A reason to hope: linking dementia research, care and services in the 21st century.
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Alzheimer Disease↗
Biomedical subjects
J Beyer
Publications and source records attributed to J Beyer.
[Intensified treatment of diabetes mellitus type I and the development of late complications].
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Diabetes Mellitus, Type 1↗
Effect of microencapsulation on oxygen distribution in islets organs.
In islet transplantation, limitation of oxygen supply may restrict graft function, particularly when encapsulated tissue is used. Therefore, oxygen tensions (PO2) in isolated islet organs (Brockmann bodies) of Osphronemus gorami were measured. In a thermostatically (37 degrees C) controlled measuring chamber, PO2 values were recorded at subsequent microelectrode positions on a radial track toward the center of the organ. In 2 independent groups, we studied the effect of fluid convection (n = 12) and microencapsulation (n = 12). In both groups, sigmoidal PO2 profiles were found, which permit differentiation in an oxygen-depleted zone surrounding the surface, a steep decline inside the tissue corresponding to the oxygen-consuming rim, and a plateau in the center without oxygen consumption which reflects necrosis. The PO2 values decreased (P < 0.001) when convection was stopped. Compared with starting values, PO2 levels at the surface were 61 +/- 3% with and 41 +/- 4% without convection. Surface values for encapsulated tissue were 44 +/- 5% compared with 64 +/- 4% in nonencapsulated tissue. In the tissue, center oxygen dropped to 27 +/- 5% with convection and to 6 +/- 3% without, and to 11 +/- 3% for encapsulated tissue compared with 22 +/- 4% for nonencapsulated tissue. The thickness of the outer oxygen-depleted zone was 81 +/- 16 microns with and 196 +/- 57 microns without convection (P < 0.001), and 188 +/- 16 microns for encapsulated and 94 +/- 14 microns for nonencapsulated tissue (P < 0.001). The oxygen-consuming rim was 295 +/- 22 microns with and 235 +/- 36 microns without convection (NS), and 216 +/- 15 microns for encapsulated and 315 +/- 24 microns for nonencapsulated tissue (P < 0.01). These results illustrate the special distribution of oxygen in isolated islet tissue and indicate that barium alginate encapsulation may worsen oxygenation mainly by expanding the "unstirred water layer" surrounding the tissue.
Alginates↗
Treatment intensification in disseminated germ-cell tumors.
Despite major improvements in the treatment of germ cell tumors the results remain unsatisfactory in patients with "poor risk" initial presentation, with inadequately responding or relapsed disease. The alternating use of noncrossresistant drugs or dose-intensified treatment regimens have not proved to be superior to conventional regimens, although the role of early treatment intensification with the use of hematopoetic growth factors or hematopoetic stem cell reinfusion warrants further investigation. In phase I/II trials patients considered incurable with conventional treatment regimens have been successfully salvaged by high-dose chemotherapy and autologous stem cell reinfusion. Several phase III trials to define the role of this novel approach are planned or ongoing in the USA and Europe.
Antineoplastic Combined Chemotherapy Protocols↗
Intra- and extracerebral blood flow changes and flushing after intravenous injection of human corticotropin-releasing hormone.
To study facial flush after systemic administration of human corticotropin-releasing hormone (hCRH) we injected 100 micrograms hCRH intravenously to ten healthy young men. The increase in facial temperature was measured by infrared camera. A significant increase in facial temperature of 1.39 degrees C +/- 0.3 was found within 7 min in all patients, which lasted up to 60 min, although facial flushing was visible in only 50% (5/10) of the probands. In a second experiment 100 micrograms hCRH was then administered to seven other healthy young men. Intra- and extracerebral blood flow velocity changes in the medial cerebral artery (MCA) and external carotid artery (ECA) were measured after hCRH administration by use of Doppler sonography. We found a decrease of intracerebral blood flow which was caused by hyperventilation and was reversible following 6% CO2 hyperventilation during a second injection of 100 micrograms hCRH. Blood flow velocity in the ECA increased by 111.5 +/- 32.9% (compared to baseline level), lasted up to 60 min after hCRH injection, and was not reversible by 6% end-tidal CO2 ventilation. We thus demonstrated that the direct vasodilatory effect of hCRH involves the ECA-supplied vascular territory only. The intracerebral vasoconstrictory effect represents the result of hyperventilation following hCRH injection. The data thus clearly suggest an interaction of hCRH and the vascular endothelium of the ECA, causing a marked blood flow velocity increase and facial flushing.
