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Introduction: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula has not been validated in patients with cancer. The present investigation was undertaken in order to study how well estimated glomerular filtration rate (eGFR) using the new CKD-EPI equation correlates with measured GFR (mGFR) by (51)chrome ethylene diamine tetraacetic acid ((51)Cr-EDTA) clearance in a group of patients with cancer not known as having cancer., Material and Methods: We investigated 185 patients with cancer who were referred for isotope measurement of GFR with (51)Cr-EDTA before initiating chemotherapy treatment. The agreement between CKD-EPI and (51)Cr-EDTA was assessed using a Bland-Altman plot. Test performance was analysed in a contingency table and bias, precision and the percentage of estimates within 30% of the mGFR (P30) were assessed., Results: Bland-Altman plot analysis showed a limit of agreement in the range from -25.59 to 27.92 ml/min./1.73 m(2). This formula was therefore not interchangeable with (51)Cr-EDTA, as the above differences are of clinical importance. Bias was low: 1.16 ml/min./1.73 m(2); P30 was high: 89.73%; and precision was 13.37 ml/min./1.73 m(2). As a screening test, the CKD-EPI had a high specificity of 98% (95% confidence interval (CI): 96 to 100%) and a high negative predictive value 97% (95% CI: 95 to 100%). The accuracy of the validation test was 96% (95% CI: 93 to 99%)., Conclusion: The CKD-EPI may be used as a screening tool for CKD in the general population, but cannot replace isotope tests when a high GFR measurement accuracy is needed.

Purpose: We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological findings., Methods: We studied 476 patients with melanoma from two melanoma centres using static scintigraphy and blue dye. A proportional odds model was used for statistical analysis., Results: The number of SNs visualized at scintigraphy increased significantly with time from injection to scintigraphy and activity left in the patient at scintigraphy, and depended on the melanoma location. The number of SNs removed at surgery increased with the number of SNs visualized at scintigraphy and time from injection to surgery. The frequency of nodal metastasis increased with increasing thickness and Clark level of the melanoma, and was highest for two SNs visualized at scintigraphy., Conclusion: This study showed that early vs. late imaging and surgery do make a difference on the outcome of the SN procedure and confirmed the importance of the scintigraphic visualization of all true SNs.

Status of the regional lymph nodes is a strong prognostic factor in patients with cutaneous malignant melanoma (CMM) and can be assessed by sentinel lymph node biopsy (SLNB). We present our technique of preoperative lymphatic mapping and intraoperative vital dye and handheld gamma probe. Our results and three years follow-up of its routine use in 198 patients with verified primary CMM are presented. Median follow-up time was 24 months (range 1-47). Metastatic regional lymph node disease was found by SLNB in 61 patients (31%) and additional metastatic nodes were found by formal node dissection in 30% of these cases. Complications were relatively mild but included one case of lymphoedema in a node negative patient. By follow-up, 13% had developed a recurrence including 26% of node positive patients and 8% of node negative patients. Mortality was also substantially higher in node positive cases with 18% dying in the follow-up period and 3% in the node negative group. The SLNB procedure was associated with a false negative rate of 8%. Using the presented technique, we found that SLNB was a useful procedure for staging patients with CMM and for selecting patients for more extensive metastatic screening and inclusion in trials of adjuvant treatments.

Background: Type 2 diabetes is associated with an increased risk of cardiovascular disease. Endothelial dysfunction is thought to be an early marker of atherosclerosis. The purpose of this study was to assess whether endothelial function, judged by measurements of flow-mediated vasodilatation (FMD) and nitroglycerine (NTG)-induced vasodilatation as well as serum levels of von Willebrand factor, was affected in patients with uncomplicated Type 2 diabetes and normal levels of urinary albumin excretion (UAE)., Subjects and Methods: Twenty-three patients with Type 2 diabetes, normal UAE and no vascular complications were examined. Twenty-three healthy subjects matched for age, gender, body mass index and resting vessel size served as controls. All participants were non-smokers. Endothelial function was assessed by high-resolution ultrasound which measures changes in diameter of the brachial artery during flow-mediated and NTG-induced vasodilatation. We also measured serum levels of von Willebrand factor., Results: In Type 2 diabetic patients FMD (3.2 +/- 0.5% vs. 4.8 +/- 0.5%, P = 0.019) as well as NTG-induced vasodilatation (15.9 +/- 0.6% vs. 18.5 +/- 0.9%, P = 0.021) were significantly reduced compared with controls. Levels of von Willebrand factor were not different between groups (0.88 +/- 0.07 vs. 0.88 +/- 0.07 in patients and controls, respectively) and were not correlated to FMD or NTG-induced vasodilatation., Conclusion: Impaired vascular reactivity is present in uncomplicated Type 2 diabetes and seems to be a more sensitive marker of vascular dysfunction than von Willebrand factor.

