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Biomedical subjects

G Kaiser

Publications and source records attributed to G Kaiser.

At least 19 recordsLinked to original sources
PubMed1992

Bispecific IgA/IgM antibodies and their use in enzyme immunoassay.

Two hybrid hybridomas secreting polymeric bispecific antibodies to human chorionic gonadotropin and calf intestinal alkaline phosphatase were produced by fusion of IgA- and IgM-secreting mouse hybridomas. Both hybrid antibodies were purified from ascitic fluid by size exclusion chromatography. An IgM-like fraction was shown to exhibit bispecific activity. Bispecificity was completely lost following mild reduction and alkylation. Both bispecific antibodies were used to develop a sensitive enzyme immunoassay for hCG.

Alkaline Phosphatase↗
PubMed1992

Pharmacokinetics of the antidepressant levoprotiline after intravenous and peroral administration in healthy volunteers.

To investigate the pharmacokinetics and the disposition of levoprotiline after i.v. and p.o. administration and to assess the absolute bioavailability, 12 healthy volunteers (11 women, 1 man) were given a 10 min i.v. infusion of 15 mg and a p.o. dose of 75 mg in a two-way crossover study. Blood and urine samples were collected after each dose. Unchanged levoprotiline and the sum of unchanged and glucuronidated levoprotiline (= total levoprotiline) were determined by a specific gas chromatographic-mass spectro-metric method. Intravenous levoprotiline was rapidly and extensively distributed into extravascular sites of the body; the steady-state volume of distribution was 18.81 kg-1. The elimination of levoprotiline from blood was independent of the dosing route, the half-life being 18.8 h. Only 1.8 and 0.6 per cent of the i.v. and p.o. dose, respectively, were excreted unchanged in the urine, whereas 57 per cent of each dose were renally excreted as total levoprotiline. The absolute bioavailability of p.o. levoprotiline was 40 per cent. About 60 per cent of the dose was subject to a first-pass effect in the liver. The systemic blood clearance of levoprotiline, determined after i.v. dosing, was 885 ml min-1, the renal blood clearance after i.v. and p.o. dosing was only 16.0 and 14.2 ml min-1, respectively. Presystemic and systemic clearance of levoprotiline occurred predominantly by direct glucuronidation.

Administration, Oral↗
PubMed1992

Surgical significance of the duplex kidney with bifid ureter.

Between 1974 and 1990 in 16 children (5 boys and 11 girls) with a duplex kidney and bifid ureter surgery was indicated. The mean age of the 15 already operated patients was 7 years (0.3-12 years). 14 had uretero-ureteric reflux, 1 had a stenosis of the ureteric bifurcation, and 1 had a lower pole pelvi-ureteric junction obstruction. An interpyelic anastomosis was performed in 14 and a ureteroneocystostomy "en bloc" in 1. The follow-up was 3-10 years with a mean of 5 years. All 15 patients had normal uroradiological findings, and out of the 9 patients with longer follow-up (more than 3 years) 7 had a significantly diminished infection rate.

Child↗
PubMed1992

Preliminary experiences with the Orbis-Sigma-System as a ventriculo-peritoneal shunt.

In the last 3 years an Orbis-Sigma system has been implanted in 40 hydrocephalic children (as a primary shunt in 28 and following another shunt system in 12). Its usefulness was tested by regular clinical examinations, head circumference measurement, ultrasonography or CT and the causes and frequency of shunt revisions. The preliminary results of a mean follow-up time of 1.4 years are discussed.

Cerebrospinal Fluid Shunts↗
PubMed1992

Intracranial lipomas.

Intracranial lipomas are very rare tumors, mostly being localized in the midline and often asymptomatic. We report on three children with intracranial lipomas (one with extension to the cervical spinal cord) diagnosed by CT and/or MR. All three had different symptoms and neurological signs. We summarize the case reports in the literature since the CT-era.

