Analysis of the deletion/insertion polymorphism of the angiotensin I-converting enzyme gene by capillary electrophoresis.
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Base Sequence↗
Biomedical subjects
M Pfohl
Publications and source records attributed to M Pfohl.
Detection of the apolipoprotein B-100 arg(3500) > gl mutation in familial defective apoB-100 by temperature-gradient gel electrophoresis.
Familial defective apolipoprotein B-100 (FDB) is caused by a point mutation in exon 26 of the apolipoprotein B gene leading to a decreased binding to the LDL-receptor. Patients with FDB have hypercholesterolemia and atherosclerotic disease. Since other mutations of apoB-100 could also cause binding abnormalities we established a temperature-gradient gel electrophoresis (TGGE) method and started to screen hypercholesterolemic patients for the presence of point mutations in this region. 4 of 43 patients were positive according to TGGE and subsequent sequencing showed the familiar guanine to adenine transition in codon 3500 in all cases.
Adenine↗
Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.
We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.
ACTH Syndrome, Ectopic↗
Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins.
Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100-150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 +/- 26 mg/dl compared to 351 +/- 65 mg/dl at baseline in the IMA-treated patients and 139 +/- 18 mg/dl compared to 359 +/- 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.
Adult↗
Acute and chronic effects on cholesterol biosynthesis of LDL-apheresis with or without concomitant HMG-CoA reductase inhibitor therapy.
To determine the acute and long-term effects of low density lipoprotein (LDL) reduction on cholesterol biosynthesis, we studied changes in the cholesterol precursors mevalonic acid (MVA) and lathosterol in patients with heterozygous familial hypercholesterolemia undergoing LDL-apheresis. Long-term LDL-apheresis in eight patients resulted in slight but insignificant increases in plasma MVA levels and lathosterol/cholesterol (L/C) ratios over 18 months. In short-term studies, six patients not on drugs and six patients treated with lovastatin or pravastatin had blood taken immediately before and after LDL-apheresis, and afterwards on days 1, 2, 3, 5, and 7. Plasma L/C ratios and MVA concentration did not change significantly on the first day after LDL-apheresis in those not on statin therapy (1.11 +/- 0.08 vs. 1.40 +/- 0.18, and 9.2 +/- 1.3 vs. 9.1 +/- 0.6 ng/ml, respectively) but increased in the statin-treated group (from 0.78 +/- 0.09 to 1.55 +/- 0.21, P = 0.003 and from 5.0 +/- 0.7 to 11.0 +/- 1.6 ng/ml, P = 0.008, respectively). There was no clear correlation between the changes in either of these precursors and the extent of reduction of total cholesterol by LDL-apheresis, but there was a strong inverse correlation with the post-apheresis LDL-cholesterol level (r = -0.77, P = 0.002 for L/C ratio; r = -0.75, P = 0.003 for MVA). Post-apheresis changes in L/C ratio and MVA were mutually correlated (r = 0.68. P = 0.01). We conclude that LDL-apheresis stimulates cholesterol biosynthesis transiently despite concomitant therapy with an HMG-CoA reductase inhibitor, the degree of stimulation being inversely related to the level to which the LDL-cholesterol was reduced.
Adult↗
Long-term changes of body weight and cardiovascular risk factors after weight reduction with group therapy and dexfenfluramine.
The aim of this work was to investigate the long-term changes of body weight and cardiovascular risk factors after weight reduction with dexfenfluramine (dF) compared to placebo (pI) and additional group therapy. There was a 3 year follow-up of obese patients after 1 year double-blind, randomized treatment with 30mg dF or pI and group therapy. The work was carried out at the outpatient clinic of University Hospital, Tübingen. Forty-eight (24 dF, 24 pI) patients were investigated with more than 120% of ideal body weight. Body weight, blood pressure, blood glucose, serum cholesterol and triglycerides were measured. During 1 year of treatment body weight fell by 11.2% (dF) and 9.1% (pI) (P < 0.001 for time, n.s. for dF/pI), systolic blood pressure by 7.3 and 9.9 mm Hg (P = 0.044/n.s.). There were no significant changes of serum cholesterol, triglycerides, and blood glucose. At the follow-up of 22 (11/11) patients 3 years later, the dF group had regained more than the lost weight; the placebo group had lost 2.4% of the initial body weight. Serum cholesterol (dF + 0.64/pI + 0.65 mmol/l, P = 0.010/n.s.), triglycerides (+0.74/+0.59 mmol/l, P = 0.002/n.s.), and blood glucose (+0.56/+0.81mmol/l, P < 0.001/n.s.) increased significantly. Systolic blood pressure increased slightly, diastolic blood pressure did not change significantly. Without appropriate prevention of weight regain even combined weight reduction therapy over a period of one year results in weight regain and deterioration of cardiovascular risk factors.