Unlabelled: The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function., Methods: Fourteen patients treated for moderate to severe CHF with diuretics and ACE inhibitors were investigated at baseline, after 4 months of maximum carvedilol treatment and after withdrawal of carvedilol., Results: Carvedilol lowered blood pressure and heart rate but increased left and right ventricular ejection fractions without changing cardiac output or pulmonary blood volume. At the same time, a minor fall was seen in glomerular filtration rate (GFR). but renal blood flow was unchanged and effective renal plasma flow slightly increased. Carvedilol also lowered the plasma levels of angiotensin II and aldosterone. All changes were reversed after withdrawal of carvedilol., Conclusions: Carvedilol augments ACE-inhibitor-induced vasodilation by lowering blood pressure, and angiotensin II beside reducing heart rate. The heart adapts to the haemodynamic alterations without changes in cardiac output and pulmonary blood volume. GFR is slightly lowered despite no changes in renal blood flow and a slight increase in effective renal plasma flow. The study emphasizes the need for control of renal function during treatment with carvedilol in patients with CHF.

The present study aimed at an investigation of the relation between arterial blood pressure and cardiac filling in patients with severe postural hypotension. Seven patients aged 49 to 84 years were studied during head-up tilt at three different tilt angles (median values: 0, 25, and 45 degrees) using intraarterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Mean arterial blood pressure was reduced from 105 mmHg (79-129) in the horizontal position to 97 mmHg (61-112) and 83 mmHg (36-93; p < 0.0001), respectively, in parallel with a reduction in left ventricular end-diastolic volume index from 59 ml m-2 (30-65) to 36 ml m-2 (23-44) and 22 ml m-2 (16-38; p < 0.001). Left ventricular contractility was high, and the postural reductions in cardiac output were unopposed by vasoconstriction. The study has demonstrated that blood pressure is strongly dependent upon cardiac filling in severe postural hypotension, and has underlined the importance of intravascular volume expansion as a measure against postural hypotension.

Autonomic denervation of the vascular bed results theoretically in a stronger dependency of blood pressure upon intravascular volume, and the study described aimed at an investigation of the relation between cardiac filling and arterial blood pressure in patients with severe postural hypotension. Seven patients were studied during head-up tilt at three different tilt angles using intra-arterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Blood pressure fell dramatically during head-up tilt due to reductions in cardiac output unopposed by vasoconstriction. The reduction in cardiac output resulted from reductions in left ventricular end-diastolic volumes with unchanged left ventricular ejection fractions and only moderate increments in heart rate. The study was demonstrated that blood pressure is strongly dependent upon cardiac filling in severe autonomic dysfunction, and that volume expansion is an important measure against postural hypotension.

The prognosis, and clinical findings related to prognosis, were examined in a consecutive series of 190 patients under 76 years of age (mean 64 years) with congestive heart failure (CHF). The aetiology of CHF was ischaemic heart disease in 66%, hypertension in 11% and cardiomyopathy in 23%. The 2-year mortality was 32%. Median left ventricular ejection fraction (LVEF) was 0.30, range 0.06 to 0.74. Eight per cent were in New York Heart Association (NYHA) class I, 46% in II, 44% in III and 2% in IV. Multivariate analysis, excluding exercise test variables, revealed seven variables with independent, significant prognostic information, (hazard ratios for death in brackets): ln (natural logarithm) (LVEF) (3.19), NYHA class III+IV (2.72), plasma urea > 7.6 mmol.l-1 (2.22), serum creatinine > 121 mumol.l-1 (2.05), serum sodium < or = 137 mmol.l-1 (2.03), pulmonary congestion on X-ray (1.86), and age > 65 years (1.86). Multivariate analysis, including exercise testing, showed the following variables to contain independent, significant prognostic information: increase in heart rate during maximal exercise < or = 35 min-1 (3.5), ln (LVEF) (3.7), serum creatinine > 121 mumol.l-1 (2.9), maximal exercise time < or = 4 min (2.3), serum sodium < or = 137 mmol.l-1 (2.5), ischaemic heart disease (2.0) and plasma urea > 7.6 mmol.l-1 (1.9). In conclusion, patients with CHF have a high risk of death despite intensive medical treatment. LVEF is a strong predictor of mortality. Both NYHA class and exercise variables have strong independent prognostic information as regards mortality in combination with LVEF, but are mutually exclusive.