Adult↗
Age-dependence of bone material quality shown by the measurement of frequency of resonance in the ulna.
In women before and after the age of peak bone mass, identical values of bone mineral density (BMD) can be obtained. However, there is a much higher incidence of osteoporotic fractures in older women. We investigated whether a deterioration of bone material quality with increasing age might contribute to this phenomenon. Material properties of bone tissue can be characterized by the modulus of elasticity, which is correlated to the square of sound transmission velocity. In this study, sound transmission velocity was determined in cortical bone by measuring the frequency of resonance in the ulna in the direction of the bone's longitudinal axis and correcting the values by multiplying by ulna length. Validation of this method indicated acceptable reproducibility: interobserver variability determined as the mean coefficient of variation was 1.82%. In a clinical study, 21 young women (22.5 +/- 1.2 years old) were compared with 21 middle-aged women (52.9 +/- 2.7 years old). Pairs were matched that had identical values of BMD in the nondominant forearm at a location representing mainly cortical bone (SPA). The product of ulna length and frequency of resonance in the ulna in the younger women was found to be 61.4 +/- 5.8 m/second, and in the middle-aged women 55.7 +/- 4.5 m/second. The difference was highly significant with P < 0.005. Our results confirm recent findings indicating a deterioration of bone material quality independent of BMD with increasing age.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Association between "diabetic thick skin syndrome" and neurological disorders in diabetes mellitus.
Skin thickness on the extremities of patients with diabetes mellitus has been described controversially. Using high resolution ultrasonography, we were able to show a significant increase in skin thickness at the forearm (P < 0.05), thigh (P < 0.001) and lower limb (P < 0.05) of diabetic patients, most prominent at the thigh. No difference in skin thickness was found at the dorsum of the foot. In addition, skin thickness was not related to the duration of diabetes, age or HbA1. A close association was found between diabetic neuropathy and increasing skin thickness. Diabetic patients with neurological disorders had a significant increase in skin thickness versus diabetic patients without neuropathy. The present findings suggest that diabetic neuropathy and abnormalities of connective tissue have a common etiological link in their development or that both are time-dependent processes. Whether changes in capillary blood flow, increase of nonenzymatic glycosylation, polyol accumulation or other metabolic disorders are responsible for these findings remains still to be established.
Adult↗
Preliminary results of a phase I/II trial of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer.
Paclitaxel represents a novel antitumour agent with demonstrated activity in cisplatin-sensitive tumours, particularly ovarian cancer. In addition, responses to paclitaxel have been observed in patients with cisplatin-refractory ovarian cancer. The role of paclitaxel in the treatment of testicular cancer has not been explored so far. Despite the generally high cure rates in patients with metastatic testicular cancer, patients with relapsed disease not responding to platin-based salvage chemotherapy have an extremely poor prognosis. In a phase I/II trial 10 patients with relapsed, cisplatin-refractory malignant germ-cell tumours were treated with paclitaxel as 6-h infusions (8 patients) or 3-h infusions (2 patients) at doses from 135 mg/m2 to 310 mg/m2 at 3-week intervals. Three patients achieved a response to paclitaxel, but disease recurred shortly in two patients after two and four cycles of therapy, respectively. One patient has remained in marker-negative partial response for more than 5 months. The toxicity of paclitaxel was tolerable for a dose range from 135 mg/m2 to 225 mg/m2. Granulocytopenia, WHO grades 3 and 4, occurred in all patients but was of short duration (median 3 days; range: 2-7 days). Other toxicities such as mucositis (5 patients grade 1), neurotoxicity (1 patient grade 1, 2 patients grade 2), infection (1 patient grade 3) and diarrhoea (1 patient grade 2) were not dose-limiting. There were no hypersensitivity reactions, but 1 patient developed severe myalgias during therapy with paclitaxel. Six patients with documented cisplatin-refractory disease were retreated with cisplatin-based chemotherapy after paclitaxel treatment and, in 4 of these, tumour responses of 3, 4, 5 and more than 5 months duration were achieved. In order to explore the role of paclitaxel in relapsed and/or cisplatin-refractory testicular cancer a phase II study using a 3-h infusion of 225 mg/m2 paclitaxel every 3 weeks, conducted by the German Testicular Cancer Study Group, is ongoing.
