Cardiovascular risk factors after bariatric surgery: Do patients gain more than expected from their substantial weight loss?

BACKGROUND: While it has been established that even limited weight loss (5-10%) improves obesity-associated cardiovascular risk factors, it is not known if considerable weight loss following laparoscopic adjustable silicone gastric banding (LASGB) results in a cardiovascular risk profile that is comparable, worse, or even better than that of matched control subjects. METHODS: Cardiovascular risk factors were compared in three groups of 24 women each: an index group that had lost considerable weight following LASGB for morbid obesity (BMI>40 kg/m(2)), a control group with the same BMI that the index group achieved after weight loss, and a pre-weight loss group of women with a BMI above 40 kg/m(2). Anthropometric measures, fasting serum glucose, insulin, lipids, C-reactive protein, and homocysteine levels were determined and insulin sensitivity was estimated using a homeostasis model assessment index (HOMA-IR). RESULTS: After bariatric surgery, the index group had a BMI of 32.0+/-0.8 kg/m(2). This resulted in a significantly better cardiovascular risk profile than that of the pre-weight loss group (BMI 42.8+/-0.6 kg/m(2)). Unexpectedly, after weight loss, the index group had significantly lower systolic blood pressure, fasting serum insulin, and HOMA-IR than the BMI-matched (32.8+/-0.9 kg/m(2)) control group. Although not significant, diastolic blood pressure, LDL-cholesterol, and CRP levels were also lower. CONCLUSION: Considerable weight loss following bariatric surgery leads to a greater improvement in cardiovascular risk factors than might be expected from the weight loss.

A double-blind, randomized comparison of omeprazole Multiple Unit Pellet System (MUPS) 20 mg, lansoprazole 30 mg and pantoprazole 40 mg in symptomatic reflux oesophagitis followed by 3 months of omeprazole MUPS maintenance treatment: a Dutch multicentre trial.

BACKGROUND: Proton pump inhibitors (PPIs) have proved to be effective in treating reflux oesophagitis. Until now, no study had compared the PPIs omeprazole Multiple Unit Pellet System (MUPS), lansoprazole and pantoprazole in patients with reflux oesophagitis. AIM: To compare omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg for treatment effect in symptomatic reflux oesophagitis. METHOD: Patients with grade I-IV symptomatic reflux oesophagitis were randomized to double-blind omeprazole 20 mg once morning, lansoprazole 30 mg o.m. or pantoprazole 40 mg o.m. Patient satisfaction and symptoms were evaluated after 4 and 8 weeks. Patients not satisfied after 8 weeks were treated for another 4 weeks with omeprazole 40 mg MUPS (open). Successful treatment was followed by 3 months' maintenance treatment with omeprazole MUPS 20 mg (patients satisfied after 4 or 8 weeks) or omeprazole MUPS 40 mg (patients satisfied after 12 weeks). RESULTS: On intention-to-treat (ITT) analysis (n = 461) at 4 and 8 weeks, respectively, 84% and 87% (omeprazole MUPS), 78% and 81% (lansoprazole), and 84% and 89% (pantoprazole) were free of heartburn. Equivalence was found between omeprazole MUPS and pantoprazole (heartburn relief), but not with lansoprazole. Patient satisfaction after 4 and 8 weeks, respectively, was 79% and 89% (omeprazole MUPS), 76% and 86% (lansoprazole), and 79% and 91% (pantoprazole). Patient satisfaction was similar in all treatment groups. During maintenance, 87% in the omeprazole MUPS 20 mg group and 81% in the omeprazole MUPS 40 mg group were satisfied after 3 months. CONCLUSIONS: Omeprazole MUPS 20 mg and pantoprazole 40 mg have equivalent efficacy in the treatment of reflux oesophagitis. Based on patient satisfaction, omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg are equally effective.

Assessment of sleep complaints and sleep-disordered breathing in a consecutive series of obese patients.

BACKGROUND/OBJECTIVE: The prevalence of sleep-related complaints (SRC) and the frequency of sleep-disordered breathing (SDB) in obese patients has not been studied extensively. We investigated SRC and SDB in a group of obese persons as part of a preoperative workup for weight reduction (bariatric) surgery. METHODS: All consecutive patients attending a weight-loss clinic for evaluation for bariatric surgery were asked to complete a questionnaire. The questionnaire consisted of a section on SRC and a validated general sleep questionnaire (Sleep Wake Experience List). The patients underwent sleep studies in which an Edentrace recorder registered heart rate, chest wall movements by impedance, airflow and oxygen saturation. RESULTS: Fifty-one patients (14 men, 37 women) were evaluated. Mean body mass index (BMI) was 45 kg/m2 (range 33-61). Eighteen patients (35%) demonstrated SDB, defined as (a) an apnea/hypopnea index 5, and/or (b) more than 2% of registration time with an oxygen saturation below 90%. There was no difference between these 18 patients and patients who did not exhibit SDB in age, sex, BMI or SRC. Seven patients had SDB of a severity warranting closer investigation and perioperative monitoring. CONCLUSION: Both SRC and SDB are common in obese patients. Limited nocturnal respiratory monitoring is indicated as part of the preoperative workup for weight reduction surgery.