Retrospective studies suggest increased postoperative morbidity among alcohol misusers. We have prospectively studied the risk associated with alcohol intake among patients undergoing surgery. We investigated 15 persons who required colorectal surgery and who were drinking at least five Danish drinks per day. These patients were matched for sex, nutrition, age, weight, cardio-pulmonary disease, diagnosis anesthesia, and surgery to 15 control persons who were consuming no more than two drinks daily. None of the patients showed signs of liver disease. The alcohol group developed more postoperative complications than controls (67 vs 20%, p < 0.05) and hospital stay was prolonged (20 vs 12 days, p < 0.05). Preoperatively, alcohol misusers had reduced left ventricular ejection fraction (54 vs 68%, p < 0.01). Delayed-type hypersensitivity responses were reduced in the alcohol group before (53 mm2 vs 78, p < 0.05) and after (18 mm2 vs 55, p < 0.01) surgery. Alcohol misusers had significantly longer bleeding times. Surgical stress responses, as assessed by changes in plasma cortisol and catecholamines, were higher among alcohol misusers (p < 0.05). Postoperative morbidity was increased in alcohol misusers without signs of liver damage. The mechanisms may include subclinical cardiac insufficiency, immunosuppression, and decreased haemostatic function. Preoperative alcohol consumption may be a more important risk factor for postoperative morbidity than previously thought.

The purpose of the study described here was to study plasma immunoreactive Neuropeptide Y (NPY) at rest and during exercise in patients with congestive heart failure (CHF) and in healthy subjects. Thirty-five patients, mean age 64 years, with CHF in optimal treatment and with a mean ejection fraction of 32%, were studied at rest and during exercise. Twelve age and sex matched healthy subjects were compared for resting values. Another nine healthy subjects were studied at rest and during exercise at a constant low load of 75W and at a high load defined as 80% of their individual maximal capacity. In patients with congestive heart failure mean plasma immunoreactive NPY at rest was 10.3 pmol l-1 and was not significantly different from the control group. No differences between patients with slight and severe CHF were found and there was no correlation between plasma immunoreactive NPY and left ventricular ejection fraction. Mean maximal exercise time was on average 6.3 min. Only three patients exercised more than 10 min. At maximal exercise mean plasma immunoreactive NPY was 10.6 pmol l-1 the same as at rest. Plasma noradrenaline was increased in CHF patients compared to healthy subjects, and rose further during exercise. In healthy subjects plasma immunoreactive NPY rose significantly on both workloads, but more on the high load (p < 0.05), when the rise was first significant after 10 min. Plasma immunoreactive NPY at rest and during exercise was not increased in CHF patients in optimal medical treatment. Consequently plasma immunoreactive NPY is not a useful marker of the severity of CHF in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study shows that for assessment of LVEF, MRI and the standard methods seem to provide information of similar value. For absolute volume measurements, MRI and RNA are superior to single plane angiography and 2 DE using the modified Simpson-rule. The time consuming transversal MRI method does not seem to be superior to the oblique multislice method, when apical aneurysms can be ruled out. MRI thus seems to be an accurate method for determination of LV stroke volume as well as for determination of LVEF and hence for diastolic and systolic volumes. MRI, however, depends of a good image quality, which is crucial especially in dilated ventricles containing stagnant or slowly moving blood.