Adult↗
CD 34 immunotyping of blasts in myelodysplasia.
We studied the expression of the hematopoietic progenitor cell antigen CD 34 in six patients with refractory anemia with excess of blasts (RAEB), five patients with RAEB in transformation (RAEB-T), and seven patients with chronic myelomonocytic leukemia (CMML). Immunocytochemical labeling of bone marrow cells was performed by an indirect immunoperoxidase method with preservation of morphological details. The cells were stained with May-Grünwald-Giemsa, photographed, destained, and immunolabeled by the immunoperoxidase technique. We found 1.5 +/- 0.5% blasts and 0.8 +/- 0.4% CD 34+ blasts in normal bone marrow. The CD 34 positivity of blasts was 53 +/- 9%. The patients with RAEB showed 1.7 +/- 1.4% CD 34+ blasts. The CD 34 positivity of blasts (11.8 +/- 5.6%) was lower than in normal bone marrow. The patients with RAEB-T had a higher percentage of CD 34+ blasts (7.3 +/- 3.4) and a higher CD 34 positivity of blasts (28.2 +/- 14.6%) than patients with RAEB. The CMML patients showed a percentage of CD 34+ blasts and a CD 34 positivity of blasts in the range of RAEB. We found an increase of promonocytes (PMC) in 5/7 patients. In some patients the PMC were CD 34 positive. Our results indicate that the increase of blasts in REAB is related to CD 34-negative blasts. With progression to RAEB-T the percentage of CD 34-positive blasts increased. Some of the CMML patients also showed a population of CD 34-positive PMC. A clone of undifferentiated CD 34-positive cells is characteristic for patients with these types of myelodysplasia.
Anemia, Refractory, with Excess of Blasts↗
Plasma glycosaminoglycans in endocrine ophthalmopathy.
With evidence on the important role of glycosaminoglycans (GAG) in the pathogenesis of endocrine ophthalmopathy (EO) having accumulated, the present study focused on the biochemical assessment of plasma GAG content in 37 EO patients as compared to 20 controls. Glycosaminoglycans were isolated from plasma samples by protein elimination, dialysis, and precipitation with ethanol and cetylpyridinium chloride. Patients (9.71, 5.09, 15.09 mg/100 ml; median, 25th, 75th percentile) exhibited significantly (p = 0.0021) higher plasma GAG levels than controls (4.6, 3.38, 6.8 mg/100 ml). Plasma GAG content was unrelated to age, sex, or antithyroid treatment. However, an even higher level of significance (p = 0.0001) was reached when discriminating between untreated patients with EO of recent onset (14.16, 10.35, 15.51 mg/100 ml) and controls. By contrast, steroid therapy of EO led to values (3.82, 1.85, 6.52 mg/100 ml) indistinguishable from those of the controls. Further statistical analysis of the results, based on a specificity of 95% for the control group, revealed a sensitivity of 91% for patients with untreated EO of recent onset, and a specificity of 100% for patients receiving steroid therapy. In comparison, plasma GAG content was determined in 8 untreated and in 6 treated EO patients by a second method already published. All untreated patients exhibited high GAG levels (median 2.23 mg/100 ml) whereas in treated EO patients normal plasma GAG values (0.17-0.34 mg/100 ml) were found. Follow-up determination of plasma GAG content in 7 patients undergoing steroid treatment unveiled a marked decrease of initially elevated values. These findings correlated well with clinical improvement of thyroid eye disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Corticotropin-releasing hormone (CRH) is a respiratory stimulant in humans: a comparative study of human and ovine CRH.
Previous experimental and clinical studies clearly demonstrated that exogenously administered CRH possesses respiratory properties. Until now, these effects were investigated using human (h) CRH in both healthy volunteers and patients under long-term respiration. We now compared the effects of hCRH with those of ovine (o) CRH in ten healthy young males. In particular it should be evaluated whether oCRH with its longer plasma half-life induces a more profound respiratory stimulation. On two separate days within two weeks, ventilation and cardiac performance were measured during steady state conditions by using a computerized cardio-pulmonary exercise testing system. In this placebo controlled double-blind-crossover study h- and oCRH (100 ug i.v. each) both augmented minute volume significantly during the observation period. Heart rate also increased after both analogues. All effects were comparable without a significant difference between both substances. There were no major side effects observable. Our data thus demonstrate that both analogues might be suitable for both diagnostic (i.e., testing of respiratory and autonomic responses) and therapeutic purposes.
