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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 253 records · Page 14Linked to original sources
PubMed1989

Effect of cyclosporin A on carbohydrate metabolism in the rat.

Liver and kidney carbohydrate metabolism was investigated in rats treated with daily doses of 15 mg/kg body weight cyclosporin A (CyA) for 2 and 8 weeks or of 50 mg/kg body weight CyA for 2 weeks. The higher dosage caused significantly reduced liver glycogen and liver glycogen synthetase activity (of both active I-form and total enzyme activity), whereas the activity of the glycogen-degrading enzyme phosphorylase (active a-form and total activity) remained unchanged. Plasma glucose and glucagon levels, as well as blood ketone bodies of these animals, increased significantly and plasma insulin decreased. In contrast, kidney glycogen and glucose content were higher in rats treated with 50 mg CyA, probably due to enhanced ketone body utilization. Reduced liver glycogen synthetase activity was also found in rats treated with 15 mg CyA. Our data suggest that hypoinsulinemia, induced by CyA, might be a contributing factor to the hyperglycemia, which is mainly due to inhibition of liver glycogen synthesis.

Animals↗
PubMed1989

Location of pulmonary stretch receptors in the guinea-pig.

The site of pulmonary slowly adapting stretch receptors (SRs) was investigated in anaesthetized, thoracotomized and artificially ventilated guinea-pigs. The location of SRs within the lungs and airways was determined by analyzing the changes of SR single fibres discharge patterns in response to (a) occlusion of the airways, (b) local probing, and (c) microinjection of the non-diffusible local anaesthetic cinchocaine into the presumed receptor site. The great majority (92%) of the 79 SRs examined was localized in small airways or in lung parenchyma ('peripheral SRs'), whereas only 8% were located in large airways, i.e., in the trachea, main bronchi and lobar bronchi ('central SRs'). The discharge responses to lung inflation and to ammonia inhalation slightly differed between these two SR groups. With the pronounced prevalence of peripheral SRs, the guinea-pig seems to take a unique position among the species examined hitherto.

Administration, Inhalation↗
PubMed1989

Local muscular strain dependent on the direction of horizontal arm movements.

Manual material handling still plays an important role in assembly work as well as in the service industry. By means of an ergonomic layout of working places, the effects of disadvantageous working conditions, especially static load resulting from unfavourable postures of the body as well as unnecessary physiological cost arising from body movements may be avoided. In this context knowledge about the optimum directions of horizontal arm movements is fundamental. Therefore by means of advanced methods of multi-channel electromyography (EMG) and applying computer assisted evaluation methods, physiological responses to one-handed horizontal material handling in a sitting position were recorded. In order to obtain myoelectric signals from the most important task-relevant muscles out of more than 40 muscle groups of the hand-arm-shoulder-system, preceding research was done also aiming at standardized lead positions for surface EMG. Groups of five young females each participated in a series of successive experiments, in which the direction of movements of the left arm was varied. The subjects worked without and with an external load imposed by weights of 0, 1, 2 and 4 kg. The movements between 20 degrees and 230 degrees--measured from the frontal plane of the subjects--included working from ahead and from behind. The lifting distance was 38 cm starting from different outward points within the reach to a fixed point near the body. Also in one test series the handling frequency was varied between 12, 24 and 48 lifts per minute. Assessment of the physiological cost by electromyographic activities (EA), especially the determination of the most stressful and least expensive directions of repetitive horizontal movements, was more effective when differentiating static and dynamic portions of muscular strain than common means of EA.

Adult↗
PubMed1989

Utility of fever, white blood cells, and differential count in predicting bacterial infections in the elderly.

A total of 221 elderly patients between the ages of 70 to 99 years who presented to a community-based teaching hospital emergency room were prospectively evaluated by assessing for fever (greater than or equal to 37.5 degrees C), leukocytosis (greater than or equal to 14,000/mm3) and bandemia (greater than 6%) as a screening method for predicting the presence of bacterial infection. Thirty-three patients had documented bacterial infections. Although with increasing body temperature the percent of patients who were infected increased, 48% of the infected elderly patients had no fever. In patients with fever, 39% had a bacterial infection compared to only 9% in the afebrile group. In patients with fever, leukocytosis, and bandemia, all patients were infected. Conversely, in the absence of fever, leukocytosis, and bandemia, only 6% had bacterial infection. All elderly patients who present with an acute or subacute change in health status or functional capabilities associated with fever, leukocytosis, or bandemia should be carefully assessed for the high probability of a bacterial infection.

Aged↗
PubMed1989

Predictors of subsyllabic durations in speech motor control.

Speech motor control timing was examined by means of a multiple correlational analysis involving interarticulatory delay and speech rate as predictor variables, and four subsyllabic time segments of the syllable [ka] as dependent variables. The hypothesis was that the two putative temporal constraints have differential predictive capacity for various segments of the syllable. Results from 11 subjects were in support of the hypothesis. Syllable onset duration was reliably predicted by the linear addition of interarticulatory delay and speech rate, while the duration of the midportion of the syllable was nearly exclusively predicted by the overall speech rate. This model was found to be applicable to all conditions of normal and clenched teeth, context-free and contextual, normally paced and rapid speech production, with minor differences in predictive capacity for different conditions.