Retrospective studies suggest that there is an increased postoperative morbidity among alcohol misusers. We have prospectively studied the risk of alcohol intake among patients undergoing surgery. We investigated 15 symptom-free subjects who required colorectal surgery and who were drinking at least 60 g of alcohol per day. These patients were matched for sex, nutrition, age, weight, cardiovascular and pulmonary disease, diagnosis, anaesthesia, and surgery to 15 control subjects who were consuming below 25 g of alcohol daily. Those drinking at least 60 g of alcohol per day developed more postoperative complications than controls (67% vs 20%, p less than 0.05) and hospital stay was prolonged (20 vs 12 days, p less than 0.05). Preoperatively, alcohol misusers had reduced left ventricular ejection fraction (median, 54% vs 68%, p less than 0.01). Delayed hypersensitivity responses were smaller in the alcohol group before (53 mm2 vs 78 mm2, p less than 0.05) and after (18 mm2 vs 55 mm2, p less than 0.01) surgery. Alcohol misusers had longer bleeding times during the first postoperative week (p less than 0.01). Surgical stress responses, as assessed by changes in plasma cortisol and catecholamines, were higher among alcoholics (p less than 0.05). Postoperative morbidity is increased in symptom-free alcohol misusers. The mechanism is probably subclinical cardiac insufficiency, immunosuppression, and decreased haemostatic function. Preoperative alcohol consumption may be a more important risk factor than previously thought.

This study was initiated to elucidate the mechanisms behind valproate-induced weight gain. Eight patients with epilepsy were studied with identical examination programs before and during the end of the first month of treatment with sodium valproate (VPA). The measurements included registration of food intake, indirect calorimetry, and determination of pancreatic and thyroid hormones, catecholamines, albumin, electrolytes, glycerol, and free fatty acids. Measurements were performed both at the basal condition and during a 3-hour oral glucose tolerance test (OGTT). After the start of VPA treatment, the mean levels during the OGTT of plasma glucose and catecholamines were significantly decreased by 7% and 25%, respectively (P less than .05). The mean ratio of insulin to glucagon decreased by 37% (P less than .01). During the glucose load, the decreases in free fatty acids were less pronounced after the start of VPA treatment, whereas the mean levels of glycerol were found to be unchanged. We detected no differences between the two periods with regard to total energy intake or macronutrient selection, energy expenditure, or thyroid hormones. As VPA is known to affect the concentration of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance.

Eight obese patients were studied before and after 2 weeks of treatment by a very-low-calorie diet (VLCD). Cardiac output and central blood volume (pulmonary blood volume and left atrial volume) were determined by indicator dilution (125I-albumin) and radionuclide angiocardiography (first pass and equilibrium technique by [99Tcm]red blood cells). Cardiac output decreased concomitantly with the reduction in oxygen uptake as the calculated systemic arteriovenous difference of oxygen was unaltered. There were no significant decreases in left ventricular contractility indices, i.e. the ejection fraction, the peak ejection rate and changes in end-systolic volume. Also the diastolic function evaluated by the peak filling rate remained normal. Furthermore, no sign of backward failure could be demonstrated since the central blood volume was not significantly increased. Both systolic and diastolic blood pressure (BP) declined. The fall in BP was caused by the reduction in cardiac output as the total peripheral resistance was unchanged. Finally, the decline in total blood volume was not significant. These findings together with a reduction in heart rate indicated that a reduced sympathetic tone via increased capacitance of the venous bed was the main operator of a reduced venous return. Thus, the haemodynamic alterations in obese patients during short-term semistarvation may be caused by the fall in oxygen uptake and produced mainly by changes in the sympathetic tone.

Eighteen patients with ischaemic heart disease were studied. Left and right ventricular volumes including cardiac output (forward flow) were determined by radionuclide angiocardiography using a double bolus and equilibrium technique. As reference, cardiac output was simultaneously measured by indicator dilution. The radionuclide technique comprised four steps: (1) a first-pass study of right ventricle; (2) a bolus study of left ventricle; (3) an equilibrium study of left ventricle; (4) determination of the distribution volume of red blood cells. Absolute volumes of left ventricle were determined from steps 2 + 3 + 4. Absolute volumes of right ventricle were calculated from stroke volume and right ventricular ejection fraction (EF) which in turn was determined from step 1 by creating composite systolic and composite diastolic images. There was an acceptable agreement between stroke volume determinations by radionuclide angiocardiography and indicator dilution (r = 0.74; P less than 0.001). Stroke volume determination by radionuclide was 83 +/- 20 ml (mean +/- SD) and by indicator dilution 84 +/- 20 ml with a difference of -1 +/- 15 ml (NS). Cardiac output determination by radionuclide was 5.24 +/- 1.37 l min-1 and by indicator dilution 5.28 +/- 1.23 l min-1 with a difference of -0.04 +/- 0.95 l min-1 (NS). Left ventricular EF was 0.44 +/- 0.14 and right ventricular EF 0.57 +/- 0.10. The intra-observer coefficient of variation for duplicate calculations of the radionuclide determinations was 5.5% for stroke volume, 2.5% for left ventricular EF and 4.8% for right ventricular EF.

