Graft-versus-host disease or graft-versus-host-like syndrome.
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Biomedical subjects
Publications and source records attributed to J Beyer.
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Cardiac involvement in 32 acromegalics was related to endocrine parameters, clinical score and duration of the disease as well as compared to that of 50 controls free of cardiac disease. Stress ECG, 24h Holter monitoring and echocardiography revealed that supraventricular premature complexes did not occur more often in acromegalics than in controls, both prevalence and severity of ventricular arrhythmia, however, were higher in patients compared to controls: 15/32 (48%) acromegalics had complex ventricular arrhythmia as compared with 6/50 (12%) normal subjects (p less than 0.01). Repetitive ventricular arrhythmia was manifest in 10/32 (31%) patients but only in 4/50 (8%) controls (p less than 0.01). Furthermore, frequency of ventricular premature complexes increased with duration of acromegaly (p less than 0.01), the severity of the former being correlated with left ventricular mass and with clinical activity score (p less than 0.01). No correlation, however, was found between the degree of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was increased (p less than 0.02) due to concentric hypertrophy. Thus, compared to controls, acromegalics show more frequent and complex ventricular arrhythmia and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.
Thyrotropin-releasing hormone (TRH) is a tripeptide and acts as a stimulator of the pituitary-thyroid axis as well as having a great number of well defined extrathyroidal functions. Studies in experimental animals have shown, that TRH also has a role as a neuromodulator within the autonomous nervous system. In this study we analyzed the effects following peripheral administration of TRH (200 micrograms, 400 micrograms) in patients with endocrinological disorders and in healthy females and males. By means of a questionnaire, patients were asked about possible (side-) effects; ventilatory and cardiovascular monitoring was performed during steady state. The pulsatile TSH-secretion pattern was analyzed and thyroid and stress hormones were measured in the blood prior to and following TRH i.v. Frequent symptoms afer TRH were feeling of heat (58%), stimulation of respiration (61%), palpitations (39%), micturition urge (52%) and restlessness (32%). Apparative monitoring demonstrated a short stimulation of respiration and an increase of heart rate. After 400 micrograms TRH i.v., blood levels of ACTH decreased slightly (p less than 0.01) but levels of T3, T4, epinephrine, norepinephrine and cortisol remained unchanged (p greater than 0.05). TSH-levels were low during daytime and showed a surge at night.
The aim of this study was to clarify the extent of bone mineral deficiency in patients with Klinefelter's syndrome on the premise that testosterone substitution could prevent this deficiency. Bone mineral density was measured by single-photon absorptiometry in 42 patients with Klinefelter's syndrome, (21 patients without therapy, 10 with testosterone substitution before the age of 20 and 11 patients with testosterone substitution beginning after the age of 20). We found significantly lower bone mineral density in patients without therapy and in patients when the therapy began later compared to normal individuals. Patients with early therapy showed a high proportion of normal values of bone mineral density. We found a positive correlation between bone mineral density and plasma testosterone and a negative correlation between plasma testosterone and age for patients without therapy. These findings suggest that low testosterone levels before or during puberty cause inadequate bone development and low bone mineral density in Klinefelter's syndrome. Only early testosterone substitution may prevent bone mineral deficiency. Later substitution no longer affects bone mineral density.
In a controlled study, the cardiac involvement and arrhythmia profile of 32 patients with acromegaly were correlated with endocrine parameters (somatomedine C, growth hormone), clinical score and duration of the disease. Data were compared with those of 50 controls free of cardiac disease. Stress ECG, 24 h Holter monitoring and echocardiography were performed. Supraventricular premature complexes occurred no more often in acromegalics than in controls. Both prevalence and severity of ventricular arrhythmia, however, were significantly higher in patients compared to controls (P less than 0.01). 15/32 (48%) acromegalic patients had complex ventricular arrhythmias (Lown III-IV) as compared with 6/50 (12%) normal subjects (P less than 0.01). Repetitive ventricular arrhythmias (Lown IV a/b) occurred in 10/32 (31%) patients, but only in 4/50 (8%) controls (P less than 0.01). Furthermore, the frequency of ventricular premature complexes increased with duration of acromegaly (P less than 0.01). No correlation was found between the severity of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was significantly increased (285 +/- 139 g, P less than 0.02) due to concentric hypertrophy. Severity of ventricular arrhythmias correlated with left ventricular mass and with clinical activity score (P less than 0.01). Thus, compared to controls, acromegalic patients show more frequent and complex ventricular arrhythmias and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.