Adult↗
Hypothalamic-pituitary activation does not differ during human and porcine insulin-induced hypoglycemia in insulin-dependent diabetes mellitus.
Although pituitary hormones play only a minor role in acute hormonal counterregulation during insulin-induced hypoglycemia, their concomitant secretion with the profound sympathoadrenal response provides an indicator of hypothalamic-pituitary activation. The release of different amounts of beta-endorphin, growth hormone, and adrenocorticotropin during human (HI) and porcine (PI) insulin-induced hypoglycemia would serve as a pointer to a different insulin species effect on hypothalamic-pituitary response. We performed a controlled, double-blind study with randomization to either HI or PI to compare insulin effects during developing and established hypoglycemia. The glucose clamp technique was used to lower the blood glucose concentration stepwise (3.3, 2.2, 1.7 mmol/l) over similar periods in ten patients with insulin-dependent diabetes mellitus. beta-endorphin, growth hormone, and adrenocorticotropin levels were determined by radioimmunoassay from arterialized blood at the above plateaus. A different action of HI or PI on peripheral glucose metabolism was not found. Pituitary hormones increased significantly during hypoglycemia (analysis of variance for hypoglycemic effects: beta-endorphin, P < 0.02; growth hormone, P < 0.04; adrenocorticotropin, P < 0.05). No insulin species effect was detected. Hypothalamic-pituitary activation during insulin-induced hypoglycemia is independent of the insulin species used, which supports earlier observations of an identical sympathoadrenal response during HI- and PI-induced hypoglycemia.
Adrenocorticotropic Hormone↗
Different effects of two methods of low-density lipoprotein apheresis on the coagulation and fibrinolytic systems.
OBJECTIVE: Immunoadsorption (IMA) and dextran sulfate adsorption (DSA) are two methods for selective extracorporeal elimination of low-density lipoproteins which are known as LDL apheresis. Their influence on haemostasis until now is widely unknown. DESIGN: The effects of both LDL apheresis procedures on the coagulation and fibrinolytic systems were compared amongst five patients treated with IMA and four patients who received a DSA therapy. SUBJECTS: All patients with severe heterozygous familial hypercholesterolaemia were participants in a long-term LDL apheresis programme with treatments every 1-2 weeks. INTERVENTION: Combined anticoagulation with heparin and citrate in IMA, and also heparin exclusively in DSA were used for the extracorporeal circulation. MEASURES: Blood samples were taken immediately before and after a single LDL apheresis and five times during the weekly interval until the next therapy. RESULTS: DSA had a significantly greater effect on standard clotting tests than IMA at the end of plasma therapy despite identical dosages of heparin. DSA caused a considerable reduction of the coagulation factors V, VIII:C, vWF:Ag, XI, XII, and prekallikrein by 48-99% at the end of apheresis treatment whereas only factor VIII:C showed a marked decrease of 72% after IMA. All abnormalities of the global coagulation tests and of most clotting factors were restored 1 day after treatment in both procedures followed by a moderate rebound phenomenon of single coagulation factors during the next few days in IMA-treated patients. CONCLUSION: DSA exerts a more profound effect on the coagulation system than IMA by a substantial co-elimination of various clotting factors in addition to the desired removal of atherogenic lipoproteins.
Adsorption↗
Spontaneous gas-forming bacterial myonecrosis caused by group B streptococci and peptostreptococci.
We present the case of a patient who spontaneously developed a severe gas-forming infection involving the voluntary muscles of both thighs. The organisms responsible were group B beta-haemolytic streptococci together with peptostreptococci. Following surgical and medical treatment, the patient fully recovered. No predisposing factors, in particular no disease causing immunocompromise, could be identified.
Debridement↗
Simple computer-assisted diagnosis of acute myocardial infarction in patients with acute thoracic pain.