Brain Neoplasms↗
PubMed1992

Low-dose oral natural human interferon-alpha in 29 patients with HIV-1 infection: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate clinical efficacy and toxicity of low-dose oral natural human interferon-alpha (nHuIFN alpha) on CD4+ lymphocyte counts and clinical symptoms in patients with HIV-1 infection. DESIGN: Double-blind, randomized, placebo-controlled trial with crossover. SETTING: Private practice specializing in the treatment of patients with AIDS. PATIENTS, PARTICIPANTS: Only patients with HIV-1 infection and CD4+ lymphocyte counts between 200 and 500 x 10(6)/l were included for study. Thirty out of thirty-one patients at study entry completed treatment with placebo, and 29 completed nHuIFN alpha treatment. Mean patient age was 36 years (range, 25-58 years). The 30 patients included 26 men, of whom 22 were homosexual, and four women; five were drug users and none were currently on zidovudine therapy, although three had been previously. INTERVENTIONS: Patients were randomly assigned to cohorts of 10 to receive either 200 IU nHuIFN alpha once daily orally absorbed or placebo with crossover after 6 weeks. MAIN OUTCOME MEASURES: Every 2 weeks, a detailed history, physical examination, and laboratory tests, including CD4+ and CD8+ lymphocyte counts, were conducted. RESULTS: There was only a slight, transient increase in mean CD4+ lymphocyte counts after 4 weeks of treatment with nHuIFN alpha, compared with a slight decline when placebo was administered. This effect reached statistical significance in a subgroup of patients only and was not sustained after 6 weeks. There were no significant changes in weight and clinical symptoms. All patients remained HIV-1-antibody-positive. Treatment-related adverse reactions were not observed. CONCLUSIONS: Our double-blind, randomized, placebo-controlled clinical trial did not confirm a previous report of efficiency of oral nHuIFN alpha. Although non-toxic, our data do not justify the widespread use of low-dose oral nHuIFN alpha in HIV-infected patients outside controlled clinical trials.

Administration, Oral↗
PubMed1991

Determination of the antidepressant levoprotiline and its N-desmethyl metabolite in biological fluids by gas chromatography/mass spectrometry.

A specific and sensitive gas chromatographic/mass spectrometric method was developed and validated for the determination of the antidepressant levoprotiline in blood, plasma and urine and the simultaneous determination of levoprotiline and its desmethyl metabolite in urine. Deuterium-labelled analogues were used as internal standards. The compounds were isolated from the biological fluids by liquid-liquid extraction under basic conditions. Following derivatization with perfluoropropionic anhydride, the samples were analysed by capillary column gas chromatography/electron impact mass spectrometry with selected ion monitoring. The analysis of spiked samples demonstrated the high accuracy and precision of the method. Blood concentrations of levoprotiline down to 0.7 nmol l-1 (1 ml used for analysis) could be quantified with a coefficient of variation of 10% or less. The method is suitable for use in pharmacokinetic and bioavailability studies of levoprotiline in humans.

Antidepressive Agents↗
PubMed1991

Enzyme sensor-FIA-system for on-line monitoring of glucose, lactate and glutamine in animal cell cultures.

Enzyme sensors for glucose, lactate and glutamine were connected via flow-injection analysis (FIA) devices to two different bioprocesses. They were used for on-line process control of perfused bioreactor systems containing mammalian cell lines producing a monoclonal antibody and recombinant interleukin-2. The biosensor system gives direct access to important process data which can be used as control parameters for long term cell cultivation systems.

Animals↗
PubMed1991

Results of extended craniectomy including supraorbital advancement in premature coronal and frontal craniosynostosis.

Between 1982-1989 an extended craniectomy including supraorbital advancement was performed in 27 infants. Age ranged from 2.5 to 10 months (median 4.5 months). Six had a premature synostosis of the frontal suture, 11 a monolateral synostosis of the coronal suture and 10 a bilateral coronal synostosis. Eighty per cent had an excellent or good result. The amount of remodelling, as measured by the orbital roof angle, showed a tendency to normalisation of the anterior fossa in the lateral projection 3-4.5 months following surgery. In some of the infants the neurological signs and psychomotor development were ameliorated by the operation. But, in monolateral cases of coronal synostoses a squint of various types was observed more frequently.