Adult↗
PubMed1989

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with renal insufficiency.

The pharmacokinetics of cefetamet after a short intravenous infusion of cefetamet (515 mg) and oral administration of 1,000 mg of cefetamet pivoxil were studied in 9 healthy subjects and in 38 patients with various degrees of renal impairment. The results showed that cefetamet elimination was dependent on renal function. After intravenous dosing, total body (CLS), renal (CLR), and nonrenal (CLNR) clearances were linearly related to creatinine clearance (CLCR; r = 0.95, 0.92, and 0.59, respectively). Elimination half-life (t1/2 beta) was prolonged from 2.46 +/- 0.33 h in normal subjects to 29.1 +/- 13.9 h in patients with CLCR of less than 10 ml/min per 1.73 m2. Correspondingly, CLS and CLR decreased from 1.77 +/- 0.27 and 1.42 +/- 0.25 ml/min per kg to 0.14 +/- 0.04 and 0.04 +/- 0.03 ml/min per kg, respectively. The volume of distribution at steady state (0.298 +/- 0.049 liter/kg) for cefetamet was not altered by renal insufficiency (P greater than 0.05). After oral administration, the elimination parameters, t1/2 beta and CLR, were insignificantly different from the intravenous data (P greater than 0.05). Furthermore, the bioavailability (F) of cefetamet pivoxil (45 +/- 13%) was not altered by renal failure (P greater than 0.05). However, maximum concentration in plasma and the time to achieve this value were significantly increased (5.86 +/- 0.74 versus 14.8 +/- 6.14 micrograms/ml and 3.9 +/- 1.1 versus 8.4 +/- 1.7 h, respectively; P less than 0.05). Based on these observations, it is recommended that patients with CLcr of <10 ml/min per 1.73 m2 and between 10 and 39 ml/min per 1.73 m2 be given one-quarter of the normal daily dose either once or twice daily. Patients with CLcr between 40 and 80 ml/min per 1.73 m2 should receive one-half of the normal dose twice daily. For patients with CLcr of <10 ml/min per 1.73 m2, it would be recommended that they receive a normal standard dose as a loading dose on day 1 of treatment.

Administration, Oral↗
PubMed1989

Single- and multiple-dose kinetics of ofloxacin in patients on continuous ambulatory peritoneal dialysis (CAPD).

To evaluate the pharmacokinetics of ofloxacin, a novel quinolone antibiotic, in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD), we investigated 6 patients in a single-dose study and 9 patients in a multiple-dose study, all without peritonitis. In the single-dose study, patients received 200 mg ofloxacin orally. Serum concentrations (Cmax) peaked at 3.1 +/- 0.3 mg/L (mean +/- SEM), 1.6 +/- 0.5 h after p.o. administration of the drug. Elimination half-life (t1/2) was 26.8 +/- 2.5 h. Peritoneal clearance accounted for 10% of the total body clearance. After 5-h dwell time, ofloxacin concentrations in the dialysate were 1.5 +/- 0.2 mg/L, which is above the MIC90 for most bacteria responsible for peritonitis in patients on CAPD. In the multiple dose study, 200 mg ofloxacin were administered twice, with a time interval of 12 h, followed by 200 mg for 9 days every morning. Mean trough serum levels were 2.6 +/- 1.0 mg/L, mean peak concentrations were 4.1 +/- 1.7 mg/L. Mean ofloxacin concentrations in the peritoneal effluent were 1.9 +/- 0.9 mg/L. It is concluded that an oral loading dose of 400 mg on the first day and a maintenance dose of 200 mg ofloxacin/day does not lead to significant accumulation, even though the elimination by the peritoneal route is only small. The proposed dosing regimen could be an adequate therapy of peritonitis and exit-site infections in patients on CAPD since levels reached in the dialysate effluent are bactericidal. The clinical usefulness in the treatment of peritonitis has to be proven in further studies.

Administration, Oral↗
PubMed1989

Single-dose kinetics of imipenem/cilastatin during continuous arteriovenous haemofiltration in intensive care patients.