In order to minimize the initial diagnostic uncertainty in patients suspected of having acute myocardial infarction, we prospectively extracted predictive variables from previous history, ECG, and clinical chemical parameters of 87 patients, who were admitted for acute thoracic pain. The variables thus extracted were: Thoracic pain in previous history, duration of pain, white blood cell count, blood glucose, creatine-kinase, and S-T elevation in the ECG. These parameters were used for formulating a mathematical model based upon univariate and multivariate statistical methods. The sensitivity of the model in the study population was 95% and the specificity 77%. Correct classification was achieved in 89% of cases. In a second phase, the prognostic index was prospectively evaluated in a second set of 122 consecutive patients. In this test population, the sensitivity was 89% and the specificity 86%. 87% of patients were classified correctly.
Adult↗
Exercise and insulin requirements.
In order to facilitate the management of sports and work for insulin injecting diabetic patients we analyzed 6 different situations: 1) In the morning before injecting insulin stepwise increasing bicycle ergometry until exhaustion with a duration of less than one half hour may be performed without previous reduction of insulin or additional oral carbohydrates. Maximal work load can thus be determined with ECG monitoring. After insulin injection we advise our patients to estimate their reaction by calculating with exercise units. One exercise unit equals 20 minutes of half maximal exercise or one hour of 30% maximal exercise. 2) Performing one exercise unit the diabetic will have to anticipate a blood glucose reduction of -60 mg/dl. In order to maintain normal blood glucose levels he will have to reduce the regular insulin bolus 3) in the morning by -3,3 IU or 4) by -1.7 IU in the evening or he should 5) take +12 g of oral glucose (quickly absorbable carbohydrates). 6) A reduction of basal rate (CSII) or NPH insulin (ICT) is not advisable for exercise up to 3 hours. On the basis of these mean values every diabetic patient has to monitor blood glucose during exercise and adapt the measures to his individual reactions.
Adult↗
[Studies with the Bactec 460 system. Isolation of Mycobacterium tuberculosis from sputum. Comparison of the radiometric with the conventional method after pretreatment with pancreatin-desogen, lauryl sulfate and N-acetyl-L-cysteine-NaOH].
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Acetylcysteine↗
Influence of strenuous exercise on albumin excretion.
Renal albumin excretion rate was 7.3 mg/24 h (SEM 0.5, range 0.6-21.0) in 66 healthy subjects. This rate increased markedly during and shortly after strenuous exercise on a bicycle ergometer (before: 5.5 +/- 0.6 micrograms/min; during and just after: 16.9 +/- 2.2 micrograms/min; P less than 0.001; n = 30). However, albumin excretion/24 h was not significantly higher during 24 h with a period of strenuous exercise than during 24 h without such exercise (10.3 +/- 0.9 mg/24 h vs 8.5 +/- 0.7 mg/24 h).
Adult↗
Endothelial function, variables of fibrinolysis and coagulation in smokers and healthy controls.
OBJECTIVE: To asses endothelial function and variables of fibrinolysis and coagulation in smokers compared to healthy controls. METHODS: Flow-associated dilation as a marker for peripheral endothelial function and intima media thickness as a marker for early morphologic vascular changes were measured in otherwise healthy smokers (n = 30, 16 males and 14 females, age: 40.6 +/- 11.3 years, body mass index 24.9 +/- 3.7 kg/m(2)) and non-smoking controls matched for age and sex using high-resolution ultrasound. Variables of the coagulation system (thrombin-antithrombin III complex, fibrinogen) and fibrinolysis (tissue-plasminogen activator, plasmin-alpha(2)-antiplasmin complex) were determined by ELISA and plasminogen activator inhibitor activity by means of a chromogenic substrate test. RESULTS: Compared to the non-smoking controls, flow-associated vasodilatation was significantly reduced (6.9 +/- 4. 4 vs. 10.5 +/- 6.2%, p = 0.01) and intima media thickness tended to be increased (0.58 +/- 0.12 vs. 0.52 +/- 0.14 mm, p = 0.08) in smokers. The thrombin-antithrombin III complex, fibrinogen, plasmin-alpha(2)-antiplasmin complex, tissue-plasminogen activator and plasminogen activator inhibitor activity did not differ between smokers and controls. CONCLUSION: Our data indicate that peripheral endothelial dysfunction is common in smokers even without major alterations in molecular markers of the coagulation and fibrinolysis system.
Adult↗