Craniofacial Dysostosis↗
PubMed1991

Cerebrospinal fluid pressure in 10-day-old rats with congenital hydrocephalus.

Rats from the H-Tx strain develop hydrocephalus through a developmental obstruction of the cerebral aqueduct. The progressive ventriculomegally is accompanied by thinning of the cerebral cortex which is already present 10 days after birth. However, a previous study found that the CSF pressure was not significantly raised until 21 days after birth. New experiments have now been performed over a 90 min. period using control and hydrocephalic 10-day-old rats under light pentobarbitone anaesthesia, in order to study the level, time-course and morphology of the resting intraventricular pressure. The mean pressure and its fluctuations were calculated for each minute. Control rats had a mean pressure of 19.3 +/- 1.23 (SEM) mm H2O (n = 9, range: 13.6-24.7) and in hydrocephalic rats, pressure was significantly higher at 23.5 +/- 1.13 mm H2O (n = 9, range: 18.1-28.3). There was no consistent trend with time and no significant difference between groups in pressure fluctuations, but at least two of the hydrocephalic rats showed episodic waves similar to "B"-waves in humans.

Animals↗
PubMed1991

The disposition of [14C]-labelled benazepril HCl in normal adult volunteers after single and repeated oral dose.

1. The disposition of [14C]-labelled benazepril HCl, an ACE-inhibitor, was studied in four normal adult volunteers after a single oral dose of 20 mg and after repeated doses of 20 mg once daily for 5 days. Radioactivity was measured in plasma, urine and faeces. The prodrug ester benazepril and the pharmacologically active metabolite benazeprilat were determined quantitatively in plasma and urine by a g.c.-m.s. method. The pattern of metabolites in urine was analysed semiquantitatively by h.p.l.c.-radiometry. 2. After a single oral dose at least 37% was absorbed, as indicated by urinary recovery. The peak plasma concentration of benazepril (0.58 +/- 0.13 nmol/g (SD] was observed at 0.5h after dose, indicating rapid absorption. Peak concentrations of radioactivity (1.88 +/- 0.48 nmol/g) and of active benazeprilat (0.84 +/- 0.25 nmol/g) were observed at 1 h after dose, demonstrating rapid bioactivation. 3. The area under the plasma curve (AUC0-96 h) of total radioactivity amounted to 9.7 +/- 1.1 (nmol/g)h, 5% of which was accounted for by benazepril and about 50% by benazeprilat. 4. Over 9 days 96.8 +/- 0.5% of the dose was excreted in urine and faeces. Urinary excretion accounted for 37.0 +/- 6.0% of the dose, 80% of which was recovered in the first 8 h after dosing. 5. In urine, only 0.4% of the dose (1% of the radioactivity) was excreted as unchanged benazepril, indicating that the compound was extensively metabolized. Benazeprilat accounted for 17% of the dose (about half of the radioactivity; 0-96 h). Glucuronide conjugates of benazepril and benazeprilat constituting approximately 11% and 22% of the radioactivity (about 4% and 8% of the dose; 0-48 h) were tentatively identified. 6. Repeated oral treatment with benazepril HCl did not influence the pharmacologically relevant kinetics and disposition parameters.

Administration, Oral↗
PubMed1991

Immunoaffinity purification of human alpha-fetoprotein (AFP) using monoclonal antibodies.

A two-step immunoaffinity isolation procedure for human alpha-fetoprotein (AFP) was developed resulting in highly purified AFP at high yield. A monoclonal antibody immunoadsorbent was used in the first step. Elution of AFP was carried out at alkaline pH by a solution of 0.5 mol/l ammonia containing 0.5 mol/l sodium chloride. To remove impurities caused by the first step, an anti-mouse immunoglobulin antibody immunoadsorbent was applied in the second step.

