[The treatment of prolactinomas during pregnancy and the lactation period].
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Bromocriptine↗
Biomedical subjects
K H Usadel
Publications and source records attributed to K H Usadel.
[Systemic infection due to group A Streptococcus pyogenes].
A 47-year-old woman developed oedematous swelling of the skin over the left hip and leg, with joint pains and reddening over joints of the hands and left ankle. 2 months before her son had had scarlet fever, following which the patient had two episodes of fever. Shortly before hospitalization she was treated with a glucocorticoid because a rheumatic disease had been suspected. On admission the blood sedimentation rate was 58/90, the white cell count was 15.100/microliters with left shift in the differential count. The swellings in arms and legs became abscesses which were incised. An abscess over the left buttock, diagnosed by 67-gallium whole-body scintigraphy, was also treated surgically. On the day of admission penicillin (10 mill. IU three times daily intravenously) and, from the 4th day onwards, gentamicin (80 mg three times daily intravenously) were administered. Histological examination of fascia and muscle biopsies revealed nonspecific inflammation without signs of malignancy, white blood culture grew group A Streptococcus pyogenes. 20 days after the surgical intervention the patient was discharged in full health. Necrotizing fasciitis caused by Streptococcus pyogenes has become more frequent in the last few years and has often been accompanied by severe systemic complications.
Fasciitis↗
Verapamil and flunarizine protect the isolated perfused rat liver against warm ischemia and reperfusion injury.
Using the model of the isolated perfused rat liver, we investigated the influence of the two pharmacologically different calcium channel blockers, verapamil and flunarizine, on changes of ion homeostasis, liver weights, pH deviations and enzyme activities during warm ischemia (37 degrees C) and reperfusion. The LDH and GLDH activities were determined and the calcium, potassium, and sodium concentrations were measured in the effluent. Warm ischemia (180 min) caused an increased enzyme release, a high influx of calcium and sodium into the liver and a massive potassium efflux current. Normoxic reperfusion led to a further increase in hepatic enzyme release and although the loss of potassium ceased, the calcium influx into the liver continued. By the end of reperfusion the liver weight had increased significantly (P < 0.01) in the control group. The two calcium entry blockers were added to the perfusate in various concentrations. Both substances protected the liver against warm ischemia and normoxic reperfusion damage, but they did not inhibit calcium inflow. However, the potassium efflux was significantly reduced by all concentration tasted (P < 0.001). After reperfusion the liver weights were significantly lower in the treated groups (P < 0.001) than in control animals. Thus, the calcium entry blockers verapamil and flunarizine protect liver cells against damage caused by warm ischemia and reperfusion. Furthermore, they prevent the disruption of intracellular potassium homeostasis, which seems to be related to improved volume regulation of liver cells.
Animals↗
Stimulation of proliferation and inhibition of function of xenotransplanted human thyroid tissue by epidermal growth factor.
A stimulation of thyroid epithelial cell proliferation by epidermal growth factor (EGF) has been repeatedly reported in different in vitro systems. Furthermore, a suppression of thyroid epithelial cell function by EGF has been described in vitro. In order to investigate the effects of EGF on the thyroid in vivo, human Graves' disease tissue was transplanted to 59 nu/nu mice. EGF was given once, and over a period of 7 days 7 times intermittently or continuously by osmotic mini pumps to mice. 3-H-thymidine histoautoradiography of transplants showed an increased 3-H-thymidine incorporation of thyroid epithelial cells and mesenchymal cells, following each form of EGF application. Thyroid epithelial cell nuclear volume, which has previously been shown to be a parameter for thyroid epithelial cell function showed a decrease following EGF application. There was a tendency to a more intensive proliferation and differentiation following intermittent EGF application compared to continuous stimulation. These results demonstrate that EGF does stimulate proliferation of thyroid epithelial as well as mesenchymal cells in vivo. The growth stimulating effect of EGF is linked with a concomitant decrease of thyroid function in vivo. The latter is most likely due to the dedifferentiating action of EGF previously shown in in vitro systems.
Animals↗
Modification of the responses of endothelin-1 to exhaustive physical exercise under simulated high-altitude conditions with acute hypoxia.