Adrenocorticotropic Hormone↗
T-lymphocyte responses in guinea pigs vaccinated with foot-and-mouth disease virus.
The guinea pig provides an alternative experimental model for analysis of the immune response against foot-and-mouth disease virus (FMDV). The cellular immune response against FMDV in this experimental animal is unknown and was analyzed by in vivo and in vitro studies. In guinea pigs immunized with an FMDV A5 vaccine, a marked change in T-lymphocyte count appeared. For analyzing which functional T-cell compartment was affected, immunofluorescence studies, using monoclonal antibodies directed against differentiation antigens on guinea pig lymphoid cells, were performed. The proliferating T-cells were predominantly CD4-positive and, therefore, helper cells. T-cells from these animals were re-stimulated in vitro with homologous inactivated virus. The antigen-specific proliferative response of the T-cells in vitro was measured using the thymidine incorporation assay. A proliferative response to FMDV was observed that depended on the dose of the antigen. High concentration of virus had an inhibitory effect on T-cell proliferation. These data indicate that the guinea pig is a useful model for analysis of T-cell mediated mechanisms in the pathogenesis and immunity of foot-and-mouth disease.
Animals↗
Hepatitis C viremia in German blood donors: serum alanine aminotransferase is not a valid marker for screening.
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Alanine Transaminase↗
The stress-, but not corticotropin-releasing hormone-induced activation of the pituitary-adrenal axis in man is blocked by alprazolam.
A number of experimental studies clearly suggest that benzodiazepines attenuate the corticotropin-releasing hormone (CRH) secretion possibly through inhibitory GABAergic neurons. There is some evidence that benzodiazepines act to inhibit stress-induced activation of the hypothalamic-pituitary-adrenal axis. A comparison of the effects of a benzodiazepine on the stress- and CRH-induced activation in man has not been undertaken so far. We thus investigated the effects of the triazolobenzodiazepine alprazolam on both the stress- and CRH-induced changes in ACTH, cortisol, and prolactin secretion in ten healthy volunteers. In addition, hemodynamic parameters were studied. The subjects received either alprazolam (0.5 mg orally) or placebo 90 min prior to administration of CRH (100 ug i.v.) and to the performance of a mental stress technique. Blood samples, blood pressure and heart rate were taken every 15 min. The administration of alprazolam led to a highly significant attenuation of the ACTH increase following the stress interview. While ACTH increased from 12.4 to 26.7 pg/ml 15 min after the stress procedure in the placebo condition, there was almost no increase following alprazolam intake. An identical effect was found for cortisol secretion. Basal levels of prolactin were slightly enhanced in the alprazolam situation, while the stress-induced increase was not attenuated. Basal and stimulated systolic and diastolic blood pressure levels and heart rate were also significantly attenuated by alprazolam intake. Following administration of CRH, the ACTH augmentation was only slightly affected following alprazolam, while there were no changes in cortisol and prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Somatostatin receptor scintigraphy in endocrine orbitopathy].
Somatostatin receptor scintigraphy with 111In-labeled octreotide proves to be a very sensitive diagnostic tool for evaluation of inflammative activity in endocrine ophthalmopathy (EO). The results of somatostatin receptor scintigraphy (SRS) in 40 patients with EO show a high orbital accumulation of 111In-octreotide in clinically active EO (4 h-median/orbit-brain-ratio: 12.6; controls 4 h-median: 5.8) Patients with clinically inactive EO (4 h-median: 7.1) show a similar orbital accumulation of radioactivity compared to controls. 5 patients with active orbital myositis also revealed an even higher orbital accumulation of radioactivity (4 h-median: 42.3). The diagnostic value of SRS lies in its ability to act as a measure of inflammation and can be useful as an activity parameter when planning therapeutic procedure as well as for EO follow-up. The results in patients with orbital myositis nevertheless do not permit a differential diagnosis with this method. The therapeutic value of 111In-octreotide in Graves' disease has yet to be established.
Adult↗
Cellular immunity and retrobulbar fibroblasts in Graves' ophthalmopathy.
