[Bariatric surgery - significance, risks, long term consequences]. / Adipositaschirurgie- Stellenwert, Risiken und Folgen.

In recent years the number of bariatric surgery has markedly increased in industrial nations. Surgery provides a more rapid decrease of body weight than conservative approach. However a long term conservative follow up therapy is mandatory to stabilize reduced weight. Due to increasing knowledge from long term follow up of surgically treated obese patients there is a growing body of evidence that frequently there is necessity of reoperations and of substitution both of trace elementsand of minerals or vitamins due to their hampered enteral resorption. Additionally therapy of surgery induced endocrine alterations not seldom is necessary.These insights are of outstanding importance because meanwhile an enlargement of the indications for bariatric surgery as a therapeutic option for metabolic disorders is being discussed. This review refers to the recent internationally published papers concerning consequences of bariatric surgery.

[Therapy for obesity--conservative and/or surgical?]. / Adipositastherapie--konservativ und/oder chirurgisch?

On comparing surgical and conservative approaches in therapy for obesity it is accepted that there is a more rapid decline in body weight after surgery than by conservative measures. In contrast to widespread convictions, it has been shown that even in extreme obesity (BMI>60 kg/m²) both a meaningful and a long-lasting reduction of body weight is possible by conservative approach. There is an increasing body of evidence that bariatric surgery, especially malabsorptive and combined forms, causes endocrine disturbances and both vitamin and micronutrient deficiencies. Furthermore, alterations in drug pharmacokinetics are possible. Even bariatric surgeons have stated that surgery neither removes the chronic disease obesity nor is its final therapy.

Is interleukin-6 concentration in the dialysate of continuous ambulatory peritoneal dialysis patients a prognostic parameter in peritonitis?

In continuous ambulatory peritoneal dialysis (CAPD) patients, peritonitis is a dangerous complication. Chemical examinations in the dialysate can be successfully used to assess permeability disturbances, hemostatic balance, and (for early detection and follow-up) cellular inflammatory reaction. In 7 CAPD patients (age: 50 +/- 15 years; dialysis duration: 40 +/- 24 months) with peritonitis episodes, and in 17 age-matched CAPD patients (age: 50 +/- 13 years; dialysis duration: 29 +/- 18 months) without peritonitis, we examined daily dialysate cell count (CC) and concentrations of albumin (ALB), immunoglobulin G (IgG), thrombin-antithrombin III complex (TAT), D-dimer (DD), and interleukin-6 (IL-6) after the long dwell (8-10 hours) over an interval of at least 14 days. In CAPD patients with peritonitis episodes, all parameters (CC, ALB, IgG, TAT, DD, IL-6) were significantly increased in the first days [IL-6 mean: 25,190 pg/mL (range: 2560-52,708 pg/mL) vs 66 pg/mL (range: 21-163 pg/mL)]; then, up to day 14 after successful therapy with antibiotics, the levels showed no differences as compared with CAPD patients without peritonitis. In the case of relapse of peritonitis (4 cases), concentration of IL-6 rose again on day 14, 1 day earlier than did the other parameters. Determination of IL-6 in the dialysate is a reliable prognostic parameter for the course of peritonitis (start, end, relapse) in CAPD patients.

Insulin-like growth factor system components in hyperparathyroidism and renal osteodystrophy.