To assess whether acute alveolar hypoxia leads to the release of endothelin-1 (ET) in vivo, ET, cortisol (CORT), and lactate (LA) levels were determined in 15 healthy subjects at rest and during exhaustive incremental cycle ergometry on two separate test days. The subjects were to breathe a gas mixture with reduced O2 content ([H] fraction of inspired O2, 0.14) on one day and normal air on the other (N). Modified responses of LA and CORT to exhaustive incremental cycle ergometry on the H day indicated elevated anaerobic tissue metabolism and increased physical stress. With acute alveolar hypoxia, the response of ET to exhaustive physical labor was found to be augmented.
Acute Disease↗
Alterations of Na+,K(+)-ATPase activity after hypoxia and reoxygenation in the perfused rat liver: an electron microscopic cytochemical study.
BACKGROUND/AIMS: Using the cerium technique for ultrastructural cytochemical studies, Na+,K(+)-ATPase activity was investigated in hypoxic and reoxygenated rat liver. METHODS: In the control group, the livers were perfused with oxygenated hemoglobin-free Krebs-Henseleit buffer for 1 h. For hypoxia (60 min), the flow rate of the perfusate was decreased and oxygen was replaced by nitrogen. For reoxygenation, the liver was reperfused under oxygenated conditions for 5 min after 60 min of hypoxia. RESULTS: In control livers, a strong Na+,K(+)-ATPase activity was detected at the basolateral membrane of hepatocytes while the apical membrane forming the bile canaliculi did not display any staining. In hypoxic livers, Na+,K(+)-ATPase activity had ceased in the plasma membrane of hepatocytes. In reoxygenated livers, Na+,K(+)-ATPase was rapidly reactivated in the basolateral hepatic membrane. The membrane of blebs generated during the hypoxic phase also showed enzyme activity. In addition, a striking accumulation of reaction product could be observed in about 10% of the apical membranes lining the bile canaliculi. CONCLUSION: The results indicate a plasticity of the Na+,K(+)-ATPase in hypoxic and reoxygenated rat liver.
Animals↗
Increase of serum insulin and stable c-peptide concentrations with exhaustive incremental graded exercise during acute hypoxia in sedentary subjects.
Hypoxia was shown to reduce insulin concentrations at rest and during exercise. However, some studies have also demonstrated increases in the hormone associated with arterial desaturation. This study was conducted in order to decide [1] whether acute alveolar hypoxia increased or decreased the circulating insulin levels, and [2] to elucidate whether interactions of insulin with other hormones were of relevance in this respect. Glucose (GLU), insulin (INS), c-peptide (CP), adrenaline and noradrenaline (CATs), atrial natriuretic peptide (ANP) and cortisol (CORT) as well as the capillary blood gases were determined in 15 healthy fasting male volunteers (age: 26.2 +/- 2.8 years, body mass index: 22.4 +/- 2.7 kg.m-2). On two separate test days the subjects breathed, in random order, either normal air (N) or a gas mixture with reduced oxygen content (H; FIO2: 0.14). Measurements were made at rest as well as during an incremental cycle exercise in a supine position (increments of 6 min and 50 W) at 100 W and 150 W, at volitional exhaustion (N: 227 +/- 36 W; H: 200 +/- 32 W) as well as in the 5th min of recovery. Arterial desaturation was seen throughout on H-day. At rest all hormones and GLU were normal and showed no influence of H. During exercise INS remained constant on N-day, increased on H-day and was significantly higher with H than with N, most pronounced at 150 W and at volitional exhaustion with 20%, respectively. For CP and GLU no significant exercise-induced changes were seen on either test day and no influence of H was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Long-term adherence to intensified conventional insulin therapy.
All diabetic patients of the outpatient clinic of the University of Frankfurt/Main, who started intensified conventional insulin therapy (ICT) between 1980 and 1991, and who could be followed for at least one year (n = 141) were evaluated retrospectively. Fourteen patients changed from ICT to continuous subcutaneous insulin infusion (CSII). No patient changed back permanently to conventional insulin therapy. Mean glycosylated hemoglobin-levels (HbA1) decreased significantly in the first year from 9.3% to 8.5% and remained at a near normal level in the following years. HbA1-levels were found not to be associated with age, age at diagnosis, weight gain, frequency of visits to the outpatient clinic, number of consultations with the dietician as well as the frequency of attendance at special seminars for ICT. These results demonstrate that ICT lowered blood glucose levels permanently, that patients were highly compliant, and that ICT was practicable and safe for long-term treatment under routine conditions without initial hospitalization and with an acceptable expenditure of time for patients and medical staff.