In Graves' ophthalmopathy (GO), retrobulbar connective tissue is infiltrated by T cells whose role in the pathogenesis of the disease was investigated in the present work. The aims included firstly to characterize subsets of blood lymphocytes and of sessile lymphocytes cloned from a retroorbital tissue specimen. Second, in counterstimulation assays, the ability of patients' T cells to influence cultivated retrobulbar fibroblasts and in turn the enhancement of lymphocyte proliferation by retrobulbar fibroblasts was investigated. Blood lymphocytes of 16 GO patients and 12 controls isolated by density gradient centrifugation and retrobulbar fibroblasts obtained from orbital decompression were alternately exposed to irradiation of 4000 rad (to suppress proliferation of either cell type), then cocultivated for 48 h. Subsequently, the cells (250,000 lymphocytes, 5000 retrobulbar fibroblasts) were incubated with [3H]thymidine for 24 h. A stimulation index representing the degree of proliferation in comparison with a control was determined. Screening of 62 retrobulbar lymphocyte clones by cell-ELISA revealed a CD4/CD8 ratio of 8.2, contrasting with a normal ratio of 2.1 in peripheral lymphocytes (as obtained by FACS analysis). Incubation of patient's lymphocytes with autologous retrobulbar fibroblasts resulted in a markedly elevated stimulation index (9.7) compared to incubation of lymphocytes with retrobulbar fibroblasts from controls (2.5). In another assay, the degree of stimulation amounted to 2.2 vs. -0.8. Retrobulbar fibroblasts were stimulated twice as much by lymphocytes of the same patient compared to retrobulbar fibroblasts from controls. The autologous reactions demonstrated suggest the presence of autoreactive T lymphocytes in GO patients directed against retrobulbar fibroblasts, which, in addition, are stimulated by these lymphocytes.
Adult↗
Microbiologic contamination of peripheral blood stem cell autografts.
We have determined the incidence and clinical significance of positive microbiologic cultures in a series of 290 peripheral blood stem cell concentrates in 95 patients undergoing multiple apheresis procedures for autologous stem cell rescue. Specimens for bacterial cultures were obtained after processing of the autografts just prior to freezing. The incidence of microbial contamination was 4.5% (n = 13). The predominant pathogenic microorganism cultured was coagulase-negative Staphylococcus (n = 11). From 8 patients with contaminated leukapheresis products 6 underwent autologous stem cell transplantation. Five patients received 1-5 culture-positive stem cell concentrates without serious sequelae, whereas the sixth patient was autografted with noncontaminated leukapheresis products, 1 concentrate contaminated with Aspergillus fumigatus being not reinfused. No microorganism present in the stem cell autograft was recovered in vivo in the posttransplantation period, although fever as a sign of infection occurred in all but 1 patient. Peripheral blood stem cell collection and ex vivo processing for cryopreservation may result in microbiologic contamination. However, our data show that infusion of contaminated stem cell autografts does not play a significant role as a source for infections in the clinical setting of autologous stem cell rescue.
Adolescent↗
In vitro and in vivo evaluations of A-80556, a new fluoroquinolone.
A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC for 90% of isolates [MIC90], 0.12 microgram/ml, relative to fluoroquinolone-susceptible strains) and Streptococcus pneumoniae (MIC90, 0.12 microgram/ml). A-80556 was also the most active of the quinolones tested against ciprofloxacin-resistant S. aureus, with an MIC90 of 4.0 micrograms/ml; that of ciprofloxacin was > 128 micrograms/ml. However, the significance of this activity is not known. A-80556 was slightly less active against Escherichia coli (MIC90, 0.06 microgram/ml) and other enteric organisms than ciprofloxacin (MIC90 for E. coli, < or = 0.03 microgram/ml). A-80556 was slightly less active against Pseudomonas aeruginosa (MIC90, 4.0 micrograms/ml) than ciprofloxacin (MIC90, 2.0 micrograms/ml) and more active against Acinetobacter spp. (respective MIC90s, 0.12 and 0.5 microgram/ml). A-80556 was also the most active compound against anaerobes. Against Bacteroides fragilis, the MIC90 of A-80556 was 2.0 micrograms/ml; that of ciprofloxacin was 16 micrograms/ml. The in vivo efficacy of A-80556 in experimental models with both gram-positive and gram-negative infections was consistent with the in vitro activity and pharmacokinetics and oral absorption in mice.
Animals↗