BACKGROUND: The insulin-like growth factor (IGF) system plays a key role in regulation of bone formation. In patients with renal osteodystrophy, an elevation of some IGF binding proteins (IGFBPs) has been described, but there is no study measuring serum levels of both IGF-I and IGF-II as well as IGFBP-1 to -6 in different forms of renal osteodystrophy and hyperparathyroidism. METHODS: In a cross-sectional study, we investigated 319 patients with mild (N = 29), moderate (N = 48), preuremic (N = 37), and end-stage renal failure (ESRF; N = 205). The ESRF group was treated by hemodialysis (HD; N = 148), peritoneal dialysis (PD; N = 27), or renal transplantation (RTX; N = 30). As controls without renal failure, we recruited age-matched healthy subjects (N = 87) and patients with primary hyperparathyroidism (pHPT; N = 25). Serum levels of total and free IGF-I, IGF-II, IGFBP-1 to -6, and biochemical bone markers including intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), and osteocalcin (OSC) were measured by specific immunometric assays. IGF system components and bone markers were correlated with clinical and bone histologic findings. Mean values +/- SEM are given. RESULTS: With declining renal function a significant increase was measured for IGFBP-1 (range 7- to 14-fold), IGFBP-2 (3- to 8-fold), IGFBP-3 (1.5- to 3-fold), IGFBP-4 (3- to 19-fold), and IGFBP-6 (8- to 25-fold), whereas IGFBP-5 levels tended to decrease (1.3- to 1. 6-fold). In contrast, serum levels of IGF-I, free IGF-I, and IGF-II remained constant in most patients. Compared with renal failure patients, pHPT patients showed a similar decline in IGFBP-5 levels and less elevated levels of IGFBP-1 (3.5-fold), IGFBP-2 (2-fold), IGFBP-3 (1.2-fold), and IGFBP-6 (4-fold) but no elevation of IGFBP-4 levels. In all subjects, free and total IGF-I levels showed significant negative correlations with IGFBP-1, IGFBP-2, and IGFBP-4 (that is, inhibitory IGF system components) and significant positive correlations with IGFBP-3 and IGFBP-5 (that is, stimulatory IGF system components). A positive correlation was observed between IGF-II and IGFBP-6. ESRF patients with mixed uremic bone disease and histologic evidence for osteopenia revealed significantly (P < 0.05) higher levels of IGFBP-2 and IGFBP-4 but lower IGFBP-5 levels. Histologic parameters of bone formation showed significant positive correlations with serum levels of IGF-I, IGF-II, and IGFBP-5. In contrast, IGFBP-2 and IGFBP-4 correlated positively with indices of bone loss. Moreover, dialysis patients with low bone turnover (N = 24) showed significantly (P < 0.05) lower levels of IGFBP-5, PTH, B-ALP, and OSC than patients with high bone turnover. CONCLUSION: Patients with primary and secondary hyperparathyroidism showed lower levels of the putative stimulatory IGFBP-5 but higher levels of IGFBP-1, -2, -3, and -6, whereas total IGF-I and IGF-II levels were not or only moderately increased. The marked increase in serum levels of IGFBP-4 appeared to be characteristic for chronic renal failure. IGFBP-5 correlated with biochemical markers and histologic indices of bone formation in renal osteodystrophy patients and was not influenced by renal function. Therefore, IGFBP-5 may gain significance as a serological marker for osteopenia and low bone turnover in long-term dialysis patients.

Prevalence of the metabolic syndrome in military and civilian flying personnel.

BACKGROUND: The metabolic syndrome (MS) affects 20-30% of the middle-aged population in highly industrialized countries, consisting of a cluster of diseases including obesity, hypertension, dyslipoproteinemia and glucose intolerance. HYPOTHESIS: If the population of flying personnel (FP) faces a high risk to develop MS, due to the specific workload of specialized aircrew, the consequences for aeromedical screening are to be reconsidered. METHODS: Data of the complete military flying personnel (MFP) of Germany were screened to develop MS-related risk factors, regular physical activity and determination of nicotin and alcohol consumption. A comparable screening of a population of German civilian flying personnel (CFP) was undertaken by questionnaire. Statistics were completed by comparison of averages by t-test for independent random-samples of different variances and testing of independence of single characteristics by chi2-test. RESULTS: Data of approximately 10,000 aircrew members were obtained. It was possible to determine a group of MFP with higher risk to develop MS later in life, called "possible future metabolics" (PFM). Comparison of PFM with the MFP control group (MCG) and CFP clearly showed that obesity, dyslipoproteinemia and hypertension are the main single and/or combined risk factors. As a new aspect, data of MFP showed possible connections between thyroideal dysfunction and the prevalence of relevant MS-risk factors. CONCLUSIONS: The purpose of this investigation was to determine the actual risk of MS in German FP and to confirm the current MS-related regular screening measures. This study revealed that German MFP and CFP show a high quality health status without significant differences between both groups. Continuing the current regular flight medical screening will prevent FP from losing its high quality health status.