Prevalence and severity of sleep disordered breathing in a group of morbidly obese patients.

BACKGROUND: Obesity may be complicated by sleep disordered breathing (SDB). The presence of SDB is associated with increased morbidity and mortality. Patient characteristics, pulmonary function tests and daytime arterial blood gas analyses may help to identify patients with SDB. These variables and the prevalence and severity of sleep disordered breathing were studied in a group morbidly obese patients. METHODS: Forty-eight patients, 19 men and 29 women who were referred to our clinic of internal medicine because of their obesity were included. Characteristics, pulmonary function tests and daytime arterial blood gas analyses of groups with different grades of SDB were compared. RESULTS: Male subjects had significantly more apnoeas/hypopnoeas per hour (AHI) (18.4 +/- 20.9 versus 4.8 +/- 9.4) with more desaturation, a lower mean saturation (92.6 +/- 4.1 versus 96.1 +/- 1.6) and a lower saturation nadir (73.8 +/- 12.0 versus 83.1 +/- 6.7). Five (26%) of the male subjects and none of the female subjects had severe SDB (AHI > or = 25). Subjects were divided into three groups according to the severity of their SDB: twenty-nine subjects (23 women and 6 men) with AHI < 5, 14 subjects (6 women and 8 men) with AHI > or = 5 and < 25 and 5 subjects, all men, with AHI > or = 25. Except for gender no significant differences were found between the three groups. CONCLUSION: Our study confirms the findings that morbidity obese men have SDB more frequently and more severely than obese women. Patient characteristics other than gender, pulmonary function tests and daytime blood gas analyses have no predictive value.

Onset of coeliac disease after a spontaneous miscarriage during a holiday in Australia: coincidence or causal relationship?

Diarrhoea contracted whilst travelling in a (sub)tropical country often has an infectious cause. However, dietary changes can also be of importance. We describe the case of a 28-year-old woman, who developed severe coeliac disease during a trip in the Australian outback. The nutritional history revealed that the patient's diet contained more wheat products during her trip than she was used to in Holland. Moreover, the onset of symptoms coincided with a spontaneous miscarriage of an 8-week-old embryo. This correlation has been described in several case reports in the literature. However, the pathophysiologic mechanism behind this correlation is unknown. Some speculative mechanisms are proposed here. Further investigations into this relationship could increase our understanding of the immunopathogenesis of coeliac disease.

Cisapride in functional dyspepsia in general practice. A placebo-controlled, randomized, double-blind study.

BACKGROUND: Functional dyspepsia is recognized as a common disorder in clinical practice. The aim of this study was to determine the efficacy and adverse effects of cisapride compared to a placebo in patients from a general practice with functional dyspepsia (FD). Secondly we investigated whether Helicobacter pylori-positive FD patients present with specific symptoms and determined the efficacy of cisapride for FD patients with H. pylori. METHODS: In a placebo-controlled double-blind study, patients were randomized to receive fixed doses of either cisapride (10 mg three times daily) or placebo. Symptoms were evaluated after 2 and 4 weeks of treatment. The selection of FD patients,collection of data, and evaluation of symptoms as well as adverse effects were performed by general practitioners. Dyspeptic patients were referred to the Gastroenterology Department in order to exclude ulcers, oesophagitis, pancreatitis and gallstones. Biopsies of gastric mucosa were taken for histological examination and H. pylori culture. PATIENTS: 121 patients entered this study (61 took cisapride, 60 placebo). There were 113 patients (56 cisapride, 57 placebo) available for analysis of the efficacy and 120 patients (61 cisapride, 59 placebo) for evaluation of adverse effects.In total 102 biopsies were tested for the presence of gastritis by histological examination. There were 30 H. pylori-positive cultures among 111 patients. RESULTS: After 4 weeks a statistically significant reduction in symptoms was found, but it was similar in the two groups. No symptoms specific for H. pylori-positive patients were found. There was not a significant difference in the response to cisapride between H. pylori-positive and H. pylori-negative patients. The difference in overall (63%) response in the cisapride group and the 44% response in the placebo group did not reach statistical significance. CONCLUSIONS: No significant difference was found between placebo and cisapride in the treatment of FD in general practice. H. pylori-positive patients did not present with specific symptoms nor did they exhibit a different response to cisapride.