Adult↗
PVU II polymorphism of LST-1 (leucocyte specific transcript-1) in type I diabetes mellitus, Graves' disease and healthy controls.
The polymorphism of the LST-1 gene (the human homologue of the mouse B144 gene) can be identified by Pvu II restriction enzyme digestion. We investigated the contribution of this RFLP to disease susceptibility in 117 patients with type I diabetes mellitus (IDDM), 110 with Graves' disease (GD) and 93 healthy controls. The distribution of the different LST-1 alleles (LST-1*1:1323 bp, LST-1*2:610 bp/713) was similar among IDDM and GD patients as well as in controls. The combination of DQA1*0501, DQB1*0201 and DQB1*0301, all predisposing to endocrine autoimmune disease, with LST-1*1 or LST-1*2 was not increased in patients. Analysis of two informative families with IDDM demonstrated cosegregation of DQA1 and DQB1 alleles with LST-1 alleles. No association of LST-1 polymorphisms with IDDM nor GD could be demonstrated.
Alleles↗
Susceptibility and resistance alleles of human leukocyte antigen (HLA) DQA1 and HLA DQB1 are shared in endocrine autoimmune disease.
Because particular human leukocyte antigen (HLA) DQ alleles are the major predisposing factors for type 1 diabetes mellitus (IDDM), we investigated whether they are shared by other endocrine autoimmune diseases. We, therefore, analyzed the HLA DQ genotypes of 171 patients with IDDM, 271 with Graves' disease (GD), 65 with Hashimoto's thyroiditis, 51 with postpartum thyroiditis, 53 with Addison's disease (AD), and 271 healthy controls. HLA DQA1 and DQB1 alleles were defined by polymerase chain reaction and sequence-specific oligonucleotide hybridization as well as by single strand conformational polymorphism analysis. HLA DQA1*0501 was significantly more frequent in IDDM (60%), GD (65%), and AD (70%) than in controls (43%); DQA1*0301 was significantly more frequent only in IDDM (67% vs. 30% controls). The heterozygous state DQA1*0301/*0501 was found in 9% of controls and 35% of IDDM (relative risk, 5.6). An arginine at position 52 on either DQA1 allele was significantly more frequent in patients with IDDM (94%), GD (80%), and AD (89%) compared with controls (66%). HLA DQB1*0201 and DQB1*0302 were more frequent in IDDM patients (*0201, 62% vs. 36% in controls, *0302, 59% vs. 19% controls), whereas DQB1*0602 was less frequent in IDDM (4%) and GD (18% vs. 31% of controls). In conclusion, endocrine autoimmunity has a common immunogenetic background; susceptibility is conferred by DQA1*0501 as well as an arginine at position 52 of DQA1 alleles, and protection against IDDM and GD is conferred by DQB1*0602.
Addison Disease↗
Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease.
Declining thyroid autoantibodies during treatment and decreased lymphocytic infiltration after treatment of patients with Graves' disease suggest immunosuppressive actions of antithyroid drugs. However, the recent report of similar relapse rates after low and high dose carbimazole treatment of Graves' disease seems to contradict the immunosuppression thesis. We therefore determined the intrathyroidal methimazole concentrations with a high performance liquid chromatography method in 17 patients undergoing subtotal thyroid resection for relapsing Graves' disease. The intensity of the intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T cells, and antigen presenting cells, and the total number of lymphocytes were identified immunohistologically with monoclonal antibodies for kappa- and lambda-immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed by morphometry. The intrathyroidal methimazole concentration and the cumulative preoperative methimazole doses did not correlate with the intensity of the intrathyroidal infiltration by any of these immunocompetent cells. Comparison of groups with significantly different intrathyroidal methimazole concentrations (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any of the intrathyroidal immunocompetent cells. These findings suggest that there is no dose-related effect of methimazole on the intensity of the intrathyroidal autoimmune process of patients with relapsing Graves' disease. They provide an explanation for why it does not seem justifiable to recommend higher methimazole doses than those required for the control of hyperthyroidism with the goal of immunosuppression.
Adult↗
Serum thyrotropin (TSH) heterogeneity in euthyroid subjects and patients with subclinical hypothyroidism: the core fucose content of TSH-releasing hormone-released TSH is altered, but not the net charge of TSH.