Influence of renal replacement therapy on outcome of patients with acute renal failure.

There are many controversial results about the influence of acute renal failure (ARF) and renal replacement therapy (RRT) on patient outcome in intensive care units. This retrospective study compared demographics. severity, course, and prognosis of ARF during 36 months (period 1, 1991 through 1993; 128 cases) and 18 months (period 2, 1994 through 1995; 141 cases). Compared with period 1, during period 2 there was a markedly increased incidence of ARF. There were no significant differences in patient demographics or etiology of renal failure, but the therapeutic approach to ARF was quite different. During period 2, RRT was started at earlier stages of renal insufficiency (that is, less elevated creatinine serum concentrations or reduced diuresis). Additionally, there was a significant increase in the numbers of continuous RRT (CRRT) replacing the discontinuous mode of dialysis treatment. Compared with period 1, mortality was reduced from 78.9 to 59.6% during period 2 (P < 0.001). There were no differences in mortality between the patients from internal and surgical wards. Mortality in patients treated with CRRT was in period 1 and in period 2 higher than mortality in patients treated with intermittent RRT, but these results are biased by a preferred use of CRRT in severely ill patients with an unstable circulatory system. These data suggest that the early onset of RRT reduces the mortality of intensive care unit patients with ARF independent of underlying diseases. An influence of the method of RRT, sex, and age on outcome of patients with ARF could not be proven.

Effects of uremic plasma on alpha- and beta-adrenoceptor subtypes.

Responsiveness of adrenergic receptors is decreased in patients on maintenance hemodialysis. In this study we investigated whether uremic plasma might affect adrenergic receptors. For this purpose we determined the effects of uremic plasma obtained from 10 patients on hemodialysis treatment (mean age 61 +/- 3 years, dialysis frequency 3 x 4 h/week, duration of treatment 3 +/- 1 years) before and at the end of the 4-hour dialysis treatment on binding of radioligands to beta1- and beta2- as well as alpha1- and alpha2-adrenoceptors. Plasma from 6 healthy volunteers served as control; the plasmas were studied in three dilutions: undiluted, 1:1 (v/v) and 1:4 (v/v) with saline diluted. Plasma from healthy control did not significantly affect the number of beta1- and beta2- or alpha1- and alpha2-adrenoceptors. On the other hand, uremic plasma significantly decreased the number of beta1- and beta2-adrenoceptors; this inhibitory effect was also observed when plasma obtained at the end of the 4-hour dialysis treatment was investigated. On the other hand, uremic plasma did not significantly decrease the number of alpha1- and alpha2-adrenoceptors. We conclude that in patients on maintenance hemodialysis, the presence of inhibitory substance(s) in uremic plasma could be - at least partly - responsible for the beta-adrenoceptor hyporesponsiveness; the mechanism leading ot alpha-adrenoceptor hyporesponsiveness, however, remains to be elucidated.

Reduced lipid concentrations during four years of dialysis with low molecular weight heparin.

Heparin is used as standard anticoagulant in the extracorporeal circuit of hemodialysis. Widespread use of this drug revealed several potentially adverse effects, such as release of lipoprotein lipase and hepatic lipase from the endothelial surface. Recently it was found that anticoagulatory potency and provocation of adverse effects are linked to different subfractions of heparin. A heparin subfraction of 4000 to 6000 Daltons rather specifically inhibits factor Xa and therefore has a very high antithrombotic potency. Its effects on release of lipases are minor. During a four year period five patients on maintenance hemodialysis were treated with this low molecular weight heparin (LMWH) subfraction. Additionally, another five patients successively received standard heparin, LMWH and again standard heparin. At all circumstances during treatment with LMWH there was a significant (0.001 less than P less than 0.05) reduction both of cholesterol and triglyceride blood concentrations. LMWH is efficient in avoiding clotting in extracorporeal circuit during hemodialysis in doses of 17 to 95 U/kg (initial dose) and 7 to 20 U/kg/hr (continuous dose).

