A 25-year follow-up study of glucose tolerance in first-degree relatives of type 2 diabetic patients: association of impaired or diabetic glucose tolerance with other components of the metabolic syndrome.

A follow-up study of first-degree relatives of type 2 diabetic patients presented the opportunity to study the association of components of the metabolic syndrome with oral glucose tolerance in these subjects. In 1992, 25 years after the first analysis of the cohort, we performed 75-g oral glucose tolerance tests and measured anthropometric data (body mass index, waist-hip ratio), insulin and C-peptide concentrations, and parameters of lipoprotein metabolism (free fatty acids, triglycerides, cholesterol, HDL cholesterol). Of 135 participants, 71 had normal glucose tolerance (GT), 22 had impaired GT, and 42 had diabetic GT (WHO 1985 criteria). Impaired glucose tolerance and diabetes were significantly (Kruskal-Wallis test) associated with advanced age (p=0.001), higher body mass index (p=0.005) and waist-hip ratio (p=0.027), systolic hypertension (p=0.031), elevated basal insulin concentrations (p<0.001), higher free fatty acids (p<0.001) and triglycerides (p=0.017), and lower HDL cholesterol (p=0.003); no associations were found with total and LDL cholesterol levels (Friedewald's formula, p=0.25). Abnormalities (obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, pathological oral glucose tolerance) were associated with significant deterioriations in all other components of the metabolic syndrome, if their number exceeded three. Disturbances of oral glucose tolerance are present in a high percentage of first-degree relatives after 25 years of follow-up (51% of those tested). Impaired or diabetic glucose tolerance in such a cohort was associated with overweight, hypertension and disturbances of lipoprotein metabolism characteristic of the metabolic syndrome. Hypercholesterolemia (LDL-cholesterol) is not a component of the metabolic syndrome in a German population with a high hereditary burden regarding type 2 diabetes. A metabolic syndrome should certainly be diagnosed if three components are present, although even in the presence of only two components, an elevated risk is evident.

Asymmetric synthesis of alpha-branched primary amines on solid support via novel hydrazine resins.

[reaction: see text]. Two novel chiral hydrazine resins for asymmetric solid-phase synthesis have been developed. The enantiopure beta-methoxyamino auxiliaries, derived from trans-4-hydroxy-(S)-proline and (R)-leucine, were attached to Merrifield resin and transformed into their corresponding hydrazines. Immobilization of various aldehydes, followed by 1,2-addition of organolithium reagents to the resulting enantiopure hydrazones and reductive cleavage from the solid support, furnished alpha-branched amines, which were isolated as their corresponding amides in good overall yields and enantiomeric excesses of up to 86%.

[Rationalization attempts: guidelines, evidence-based medicine]. / Rationalisierungsbestrebungen: Leitlinien, evidence based medicine.

"Guidelines" as well as "evidence-based medicine" are not primarily economical control instruments, but serve to improve the quality of medical care from a patient-oriented point of view. It is characteristic of evidence-based medicine (EBM) that its exponents base medical actions on the best evidence of usefulness and effectiveness available. The most important evidence is to be gathered from high-quality studies, so-called controlled clinical trials. This requires a certain mental readiness and, moreover, certain skills with regard to the search for studies and the capability to interpret data in an adequate way. At the moment only a small "elite" of physicians is capable to orient to EBM independently. This is why the approach via the development and implementation of evidence-based guidelines is the more important. Guidelines are systematically developed decision-making aids, in the sense of so-called "corridors of action", for medical procedures in special health problems. Only guidelines stating the level of existing evidence for every statement can be called evidence-based. A Clearinghouse at the Agency for Quality in Medicine (AQUMED) supports and promotes scientifically based and practical guideline programs in medicine. At the heart of the present discussion is the question of how to achieve the widespread use in medical care of the findings summarized in guidelines.

[Differential indications for thyroid gland operation]. / Differentialinkikation zur Schilddrüsenoperation.

Although the case for thyroid surgery is based on morphologic and physiologic criteria, it is mainly based on individual therapeutic goals. The goals are influenced by various biographic, medical and personal facts and by many environmental conditions. Thus, there is no rationale for cataloguing indications. With the euthyroid goitre the indication for surgery is usually given by the size of the thyroid gland, especially since it has become clear in various studies that with drug therapy the achievable size reduction is rather small. With Graves' disease the pros and cons of the three main methods, surgery, medical treatment or radioiodine, have to be considered in each case. Surgery is mainly indicated when the goal is a rapid and reliable normalization of the hormonal status. Thyroid autonomy is a clear-cut case for radioiodine. Only isolated autonomous nodules can equally well be treated by surgery. In addition, a case for surgery is given when besides the autonomy a large goitre is present. A special indication is iodine-induced thyrotoxicosis that cannot be normalized by medical treatment. All kinds of thyroid carcinoma, with very few exceptions, usually have to be operated on as the first choice.