The aims of the present study were to determine the influence of brief subclinical hypothyroidism on the isoforms of serum thyrotropin (TSH) and to examine the net charge of TSH in different metabolic states. Sera were obtained from euthyroid subjects (n = 7) and from patients with subclinical hypothyroidism (n = 8) before and 30 min after the intravenous administration of 200 micrograms thyrotropin-releasing hormone (TRH). The TSH from human pituitary extracts (IRP 68/38), basal and TRH-stimulated serum TSH was immunoconcentrated and further analysed by isoelectric focusing (IEF) and lentil lectin affinity chromatography. TSH immunoreactivity was determined in each specimen or fraction with an automated highly sensitive chemiluminometric TSH assay. We found that basal TSH in subclinical hypothyroidism, and TRH-released TSH in euthyroidism and in subclinical hypothyroidism is distributed in a similar neutral to acidic pattern, which significantly differs from the more alkaline to neutral isoform pattern of intrapituitary TSH (P < 0.05). IEF analysis of pituitary standard TSH revealed 3 major peaks (pI values 7.5; 6.6; 5.8) whereas in most euthyroid or subclinically hypothyroid subjects 5 peaks were found. Lentil lectin affinity chromatography revealed that TRH-released TSH in euthyroid subjects has more core fucose residues than TSH from patients with subclinical hypothyroidism (64.6 +/- 6.7 vs 12.5 +/- 2.7%, P < 0.0001). Thus pituitary standard TSH seems to be less mature material than circulating TSH. Perhaps no alteration in the IEF pattern of TSH was detected during early hypothyroidism because sialylation of TSH was increasing as sulfatation was decreasing. Nevertheless, a change in the core fucose content of TSH was detectable by lentil analysis.
Adult↗
Endothelin during cardiovascular surgery: the effect of diltiazem and nitroglycerin.
To investigate whether the vasoconstrictor peptide endothelin (ET) is elevated during cardiovascular surgery and might predispose to perioperative vasoconstriction and ischemia, we compared the effect of the calcium channel blocker diltiazem with that of the nitric oxide (NO) donor nitroglycerin on ET and hemodynamics in 32 patients undergoing coronary artery bypass grafting (CABG). Following a double-blind protocol, 16 patients (3 women, 13 men; ages 63 +/- 10 years) received 1 microgram/kg/min nitroglycerin and 16 patients (5 women, 11 men; ages 64 +/- 8 years) received 3 micrograms/kg/min diltiazem intravenously 30 min before until 12 h after CABG. ET was measured in the superior vena cava before, during, and 1 h after CABG. Compared with ET levels before CABG, ET was significantly elevated during CABG and further increased after CABG (p < 0.05). During and after surgery, ET levels were lower in patients receiving diltiazem than in those receiving nitroglycerin (both p < 0.01). Mean arterial blood pressure and heart rate were lower in patients receiving diltiazem compared with those receiving nitroglycerin (both p < 0.05). These data demonstrate that diltiazem is more effective than nitroglycerin in preventing ET increase during cardiovascular surgery. Studies using ET receptor antagonists may be useful in assessing the clinical relevance of ET levels with respect to the risk for perioperative vasoconstriction and ischemia.
Aged↗
The somatostatin analogue octreotide protects against ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa.
Somatostatin 14 and various derivatives protect rat gastric mucosa against ethanol-induced lesions. Their mechanism of action is unknown. We investigated the effect of two somatostatin derivatives, octreotide and 5-(L)-citrullin-octreotide, on ethanol-induced hemorrhagic lesions, microcirculatory stasis and elevated vascular permeability in the rat stomach, with the goal to elucitate the pharmacological and microcirculatory mechanisms behind the gastroprotective effect. Radioligand studies revealed a high affinity of octreotide for the somatostatin receptor (IC50 = 5 x 10(-10) mol/l), in contrast to 5-(L)-citrullin-octreotide (IC50 = 3 x 10(-6) mol/l). This was in good agreement with the inhibition of growth hormone release from rat anterior pituitary cells (octreotide: IC50 = 1.2 x 10(-10) mol/l; 5-(L)-citrullin-octreotide: IC50 = 3 x 10(-6) mol/l). Intragastric administration of ethanol to rats resulted in lesions of the gastric mucosa affecting 18.9 +/- 3.1% of the area of the glandular stomach. Octreotide reduced the area to 6.4 +/- 1.7% (P < 0.05). The dose-response curve was bell-shaped. 5-(L)-citrullin-octreotide was totally devoid of any protective activity (dose range: 0.1 ng/kg to 0.1 mg/kg). We further investigated the effect of the two peptides on ethanol-induced microcirculatory stasis and elevated vascular permeability. Ethanol in a concentration of 50% induced an increase in microvascular permeability, measured by the extravasation of the tracer fluorescein-isothiocyanate-dextran (molecular weight 150,000). Pretreatment with octreotide (0.1 ng/kg s.c.) prevented stasis and reduced capillary permeability significantly. 5-(L)-citrullin-octreotide had no effect on ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Typing of the HLA-DRB3 gene by temperature gradient gel electrophoresis. Prediction of the resolution of four allelic fragments by computational simulation of DNA melting.
