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Biomedical subjects

J Beyer

Publications and source records attributed to J Beyer.

At least 163 records · Page 9Linked to original sources
PubMed1997

A second form of infectious bursal disease virus-associated tubule contains VP4.

Preparations of density gradient-purified infectious bursal disease virus (IBDV) were found to contain full and empty icosahedral virions, type I tubules with a diameter of about 60 nm, and type II tubules 24 to 26 nm in diameter. By immunoelectron microscopy we demonstrate that virions and both types of tubular structures specifically react with anti-IBDV serum. In infected cells intracytoplasmic and intranuclear type II tubules reacted exclusively with an anti-VP4 monoclonal antibody, as did type II tubules in virion preparations. The immunofluorescence pattern with the anti-VP4 antibody correlated with electron microscopical findings. Neither purified extracellular nor intracellular virions were labeled with the anti-VP4 MAb. Our data show that the type II tubules contain VP4 and suggest that VP4 is not part of the virus particle.

Animals↗
PubMed1997

Randomized, double blind, placebo-controlled trial of low dose iodide in endemic goiter.

Iodine (I) is essential for normal thyroid function, and the majority of subjects tolerate a wide range of dietary levels. However, a subset of individuals upon exposure to normal or elevated levels of I develop thyroid dysfunction and autoimmunity. In this double blind trial, we evaluated efficacy and tolerability of low dose I in adults with euthyroid, diffuse, endemic goiter. Sixty-two subjects were randomly assigned I (0.2 mg/day) or placebo for 12 months. After termination of therapy, both groups were followed for a further 6 months. Thyroid sonography and determinations of thyroid-related hormones, urinary I excretion per 24 h, and thyroid antibodies were carried out at baseline and at 3, 6, 9, 12, 15, and 18 months. Markedly elevated urinary I values were found during therapy in subjects receiving I (32 at baseline vs. 213 micrograms/24 h at 12 months; P = 0.0001) compared to placebo (34 and 33 micrograms/24 h, respectively; P < 0.0001 vs. I). I substantially reduced thyroid volume (29 vs. 18 mL at 12 months; -38%; P = 0.0001), and at 18 months, the therapeutic effect was sustained. In the placebo group, no significant changes were observed. High microsomal and thyroglobulin autoantibody titers were present in 3 of 31 (9.7%) subjects receiving I, and I-induced hypo- and hyperthyroidism developed in 2 and 1, respectively. Fine needle biopsy revealed marked lymphocytic infiltration in all 3 cases. After withdrawal of I, thyroid dysfunctions spontaneously remitted, and antibody titers as well as lymphocytic infiltration decreased markedly. Follow-up of these 3 subjects for an additional 2 yr showed normalization of antibody titers in 2. Thus, among subjects with endemic goiter, low dose I successfully normalized thyroid volume and body I supplementation; nevertheless, reversible I-induced thyroid dysfunctions and autoimmunity were observed in nearly 10% of the subjects.

Adult↗
PubMed1997

[Insulin therapy in type II diabetes].

The results of conventional intensified insulin therapy (4 injections per day) in type II diabetics correspond more to those of conventional therapy (2 injections per day). Compared to a conventionally treated collective with strict dietetic regimen the intensified treated type II diabetics did not lead to an improved metabolic control. The frequency of hypoglycemic episodes did not differ in both collectives. Intensified insulin therapy is associated with subjectively increased comfort and increased life quality despite the seldom use of the advantages of the therapy. The management of the intensified therapy probably has to be learned in an earlier stage of life and requires repeated and more intensified education in elderly patients. The regression of typical late complications of diabetes mellitus as seen in the DCCT may possibly be achieved by a greater effort in therapy and empowerment of the patient.

Aged↗
PubMed1997

[Prediction of pharmacological effect of octreotide in acromegaly by means of 111In-pentetreotide scintigraphy and calculation of a pituitary uptake index].

AIM: The aim of our prospective study was to optimize the determination of the pituitary somatostatin receptor status by means of 111-In-pentetreotide scintigraphy and to compare it intraindividually with the pharmacological effect of octreotide in active acromegaly. METHODS: In n = 22 patients with growth hormone (GH) secreting pituitary adenoma, 111-In-pentetreotide scintigraphy was performed, and the specific radionuclide accumulation in the pituitary area (evaluation visually as well as semiquantitatively by means of ROI technique and calculation of various uptake indices) was correlated with the acute drop of GH after administration of 100 micrograms octreotide s. c. (octreotide acute test). RESULTS: The uptake index we propose (cts/pixel-ratio circular pituitary ROI: irregular cerebrum ROI after background correction in the sagittal SPECT slice with maximum pituitary uptake 24 h p.i.) correlates best with the pharmacological effect (acute decrease of GH levels) of octreotide; its upper normal limit amounts of 3.5. CONCLUSION: As often the normal pituitary gland can be visualized scintigraphically, the purely visual differentiation between a normal and a pathological receptor status sometimes is equivocal. A pituitary uptake index, calculated by means of a standardized ROI technique, facilitates this discrimination and so contributes to select possible responders for a treatment with octreotide.