[Motility disorders of the esophagus in patients with apoplectic infarct during the acute illness phase]. / Motilitätsstörungen der Speiseröhre bei Patienten mit apoplektischem Insult während der akuten Krankheitsphase.

BACKGROUND: Prolonged oropharyngeal dysphagia occurs in up to 45% of patients presenting with a unilateral hemiplegic stroke. The aim of this study was to investigate esophageal motility in patients with hemiplegic stroke and to evaluate, whether detected motility disorders improve within 10 days after the beginning of symptoms. PATIENTS AND METHODS: Fifteen patients with hemiplegic stroke and dysphagia underwent esophageal manometry within the first 2 days after admission to the hospital and 10 days later. Eighteen healthy volunteers served as controls. RESULTS: The following parameters showed no significant differences between the 2 study days (day 2: day 10: controls, p-value [comparison with controls]): resting pressure of the lower esophageal sphincter: 21 +/- 3 mm Hg: 20 +/- 3 mm Hg: 18 +/- 2 mm Hg, NS, contraction amplitude: 67 +/- 8 mm Hg: 72 +/- 11 mm Hg: 78 +/- 9 mm Hg, NS, duration of contraction: 4.2 +/- 1.0 s: 4.2 +/- 0.9 s: 2.2 +/- 0.7 s, p < 0.001, and contraction velocity: 6.3 +/- 1.1 cm/s: 5.2 +/- 0.9 cm/s: 3.2 +/- 0.8 cm/s, p < 0.001. As far as the contraction pattern was concerned, on both study days significant pathologic contraction patterns were seen compared with normal controls. Normal propulsive contractions were seen in 54 +/- 5%: 60 +/- 6%: 96 +/- 5%, p < 0.001. Patients with no dysphagia after 10 days still had demonstrable abnormal motility patterns. CONCLUSION: The findings indicate that manometrically demonstrable pathologic motility patterns of the tubular esophagus in patients without oropharyngeal dysphagia after 10 days do not induce the symptom dysphagia. The function of the esophagus seems not to be impaired by these measurable pathologic contractions.

Risk of iodine-induced thyrotoxicosis after coronary angiography: an investigation in 788 unselected subjects.

In this study, the risk of iodine-induced thyrotoxicosis in unselected patients from an iodine-deficient area was investigated. The patients were consecutively enrolled. Thyroid hormone values and urinary iodine excretion were determined before, as well as 1, 4 and 12 weeks after iodine contamination by coronary angiography. Two of 788 unselected patients developed hyperthyroidism within 12 weeks. The two patients did not belong to a risk group for iodine-induced thyrotoxicosis (i.e. old people, patients with goiter or possible thyroid autonomy, low TSH). Both patients had normal TSH levels at baseline and ultrasound of the thyroid was without evidence of nodules. The study shows that in euthyroid unselected patients from an iodine-deficient area short-term iodine contamination by contrast media rarely leads to hyperthyroidism. On account of these facts, prophylactic therapy, e.g. by perchlorate or thiamazole, is not generally recommended, because the risk of side-effects is perhaps even greater than the risk of iodine-induced thyrotoxicosis.

[Esophageal manometric studies in patients with an apoplectic stroke with/without oropharyngeal dysphagia]. / Manometrische Untersuchungen der Speiseröhre bei Patienten mit apoplektischem Insult ohne und mit oropharyngealer Dysphagie.