Four alleles are currently recognised at the HLA-DRB3 locus (DRB3*0101, DRB3*0201, DRB3*0202 and DRB3*0301). We studied whether 271 bp fragments of the polymorphic second exon, which were prepared using the polymerase chain reaction, could be typed using temperature gradient gel electrophoresis. Thermal stability curves for the allelic DNA molecules were calculated by computer simulation and the results were validated experimentally. The DRB3*0201 and DRB3*0202 derived homoduplexes were predicted to have identical thermal stability. Thus, only three denaturation and relative mobility curves were obtained for the four homoduplex fragments DRB3*0101, DRB3*0201, DRB3*0202 and DRB3*0301. Computational analysis predicted that DRB3*0201 and DRB3*0202 could be distinguished by electrophoresis of artificially generated heteroduplexes. When verified experimentally, the results of the theoretical analyses were confirmed. We conclude, that computational simulation of the melting behaviour of DNA molecules permits the resolution of allelic sequences to be predicted by temperature gradient gel electrophoresis. We also demonstrate that temperature gradient gel electrophoresis is a powerful tool for the assessment of HLA genotypes. It may have wide application in transplantation immunology and in the study of disease associations of allelic variation at the HLA loci.
Alleles↗
[The nephroprotective effect of ramipril. Effect on blood pressure and metabolic control in insulin-treated patients with type-2 diabetes mellitus].
AIM: Investigation of the impact of blood pressure and metabolic control on the nephroprotective effect of ramipril in insulin-dependent diabetics. METHOD: Within the framework of an open prospective therapeutic trial, 18 hypertensive, insulin-treated diabetics received ramipril, 5 mg/day, for an average period of 11 months. All the patients had previously received various forms of antihypertensive medication, and had microalbuminuria. RESULTS: Urinary excretion of albumin and N-acetyl-beta-D-glucosaminidase decreased in 13 patients (group 1), but increased in the remaining five patients (group 2). Blood pressure clearly decreased in group 1, but remained constant in group 2. In terms of clinical and biochemical data, the group 2 patients differed from those in group 1, having a lower age, a shorter history of diabetes and higher hemoglobin A1c levels despite higher doses of insulin. CONCLUSIONS: The present observations show that inadequate metabolic control and refractory hypertension in type 2 diabetics accelerate progression of diabetic nephropathy, and may thus negate the nephroprotective effect of the converting enzyme inhibitor, ramipril.
Aged↗
Elevated endothelin 1 levels in critical illness.
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Critical Illness↗
Elevated endothelin levels in patients with hyperlipoproteinemia.
We determined lipoproteins, apolipoproteins, and endothelin in 98 patients (58 female and 40 male, age 18-72 years) with hyperlipidemia (plasma cholesterol > 2.5 g/l and/or triglycerides > 2.0 g/l) and in 50 healthy subjects (20 female, 30 male, age 19-68 years). In patients with hyperlipidemia endothelin levels were elevated compared to healthy controls. Patients with plasma cholesterol above 2.5 g/l had higher endothelin and lipoprotein(a) concentrations than patients with plasma cholesterol levels less than 2.5 g/l. A positive correlation was found between the concentrations of endothelin and apolipoprotein B (r = 0.2137; P < 0.013). Smoking patients with lipoprotein (a) above 300 mg/l had higher endothelin levels than both nonsmoking patients with lipoprotein (a) above 300 mg/l and smokers with normal lipoprotein(a). In smokers endothelin correlated positively with Lp(a) (r = 0.709; P < 0.01). No correlation was found between endothelin and triglycerides nor between endothelin and age or sex. The results suggest that the vasoconstrictor endothelin contributes to the increased vasal tone in hyperlipidemia. Because endothelin also has mitogenic properties, it may play a relevant role in the development of premature atherosclerosis in patients with hyperlipidemia.
Adolescent↗