Theoretical approach and clinical application of kinetic modelling in dialysis.

Using kinetic modelling for shaping profile dialysis, we present a promising approach to improve the cardiovascular stability of patients during dialysis treatment. In order to obtain an insight into the physiological mechanisms of increased stability, a model considering alterations of electrolytes and water distribution and of acid-base status was developed. This algorithm was used for the evaluation of 114 dialysis sessions, which were performed with highly individualised profiles. Each profile was developed for one patient by trying empirically to prevent episodes of hypotension as well as other clinical problems throughout dialysis. The main advantage of profile dialysis compared to standard bicarbonate dialysis, for example, is a reduced water influx into the cell during the treatment. According to our clinical and theoretical results a correlation between water influx into the cell and time of occurrence of hypotensive episodes in individuals can be assumed. Hypotension usually starts after 0.5 litres of water have entered the intracellular space, regardless of the time necessary for this fluid shift.

[Modification of physical fitness of patients with coronary heart disease with nifedipine during a stay at altitude]. / Beeinflussung der körperlichen Leistungsfähigkeit von Patienten mit koronarer Herzkrankheit durch Nifedipin während eines Höhenaufenthaltes.

With this study including 9 patients with angiographically proven coronary heart disease it could be shown that a monotherapy with nifedipine in the galenic preparation as Adalat SL (Bayer AG, Leverkusen, FRG) is efficient in reducing myocardiac ischemia and concomitantly raising working capacity during bicycle ergometry as well after first time application of this drug as after continuous therapy with 1 tablet twice daily during 4 weeks. This findings are true both at normal environmental conditions (1000 ft above sea level) and at conditions of altitude induced hypoxia (9000 ft above sea level), simulated in a hypobaric chamber. There was no development of drug tolerance during continuous therapy with 1 tablet of Adalat SL twice a day. Out of these findings the conclusion can be drawn that in patients with coronary heart disease receiving protective therapy with Adalat SL there is no remarkably higher risk of episodes of angina pectoris or even myocardiac infarction at altitudes up to 9000 ft above sea level than is to be expected during daily life.

[Hemodynamics and coronary dynamics under ISDN long-term therapy]. / Hämodynamik und Koronardynamik unter ISDN-Langzeittheraie.

Although nitrates are among the oldest drugs in cardiology the problem of tolerance is a scientific challenge of today. We examined and compared the effects of initial and chronic therapy (4 weeks) with 1 X 1 ISDN 120 mg sustained release in 9 patients with coronary heart disease and impaired left ventricular function. At intraindividually identical workloads (average 50 +/- 12 watt) there was a reduction of PCWPm from 32.5 +/- 9.5 to 19.7 +/- 9.8 mm Hg. This reduction of PCWPm during bicycle ergometry was fully achieved in long-term therapy. With the first dose of ISDN cardiac index (CI) at maximum workload increased from 6.0 +/- 1.2 to 6.8 +/- 1.3 l/min/m2; during chronic therapy cardiac index improved from 5.3 +/- 1.3 to 6.6 +/- 1.1 l/min/m2. Exercise capacity during bicycle ergometry in the sitting position increased concomitantly from 414 to 686 watt X min. In long-term therapy there was a further significant improvement to 772 watt X min. ST-segment depression, measured as sum of ST-depression in all 12 standard ECG leads decreased from 0.63 mV before medication to 0.11 mV after the first dose and to 0.16 mV in long-term therapy. The investigation of ventricular function during ventriculography and the investigation of coronary vasomotion during coronary angiography after ergonovine maleate i.v. and ISDN s.l. also demonstrated the full nitrate effect in long-term therapy.