We compared the weight-reducing effect of diet and gastroplasty with that of diet alone in a randomized trial in 60 morbidly obese patients followed for two years. Initial median body weight was 120 kg in patients randomly assigned to gastroplasty plus diet and 115 kg in those assigned to diet alone. Maximum weight losses did not differ significantly between the groups (26.1 kg in the gastroplasty group and 22.0 kg in the group treated with diet alone, P greater than 0.05). The risk of a Type II error with a true difference larger than 9.5 kg was less than 5 per cent. However, the group treated with diet alone regained significantly more weight after maximum weight loss had been achieved, so that the gastroplasty group had a more favorable net outcome at two years (P less than 0.05).

Seventeen patients with stable body-weights who had undergone a jejuno-ileal bypass for obesity, and 25 obese patients matching in sex, age and height were studied. Median serum concentration of free triiodothyronine (3.7 pmol/l) in the jejuno-ileal bypass patients was significantly (P less than 0.001) decreased by 18 per cent (95 per cent confidence limits: 11-27 per cent). Correspondingly median serum concentration of total triiodothyronine (1.47 nmol/l) was significantly (P less than 0.0001) decreased by 18 per cent (95 per cent confidence limits:11-27 per cent). The medium serum concentrations of free thyroxine (27.5 pmol/l) and total thyroxine 94 nmol/l) were of equal size in jejuno-ileal bypass patients and obese patients. In the bypass patients the median serum concentration of thyroxine-binding prealbumin (3.9 micromol/l) ws significantly (P less than 0.05) decreased by 13 per cent (95 per cent confidence limits: 7-27 per cent), whereas no significant changes could be demonstrated in thyroxine-binding globulin.

Fourteen patients with jejunoileal bypass for obesity were treated for one week with a calcium supplement of 3g daily. During this period diarrhoea was significantly (P < 0.005) reduced by 23 per cent (97 per cent confidence limits: 7-46 per cent). Ten of the patients had hyperoxaluria (median value 961 mumol/24 h; range 633-2742 mumol/24 h). The treatment with calcium significantly (P < 0.005) decreased the concentration of oxalate in urine by 23 per cent (98 per cent confidence limits: -5-+54 per cent). The calcium supplement did not increase urinary calcium-excretion rate or albumin-corrected serum calcium.

Glomerular filtration rate (GFR), concentration of total cortisol in plasma, and urinary excretion rate of free cortisol were determined in five females 1-5 years after jejunoileal bypass operation for obesity. The overweight of the patients had decreased from 97 per cent (range 82-147 per cent) to 25 per cent (range 0-39 per cent). The measured values were compared to previously published results in 16 female obese patients (median overweight 86 per cent) and in 16 female controls with normal body weight, all comparable with respect to age and height. Median GFR in the jejunoileal bypass patients (100 ml/min) was significantly (P less than 0.006) decreased compared to median GFR in the obese patients (129 ml/min), but did not differ significantly from that in the controls with normal body weight (104 ml/min). The median values of plasma cortisol and urinary excretion rate of free cortisol in the bypass patients were lower than those in the obese females, but the differences were not significant. The present results suggest that the increased GFR in obese subjects is related to the state of obesity.

Eighteen euthyroid, grossly-obese females without characteristics of Cushing's syndrome were studied. The absolute urinary excretion rate of 17- ketogenic steroids was increased in 13 patients, whereas the excretion rate of urinary free cortisol was slightly elevated in four out of 15 patients. The urinary excretion rate of 17-ketogenic steroids was significantly (P less than 0.005) positively correlated (rs = 0.66) with the serum concentration of free triiodothyronine, whereas no correlation with the serum concentration of free thyroxine could be demonstrated. The urinary excretion rate of urinary free cortisol was not correlated with the serum concentration of free triiodothyronine or free thyroxine. The study indicates that the increased absolute urinary excretion rate of 17-ketogenic steroids in obesity is a result of increased cortisol metabolism and may be due to actions to triiodothyronine.

