[Drug interactions--their impact on safe drug therapy in the example of the new thiazolidinedione group (glitazone)]. / Arzneimittelinteraktionen--ihre Bedeutung für eine sichere Therapie am Beispiel der neuen Wirkstoffgruppe der Thiazolidindione (Glitazone).

Troglitazone (CAS 97322-87-7), rosiglitazone (CAS 155141-29-0) and pioglitazone (CAS 111025-46-8) represent novel agents for the treatment of diabetes mellitus. Very often such patients receive several drugs at the same time and consequently their interaction potential needs to be known, especially as troglitazone was recently withdrawn from the market partly because it inhibited and induced drug metabolism.

[Weight reduction, statins or fibrates? How to reach lipid goal values in diabetic patients]. / Abspecken, Statine oder Fibrate? Wie Sie bei Diabetikern die Lipid-Zielwerte erreichen.

Diabetics have a greatly increased risk for cardiovascular disease. At the center of the pathogenesis is the elevated blood sugar, insulin resistance and hyperinsulinemia. Treatment must therefore be aimed at controlling glucose metabolism (HBA1c < 7.0%) and lipid metabolism (LDL conc < 100 mg/dL, triglycerides < 150 mg/dL). Blood pressure should not exceed 130/85 mmHg. In addition to changes in lifestyle--low-fat, calorie-controlled diet and increased physical activity--lipid-lowering medication can rarely be done without. On the basis of the results of large interventional studies, the CSE inhibitors are particularly to be recommended. While the domain of the fibrates is the lowering of triglycerides, no comparative data on the usefulness of this group of substances are currently available.

Immunoradiometric assay for intact human osteocalcin(1-49) without cross-reactivity to breakdown products.

BACKGROUND: Osteocalcin (Oc), a serum marker of bone turnover, circulates in several forms. We developed an assay for intact human Oc and investigated its clinical features. METHODS: We generated goat antibodies and N- and C-terminal Oc. The former was used on solid phase (polystyrene beads), and the latter was used as the tracer in an IRMA. RESULTS: The assay was linear with no cross-reactivity to Oc(1-43), total imprecision (CV) of <10%, and recovery of 100% +/- 10%. Assay values for intact Oc in EDTA plasma samples were unchanged at 18-25 degrees C for 6 h. Values for intact Oc in serum, EDTA plasma, and heparin plasma samples did not change after storage on ice for 8 h. Serum samples from patients with various conditions were stored at -70 or -135 degrees C for up to 5 years and yielded z-scores comparable to an Oc(1-43) IRMA for all conditions except for renal failure. In renal failure, the Oc(1-43) assay values were increased, whereas the intact assay values were in the reference interval. CONCLUSION: Decreases in Oc assay values are inhibited by calcium chelation, and slowed by reduced temperatures. The described assay for intact Oc allows improved specificity for bone compared with an assay for Oc(1-43).

Topical calcipotriene for morphea/linear scleroderma.

BACKGROUND: Morphea and linear scleroderma are characterized by erythema, induration, telangiectasia, and dyspigmentation. There is no universally effective treatment. Oral calcitriol has been beneficial in the treatment of localized and extensive morphea/scleroderma, but the use of topical calcipotriene has not been reported. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of topical calcipotriene 0.005% ointment in the treatment of localized scleroderma. METHODS: In a 3-month open-label study, 12 patients aged 12 to 38 years with biopsy-documented active morphea or linear scleroderma applied calcipotriene ointment under occlusion twice daily to plaques for 3 months. The condition of each patient had previously failed to respond to potent topical corticosteroids and, for some patients, systemic medications. Efficacy was assessed at baseline, 1 month, and 3 months. Levels of serum ionized calcium, intact parathyroid hormone, and 1,25-dihydroxyvitamin D and of random urinary calcium excretion were measured. RESULTS: During the 3-month trial, the condition of all 12 patients showed statistically significant improvement in all studied features. No adverse effects were reported or detected through laboratory monitoring of mineral metabolism. CONCLUSION: Topical calcipotriene 0.005% ointment may be an effective treatment for localized scleroderma, but double-blind placebo controlled studies are needed for confirmation.

Obstructive sleep apnoea and diabetes mellitus: the role of cardiovascular autonomic neuropathy.