Acromegaly↗
PubMed1997

[Endoscopic therapy of incidentaloma].

Since 1992 endoscopic surgical techniques have gained importance in adrenal gland surgery. In this review the actual laparoscopic and retroperitoneoscopic techniques and results-taking the own case material into consideration-are represented. The laparoscopic, transperitoneal adrenalectomy shows a low rate of complications (12%). Disadvantages of the transperitoncal approach are the risk of an intraabdominal injury and the problems caused by adhesions after abdominal operations. The retroperitoneoscopic access to the adrenal gland avoids disadvantages of the transperitoneal approach. Concerning the rising frequency of accidentally diagnosed tumors of the adrenal gland the retroperitoneoscopic approach represents a technique which allows a removal of these tumors up to a size 6 centimeters with low morbidity. In case of large tumors of the adrenal gland (size > 6 centimeters) suspected for malignancy we see the indication for the transperitoneal approach.

Adrenal Gland Neoplasms↗
PubMed1996

Decreased sympatho-adrenal activity in diabetic patients with autonomic dysfunction following mental stress.

The sympathetic nervous system is of major importance in the regulation of numerous physiological functions. While it is clearly established that there is a decreased noradrenergic status in people with autonomic neuropathy, the epinephrine secretion is much more controversial. Basal and mental stress-stimulated plasma catecholamine levels were measured in 42 diabetic patients with and without pathological cardiovascular function tests and in 13 healthy, non-diabetic control subjects. In addition, the excretion of catecholamines was measured in a 24 h urine collection and compared with the stress stimulated plasma levels. During mental stress exposure a diminished epinephrine secretion was found in diabetic patients with autonomic neuropathy compared with diabetic patients without neuropathy and the healthy control group (p < 0.05: respectively). The decreased epinephrine response to mental stress was strongly correlated with a diminished urinary excretion of this "neurotransmitter' (r = 0.46; p < 0.01). Diabetic patients suffering from cardiovascular autonomic neuropathy exhibit a diminished sympatho-adrenal response following mental stress exposure. Both measurement of urinary and mental stress stimulated plasma epinephrine levels following mental stress provide reliable information regarding sympatho-adrenal activity in diabetic patients.

Adrenal Glands↗
PubMed1996

The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors.

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Diurnal variation of corticotropin-releasing factor binding sites in the rat brain and pituitary.

1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal (HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF system are subject to diurnal variations. 2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala, bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus, hippocampus, and locus ceruleus of rats by in vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also established for plasma CRF and corticosterone. 3. The diurnal pattern of plasma CRF does not correlate with the pattern of plasma corticosterone. Within the brain, CRF binding in the basolateral nucleus of the amygdala showed a U-shaped curve with maximum levels in the morning and a wide hallow between 1500 and 0100. A biphasic profile with a small depression in the afternoon and a more pronounced depression in the second half of the activity period is characteristic for the other brain areas and the pituitary. The profile for the pituitary correlates with those for the BNST and the area of the locus ceruleus. Furthermore, the diurnal pattern of CRF binding sites in the BNST correlates with that of the hippocampus, and the daytime pattern of the visceral cortex is similar to that of both the hippocampus and the BNST. 4. Since the CRF-binding profiles in the brain and the pituitary clearly differ from the profiles of both plasma CRF and corticosterone, one may assume that the diurnal pattern of central CRF binding sites is not directly coupled to the activity of the HPA axis.

Animals↗
PubMed1996

Novel mechanism of macrolide resistance in Streptococcus pneumoniae.

The mechanism of macrolide resistance was examined in 73 clinical isolates of Streptococcus pneumoniae. Two distinct resistance phenotypes were observed: high-level macrolides-lincosamides-streptogramin B (MLS) resistance and low-level macrolide resistance with lincosamide susceptibility. High-level MLS resistance was associated with the presence of ermAM. Strains with the low-level resistant phenotype (novel) were negative for ermA, ermC, ermAM, ereA, ereB and msrA by polymerase chain reaction (PCR) amplification with gene-specific primers. Ribosomes isolated from novel strains bound the same amount of [14C]-erythromycin as ribosomes from sensitive strains. These novel strains also did not inactivate the macrolide. The novel mechanism was found in 41% of the erythromycin resistant S. pneumoniae examined.

Anti-Bacterial Agents↗
PubMed1996

Human corticotropin-releasing hormone and thyrotropin-releasing hormone modulate the hypercapnic ventilatory response in humans.

