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Biomedical subjects

K H Usadel

Publications and source records attributed to K H Usadel.

At least 145 records · Page 8Linked to original sources
PubMed1993

Analgesic effect of the somatostatin analogue octreotide in two acromegalic patients: a double-blind study with long-term follow-up.

Two acromegalic patients with severe headache were treated with the somatostatin analogue, octreotide (Sandostatin). A double-blind study of octreotide versus placebo in which pain intensity was measured using a visual analogue scale (VAS) was performed initially with these patients. A rapid (within 4-15 min) pain relief occurred lasting 2-8.5 h after injection of 100 micrograms of octreotide, an effect that was not reversed by intravenous (i.v.) naloxone. These 2 acromegalic patients then received treatment for 71 and 82 months, respectively, with doses starting at 500 micrograms/day and 1500 micrograms/day, respectively, without evidence of either tolerance or dependence, although the effect of octreotide on headache appears to be selective. No unwanted sedative effect has been observed. A screening procedure with injection of 50 micrograms of subcutaneous (s.c.) octreotide was performed in 11 other patients with chronic severe pain associated with various conditions. Only 3 patients (2 with diabetic polyneuropathy and 1 with bone pain associated with myelodysplastic syndrome) reported more than 50% pain relief. In the insulin-dependent diabetic patients the double-blind check was not performed due to the risk of octreotide-induced hypoglycemia. In the patient with bone pain the same double-blind check as in the acromegalic patients could not confirm the analgesic effect. It may thus be concluded that octreotide appears to be useful for the treatment of both chronic and acute severe painful conditions in acromegalic patients. However, since its analgesic effect in our patients was confined to headaches only, further controlled studies must be carried out in order to determine appropriate target groups.

Acromegaly↗
PubMed1993

Arterial constriction, ischemia-reperfusion, and leukocyte adherence in acute pancreatitis.

We investigated microcirculatory changes in sodium taurocholate (ST)-induced pancreatitis. Groups of rats received as tracer either fluorescein isothiocyanate-dextran or acridine orange intravenously. The microcirculation of the exposed pancreas was observed by use of a video camera attached to an epi-illumination microscope. Vessel diameters and plaques of adherent leukocytes were measured with a digital image-analyzing system. In contrast to 0.4 ml of saline, intraductal infusion of ST (4%, 0.4 ml) induced a constriction of interlobular pancreatic arteries of 79 +/- 2% (P < 0.01) within 2 min. This constriction could not be antagonized by the leukotriene antagonist CGP-35949B. The radical scavengers superoxide dismutase (SOD) and N-(2-mercaptopropionyl)glycine (MPG) prevented the arterial constriction. Constriction of pancreatic arteries was accompanied by a decrease of erythrocyte velocity in the pancreatic capillaries. Flux in the head of the pancreas measured by laser-Doppler velocimetry decreased from 300 +/- 69 to 74 +/- 23 perfusion units (P < 0.01) after 446 +/- 159 s. Subsequently an increase of perfusion values was observed indicating reperfusion phenomena. ST induced leukocyte adherence to the walls of interlobular veins forming plaques constituting 39% of the observed venular cross section within 6 min. The leukotriene antagonist, SOD, or MPG prevented leukocyte adherence. Arterial constriction followed by ischemia-reperfusion and leukocyte adherence to venular endothelium during the reperfusion period represented the sequence of microcirculatory changes in ST-induced pancreatitis. The radical scavengers SOD and MPG prevented arterial constriction and leukocyte adherence to venular endothelium, indicating the involvement of free radicals in the pathogenesis of ST-induced pancreatitis in the rat.

Acute Disease↗
PubMed1993

Lack of intrathyroidal tumor necrosis factor alpha in Graves' disease.