Twelve morbidly obese patients and 17 patients treated for obesity by jejunoileal shunt operation were studied. A 50-g oral glucose load (OGTT) and an intravenous glucose infusion were carried out to study a) the relation between the plasma gastric inhibitory polypeptide (GIP) levels after oral glucose and the type of jejunoileal bypass performed and b) the importance of endogenous GIP as an incretin in man. The GIP release during OGTT and incretin effect were normal in the obese patients. After jejunoileal shunt, measuring 48 cm and with a ratio of 3:1 between the jejunal and ileal segments, the GIP release and the incretin effect were significantly reduced. Incremental increase in plasma GIP and OGTT was significantly correlated to the incretin effect in these patients. After jejunoileal shunt with the reverse ratio of proximal and distal intestine the incretin effect was significantly higher in spite of a comparable GIP release. Five patients after ileoascendostomia for familial hypercholesterolemia had significantly supernormal GIP release during OGTT but normal incretin effect. The findings indicate the insulinotropic effect of GIP and are in accordance with the concept that incretins other than GIP are released from the distal intestine.

Obese patients, age 18-60 years, overweight 20-80 per cent, entered a controlled, clinical study comparing the effects of two anorectic drugs, ie a prescription containing ephedrine and caffein ('Elsinore pills') and diethylpropion, with placebo. All 132 patients were instructed in a 1200-kcal diet, and 108 patients completed 12 weeks' treatment. There was a significantly better effect on body weight of diethylpropion (39 patients, median weight loss 8.4 kg, P less than 0.01) as well as of 'Elsinore pills' (38 patients, median weight loss 8.1 kg, P less than 0.01) compared to the effect of placebo treatment ( 31 patients, median weight loss 4.1 kg). Four patients treated with diethylpropion, and four patients treated with 'Elsionore pills' were withdrawn because of complaints of exaltation, tremor and insomnia. Tremor, in some cases only transient, was significantly more frequent in the 'Elsinore pill' group, but no serious side effects were observed.

Serum concentrations of total triiodothyronine (T3) and thyroxine (T4) were determined in 28 obese out-patients before and after 12 weeks of treatment with a conventional slimming diet of 5.2 MJ (1245 kcal). Twenty-one of the patients were also given central stimulating anorectics (diethylpropion and 'Elsinore-pill' containing ephedrine). The median weight loss was 8.1 kg (range 0.4-19.1 kg). After the treatment a small, but significant (P less than 0.02), fall in serum T3 could be demonstrated whilst serum T4 was unaffected. The median fall in T3 in percentage of pretreatment value was 9 per cent (96 per cent confidence limits: 4-16 per cent). Neither serum T3 nor serum T4 correlated with the initial body weight, overweight or energy intake. In the patients treated with anorectics serum T4 was not elevated after 12 weeks, indicating that a possible sympatomimetic effect of central stimulating anorectics upon the thyroid gland is only temporary.

Twenty-two consecutive obese patients were given very-low-calorie diet (VLCD) in the form of a casein and lactose preparation dissolved in orange juice containing 43.0 g protein, 30.4 g carbohydrate and 1.1 g lipid in a total of 317 kcal (1.3 MJ) daily. VLCD was given intermittently in eight-week periods alternating with three-week periods of conventional diet (900-1200 kcal, 3.8-5.0 MJ) to ensure recuperation of lean body mass and to establish a therapy which may facilitate indefinite patient compliance. In case of persisting hunger, diethyl-propion was given in small doses. The median observation time was nine weeks (range 1-37 weeks). The median weight loss was 15.5 kg (range 3.8-39.2 kg), and the median overweight decreased from 85.5 per cent (range 43-135 per cent) to 61.0 per cent (range 19-100 per cent). Blood glucose and cholesterol fell significantly (P < 0.01), and no major side-effects were observed.

