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Biomedical subjects

J Beyer

Publications and source records attributed to J Beyer.

At least 235 records · Page 13Linked to original sources
PubMed1994

Tight binding of clarithromycin, its 14-(R)-hydroxy metabolite, and erythromycin to Helicobacter pylori ribosomes.

Clarithromycin is a recently approved macrolide with improved pharmacokinetics, antibacterial activity, and efficacy in treating bacterial infections including those caused by Helicobacter pylori, an agent implicated in various forms of gastric disease. We successfully isolated ribosomes from H. pylori and present the results of a study of their interaction with macrolides. Kinetic data were obtained by using 14C-labeled macrolides to probe the ribosomal binding site. Clarithromycin, its parent compound erythromycin, and its 14-(R)-hydroxy metabolite all bound tightly to H. pylori ribosomes. Kd values were in the range of 2 x 10(-10) M, which is the tightest binding interaction observed to date for a macrolide-ribosome complex. This tight binding was due to very slow dissociation rate constants of 7.07 x 10(-4), 6.83 x 10(-4), and 16.6 x 10(-4) min-1 for clarithromycin, erythromycin, and 14-hydroxyclarithromycin, respectively, giving half-times of dissociation ranging from 7 to 16 h, the slowest yet measured for a macrolide-ribosome complex. These dissociation rate constants are 2 orders of magnitude slower than the dissociation rate constants of macrolides from other gram-negative ribosomes. [14C]clarithromycin was bound stoichiometrically to 50S ribosomal subunits following incubation with 70S ribosomes and subsequent separation of the 30S and 50S subunits by sucrose density gradient centrifugation. These data predict that the lower MIC of clarithromycin compared with that of erythromycin for H. pylori is likely due to a faster rate of intracellular accumulation, possibly because of increased hydrophobicity.

Centrifugation, Density Gradient↗
PubMed1994

Effects of thyrotropin- and corticotropin-releasing hormone on blood pressure and plasma catecholamines in the anesthetized rat.

The neuropeptides thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) have been found to be potent stimulators of the autonomic nervous system in both experimental animals and humans. We studied the effects of different doses of CRH and TRH given intracerebroventricularly in the urethane-anesthetized rat and a single dose of CRH in the chloral hydrate-anesthetized rat to elucidate the effects of these peptides in the unconscious state. All TRH doses studied enhanced blood pressure and noradrenaline and adrenaline secretion. Surprisingly, there were no blood pressure increases following administration of 0.4, 1.3 and 1.7 nmol CRH. In general, there was a tendency for blood pressure to decrease with the largest drop observed after 1.7 nmol CRH. Our data suggest that only TRH clearly augments blood pressure and catecholamine secretion in the anesthetized animal, while CRH does not exert major effects under the two anesthetic conditions employed.

Animals↗
PubMed1994

High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.

PURPOSE: This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS: Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS: The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION: High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.

Adult↗
PubMed1994

[Cardiopulmonary stress in hyperthyroidism].

Spiroergometry might be applicable to detect alterations of cardiopulmonary functions related to hyperthyroidism. Thus, cardiac and respiratory changes as well as work capacity in hyperthroid female patients were to be assessed with the help of the Cardiopulmonal Exercise Test System. Twelve female hyperthyroid patients with Graves' disease of whom all were controlled in euthyroidism, were examined. Eighteen euthyroid female patients in whom intracardiac catheter examination ruled out cardiopulmonary disease served as controls. The anaerobic threshold was determined by means of the V-slope method. An echocardiography was performed in all patients. Ergometry was performed in a semisupine position using a continuous ramp protocol of 20 watt/min. A markedly reduced work capacity, and a high heart rate in rest and exercise were found. In the ratio heart rate/oxygen uptake a lower rise (p = 0.001) due to a decreased growth in the heart rate was noticed. Regarding the pulmonary system a decreased tidal volume in hyperthyroidism (p = 0.021), and a higher breathing frequency (p = 0.003) were recognized, as well as an impaired oxygen consumption, in comparison with the euthyroid state. Also, echocardiographically an increased cardiac index (p = 0.008) and a markedly reduced stroke volume (p = 0.005) in comparison to the control group were observed. Heart rate, work capacity, oxygen uptake, and the ratio heart rate to oxygen uptake were normalized in euthyroidism. With the help of the CPX-System noninvasive measure of marked cardiopulmonary changes in hyperthyroidism are possible, especially the lower growth of the heart rate in exercise, which might be the limiting factor of work capacity.

Adult↗
PubMed1994

Automated bone marrow concentration using the Fresenius AS 104 blood cell separator.

We concentrated freshly taken bone marrow (BM) pooled from 21 patients from an original 1.265 ml (+/- 537 ml) down to 128 ml (+/- 36 ml) within 40-70 min with a modified version of the 'grancollect protocol' on the Fresenius AS 104 blood-cell separator using the P1-Y set. An average of 47% (+/- 21%) fo the initially present mononuclear cells and 68% (+/- 47%) of the colony-forming cells could be obtained in the concentrate. The erythrocyte concentration was reduced to 7% (+/- 4%) of the original amount. The technique described is very effective and makes is possible to obtain a BM cell population that is suitable for both immunomagnetic purging and cryopreservation or transplantation, e.g. in the case of blood group incompatibility.