Knowledge of conditions associated with an increased prevalence of obstructive sleep apnoea (OSA) may help to identify patients with OSA and might give some insight into the pathogenesis of OSA and its sequelae. A number of earlier, smaller studies hinted at an association between diabetic cardiovascular autonomic neuropathy (AN) and OSA. The present study was, therefore, conducted with the aim of establishing the prevalence of OSA in diabetics with AN and of determining whether OSA is more prevalent in diabetics with AN, than in those without. We studied two groups of diabetic patients: 23 with and 25 without AN. All patients were evaluated for possible OSA (apnoea/hypopnoea index > or = 10) using initial ambulatory screening followed by polysomnography. Six patients with AN (26%) were found to have OSA, but none of the patients without AN met the diagnostic criteria (p<0.01). When the patients with OSA were compared to those without, no differences were found in terms of age, sex, body mass index or diabetes type or duration. In conclusion, about one in four diabetic patients with autonomic neuropathy suffers from OSA. Thus, obstructive sleep apnoea is more prevalent in diabetic patients with autonomic neuropathy, than in those without.

Simultaneous determination of oxalate, citrate and sulfate in children's plasma with ion chromatography.

To improve our understanding of both diagnosis and treatment of diseases of oxalate metabolism, we first set out to establish a new ion-chromatographic method to determine normal plasma levels of oxalate, citrate and sulfate from single plasma samples. In 50 infants and children (23 girls, 27 boys, aged 0.2 to 17 years) with normal renal function, blood was drawn in Li-heparin tubes, placed on ice and preserved immediately with 40 microliters M HCl/ml plasma in two ultracentrifugation steps. For measurement, plasma was injected onto an ion chromatography system with NaOH as the mobile phase, and then run as a linear gradient from 5 mM to 52.5 mM over 21 minutes. Analysis yielded measurable and reproducible oxalate (6.43 +/- 1.06 microM/liter), citrate (79.3 +/- 27.4 microM/liter) and sulfate (235.0 +/- 85.3 microM/liter) levels, without any age and gender specific differences. The least detectable plasma oxalate level was < 0.3 microM with a high reliability and reproducibility (coefficient of variance 1.95 to 4.75%). In conclusion, we established a reproducible, precise method to determine the relevant plasma anions involved in mineral metabolism, which heretofore have not been easily measurable. Studies of diseases of oxalate and citrate metabolism are ongoing on the basis of the normal plasma values achieved in this study.

Effects of therapy with recombinant human growth hormone on insulin-like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury.

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone fomation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg.day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 +/- 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level IGFBR-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

[Obesity: entrance port to multimorbidity]. / Adipositas: Eintrittspforte zur Multimorbidität.

Obesity is an essential risk factor for hypertension, coronary heart disease and stroke as well as for metabolic disturbances, especially for type 2 diabetes, hyper- and dyslipidemia, and it is responsible for the metabolic syndrome with insulin resistance and hyperinsulinemia. Disturbances in the lung function are also induced by obesity, as a higher risk for arthrosis on the lower extremities. Some oncological diseases like breast-, endometrial-, and prostatic cancer are associated with obesity. It is evident, that the fat distribution plays an important role in the development of obesity associated diseases: the accumulation of visceral fat has a higher risk as the peripheral fat, probably due to the different metabolism.

Dysregulation of calcium homeostasis after severe burn injury in children: possible role of magnesium depletion.

OBJECTIVE: To determine the cause and extent of hypocalcemia observed in children after severe burns. DESIGN: We studied 10 children with burns covering 57% +/- 17% (SD) body surface area, ages 9.6 +/- 4.7 years, who were admitted consecutively during a 6-month period. Diet supplied a minimum of 2.7 gm/m2 of calcium, 0.3 gm/m2 of magnesium, and 2.2 gm/m2 phosphate. Blood specimens were obtained daily for 10 +/- 5 days for the following tests: (1) simultaneous analysis for ionized calcium, magnesium, and intact parathyroid hormone (group A); (2) two of these children, randomly selected, had serial 2-hour determinations on a single day (group B); (3) a modified Ellsworth-Howard test, consisting of a 10-minute infusion of synthetic parathyroid hormone 18 +/- 10 days post-burn and associated changes in urinary cyclic adenosine monophosphate excretion and renal threshold phosphate concentration (group C). Three of these children, when normomagnesemic, also received a standard magnesium infusion to determine magnesium retention (group D). Data were analyzed with chi-square, regression analysis, and non-parametric testing as appropriate. RESULTS: All patients showed sustained hypocalcemia and hypomagnesemia; intact parathyroid hormone response was inappropriately low and response to synthetic parathyroid hormone infusion was blunted. Lowest ionized calcium levels were associated with hypomagnesemia. CONCLUSION: Hypoparathyroidism and blunted renal response to parathyroid hormone suggest that magnesium depletion may contribute to their pathogenesis. Magnesium repletion and monitoring are recommended.

[Type II diabetic patients in general practice. A regional questionnaire survey--analysis and consequences]. / Typ-II-Diabetiker in allgemeinmedizinischen Praxen. Eine regionale Fragebogenerhebung--Analysen und Konsequenzen.