Fifty-seven patients allocated at random to either diet supported by gastroplasty or very-low-calorie diet (VLCD) were followed for 5 years. One patient was lost to follow-up 1 year after surgery. Data were analyzed by survival statistics and success was liberally defined as a maintained weight loss of at least 10 kg. The cumulative success rate declined steadily in both groups, but it remained higher in the gastroplasty group (16 versus 3 percent, the 95 percent confidence limits being 11-21 percent and 1-5 percent, respectively; P less than 0.05). At 5 years, eight of 27 gastroplasty patients (30 percent, 95 percent confidence limits 14-50 percent) had not relapsed. Of 30 VLCD patients, relapse had not occurred in five (17 percent, 6-35 percent). The weight loss of patients without relapse did not differ significantly (medians of gastroplasty and VLCD patients 18 kg and 27 kg, respectively). Complications and side-effects were more numerous and serious among the gastroplasty patients. Although in this long-term study, the horizontal gastroplasty proved to be somewhat more effective than the diet alone, the surgical risks and the unsatisfactory maintenance of weight loss speak against the use of this operation.

Blood pressure (BP) was followed simultaneously with body weight in 134 morbidly obese patients randomized to either jejunoileal bypass (101 patients) or dietary treatment (33 patients). After a median observation time of 24 months (range 12-48 months) body weight fell significantly from a median of 124.0 kg to 81.2 kg in the jejunoileal bypass patients whilst median BP decreased significantly from 140/85 mmHg to 120/80 mmHg. In the patients treated with diet, body weight decreased significantly from a median of 129.0 kg to 119.0 kg after a median observation time of 18 months (range 9-36 months) whereas the median BP of 140/90 mmHg was unaffected. The fall in BP after weight loss was significantly positively correlated with the height of BP before the weight loss. The correlation could not be explained by a greater weight loss in the patients with initially high BP. Furthermore, a significantly positive correlation between BP changes and body weight changes was demonstrated, but this correlation was lesser than the above-mentioned. The study shows that the beneficial effect of a weight loss upon BP in obese patients is greater the higher the initial BP is, but also that a normal BP is only little affected and explained mainly by cuff artifact.

Thirteen postobese patients with stable body weights were studied and compared with obese patients and normal subjects. Six had previously been treated with a very-low-calorie diet (VLCD) whereas seven had been treated with gastroplasty (GP). The median observation time of post-obesity was 20 months for GP patients, but significantly (P less than 0.001) shorter by 2 months in VLCD patients. The median serum concentration of free triiodothyronine (T3) was significantly (P less than 0.005) reduced in the postobese VLCD patients (3.4 pmol/l) but normal in postobese GP patients (4.2 pmol/l) and obese patients (4.5 pmol/l). The serum level of total T3 was correspondingly lowered in the postobese VLCD patients. Also the postobese GP patients had a small, but significant (P less than 0.01) reduction in the median serum concentration of total T3 suggesting a slight decrease in the binding capacity. The serum levels of thyroxine-binding globulin and thyroxine-binding prealbumin were normal in both postobese and obese patients. Furthermore, the serum levels of thyroxine were normal showing that the postobese patients were euthyroid. The study shows that serum concentrations of T3 are not associated with body weights and low serum concentration may be seen in postobese patients after VLCD.

Serum free triiodothyronine decreased significantly (P < 0.02) by 18 per cent (range from -8 to +47 per cent) in 13 grossly obese patients after 11 days (median) treatment (range 8-18 days) with a very-low-calorie diet consisting of 43.0 g protein, 30.4 g carbohydrate and 1.1 g lipid. Also a significant decrease was found in serum total triiodothyronine (P < 0.007), thyroxine-binding globulin (P < 0.008) and thyroxine-binding prealbumin (P < 0.005). No significant changes in serum free thyroxine, total thyroxine and TSH could be demonstrated.

The serum levels of the three major vitamin D metabolites [25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyitamin D (1,25-(OH)2D), 24,25-dihydroxyvitamin D (24,25-(OH)2 D)] and immunoreactive parathyroid hormone (iPTH) were measured in 14 morbid obese patients, who later on were subjected to jejunoileal bypass surgery. The preoperative median values of 25-OHD and 24,25-(OH)2D were reduced compared with controls (P less than 0.001), whereas elevated concentrations were found of 1,25-(OH)2D (P less than 0.005). Median levels of iPTH in the obese group were significantly higher than those found in normal subjects (P less than 0.001). A decrease was observed in serum concentrations of all three vitamin D metabolites following jejunoileal bypass (P less than 0.005). An increase in the serum levels of iPTH and alkaline phosphatase was seen postoperatively (P less than 0.002), probably indicating a secondary hyperparathyroidism. The results show that the vitamin D metabolism is slightly abnormal in severely obese patients. Jejunoileal bypass is followed by severe disturbances of vitamin D metabolism.