Automation↗
PubMed1994

[Molecular biological screening of viruses important to transfusion medicine].

The usefulness of the direct virus detection by polymerase chain reaction (PCR) and reverse transcription/polymerase chain reaction (RT PCR) for blood donor screening was investigated, including the following viruses: cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency type 1 virus (HIV1). Hepatitis C viraemia was detected by RT PCR in 97% of anti-HCV-positive haemophiliacs, in 48% of anti-HCV-positive hepatitis patients, in only 21% of anti-HCV-positive blood donors from North-West Germany, and not at all in 945 blood donors with elevated serum ALT. In order to compare HIV1 detection by PCR and by p24 antigen determination, we tested 34 anti-HIV1-positive AIDS patients for p24 antigen, HIV1 RNA and HIV1 provirus DNA. 97% had HIV1 provirus DNA, 35% had HIV RNA, but only 30% had p24 antigen. A multiplex PCR specific for HBV, HCV and HIV1 (RNA and DNA) was developed for the investigation of a blood donor population from Namibia, where HBV and HIV1 infections occur more frequently than in German blood donors. The prevalence of anti-HIV1 antibodies in this population was 0.6%. HIV1 RNA was never detected in the plasma of 2,569 anti-HIV1-negative donors. HIV1 provirus DNA was present in 75% of the 16 anti-HIV1-positive individuals. None of these anti-HIV1-positive blood donors was also positive for p24 antigen. CMV infections and reactivations in 130 immunocompromised heart transplant patients and in 420 healthy anti-CMV-positive blood donors were monitored using cytochemical detection of CMV early antigen, and PCR. CMV DNA was neither detected in the plasma nor in the leucocytes of any anti-CMV-positive blood donor. During the course of CMV reactivation in immunocompromised heart transplant patients, CMV DNA was always detectable first in granulocytes and afterwards in the plasma. The cytochemical demonstration of CMV early antigen was typically delayed by several days and was observed in only 11% of those blood samples which contained CMV DNA in leucocytes. The determination of CMV DNA in leucocytes proved to be the most sensitive method to detect viraemia. Thus, CMV detection in leucocytes is the method of choice for the monitoring of transplant patients. This method is also promising for blood donor screening. The sensitive routine monitoring of blood donations for virus infections by multiplex PCR is practicable. However, nucleic acid must be extracted both from the plasma and from the cellular compartments of blood in order to detect HIV and CMV provirus DNA. Lysate from EDTA blood is a suitable material for this purpose. The determination of the surrogate marker serum ALT activity is of no use in hepatitis C screening, and determination of p24 antigen is not required in HIV1 screening.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Comparison ov anti-HCV tests of the first and second generation and suggestions for a re-entry program].

After following up approximately 200,000 blood donors with 1st- and 2nd-generation anti-HCV tests the authors suggest: 1) to neglect earlier 1st-generation-positive anti-HCV results when the donor is negative in 2nd-generation ELISAs; 2) after a donation positive in a 2nd-generation test the following donation must not be used even if it is negative; a third, negative donation can be used; 3) a donor with two different donations positive in 2nd-generation ELISAs should be excluded from the donor pool.

Blood Donors↗
PubMed1993

[Driver's license and diabetes. Legal and social medicine aspects].

The diagnosis of diabetes mellitus is accompanied by a lot of personal and social consequences for the patient himself. One of the most important problems is the influence of the disease on the patients driving skills. This aspect is discussed according to the recommendations of the German ministry of traffic, and advice is given for the diabetic patient taking part at the daily traffic as a car driver.

Accidents, Traffic↗
PubMed1993

The phenomenon of a high triglyceride response to an oral lipid load in healthy subjects and its link to the metabolic syndrome.

Excessive postprandial triglyceride (TG) responses despite normal fasting TG levels have been described in single cases within small groups of healthy subjects and in patients with obesity or precocious atherosclerosis, known to be associated with high insulin fasting levels. To clarify this association, fasting and postprandial TG and insulin levels were studied in 113 healthy young (25.7 +/- 2.6 years), normal weight (body mass index 20.8 +/- 2.3 kg/m2) male subjects who were selected from among 117 subjects on the basis of TG fasting levels < 200 mg/dl. After a 12-hour fast a standardized liquid lipid load was administered containing 58 g mainly saturated fat and 1,017 kcal energy. Both fasting TG values and postprandial TG peak values showed bimodal frequency distributions. Statistical analysis of fasting TG discriminated two groups: a low fasting TG group with normally distributed values < 150 mg/dl (mean +/- SEM: 79.5 +/- 2.7 mg/dl; n = 104) and a high fasting TG group > 150 mg/dl (194.5 +/- 7.2 mg/dl; n = 13). Likewise, two groups could be differentiated according to their maximal postprandial TG response (TG max) to the lipid load: (1) normal responders with TG max < 260 mg/dl (mean +/- SEM: 123 +/- 4.8 mg/dl; n = 96) and (2) high responders with TG max > 260 mg/dl (272.5 +/- 20.5 mg/dl; n = 17). Fasting TG and TG max were highly correlated (r = 0.745; p < 0.0001). However, 9 of 17 (53%) high responders had fasting TG < 150 mg/dl, which means that the prediction of high response is only 47.0% based on fasting TG values. Fasting insulin levels were significantly higher in high responders than in normal responders, whereas they did not differ between the low and high fasting TG group. In conclusion, the bimodal frequency distribution of TG max after a lipid load permitted the differentiation of two groups, normal responders and high responders, with higher fasting insulin levels, which might indicate a link to the metabolic syndrome.