Human corticotropin-releasing hormone (hCRH) and thyrotropin-releasing hormone (TRH) are known to stimulate ventilation after i.v. administration in humans. In a placebo-controlled, single-blind study we aimed to clarify if both peptides act by altering central chemosensitivity. Two subsequent CO2-rebreathing tests were performed in healthy young volunteers. During the first test 0.9% NaCl was given i.v.; during the second test 200 micrograms of hCRH (n = 12) or 400 micrograms of TRH (n = 6) was administered i.v. Nine subjects received 0.9% NaCl i.v. during both rebreathing manoeuvres. The CO2-response curves for the two tests were compared within the same subject. In the hCRH group a marked parallel shift of the CO2-response curve to the left was observed after hCRH (P < 0.01). The same effect occurred following TRH but was less striking (P = 0.05). hCRH and TRH caused a reduction in the CO2 threshold. The CO2-response curves in the control group were nearly identical. The results indicate an additive effect of both releasing hormones on the hypercapnic ventilatory response in humans, presumably independent of central chemosensitivity.

Carbon Dioxide↗
PubMed1996

Intensive insulin therapy with insulin lispro in patients with type 1 diabetes reduces the frequency of hypoglycemic episodes.

In a randomized, open-label, controlled cross-over trial, 107 patients with type 1 diabetes were treated with either regular human insulin or insulin lispro, a rapid-acting insulin analogue. After a lead-in period of 2 to 4 weeks, the patients were randomized to receive intensified insulin treatment with one of the insulins. NPH-human insulin was used for basal substitution in both groups. The crossover took place after 3 months of treatment. Efficacy and safety of the drugs were established by the assessment of hemoglobin A1c, pretest blood glucose, 1 and 2-hour postprandial glucose excursions, number of hypoglycemic episodes, daily insulin doses, body weight, insulin antibodies, and the number and severity of adverse events. A questionnaire comprised of four primary domains was used to measure some quality of life aspects of the patients. Both treatment regimens were well tolerated. While no differences were seen in the hemoglobin A1c values, there was a trend for a decrease in the pretest blood glucose levels and significant decreases of the 1 and 2-hour postprandial glucose excursions in the patients treated with insulin lispro. The number of hypoglycemic episodes was also significantly lower in the insulin lispro treatment period. The evaluation of the quality of life questionnaire revealed an improvement in the patients treatment satisfaction for the insulin lispro group. During treatment with insulin lispro, the basal insulin doses increased slightly. However, the total daily insulin doses decreased to a greater extent with insulin lispro as compared to regular human insulin. Human insulin-specific antibody binding values at endpoint were not different for the two treatments. In conclusion, intensive insulin treatment with insulin lispro therapy results in improved postprandial glycemic control and HbA1c levels at least equal to the treatment with regular human insulin but with less hypoglycemia and more treatment satisfaction for the patient.

Adult↗
PubMed1996

Growth hormone substitution in growth hormone-deficient adults: effects on collagen type I synthesis and skin thickness.

Growth hormone stimulates collagen type I synthesis. Collagen type I is a common matrix compound in a large number of connective tissues. The aim of our study was to prove whether a stimulation of collagen type I synthesis might be accompanied by a deposition of collagen type I in the skin (cutis). Twenty growth hormone-deficient hypopituitary patients were included in a randomised, double-blind, placebo controlled, prospective, twelve-month study (eighteen patients assessable at the end of the study). The patients were treated with recombinant human growth hormone 0.25 U/kg/week subdivided in daily subcutaneous injections beginning with half the dosage during the first four weeks. During the first six months half of the patients were treated with placebo. PICP, the indicator of collagen type I synthesis, was increased after six months of therapy when compared to placebo. Skin thickness measured by ultrasound at the forearm and mechanically at the dorsum of the hand with strong compression of the skin both increased significantly following growth hormone substitution. Our data indicate that the stimulation of collagen type I synthesis by growth hormone substitution is followed by a deposition of collagen type I in the skin.

Adult↗
PubMed1996

T cells and orbital connective tissue in endocrine orbitopathy.

In order to analyse the immunological changes in patients with endocrine orbitopathy (EO) the antigenic character of orbital connective tissue was studied. Counter-stimulation assays of patients' lymphocytes with autologous retrobulbar fibroblasts resulted in a markedly increased lymphocyte proliferation in comparison to incubation with retrobulbar control fibroblasts. Proliferation tests of retrobulbar T cell lines showed significant responses to autologous retro-orbital connective tissue proteins, with molecular weights of 6-10 kD and 19-26 kD. Phenotypic analysis of orbital T cell lines indicates that they consisted predominantly of CD4+ cells. Hyaluronic acid production of orbital fibro blasts following co-cultivation with lymphocytes of EO patients or controls revealed a threefold increased synthesis in patients with EO. Furthermore, distribution pattern of orbital extracellular matrix glycosaminoglycans (GAG) differs in EO patients in comparison to controls. The results suggest the presence of autoreactive T cells directed against antigens of orbital fibroblasts, whose stimulation results in an augmented GAG synthesis in patients with EO.

Connective Tissue↗