In vitro tumor necrosis factor alpha (TNF alpha) exerts a synergistic action on HLA class II expression and a cytotoxic action in FRTL-5 cells. Therefore, a role for TNF alpha as a local mediator of cell destruction in thyroid autoimmunity has been postulated. To elucidate the in vivo significance of these and other in vitro findings for the pathophysiology of Graves' disease we investigated 11 thyroid glands of patients suffering from Graves' disease for TNF alpha. In situ hybridization was done with a TNF alpha probe synthesized with T7 polymerase on a 750-base pair EcoRI fragment of the coding region. Primers at positions 152 and 854 in the TNF alpha copy DNA sequence were used for reverse polymerase chain reaction (PCR) amplification of TNF alpha in 5 patients. Immunohistological staining for TNF alpha was done with a mouse monoclonal antibody. We could not detect any TNF alpha and TNF alpha messenger RNA in thyroid tissue of 11 patients suffering mostly from relapsing Graves' disease by immunohistology and in situ hybridization as well as reverse PCR, respectively. A faint signal could be detected by reverse PCR in control thyroid tissue from a patient with recurrent goiter. This lack of intrathyroidal TNF alpha in relapsing Graves' disease is in accordance with a lack of increased TNF alpha production by T cell clones isolated from Graves' disease thyroid glands and contrasts with previous in vitro results. Since protective TNF actions have been demonstrated in other autoimmune diseases it could therefore be envisaged that the lack of intrathyroidal TNF alpha may be associated with the relapse of Graves' disease in our patients.

Actins↗
PubMed1993

Correlation of microsomal antibodies with the intensity of the intrathyroidal autoimmune process in Graves' disease.

Graves' disease is an organ-specific autoimmune disease, and intrathyroidal lymphocytes seem to be the major source of thyroid autoantibodies. Consequently, the intensity of the intrathyroidal lymphocytic infiltration is generally believed to reflect the activity of the autoimmune process. We, therefore, investigated the correlation of microsomal (enzyme immunoassay), thyroglobulin (RIA), and TSH receptor antibodies (RRA) with the degree of intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T-cells, antigen-presenting cells, and the total number of lymphocytes. The immunocompetent cells were identified immunohistologically with monoclonal antibodies for immunoglobulins kappa and lambda, UCHL1, and the S100 antibody, respectively, in 26 thyroid glands of patients suffering from Graves' disease. The intensity of lymphocytic infiltration was determined by the point-counting method and by counting all lymphocytes and the labeled lymphocytes in 3 x 51 visual fields or 3 slides/thyroid gland. Microsomal antibodies correlated significantly (P = 0.001) with the total number of lymphocytes (r = 0.86), kappa (r = 0.71), lambda (r = 0.71), UCHL1 (r = 0.9), and S100 (r = 0.9) positive cells. These correlations were also significant for thyroglobulin antibodies. However, TSH receptor antibodies showed no significant correlations with any of the populations of immunocompetent cells. Patients with preoperatively undetectable TSH receptor or microsomal antibodies showed a broad variation of intrathyroidal infiltration by the immunocompetent cells investigated. Microsomal antibody titers, therefore, seem to reflect the intensity of the intrathyroidal autoimmune process in Graves' disease better than TSH receptor antibodies. However, the broad baseline variation in intrathyroidal infiltration observed with nondetectable thyroid antibodies will not always allow determination of the intensity of the intrathyroidal autoimmune process from microsomal or thyroglobulin antibody titers.

Adult↗
PubMed1993

Treatment of macroprolactinoma with the new potent non-ergot D2-dopamine agonist quinagolide and effects on prolactin levels, pituitary function, an the renin-aldosterone system. Results of a clinical long-term study.

The oral non-ergot D2-dopamine agonist quinagolide (CV 205-502, CAS 87056-78-8) has proven to be highly effective in suppressing elevated prolactin (PRL) levels. It was the aim of this study to search for possible interference of the drug with other endocrine systems which are partly under dopaminergic control, and to compare such effects to those of previously investigated prolactin inhibitors. Twelve patients suffering from macroprolactinoma were treated for at least 6 months with daily doses ranging from 50 up to 300 micrograms. During the first two months, individual doses were gradually increased either until serum PRL levels reached the normal range (n = 7) or until side effects made a further dose increase intolerable (n = 5). Mean basal PRL level fell from 255 +/- 65 (SEM) ng/ml before treatment to 19 +/- 8 ng/ml, after the definite dose was reached (p < 0.01). Luteinizing hormone (LH) rose from 0.6 +/- 0.8 (SD) to 1.7 +/- 1.6 mU/ml (p < 0.05). While basal levels of aldosterone, renin, follicle-stimulating hormone (FSH), triiodothyronine (T3), testosterone, and estradiol in females were not affected by the treatment, we found a significant rise in thyroxine (T4) and a decrease of estradiol in males. Blood pressure and renal clearances of creatinine, sodium, potassium, and chloride failed to show any significant change. Following stimulation with metoclopramide, aldosterone and renin rose sharply before treatment was initiated. When the test was repeated during treatment, the increase of plasma renin was slightly dampened, whereas the rise of aldosterone remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[The role of human atrial natriuretic peptide on pathogenesis of nephropathy in patients with type I diabetes mellitus].