[Bariatric surgery using an adjustable gastric band for morbid obesity: initial 30 patients in The Netherlands]. / Bariatrische chirurgie met een variabele maagband voor morbide obesitas: eerste 30 patiënten in Nederland.

OBJECTIVE: Early evaluation of efficacy and safety of Adjustable Silicone Gastric Banding (ASGB) in the treatment of morbid obesity. DESIGN: Descriptive. SETTING: Red Cross Hospital, Beverwijk, the Netherlands. METHOD: In the period September 1991-September 1993, 30 eligible patients (5 men and 25 women, median age 37 years (range 22-60), median excessive weight 63 kg (18-94), median body mass index (BMI) 43 kg/m2 (28-53)) were operated. A horizontal gastroplasty was performed resulting in a pouch of 25 ml and a new stomach outlet with a diameter of 12 mm. The volume of the band may be increased in order to diminish the diameter of the outlet according to clinical needs postoperatively. RESULTS: The follow-up was 10 months in 13 of the 30 patients. After 6 months median BMI was 33 kg/m2 (23-38) and median loss of excessive weight 53% (27-94), after 10 months these 28 kg/m2 (23-38) and 67% (27-98) respectively. No patients died perioperatively; 52 gastric band adjustments were necessary in 17 patients. Complications consisted of: band dislocation (1 patient), functional stenosis (2), gastric perforation (2) and wound infection (1). Four patients needed reoperation. CONCLUSION: In this short term follow-up ASGB gave a good weight reduction. Advantages of ASGB are the reversibility of the operation and the adjustable outlet.

Effect of cisapride on relapse of reflux oesophagitis, healed with an antisecretory drug.

Maintenance treatment with cisapride was evaluated in 298 patients in whom reflux oesophagitis had been healed with antisecretory drugs. Initially, 34% of the patients had grade-I oesophagitis, 33% had grade II, and 33% had grade III. The patients were treated with 20 mg cisapride twice daily or placebo for 6 months or until endoscopic relapse was shown if this occurred earlier. Survival analysis showed that cisapride significantly prolonged the time to endoscopic relapse in grade-I patients (P = 0.02). The intergroup difference in symptomatic relapse in all patients was also significant (P = 0.010). The effect of cisapride was less clearcut in grade II or III, and/or in patients healed with omeprazole. Factors associated with early relapse were placebo therapy, prior omeprazole therapy, duration of pre-trial symptomatic period, and initial endoscopic severity grade. Adverse experiences were limited; diarrhoea was reported by 9% of the cisapride patients.

[Scintigraphy using I 131 iodobenzylguanidine and malignant melanomas]. / Scintigrafie met behulp van joodbenzylguanidine I 131 en het maligne melanoom.

The successful use of iodine-131-meta-iodobenzylguanidine (I-131-MIBG) scintigraphy for diagnosis of phaeochromocytoma and neuroblastoma stimulated investigation into its diagnostic and therapeutic usefulness in other neural crest tumours. It appears that there is a difference in capacity to absorb I-131-MIBG between the different tumour types. In I-131-MIBG scintigraphy of carcinoids there are more false negative results in comparison with phaeochromocytomas and neuroblastomas. Melanoma, also a neural crest tumor, turned out to be false negative in 100% of the cases reported until 1989. The authors present a case of a malignant melanoma with metastases in liver and stomach, concentrating I-131-MIBG. Biochemical examination demonstrated that this particular tumour was metabolically very active. It is suggested that the I-131-MIBG-positive scintigram of the melanoma may be related to the level of metabolic activity. By biochemical screening in proven cases of malignant melanoma it may be possible to select cases in which I-131-MIBG scintigraphy is worthwhile with a view to therapeutic application of I-131-MIBG.

Effects of cisapride on constipation due to a neurological lesion.

Two patients with intractable constipation and an atonic bladder due to a partial spinal cord lesion and sacral nerve lesion are described. Treatment with cisapride (4 x 10 mg daily) was undertaken. After a few days the stool passed spontaneously. The effect was dose-dependent and has been maintained for at least 40 months. Normal bladder function was not achieved.

A reproducible model of acute hepatic failure by transient ischemia in the pig.