The single i.v. dose kinetics of a fixed combination of imipenem/cilastatin were investigated in ten critically ill patients treated by continuous arteriovenous haemofiltration (CAVH). Eight patients suffered from acute renal failure and two had normal renal function. Both drugs were measured in plasma and ultrafiltrate by high-performance liquid chromatography. While the pharmacokinetics of both drugs are almost identical in patients with normal renal function, we found the following dissociation of pharmacokinetic parameters in our patients with renal failure: for imipenem the total clearance and elimination half-life was 104 +/- 12 ml/min and 2.2 +/- 0.1 h, respectively, and for cilastatin 29 +/- 10 ml/min and 13.8 +/- 4.5 h. The pharmacokinetics of imipenem and cilastatin differ from each other in renal failure because imipenem, unlike cilastatin, undergoes marked elimination by non-renal pathways. Our results did not differ from previously reported data in healthy volunteers and patients with impaired renal function. Elimination of imipenem by CAVH was low (7% of the dose). As a consequence of the unsatisfactory non-renal clearance of cilastatin, however, the fraction of the dose removed by CAVH was significantly greater (approximately 30%) than that of imipenem. This did not, however, correct the dissociation of the pharmacokinetic profiles of the two drugs. In conclusion, the dose of imipenem/cilastatin in critically ill patients with renal failure treated by CAVH should be modified according to renal function but elimination by CAVH does not need to be considered.

Acute Kidney Injury↗
PubMed1989

Plasma catecholamine and cardiovascular responses to nifedipine in hypertensives WHO-stage II.

77 patients with arterial hypertension were consecutively examined. An evaluable echocardiogram could be recorded for 75 patients. 54 (72%) had non-pathological cardiac findings, 15 (20%) showed concentric left ventricular hypertrophy of the heart (mean left ventricular muscle mass (LVM) 2.5 g/kg or 113 g/m2; mean LVM/EDV 1.6 g/ml). 6 patients had an excentric hypertrophy of the left ventricle (8%). The influence of 10 mg nifedipine (Adalat) sublingual on the heart, blood pressure and sympathetic activity was examined in 15 patients with left ventricular hypertrophy of the heart. 5-10 min after administration, a significant decrease in systolic and diastolic pressures (p less than 0.05) and an increase in plasma noradrenaline (p less than 0.05) and heart rate (p less than 0.01) could be registered. The thickness of the posterior wall and septum decreased in 8 to 10 of the 15 patients, EDV, shortening fraction and ejection fraction increased in 8 of the 15 patients. A reduction in peripheral resistance, sympathetic counterregulation accompanied by an increase in heart rate, shortening and ejection fractions with increased enddiastolic volume and decrease in wall thickness can be observed as the gross effect in the majority of the 15 patients with left ventricular concentric hypertrophy. The decrease in wall thickness as a relaxation effect should not be confused with a regression of hypertrophy, whereby the mass-volume ratio shifts toward the normal range under nifedipine.

Administration, Sublingual↗
PubMed1988

[Regional intra-arterial chemotherapy with Dacarbazine in isolated liver metastases of a malignant melanoma].

A 58-year-old woman underwent regional intra-arterial chemotherapy for hepatic metastases of a malignant melanoma, because at the time no other organ metastasis was demonstrable. Dacarbazine was injected as a bolus on five successive days, four weeks apart, after which there were several days of fever and the urinary melanogen test became positive. At first the patient clearly improved and was again able to walk. But four months after the start of treatment she died in a hepatic coma.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1988

A study of the occurrence of HLA DR2 in 124 narcoleptics: clinical aspects.

The authors examined HLA antigens in 124 narcoleptics. In addition to narcolepsy, 122 patients suffered also from cataplexy. The two patients without cataplexy suffered also from sleep paralysis and hypnagogic hallucinations. These two symptoms were also present in many of the other patients. HLA group DR2 was found in 120 patients including all six symptomatic cases. In four patients HLA DR2 was not present. Two of these were fully pronounced narcolepsy-cataplexy cases whereas the two other did not suffer from cataplexy. Since several other cases with negative DR2 have already been published it is necessary to admit the existence of DR2-negative narcolepsy, albeit very rare. Among 5 patients with isolated sleep paralysis HLA DR2 was present in one familial and 1 sporadic case. The authors further discuss some aspects of the classification of narcolepsies in the light of recent HLA studies as well as their delimitation from idiopathic hypersomnia.

Cataplexy↗
PubMed1988

Peritoneal kinetics of different drugs.

In patients on peritoneal dialysis drug movement across the peritoneum depends on the physiology of the peritoneal membrane, the physiochemical properties of the drug, the dialysis regimen and the basic pharmacokinetic properties of the particular pharmacon. Besides the low dialysate flow rate in continuous ambulatory peritoneal dialysis (CAPD), the latter point-drug kinetics-is thought to be of major importance for the influence of CAPD on drug kinetics. The eliminative potency of CAPD for drugs is limited due to the low dialysate outflow rate, an unfavorable ratio of the dialysate to the body volumes of distribution, the usually low ratio of the peritoneal to body clearance and the effect of drug protein binding. With intraperitoneal application, the drug appears rapidly in the circulation. This again results from the large differences in the volumes of the body to the peritoneal compartments, leading to a high concentration gradient across the peritoneal membrane. Thus a rapid disappearance of a pharmacon from the peritoneal cavity following intraperitoneal application combined with an insufficient drug elimination by CAPD may be explained by basic pharmacokinetic considerations. Unidirectional peritoneal transport of a particular drug has so far not been demonstrated.

Administration, Oral↗