Antibodies, Monoclonal↗
PubMed1991

Production and characterization of monoclonal antibodies against carcinoembryonic antigen (CEA).

In the experiments presented here 22 monoclonal antibodies (MoAbs) were produced which reacted with the tumor marker carcinoembryonic antigen (CEA). Eleven of the MoAbs reacted neither with peripheral blood granulocytes nor with purified spleen NCA-60 kDa and were therefore regarded as "CEA-specific". Only three antibodies of this group reacted exclusively with CEA-180 kDa. Eight MoAbs reacted with CEA-180 kDa and with CEA-like substances of lower molecular mass (of 160 kDa and/or 120 kDa) present in colon carcinoma cells as determined by immunoblotting. These molecules seem to be different from the classical non-specific cross-reacting antigens (NCAs) present in peripheral blood granulocytes. In contrast to that, the other 11 anti-CEA MoAbs recognized in addition to CEA-180 kDa also NCAs on granulocytes. Six of them were reactive with a purified spleen NCA-60 kDa preparation. These MoAbs bound also to reduced and alkylated CEA-180 kDa (CEA r/a), i.e. they recognize sequential epitopes. All 22 MoAbs reacted with CEA expressed in different human tumor cell lines as determined by immunocytological analysis. But six of them did not bind to the surface of these cells when tested in a radioimmuno-binding assay. It was concluded that the epitope(s) recognized by these antibodies are involved in cell membrane anchoring of the CEA-molecules.

Antibodies, Monoclonal↗
PubMed1991

Do electronic fetal heart rate monitors improve delivery outcomes?

Since the development of electronic fetal heart rate monitors, there has been considerable debate over observable benefits of their use. Early uncontrolled observational studies and retrospective case studies suggested that fetal distress detected by monitoring could help lower both intrapartum and neonatal death rates, serving a utility among high risk deliveries. However, these studies were conducted at a time when neonatal intensive care units and advancing technologies were also beginning to markedly influence perinatal mortality. Randomized clinical trials of the past 10 years have compared electronic monitoring to routine periodic auscultation and have consistently failed to demonstrate a statistically significant difference in either the perinatal mortality rate or the outcome of high risk pregnancies. A few of these studies, however, did report a lower incidence of neurological complications within the monitored deliveries. The latest research, though, has failed to substantiate any long-term neurological benefits from electronic monitoring.

Electronics, Medical↗
PubMed1990

The influence of hepatic cirrhosis on the pharmacokinetics of benazepril hydrochloride.

The influence of hepatic disease on the pharmacokinetics of the new ACE inhibitor, benazepril hydrochloride, was evaluated in 12 male patients suffering from liver cirrhosis. The patients received a single oral 20 mg dose. The plasma concentrations and urinary excretion of unchanged benazepril and its active metabolite benazeprilat were determined. Compared with a historical control group of healthy volunteers treated with the same benazepril. HC1 dose, the plasma concentrations of benazepril were doubled in the cirrhotic patients. However, the time to reach maximum concentration (0.5 h) was not affected. The plasma kinetics and the urinary excretion of the metabolite benazeprilat were not significantly altered: Area under the curve and maximum concentration as well as time to maximum concentration (1.5 h) were comparable with those in the healthy subjects. There was also no significant difference between the two populations for the total urinary excretion and the renal clearance of benazeprilat. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 94 per cent, respectively). In conclusion, the rate and the amount of bioactivation of the inactive prodrug benazepril to the active benazeprilat were virtually unaffected by hepatic cirrhosis. Thus, there seems to be no need for dosage adjustment of benazepril hydrochloride in patients suffering from cirrhosis of the liver.

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of the ace inhibitor benazepril hydrochloride in the elderly.

The pharmacokinetics and pharmacodynamics of a single oral dose benazepril.HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19-32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20-40% greater. The elimination half-life of benazeprilat during the first 24 h after dosing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml.min-1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