A model of transient acute hepatic failure has been developed in the pig. Three days after a functional end-to-side portacaval shunt was introduced, 15 ambulant animals underwent total liver ischemia for 4 to 6 h by the closure of a mechanical clamp surrounding the hepatic artery. Four of the eight animals subjected to 4 hr of ischemia survived. All but one of the animals undergoing 6 hr of hepatic ischemia developed grade 4 encephalopathy after 24 to 30 hr and died within 50 hr. Quantitative estimation of liver cell necrosis revealed less than 40% necrosis in the survivors, and approximately 62% (range 49-75%) in animals who died of hepatic coma. As far as the putative toxins are concerned, significant differences were found between animals undergoing 4 and those undergoing 6 hr of ischemia, especially in the plasma ammonia levels and the plasma ratios for tyrosine and phenylalanine. Plasma arginine levels had fallen to zero in both groups at 24 hr and only rose to preischemic values in animals who survived. This large animal model fulfills the accepted criteria of potential reversibility, reproducibility, and death due to hepatic failure.

Objective measurement of hepatic encephalopathy in pigs by means of spectral analysis and evoked responses.

Objective measurement of hepatic encephalopathy by means of spectral analysis of the electroencephalogram (EEG), visual-evoked potentials (VEP) and brainstem auditory-evoked potentials (BAEP) was studied in pigs with ischemic hepatic necrosis. The mean dominant frequency (MDF) and the relative power of the delta frequency band (% delta power) showed significant changes with increasing encephalographic grades of encephalopathy: MDF dropped from 7.0 +/- 0.5 (grade 0) to 2.7 +/- 0.3 Hz (grade 3 encephalopathy) and % delta power increased from 52 +/- 7 (grade 0) to 83 +/- 6% (grade 3). The patterns of the VEP in pigs corresponded to those of the human VEP. However, significant differences in either latency time of the peaks or the peak amplitude with increasing stages of hepatic encephalopathy could not be found. The BAEP registered for pigs were reproducible but also were not as useful as spectral analysis for grading hepatic encephalopathy.

Auxiliary transplantation of part of the liver improves survival and provides metabolic support in pigs with acute liver failure.

In pigs subtotal ischemic liver cell necrosis was induced 4 days after auxiliary transplantation of 60% of the liver of an MLC-compatible donor (ATPL group, n = 13). In control animals (n = 14) temporary liver ischemia was preceded by division of the hepatic ligaments and creation of an end-to-side portacaval shunt. In the ATPL group six animals died of gastric hemorrhage, intestinal strangulation, or sepsis. The remaining seven animals survived in excellent condition until sacrifice 26 days after the induction of liver ischemia. Excellent graft function was demonstrated by uptake and excretion of 99mTc-HIDA at cholescintigraphy, ammonia detoxification, synthesis of clotting factors and glucohomeostasis. EEG recordings in the animals that underwent transplantation did not change from preischemic levels. Evidence of hepatic regeneration was found in the transplanted livers but could not be demonstrated in the damaged host livers. The control animals died in coma within 72 hours. These results indicate that auxiliary transplantation of a partial liver provides metabolic support and improves survival in animals with induced acute liver failure.

In vivo experiments with powder charcoal haemoperfusion (filmadsorber) in a pig model of hepatic failure.

The filmadsorber, an experimental haemoperfusion column containing activated powder charcoal embedded in a colloidal film, has been tested in pigs with ischaemicnecrosis of the liver. Haemoperfusion with a flow of 200 ml/min was performed for a duration of 4 to 6 hours. Bile acid clearances varied between +/- 52 ml/min (1st hour) and +/- 23 ml/min (6th hour). Clearances for aromatic amino acids were initially even higher (phenylalanine 115, tyrosine 112 and methionine 46 ml/min). No ammonia was removed. Side-effects were minimal, although platelets fell 24 +/- 15%. We conclude that haemoperfusion with the filmadsorber is well tolerated and associated with high clearances for bile acids and some amino acids, particularly in the first hours of treatment.

Large-pore hemodialytic procedures in pigs with ischemic hepatic necrosis; a randomized study.