Divergent findings in recent clinical and experimental studies have caused considerable controversy as to whether or how elevated plasma levels of human atrial natriuretic peptide (hANP) may contribute to the pathogenesis of diabetic nephropathy in type I diabetic patients. Therefore, we decided to examine potential changes of urinary albumin excretion (UAE), urinary excretion of alpha-1-microglobulin (A-1-M), mean arterial blood pressure (MAP), hANP levels, creatinine clearance and HbA1 in the course of a prospective one-year study in 19 patients (13 females, six males, age 29 +/- 2 years). All patients had intensified insulin treatment. Seven patients at increased risk for eventually developing nephropathy (group 1) were identified by repeatedly showing elevated UAE ( > 30 mg/24 h). The other patients served as controls (group 2). Patients in group 1 differed from those in group 2 in increased A-1-M (maximal difference, 10.1 +/- 1.5 vs. 5.5 +/- 1.0 mg/l, p < 0.01). In the second half of the study, 43% of the MAP measurements in group 1 exceeded 100 mmHg in comparison to 19% in group 2 (p < 0.01). Simultaneously, 38% of the hANP levels in plasma in group 1 were higher than 25 pg/ml (upper limit of normal range) in comparison to 15% in group 2 (p < 0.05). There were no differences in creatinine clearance between both groups. 58% of the HbA1 concentrations measured in group 1 in the course of the study exceeded 8.5% in comparison to 47% in group 2 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Mental and physical state in subclinical hyperthyroidism: investigations in a normal working population.

We investigated whether subclinically hyperthyroid individuals selected from a nonpatient working population exhibit similar impairments to those found in studies with patients. Sixteen subclinically hyperthyroid subjects without apparent reason (SH-0) and 15 subclinically hyperthyroid subjects on levothyroxine (SH-T4) were compared with 27 euthyroid controls with respect to signs and symptoms of hyperthyroidism, sleep, depressivity, ability to concentrate, anxiety, and other dimensions of well-being. We found that SH-T4 exhibited significantly higher TT4 levels, TT4/TBG ratios, and more palpitations than controls. Furthermore, they slept less. The SH-0 subjects reported being in a better mood and less touchy than controls. Psychometric results of all groups were within the normal range. A comparison of this study to previous studies reveals that TT4 levels or TT4/TBG ratios may play a crucial role in the development of the predominantly nervous symptoms in subclinical hyperthyroidism. Possible reasons for the discrepancies between results in hospital and nonhospital settings are discussed.

Adult↗
PubMed1992

[Effect of metabolic control on the renal effects of human atrial natriuretic peptide-(95-126) (urodilatin) in normotensive patients with type I diabetes mellitus].

To examine the impact of metabolic control on renal responses to human atrial natriuretic peptide (hANP) in type 1 diabetes mellitus, 13 patients with HbA1 less than 8.5%, nine patients with HbA1 greater than 8.5% and ten healthy volunteers were studied. According to a randomized, single-blind trial design, 0.5 and 2.0 micrograms/kg hANP-(95-126) (Urodilatin) (Bissendorf Peptide, Hannover) or placebo were given as iv bolus injections at 90-minute intervals. Patients with HbA1 greater than 8.5% differed from those with HbA1 less than 8.5% in longer diabetes duration, more prevalent retinopathy and neuropathy and increased somatomedin C levels and urinary albumin excretion (p less than 0.05). In response to hANP, patients with HbA1 greater than 8.5% had decreased responses of urinary volume and sodium excretion in comparison to patients with HbA1 less than 8.5% (p less than 0.05) in whom renal responses to hANP did not differ from controls. Despite similar hANP levels, hANP-stimulated urinary cGMP excretion in patients was higher than in controls (p less than 0.01). Impaired renal responses to hANP in diabetes patients with insufficient glycemic control apparently contribute to the mechanisms of diabetic sodium retention. Near-normoglycemia may prevent this phenomenon which is intimately involved into the pathogenesis of diabetic nephropathy.