Adult↗
PubMed1993

[Backache and osteoporosis in perimenopausal women].

Osteoporosis is thought to represent one of the main causes of back pain in perimenopausal women. One hundred perimenopausal women (45 to 60 years) who were consecutively admitted in order to clarify the cause of their back pain were examined. In 20% disc degenerations were found. Other degenerative disorders (osteoarthritis) of the spine without coincident scoliosis were found to be the second most common cause of pain in 19%. Scoliosis due to different leg length was detected in 15%, idiopathic scoliosis in 13%. Spondylolisthesis occurred in 7% even more frequently than osteoporosis with vertebral deformities in 6%. Non-osteoporotic vertebral deformities were seen as often as osteoporotic ones. Rare diagnoses among others were seronegative spondyloarthropathy and fibrositis. Our results indicate that back pain in women up to 60 years is mostly due to degenerative disorders of the spine. Osteoporosis with vertebral deformities as cause of pain is quite rare. Comparing bone mineral density of the distal forearm (SPA) of the patients with back pain not due to manifest osteoporosis (98 +/- 15% of age related mean) with those of 50 asymptomatic women (96 +/- 14%) and 50 female patients with pain in other regions of the skeleton (103 +/- 17%) in the same age group, there was no evidence for any relation between low bone mineral density and skeletal pain.

Female↗
PubMed1993

Predictive value of liver slices for metabolism and toxicity in vivo: use of acetaminophen as a model hepatotoxicant.

To establish the usefulness of liver slices as predictive models for in vivo metabolism and toxicity, acetaminophen was used as a model hepatotoxicant for which the role of metabolism in toxicity is well documented. Acetaminophen was incubated with liver slices prepared from the rat and hamster since these species differ in susceptibility to acetaminophen-induced hepatotoxicity. Formation of acetaminophen metabolites (sulfate, glucuronide, and glutathione conjugate), slice glutathione levels, and slice histopathology were assessed. Acetaminophen (0.5, 1, and 2 mM) induced a dose-dependent depletion of glutathione in hamster slices (sensitive species) but not rat slices (insensitive species). Formation of the acetaminophen toxic metabolite, as measured by glutathione conjugate formation, was much lower in rat slices compared with hamster slices. Rat slices also showed greater activity of the nontoxic sulfation and glucuronidation pathways. These data predicted an 11-fold greater susceptibility to toxicity in the hamster based on the proportion of the dose metabolized to the reactive species. In vivo data, using hepatic glutathione depletion as an indicator of toxic metabolite formation, would predict a similar difference (13.3-fold) between the hamster and the rat. To ascertain if the characteristic centrilobular lesion induced by acetaminophen in vivo could be reproduced in vitro, liver slice histopathology was assessed 6 and 12 hr after a 2-hr treatment with acetaminophen (2 mM). Discrete damage to the centrilobular regions of the liver were noted in hamster but not rat slices. Overall, based on metabolite formation, glutathione depletion, and slice histopathology, the liver slices were excellent predictors of acetaminophen hepatotoxicity in vivo.

Acetaminophen↗
PubMed1993

Comparison of 5 vs 10 micrograms/kg per day of GM-CSF following dose-intensified chemotherapy with cisplatin, etoposide, and ifosfamide in patients with advanced testicular cancer.

Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with "poor-risk" (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose-intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1-5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 micrograms/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 micrograms/kg than for those with 5 micrograms/kg per day of GM-CSF (9 vs 13 days; p < 0.05). The median duration of thrombocytopenia < 20,000/microliters after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 micrograms/kg of GM-CSF (4 vs 9 days; p < 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 micrograms/kg per day of GM-CSF. The dose of 5 micrograms/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Architecture in cortical bone and ultrasound transmission velocity.

The square of ultrasound transmission velocity in a material is correlated to the modulus of elasticity, which is an indicator of its mechanical properties. This might make the measurement of ultrasound transmission velocity useful in the noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic material but is architecturally structured. The aim of our study was to investigate and especially to quantify the influence of architecture in cortical bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound transmission velocity was measured parallel and perpendicular to direction of Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/- 29 m/s perpendicular to Haversian channels respectively (p < 0.001). Our results clearly indicate that there is an important influence of architecture in cortical bone on ultrasound transmission velocity which has to be taken into account in its clinical use.

Animals↗