In 13 healthy, male nonsmokers (mean age: 25.7 +/- 2.4 years) with normal fasting triglycerides we investigated postprandial changes of triglycerides in several lipoprotein fractions. After a 12-hour overnight fast they ingested a standardized lipid load (1,017 kcal) including 30,000 IU retinyl palmitate. Postprandially, total triglycerides increased significantly (p < 0.001) to a peak value of 221 +/- 81 mg/dl at 5 h. Two subjects had an exceptionally strong triglyceride response (peak values: 363 and 390 mg/dl). They had the highest levels of retinyl palmitate in the chylomicron and the nonchylomicron fraction, and one of them showed elevated intermediate-density lipoprotein values throughout the test period. In addition, they showed an altered early and an increased late postprandial insulin response. Thus, our data provide evidence that an exaggerated postprandial triglyceride response may point to an increased atherogenic risk even in healthy subjects with normal fasting triglycerides.
The exact role of retrobulbar fibroblasts in the immunopathogenesis of endocrine ophthalmopathy still remains to be elucidated. To evaluate the in vitro influence of humoral immunity on retrobulbar fibroblasts, the effects of immunoglobulin G as well as of the sera of 50 euthyroid patients with endocrine ophthalmopathy and 30 controls on both porcine and human (patients' and controls') retrobulbar fibroblasts were measured by means of several assays: a colorimetric test involving a heterocyclic chemical, a tetrazolium bromide, was applied to quantify the activity of mitochondrial dehydrogenases; the incorporation of 3H-thymidine was determined as a sensitive parameter for cell proliferation, and an enzyme-linked immunosorbent assay was to reveal specific binding of antibodies to the cells. There was consistently no significant difference between patients' (untreated or treated) and controls' IgG to bind to, to activate or to stimulate the proliferation of porcine and human (patients and controls) retrobulbar fibroblasts. The effects of patients' heat-inactivated and non-inactivated sera were indistinguishable from those of the controls. Incubation of autologous sera, however, led to an activation of retrobulbar fibroblasts which was both higher than the median caused by the patients' group and that engendered by incubation of autologous IgG. Yet, a significant role that humoral immunity might play directly on retrobulbar fibroblasts could not be detected in the experiments conducted in this study.
In both human and animal studies a stimulatory effect of corticotropin-releasing hormone (CRH) on respiration and on cognitive parameters has been demonstrated. Our own studies employing human CRH (hCRH) iv in healthy volunteers and different groups of patients have shown hCRH to be a safe drug. We prospectively studied the clinical effects of a standardized dose of 100 micrograms hCRH iv in 12 elderly patients following major abdominal surgery who remained comatose and were under prolonged respirator therapy over a mean period of 37 days. Cardio-respiratory parameters, blood gas values, plasma cortisol and catecholamines were evaluated before and 30 min following hCRH injection. Furthermore, vigilance was tested using a score system. Ventilation was markedly enhanced following hCRH injection while the cardiovascular parameters were only moderately affected. Vigilance was augmented in all subjects and improved impressively in five patients. The changes were of great benefit for the patients treated and supported their respirator weaning procedures and mobilization training.
The effects of humoral and cell-mediated immunity on the glycosaminoglycan synthesis of retrobulbar fibroblasts was evaluated in patients with endocrine ophthalmopathy. After incubation with IgG and sera, secreted glycosaminoglycans, radiolabeled with D-6-3H-glucosamine and 35sulfate, were precipitated with cetylpyridinium chloride and ethanol. Hyaluronic acid synthesis of human retrobulbar fibroblasts after incubation with sera and IgG and after co-culture with lymphocytes was assessed by means of a radiometric test. Patients' IgG, compared to controls', accounted for a higher secretory stimulation of porcine retrobulbar fibroblasts (as measured by cetylpyridinium chloride precipitation) after 24 and 48 h. Contrasting with 24 h incubation time, glycosaminoglycan values after 48 h were increased two to threefold. Patients' and controls' sera caused earlier and stronger, yet indistinguishable glycosaminoglycan production. Non-sulfated hyaluronic acid was the preponderant glycosaminoglycan secreted into the media by retrobulbar fibroblasts. As assessed with the radiometric test, incubation with patients' and controls' sera and IgG did not reveal a significant difference in stimulating the hyaluronic synthesis of patients' and controls' retrobulbar fibroblasts. When measuring the hyaluronic acid synthesis of controls' and patients' retrobulbar fibroblasts after co-cultivation of lymphocytes, however, patients' lymphocytes had a marked ability to increase the hyaluronic acid concentration compared to controls' lymphocytes. The hyaluronic acid concentration after incubation of a patient's retrobulbar fibroblasts with autologous lymphocytes was markedly more elevated than the intrinsic hyaluronic acid production of retrobulbar fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The metabolism of phenol in the terrestrial snail Cepaea nemoralis was studied after injection into the haemocoel of the dorsolateral foot region. 2. Excreted metabolites, and metabolites extracted from the body, were analysed by h.p.l.c. In addition to phenyl beta-D-glucoside, arbutine (quinol beta-D-glucoside), a new conjugate of phenol, was detected.