BACKGROUND AND OBJECTIVE: As many as 45% of all strokes can lead to permanent dysphagia, usually considered to be due to abnormal oropharyngeal coordination of contraction. It was the aim of the study to compare oesophageal motility in stroke patients with and without dysphagia. PATIENTS AND METHODS: The study group consisted of 36 patients (13 men, 23 women, mean age 74.1 +/- 11.3 years) who had sustained a stroke (19 [mean age 70.6 +/- 10.5 years] with and 17 [mean age 77.6 +/- 10.5 years] without dysphagia). All these patients underwent oesophageal manometry within 2 days after hospital admission. RESULTS: There were significant differences in the mean proportion of regular peristaltic waves in the distal oesophagus, 93.5 +/- 1.1% in patients without but in only 53.5 +/- 4.4% of those with dysphagia (P < 0.0001). Measurement of the proximal oesophagus showed 93.2 +/- 3.4% and 62.1 +/- 7.3% respectively. There was no significant difference between these two patient cohorts with regard to the resting pressure in the upper and lower oesophageal sphincters as well as in the amplitude and duration or speed of contraction in the region of the smooth and striated oesophageal muscles. CONCLUSIONS: In patients after a stroke who have dysphagia abnormalities of oesophageal motility are also of importance for their symptoms, being due less to pressure relations than to abnormal contraction patterns.

[Modern diagnosis and classification of diabetes mellitus]. / Moderne Diagnostik und Klassifikation des Diabetes mellitus.

In July 1997, the American Diabetes Association (ADA) has published new recommendations for the diagnosis and classification of diabetes mellitus. Except for gestational diabetes they should be identical to the new WHO recommendations (not yet published). From now on, only the fasting glucose should be used for clinical routine. The oral glucose tolerance test is no longer recommended for this purpose. The diagnostic cut-off level for fasting glucose was decreased from 140 mg/100 ml (venous plasma) to 126 mg/dl, and the range between 110 and 125 mg/100 ml was defined as impaired fasting glucose (IFG), a new diagnostic category introduced in analogy to impaired glucose tolerance (IGT). The lower diagnostic cut-off level for fasting glucose has been proposed because the risk of developing diabetic late complications (predominantly at the vascular system) is already increased in blood glucose ranges thought to be normal. The diagnostic criteria for gestational diabetes are unchanged and still discrepant between ADA and WHO. The two major forms of diabetes should be designated only as type 1- and type 2-diabetes with respect to etiology and pathogenesis. Type 1-diabetes was subdivided into an immune-mediated and into an idiopathic form. MODY (maturity-onset type diabetes in young people) was listed separately from type 2-diabetes under the category of genetic defects of beta-cell function, also mitochondrial diabetes (maternally inherited diabetes and deafness). Malnutrition-related diabetes has been omitted as a major form of diabetes.

[Undesired drug effects after taking chlormezanone (Muscle Trancopal) with lethal results]. / Unerwünschte Arzneimittelwirkung nach Einnahme von Chlormezanon (Muskel Trancopal) mit letalem Ausgang.

HISTORY AND CLINICAL FINDINGS: A 34-year-old woman was admitted for treatment of toxic epidermolysis of the skin and mucosa. 16 days previously she had started to take chlormezanone (Muskel Trancopal) and some other medications for pain in the shoulder and neck. On admission she had a fever of 39 degrees C and, in addition to the epidermolysis, diffuse abdominal pain on pressure and blood-streaked stool. INVESTIGATIONS: Liver enzyme activities (GOT 979 U/I, GPT 1496 U/I, gamma GT 201 U/I) alkaline phosphatase 515 U/I), bilirubin (3.9 mg/dl) and pancreatic enzyme activities were raised. Sonography was nondiagnostic, computed tomography demonstrated only a small amount of ascites. TREATMENT AND COURSE: The epidermolytic lesions, cholestatic hepatitis and pancreatitis markedly regressed under aseptic wound treatment, antibiotics and parenteral nutrition. Persistent blood-streaked stools and bilateral pneumonia with progressive respiratory failure developed. Despite intensive medical care the patient died after 14 days from protracted sepsis with multi-organ failure. Autopsy additionally revealed adult respiratory distress syndrome and complete loss of colonic mucosa. CONCLUSION: The severe course of a toxic epidermal necrosis with fatal outcome is the first such case reported in Germany that very probably was caused by chlormezanone. 4 weeks after this case was reported to the German Doctors' Drug Commission, the manufacturers of the drug withdrew it from the market.

[A rare form of heart metastasis: hypernephroma. Successful surgical treatment]. / Seltene Form von Herzmetastasen: Hypernephrome. Erfolgreiche chirurgische Behandlung.

An unusual cardiac metastasis, occurring in a 63-year-old man 19 years after nephrectomy because of renal cell carcinoma, is reported. The tumor extended from the right ventricle apex to the mid-portion of the interventricular septum. A complete excision could be achieved. To our knowledge, this is the third case of a renal cell carcinoma metastasis to the right ventricle which could be detected during a patient's lifetime and treated surgically. A review of the literature is also reported.