Adult↗
PubMed1992

[Long-term antihypertensive therapy of diabetic patients with felodipine. Effects of treatment on blood pressure and kidney function parameters].

AIMS: Detection of possible effects on renal function parameters of long-term antihypertensive treatment administered to patients with diabetes mellitus. STUDY DESIGN: Prolongation of an open trial, initially planned for one year, on the effect of felodipine 10 mg/day in diabetics (Fortschr. Med. 109 (1991), 53-56). Continued treatment of 7 hypertensive insulin-dependent diabetics (mean age 58 +/- 3 years, HbA1 8.2 +/- 0.3%) over a period of between 24 and 32 months. RESULTS: The lowered blood pressure (from 160/94 to 150/82 mmHg; p less than 0.05) persisted. In the first 6 months of treatment, urinary albumin excretion (UAE) remained constant. Thereafter it increased (p less than 0.05 as compared with the figure seen after 6 months' treatment) to a degree that varied from one patient to another; overall, the UAE figures showed a relatively large intra-individual fluctuation during long-term therapy. Metabolic parameters remained uninfluenced by felodipine. CONCLUSIONS: It cannot be excluded that progression of diabetic renal disease cannot be adequately prevented by long-term treatment with calcium antagonists such as felodipine.

Blood Pressure↗
PubMed1992

[Successful multiple resuscitation in flecainide poisoning].

After a family quarrel a 37-year-old woman swallowed, with suicidal intent, a large number of flecainide tablets (exact amount unknown) together with alcohol. On admission to hospital some hours later her pupils were fully dilated, fixed and of irregular outline; she was unconscious and in cardiorespiratory failure. Nine hours after admission several episodes of ventricular fibrillation and asystole occurred, two of them lasting for 2 and 3 hours, respectively, before successful resuscitation (after defibrillation). The highest plasma flecainide level, between 3 and 10 hours after swallowing the drug, was 6160 ng/ml, i.e. six times the maximal therapeutic level. Under the influence of flecainide the ECG of the previously healthy woman had shown idioventricular rhythm with marked QRS widening and Q-T prolongation. The tachyarrhythmias, at times torsades de pointes, were successfully treated with high doses of lidocaine (4 g daily) after repeated defibrillations. As a late complication the patient went into acute left ventricular failure with pulmonary edema and pneumonia. There were no recognizable permanent sequelae on discharge 37 days after admission.

Adult↗
PubMed1992

Renal long-term effects of calcium antagonist treatment in patients with diabetes mellitus.

Although calcium antagonists have long been introduced into antihypertensive treatment, little is known of their renal long-term action in patients with diabetes mellitus, diabetic nephropathy, or hypertension. Much of the current information concerning this issue is from short-term studies. While urinary albumin excretion, a major indicator of glomerular damage in patients with diabetes mellitus, remains unchanged or even increases during short-term calcium antagonist treatment in type 1 diabetic patients, it is mostly reduced in type 2 diabetic patients, especially by diltiazem and nicardipine. There have been discrepant observations in studies lasting 6-months or longer. In many of the studies, urinary albumin excretion is not decreased by calcium antagonist treatment, although blood pressure is well controlled. Albuminuria is markedly reduced, however, after nitrendipine or diltiazem treatment. While calcium antagonists such as diltiazem, nicardipine, or nitrendipine may be as efficacious as converting enzyme inhibitors in preventing the progression of diabetic kidney disease in diabetic patients, the beneficial efficacy of others is less apparent. Reduced albuminuria may be more difficult to attain in macroalbuminuric patients with advanced nephropathy. However, considerations on the potential effects of calcium antagonist long-term treatment on cardiovascular morbidity or mortality in diabetic patients should not be overlooked when their renal action is under discussion. Thus, further studies are needed to define the role of calcium antagonists more precisely in the long-term treatment of diabetic patients with hypertension or diabetic nephropathy.

Albuminuria↗
PubMed1992

HLA-DRB3 gene alleles in Caucasian patients with Graves' disease.