In the offices of 26 general practitioners in Upper Franconia, Germany, a complete survey of all type II diabetics was carried out. A total of 2,180 type II diabetics were analyzed in terms of age, sex and treatment with diet alone, tablets, or insulin. On average, each office is looking after 7.8% such diabetics, whose median age was 70 years, with 79% being older than 60. The considerable difference in the distribution of diabetics treated with diet alone, tablets or insulin among the various doctor's offices are discussed. The significance of inter-physician differences with respect to decision-making, e.g. when to start the patient on insulin, is examined. The data point up a need for the auditing of general practitioners.

Long-term reduction in bone mass after severe burn injury in children.

OBJECTIVE: Because burn victims are at risk of having bone loss, a cross-sectional study was undertaken to determine whether severe burn injury had acute and long-term effects on bone mass or on the incidence of fractures in children. METHODS: Dual-energy x-ray absorptiometry of the lumbar portion of the spine was performed on 68 children: 16 moderately burned (15% to 36% of total body surface area) and 52 age-matched severely burned (> or = 40% of total body surface area). Twenty-two severely burned children were hospitalized and studied within 8 weeks of their burn, and 30 others were studied approximately 5 years after discharge. In the severely burned group, both hospitalized and discharged, serum and urine were analyzed for calcium, phosphorus, intact parathyroid hormone, osteocalcin, and type I collagen telopeptide. RESULTS: Sixty percent of severely burned patients had age-related z scores for bone density less than -1, and 27% of severely burned patients had age-related z scores for bone density less than -2 (p < 0.005, for each). In the moderately burned group, 31% of patients had z scores less than -1 (p < 0.005 vs normal distribution), but only 6% had z scores less than -2 (p value not significant). There was evidence of increased incidence of fractures after discharge in the severely burned patients. Biochemical studies were compatible with a reduction in bone formation and an increase in resorption initially, and with a long-term persistence of low formation. CONCLUSION: We conclude that acute burn injury leads to profound and long-term bone loss, which may adversely affect peak bone mass accumulation.

Dose-response of simvastatin in primary hypercholesterolemia.

In an 8-week, placebo-controlled multicenter study, the efficacy of dose levels of simvastatin 2.5, 5, 10, 20, and 40 mg was evaluated in 166 patients with hypercholesterolemia, of whom 163 completed the trial. The entry criteria were serum total cholesterol (TCHOL) between 6.2 and 7.8 mM and low-density lipoprotein (LDL) cholesterol between 4.3 and 50 mM on a standard diet and after the 2-week run-in period of placebo treatment. Mean percentage changes in serum lipids in each simvastatin-treated group from baseline were statistically significant. Of treated patients, 0% (placebo), 11% (2.5 mg), 7% (5 mg), 33% (10 mg), 42% (20 mg) and 55% (40 mg) had at least 40% reduction from baseline LDL cholesterol value. After 8 weeks of treatment, 0% (placebo), 11% (2.5 mg), 25% (5 mg), 26% (10 mg), 31% (20 mg), and 55% (40 mg) of patients treated reached a TCHOL level of < or = 5.2 mM. There was a significant linear dose response with regard to the decrease in LDL cholesterol, TCHOL, and triglycerides (TG) and the increase in high-density lipoprotein (HDL) cholesterol after 8 weeks of therapy. No serious clinical or laboratory adverse events related to simvastatin were observed even at higher doses. At each dose level, simvastatin reduced TCHOL and LDL cholesterol. Doses of simvastatin > or = 5 mg moderately increased HDL cholesterol and reduced serum TG. Simvastatin therapy resulted in major improvement in serum lipoprotein profile, particularly at higher doses.

The influence of supportive nutritional therapy via percutaneous endoscopically guided gastrostomy on the quality of life of cancer patients.

Between April 1987 and May 1990 a total of 212 consecutive patients with tumours in the head and neck region were admitted to a prospective study comparing planned prospective enteral nutrition via percutaneous endoscopically guided gastrostomy (PEG; n = 47) and oral nutrition (n = 134). The nutritional status (anthropometric and laboratory chemical parameters) and the quality-of-life index according to Padilla et al. [Res Nurs Health 6:117-126 (1983)] were determined prior to radiotherapy, 2, 4, 6 weeks later during radiotherapy and 6, 12 and 18 weeks after completion of radiotherapy. The quality-of-life score of the orally nourished patients decreased quickly during radiotherapy and improved only slowly afterwards. Although PEG patients had a worse starting score, their quality-of-life index did not deteriorate during therapy (statistically significant difference between the two groups). The same applies to the nutritional status. These results show that an early and constant enteral nutrition by PEG can stabilize the nutritional state and the quality of life of patients with tumours of the head and neck area during radiotherapy.