In order to define further the therapeutic role of hemodialytic procedures in acute hepatic failure, 20 pigs with ischemic hepatic necrosis underwent randomized hemodialysis against an electrolyte solution (n = 6), hemofiltration with re-infusion of an electrolyte solution (n = 5), control hemofiltration with re-infusion of autologous ultrafiltrate (n = 4) or no extracorporeal procedure at all (n = 5). Pigs on hemodialytic procedures survived significantly longer (51 +/- 11 hrs) than controls (36 +/- 8 hrs). There were no differences in the duration of survival between hemodialysis and hemofiltration, nor between controls undergoing and those not undergoing an extracorporeal procedure. Electroencephalograms showed more rapid (p less than 0.05) deterioration in control animals than in the treatment group. Putative toxins such as ammonia, glutamine, tyrosine, tryptophan, and methionine all decreased transiently in the treatment group; in the control group a continuous increase in the levels of the putative toxins was observed. Comparison of all pigs surviving 35 hrs or less (n = 6) and animals surviving more than 45 hrs (n = 7) showed that long-term survival was significantly associated with lower plasma ammonia and methionine concentrations and fewer abnormalities on the electroencephalogram 10 hrs after the start of extracorporeal procedures; moreover six of the 7 long-term survivors underwent hemodialysis or hemofiltration procedures. We conclude that hemodialytic procedures prolong survival in pigs with ischemic hepatic necrosis by slowing the development of encephalopathy; this effect of hemodialytic procedures may be mediated by the lowering of plasma ammonia and methionine levels.

Objective measurement of hepatic encephalopathy by means of automated EEG analysis.

Automated analysis of the electroencephalogram as an objective measurement of hepatic encephalopathy for the individual patient was investigated. The mean dominant frequency of patients with grades 0 and 1 hepatic encephalopathy was in the normal range (greater than or equal to 6.4 Hz); grade 1 hepatic encephalopathy, however, was characterized by abnormal relative power of theta activity of more than 35%. Twelve out of 34 patients with clinical grade 0 hepatic encephalopathy also had an elevated power of theta activity and probably therefore latent hepatic encephalopathy. Patients with grades 2, 3 and 4 hepatic encephalopathy had a low mean dominant frequency (less than 6.4 Hz) and could be identified by a biphasic power spectrum (theta and delta peaks, grade 2) or by a high power of delta activity (greater than or equal to 70%, grade 3-4). We conclude that automated EEG analysis based on the parameters mean dominant frequency and the relative powers of the delta and theta band is very suitable for objective classification of hepatic encephalopathy in individual patients.

Incidence of endotoxemia in pigs with ischemic hepatic necrosis treated by hemodialysis. Prevention of endotoxemia with lactulose.

The incidences of endotoxemia and bacteremia were evaluated in 30 pigs with ischemic hepatic necrosis treated by hemodialytic procedures. Prior to induction of hepatic ischemia, ten pigs underwent bowel cleansing by means of an oral dose of magnesium sulfate, and 20 received a combination of magnesium sulfate and lactulose. Endotoxemia and bacteremia seldom occurred during the development of hepatic encephalopathy, but the incidence of both increased markedly shortly before death. Pigs pretreated with magnesium sulfate and lactulose however did not develop preterminal endotoxemia. A significant relation between endotoxemia or bacteremia and survival was not found, irrespective of pretreatment with lactulose. Of the positive limulus tests, 67% were accompanied by a positive blood culture, while 42% of all positive blood cultures were associated with a positive limulus test. Dialysis with dialysates contaminated with endotoxins did not increase the risk of endotoxemia. It is concluded that in an animal model of ischemic hepatic necrosis (1) endotoxemia and bacteremia appear mainly in the preterminal stage, but do not influence the duration of survival significantly; (2) lactulose prevents endotoxemia and (3) dialytic procedures do not increase the risk of endotoxemia and bacteremia.

Comparison of large-pore membrane haemodialysis and cross-dialysis in acute hepatic insufficiency in pigs.

We studied the duration of survival and the removal of putative toxins in forty pigs with ischaemic hepatic necrosis, undergoing haemodialysis or cross-dialysis with a large-pore membrane. Ischaemic hepatic necrosis was induced in conscious animals by tightening a loop around the hepatic artery 3 days after construction of a portocaval shunt. Pigs treated by a dialysis procedure survived significantly longer (45.2 +/- 11.9 h) than controls (26.3 +/- 5.4 h). There was no difference between haemodialysis and cross-dialysis. Blood ammonia initially dropped significantly (P less than 0.05) more during haemodialysis (560 +/- 107 leads to 210 +/- 51 mumol/l) than during cross-dialysis (596 +/- 131 leads to 398 +/- 81 mumol/l) but it subsequently increased beyond initial values despite efficient removal during continuous dialysis. Removal of ammonia was greater during cross-dialysis than during haemodialysis, but haemodialysis was more effective in the removal of the ammonia precursors glutamine and urea. We conclude that dialysis procedures can prolong survival in pigs with ischaemic hepatic necrosis. The removal of ammonia-precursors is more effective in the prevention of hyperammonaemia than the removal of ammonia itself. Since dialysis cannot prevent progressive hyperammonaemia, control of excessive toxin production seems mandatory for effective hepatic support.