Serum concentrations of free triiodothyronine (T3) and total T3 were measured in 25 grossly obese patients with constant body weight and no dietary restrictions. The results were compared with serum free T3 and total T3 in 55 non-obese volunteers matched in sex and age. Median serum concentration of free T3 (4.5 pmol/l) and total T3 (1.80 nmol/l) in the obese patients were not significantly (P greater than 0.10) different from free T3 (4.6 pmol/l) and total T3 (1.84 nmol/l) in the normal persons. The risk of type II error (P beta) for overlooking a possible, true difference between obese and normal persons were estimated. If there is a difference in the mean value of free T3 then it is less than 0.5 pmol/l (P beta less than 0.05), corresponding to 12 per cent of the mean value of free T3 in the normal persons. If there is a difference in the mean value of total T3 then it is less than 0.21 nmol/l (P beta less than 0.01) corresponding to 11 per cent of the mean value of total T3 in the normal persons. The caloric and carbohydrate intakes were estimated in 17 of the obese patients and showed no significant correlations with serum free or total T3. The study indicates that the thyroid function per se is normal in obesity and adapts to increasing body weight by enhanced production of thyroid hormones and thereby sustaining a normal serum concentration of free T3.

Consecutive patients, between 18 and 54 years, suffering from morbid obesity (greater than or equal to 60 per cent overweight) are being randomized to either gastroplasty a.m. Gomez or to a very-low-calorie diet (341 kcal, 1.43 MJ) based on a high-value protein powder with an admixture of calcium, phosphate, sodium, chloride, and magnesium. Through a supplementary daily vitamin-mineral capsule and three tablets of potassium chloride the total regime complies with the 1980 RDA. After initial hospitalization, both groups are seen as out-patients. Twenty-eight patients have so far been studied and none has dropped out. Preliminary results show a substantial weight lose without significant differences between the groups.

Glomerular filtration rate (GFR) was measured in 16 obese women aged 28-48 years (overweight 65-110 per cent) and compared to GFR in 16 non-obese women of the same age and height. None of the women had signs of nephrourological disorders. GFR was determined from the total 51 Cr-EDTA plasma clearance measured by a simplified single-injection technique. In the obese women GFR (median value 129.0 ml/min) was significantly (P less than 0.002) increased by 24.6 per cent. The urinary excretion rate of 17-ketogenic steroids was increased in nine out of 14 obese women, but no correlation with GFR could be demonstrated. GFR in the obese women showed a significant positive correlation with the plasma cortisol concentration (rs = 0.77; P less than 0.01) and with the urinary excretion rate of free cortisol (rs = 0.78; P less than 0.01). Whether the correlation between the plasma cortisol concentration and the increased GFR in obese women is causal needs further investigation.

Blood pressure (BP) and arm circumference were measured in 44 normotensive and borderline hypertensive obese patients during treatment with either a very low calorie diet or diet supported with gastroplasty. The patients had reductions in sodium, energy, and carbohydrate intake. BP was determined with both a normal cuff (12-by-35 cm bladder) and a large cuff (15-by-43 cm bladder), using a random-zero sphygmomanometer. Both systolic and diastolic BP declined (p less than 0.005) (from 133 to 124 +/- 4 mmHg and from 87 to 81 +/- 3 mmHg (mean +/- SED), respectively), but reached a plateau after an average weight loss of 11 kg. No further reduction in BP was seen despite a maximal weight loss of 40 kg. At the same time arm circumference decreased from 36.4 to 30.5 cm. Moreover, the study showed that reductions in systolic and diastolic BP were closely associated with the pretreatment BP but not with the weight loss. The normal cuff overestimated the systolic BP by 8 +/- 4 mmHg and the diastolic BP by 6 +/- 3 mmHg (mean +/- SED) in patients with arm circumference of 35 cm and more.