[Total parenteral nutrition in the home of 498 patients with tumor diseases]. / Totale parenterale Heimernährung bei 498 Patienten mit Tumorerkrankungen.

Results of home parenteral nutrition in cancer patients were evaluated by analyzing files from 498 individuals. The predominant malignancies were cancer of the stomach (44% in men, 29% in women), the colon or the ovaries, respectively. Most patients (71%) admitted to home parenteral nutrition were severely malnourished, based on a Broca-Index of 0.8 or less. The majority (78%) of these subjects gained weight while on home parenteral nutrition. The remainder 22% continued to loose weight. Median survival was 64 (one to 720) days.

[Effect of acarbose on injection-eating interval in type I diabetes. Preliminary contribution]. / Einfluss von Acarbose auf den Spritz-Ess-Abstand beim Typ-I-Diabetes. Vorläufige Mitteilung.

In a pilot study, 7 patients with Type I diabetes received three daily doses of 100 mg acarbose for three days within the framework of intensified insulin therapy. At the same time, the 30 minute interval normally observed between injection and eating was abandoned. The blood glucose levels measured one hour post-prandial in diabetics taking acarbose and not observing the injection-eating interval were lower than those measured prior to acarbose and while observing the interval. Large-scale controlled studies are needed to investigated the theory that in insulin-dependent diabetics taking acarbose, observation of the injection-eating interval can be abandoned.

T cell activation by mycobacterial antigens in inflammatory synovitis.

To define which mycobacterial antigens were responsible for the activation of synovial fluid T lymphocytes, acetone-precipitated Mycobacterium tuberculosis (AP-MT) antigens were separated into five fractions following polyacrylamide gel electrophoresis and added to the mononuclear cell cultures of patients with inflammatory synovitis. Fractions 2 (50 to 70 kDa) and 5 (less than 28 kDa) resulted in significantly more proliferation than that of fractions 1, 3, and 4. The response to a purified mycobacterial 65-kDa heat shock protein (hsp), which migrated in fraction 2, was highly correlated (r = 0.89, P less than 0.001) with the response to the crude AP-MT. The proliferative response to a different hsp. the Escherichia coli DnaK, by synovial fluid lymphocytes was marginal. Analysis of the synovial fluid T cell response to mycobacterial culture filtrates by T cell Western blotting revealed dominant responses to antigen(s) in the range of 31 to 21 kDa in each responding patient, although no other consistent pattern of T cell activation was noted. Three lines of evidence suggested that the response to the low molecular weight fractions was directed against degradation fragments of the 65-kDa protein. These observations suggest that the activation of T lymphocytes obtained from inflammatory synovial fluids by crude mycobacterial antigens was due in large part to recognition of the 65-kDa mycobacterial hsp.

Percutaneous endoscopically guided gastrostomy in patients with head and neck cancer.

In 212 patients with tumors in the head and neck region the nutritional status prior to, during, and following radiotherapy, was determined by body measurements and biochemical and immunological parameters. In 165 orally fed patients the nutritional parameters deteriorated rapidly under radiation and afterwards recovered only slowly and incompletely, 31 patients requiring PEG during radiotherapy. By contrast, 47 patients with a poor initial status who had a prospectively performed percutaneous endoscopically guided gastrostomy (PEG) experienced an amelioration of their nutritional status even before radiotherapy ended. The subjective status of the patients was assessed using the Padilla quality of life index. Here, too, the PEG patients had significantly worse initial values than the orally fed patients. As with the objective indicators of nutritional status a significant deterioration was seen in the orally fed patients during radiotherapy, while the scores of the PEG patients remained constant. We consider early institution of a carefully monitored enteral feeding by PEG useful for stabilizing the nutritional status of patients with tumors in the head and neck region, and therefore recommend, when aggressive multimodal therapy is planned-and particularly if primary malnutrition is already obvious-prophylactic performance of PEG prior to the start of therapy.

[Scientific approach in nutrition medicine and the example of diet fads]. / Wissenschaftlichkeit in der Ernährungsmedizin und das Beispiel der Aussenseiterdiäten.

The dietetics, seen from the historic point of view, have been more of an empirical science, yet in the past few decades they have developed a more rational, scientific basis. Unfortunately, this view is not shared by all, especially by those responsible for research policies of universities. Therefore it is not surprising that so-called "fad-diets" have gained in popularity despite the fact that these diets have not been scientifically proven as valuable. The most well known of these diets are the Schroth-, and F. X. Mayr-cure, the Evers-, Hay's, Atkins-, and Point-diet. Almost every day new diets are introduced to the public via uncritical mass media. These types of diets have nothing to do with modern throphotherapy.