks did not induce fever and was very well tolerated. Haematological alterations included a sustained two- to threefold increase of thrombocyte counts, peaking at 4 weeks, as well as an increase in neutrophils and basophils. The number of bone marrow megakaryocytes at 4 and 9 weeks was not increased, but the ploidy grade was augmented. An acute-phase protein response was observed within 24 h after the first IL-6 administration, which reached a maximum after 1 week. The acute-phase protein response was not accompanied by functional or morphological signs of hepatocellular damage. Increased immunoglobulin and soluble IL-2 receptor in the serum levels reflected systemic immunostimulation. Recombinant hIL-6 was also given to rats at 500 micrograms kg-1 day-1 s.c. for 4 weeks, where it induced a stimulation of thrombopoiesis associated with increased platelet counts within 1 week. Furthermore, rhIL-6-treated rats had signs of immunostimulation and increased acute-phase reactants in serum, as in marmosets. There was no evidence of renal glomerular or hepatic pathology.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMedDate not supplied

Improvement of the catalytic properties of penicillin G acylase from Escherichia coli ATCC 11105 by selection of a new substrate specificity.

Cloned penicillin G acylase (PGA) from Escherichia coli ATCC 11105 was mutagenized in vivo using N-methyl-N'-nitro-N-nitrosoguanidine. Mutants of PGA were selected by their ability to allow growth of the host strain E. coli M8820 with the new substrates phenylacetyl-beta-alanyl-L-proline (PhAc-beta Ala-Pro) phthalyl-L-leucine (Pht-Leu) or phthalylglycyl-L-proline (Pht-Gly-Pro) as sole source of proline and leucine respectively. PGA mutants were purified and immobilized onto spherical methacrylate (G-gel). The immobilized form of mutant PGA selected with (PhAc-beta Ala-Pro) hydrolyzed 95% of 9 mmol penicillin G 30% faster than wild-type PGA using the same specific activities. The specific activity of the soluble enzyme was 2.7-fold, and inhibition by phenylacetic acid was halved. Immobilized PGA mutant selected with Pht-Gly-Pro hydrolyzed penicillin G 20% faster than wild-type PGA. The Km of the soluble enzyme was increased 1.7-fold. Furthermore, the latter two mutants were also 3.6-fold more stable at 45 degrees C than wild-type PGA. The specific activity of the mutant selected with Pht-Leu was 6.3-fold lower, and inhibition by phenylacetic acid was increased 13-fold.

Enzyme Stability↗
PubMedDate not supplied

Open questions in the case management of sick children.

Despite much progress in the specific treatment of diseases in children, some basic management questions remain controversial. Examples for this are fluid management of children with infectious diseases and the control of fever in children. Fluid restriction in children with meningitis has been recommended by several authorities in the field; the basis for these recommendations is reviewed, and reasons are outlined why these recommendations may not be appropriate. Similarly, there are few data on which to base recommendations for fluid management in severe pneumonia and cerebral malaria. Some activities supported by WHO are presented. In the management of fever, opinions vary whether fever is a useful protective factor in combating infections, or whether fever might be harmful and should be lowered. Results of a recent survey of experts on this topic are presented, and the research agenda in the field of supportive management of childhood infections is outlined.

Child↗
PubMedDate not supplied

Clinical safety and tolerability of losartan.

Losartan is a novel orally active nonpeptidal antihypertensive agent that specifically blocks the angiotensin II type 1 receptor. This paper compares the short- and long-term safety and tolerability of losartan with those of placebo. Approximately 3800 patients with mild-to-severe essential hypertension were enrolled in 16 double-masked and 4 open clinical trials worldwide. Of these, approximately 2900 were treated with losartan either alone or in combination with other antihypertensive drugs. These trials included patients with diabetes mellitus (n = 133). An additional 5 trials enrolled hypertensive patients with compromised renal function (n = 115) or heart failure (n = 220). Losartan dosages primarily ranged from 10 to 150 mg once daily, with most patients receiving 50 to 100 mg per day. Hypertension trials generally lasted 12 weeks. The most frequently reported adverse events were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups. Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo. The overall incidence of clinical and laboratory adverse events in the losartan- and placebo-treated groups was similar among patients with hypertension and either diabetes mellitus, renal impairment, or heart failure. The data suggest that losartan can be safely administered in hypertensive patients with concomitant illnesses. It can be considered for first-line therapy and is suitable as an alternative therapy in patients already experiencing side effects with other agents.

Adult↗
PubMedDate not supplied

Valsartan, a new angiotensin II antagonist: antihypertensive effects over 24 hours.

This study was done to assess the antihypertensive efficacy of once-daily valsartan 20 mg, 80 mg, 160 mg, and 320 mg over 24 hours using ambulatory blood pressure monitoring (ABPM). A total of 217 adult outpatients with uncomplicated essential hypertension (office mean sitting diastolic blood pressure [DBP] of > or = 95 to < or = 115 mm Hg) participated in this multicenter, double-masked, placebo-controlled study. Patients were randomized to receive valsartan 20 mg, 80 mg, 160 mg, 320 mg, or placebo for 8 weeks. Twenty-four-hour ABPM was done at baseline and after 8 weeks of treatment. All valsartan doses produced significant decreases in average ambulatory systolic blood pressure (SBP) and DBP over 24 hours compared with placebo. A trend to greater reductions compared with placebo was observed for doses of valsartan 80 mg and greater (80 mg, -6.61 mm Hg DBP, -11.04 mm Hg SBP; 160 mg, -5.51 mm Hg DBP, -10.61 mm Hg SBP; 320 mg, -8.44 mm Hg DBP, -14.34 mm Hg SBP) compared with valsartan 20 mg (-3.52 mm Hg DBP, -5.92 mm Hg SBP). Valsartan produced consistent reductions compared with placebo during both day (> 6 AM to < or = 10 PM) and night (> 10 PM to < or = 6 AM). However, in all groups, the circadian pattern of blood pressure over 24 hours was preserved and was similar to that observed at baseline (but shifted into the normotensive range in a parallel fashion). The data show that single daily doses of valsartan 80 mg and greater provide effective control of both DBP and SBP over a 24-hour period without loss of diurnal variation.

Antihypertensive Agents↗
PubMedDate not supplied

[Value of electroencephalographic serveillance in the framework of resuscitation in coma caused by acute drug intoxication].

The authors carried out long-term clinical and E.E.G. studies on 100 cases of acute drug poisoning. They made the following conclusions: - in unexplained coma, the E.E.G. can indicate toxic aetiology and may sometimes even suggest which drug is responsible, especially for certain chemical groups (barbiturates, phenothiasines, benzodiazepines); - the E.E.G. picture contributes a valuable indication of the depth of coma; the way in which it evolves affects the prognosis; - the effectiveness of therapy may be judged by monitoring cerebral electrical activity.

Acute Disease↗