Graves' disease (GD) is a human leukocyte antigen (HLA) linked organ-specific autoimmune disease. In German GD patients the disease is associated with HLA specificities of the HLA-DRw52 family (HLA-DR3, -DR5, and DR6; HLA-DRB3 positive HLA haplotypes). Recently, a strong association with a HLA-DRB3 restriction fragment length polymorphism gene has been described. To study HLA-DRB3 alleles and their association with the disease, a large cohort of controls (n = 3724) and GD patients (n = 304) was analyzed. HLA-DR allelic combinations revealed an increase in HLA-DR3/DR5 heterozygous patients (relative risk 2.9; P < 0.001). HLA-DRB3 alleles, as defined by DNA typing in HLA-DR matched groups revealed a significant increase in DRB3*0101 homozygosity (relative risk 17.5; P < 0.001) in HLA-DR3 homozygous patients. In GD patients with ophthalmopathy (grade II or higher, according to Werner) DRB3*0101/*0202 heterozygosity revealed an increased relative risk of 5.5 (P < 0.001). Non-HLA-DR3 homozygous, DRB3*0101/*0202 heterozygous patients were at the highest risk for endocrine ophthalmopathy (relative risk 10; P < 0.001). Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA-DRB3 genes.

Alleles↗
PubMed1992

Gallstones in acromegalic patients undergoing different treatment regimens.

The frequency of gallstones during long-term treatment with the somatostatin analogue octreotide reported in different studies varies from 0% to 50%, the reason for this variation being unknown. Therefore, we examined 58 acromegalic patients undergoing different treatment regimens for the frequency of gallstones. Thirteen were treated with octreotide, 20 with bromocriptine, and 25 had no medical treatment after successful neurosurgery. Also, 58 patients without known gallbladder disease served as controls. The postprandial gallbladder contraction was also investigated in 27 acromegalic patients (10 with octreotide, 10 with bromocriptine, and 7 with no medical therapy). Ten of the 58 acromegalic patients were found to have gallstones, 4 of 25 receiving no medical treatment, 4 of 20 treated with dopamine agonists, and 2 of 13 treated with octreotide. In 9 of the 58 control patients, gallstones were detected. Although in the octreotide group the gallstones were newly formed under therapy, there was no difference in gallstone prevalence between the different treatment regimens and the control group. However, the postprandial gallbladder contraction was significantly more often inhibited during octreotide therapy, and this effect was most pronounced during the first hours following injection. Differences in the timing of injections therefore may be an explanation of the variable incidence of cholelithiasis in the different studies.

Acromegaly↗
PubMed1992

Subclinical hyperthyroidism: physical and mental state of patients.

We investigated whether subclinical hyperthyroidism [subnormal basal thyroid-stimulating hormone (TSH) level, attenuated TSH response to thyrotropin-releasing hormone (TRH) stimulation, peripheral thyroid hormones within normal range] is accompanied by physical and mental changes. Thirty-five subclinically hyperthyroid patients (27 female, 8 male) were compared with 60 overtly hyperthyroid patients (51 female, 9 male) and with 28 euthyroid control patients (18 female, 10 male) with respect to physical symptoms, affective state, short-term memory, ability to concentrate and psychomotor performance. Patients with subclinical hyperthyroidism ranged between the other two groups. The major difference between controls and subclinically hyperthyroid patients was an increase in frequency of nervous symptoms and symptoms due to an increase of metabolic rate and thermal regulation changes. The major differences between subclinically hyperthyroid and overtly hyperthyroid patients were psychomotor impairment and symptoms of increased metabolic rate. Self-ratings of affective state tended to be similar in patients with subclinical and overt hyperthyroidism. The ability to concentrate and short-term memory were not impaired in any group. Symptoms in patients with subclinical hyperthyroidism probably result from central changes which lead to attenuated TSH responses to TRH, or from elevated but still normal thyroxine levels, which possibly enhance the effect of catecholamines.

Adult↗
PubMed1992

Evidence for pulsatile secretion of human atrial natriuretic peptide in healthy subjects.

The secretion pattern of human atrial natriuretic peptide (hANP) was investigated in 8 healthy male volunteers. Blood was drawn in 2 minute intervals for 90 minutes and in a second study in 4 minute intervals for 180 minutes. Base-line hANP plasma levels varied in a pulsatile secretion pattern of regular pulses every 9 +/- 1 minutes. Additionally long-term oscillations of 34 +/- 4 minutes were found. These data suggest that under basal conditions hANP varies in a pulsatile fashion.

Adult↗