Glycosaminoglycan (GAG) accumulation in the retrobulbar space of patients with thyroid-associated ophthalmopathy (TAO) has been documented in a number of immunohistochemical studies. In order to gain further insight into possible immunopathogenic mechanisms, the influence of humoral immunity on retrobulbar fibroblasts (RF) as GAG producing cells as well as on GAGs themselves was investigated. The effect of lymphocytes on hyaluronic acid (HA) synthesis of RF as well as in turn the influence of RF on lymphocytes were evaluated. In search of methods which would facilitate management of patients with TAO and allow assessment of disease activity, GAGs were determined in both urine and plasma. Immunoglobulin G (IgG) of patients with TAO were found to markedly stimulate the 3H-GAG secretion of RF. Patients with TAO exhibited significantly greater antibody values directed against HA than controls. Preliminary results concerning the influence of lymphocytes on RF indicate a tendency for patients' lymphocytes to increase the synthesis of HA. Furthermore, these lymphocytes in turn were stimulated more by irradiated autologous RF than by irradiated heterologous RF. Urine and plasma GAG determination proved to be suitable for the routine assessment of disease activity and outcome of therapy. In conclusion, GAGs seem to play an important role in the pathogenesis of the disease and their measurement may provide aid to the endocrinological evaluation of patients with TAO.
Stimulation of lymphocytes with mitogens and antigens is an established model for in vitro testing of immunoreactivity. Due to the great variability of blastogenic response the interpretation of these results is difficult. Our results suggest that multivariate experiments and statistics improve the interpretation.
Excluding blood donations with elevated serum ALT from transfusion is only justified under the assumption that these more frequently transmit unrecognized hepatitis infections. The distribution of such infections in the donor population (with respect to age and sex) should be similar to that of hepatitis B and C, respectively. The prevalence of the latter two infections among our blood donors is the same in both sexes. The exclusion rate, however, is 3-4 times higher for men if equal ALT limits are applied. We therefore determined which ALT limits would give equal exclusion rates for donations of male and female blood donors in order to balance the risk of unrecognized hepatitis in blood donations from the two sex groups. In a second step, we also took each donor's age group into account and determined individual ALT limits for different age and sex groups.
Forty patients with germ cell tumors were treated with carboplatin 1500-2000 mg/m2, etoposide 1200-1600 mg/m2 and ifosfamide 0-10 g/m2 plus mesna followed by autologous stem cell reinfusion. A pruritic maculopapular rash was observed in 10 patients usually starting on the last day of chemotherapy. Lesions remained localized to the extremities in four patients. In six they became confluent and progressed also involving the trunk and face. Facial edema and painful swelling of hands and feet also occurred in this latter group. No ulcerations or bullae formation were seen and changes resolved spontaneously in all patients within 3 weeks leaving marked hyperpigmentation in involved areas. Renal function declined in nine of 10 patients concomitantly with evolving cutaneous changes, but recovered in all except one. Cutaneous side effects were more frequent with increasing doses of etoposide and carboplatin and in patients with deteriorating renal function. Plasma concentrations during high-dose chemotherapy should be monitored to avoid excessive serum levels and toxicity, especially in patients at risk of renal dysfunction.
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Synthetic human and ovine corticotropin-releasing hormone (hCRH, oCRH) are commonly used as a diagnostic tool of the hypothalamo-pituitary-adrenal axis. In this paper reports about side effects after various modes of CRH-application are analyzed and compared to our corresponding data of human studies with hCRH and oCRH. Generally, CRH is well tolerated after single administration and interval-application of standard doses, although minor side effects appear sometimes after higher doses (greater than 200 micrograms hCRH, oCRH) of CRH-bolus-injections. Predominantly the cardiovascular system (e.g. tachycardia, hypotension, flushing) is affected; neuropsychological symptoms are only seen sporadically (e.g. dizziness). Long term continuous infusion (several hours) of low CRH-doses (hCRH, oCRH) are well tolerated but side effects appear (see above) when cumulated doses of 200 micrograms-300 micrograms/h are given. Standard doses of hCRH and oCRH are also well tolerated in severely ill patients; it has to be considered that higher doses may provoke marked side effects in persons with neurologic disorders, in subjects with coronary heart disease and in patients with endocrinological disorders of the pituitary-adrenal axis, especially in those subjects in whom the blood-brain-barrier may have been damaged (e.g. head injury, intracranial operation). Single hCRH- and oCRH-bolus-injections in standard doses have a very low rate of complications, "non-standard" doses should provisionally be used only in clinical studies with well designed safety-precautions.
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