Conjunctival polyploid cells and donor-derived myofibroblasts in ocular GvHD.

After allogeneic hematopoietic stem cell transplantation (allo-SCT), ocular GvHD is a common complication, typical symptoms being dry eye syndrome with features of fibrosis. In this study, we have identified and quantified two cell types-myofibroblasts (MFB) and polyploid (PP) cells-in the conjunctival surface of allo-SCT patients (pts) and have explored their kinetics and association with local and systemic GvHD. Results are compared with control groups of (a) pretransplant samples from allo-SCT patients, (b) recipients of autologous transplantation (auto-SCT) and (c) healthy controls. Imprint cytologies were obtained by pressing the conjunctival surface with a sterile, non-abrasive cellulose acetate filter (Millipore). After retraction, typically a monolayer of the outermost cells of the epithelium were retrieved. MFB were identified by immunofluorescent (IF) staining for alpha-smooth muscle protein. PP cells were detected by aberrant chromosome content analyzed via X/Y-FISH (X/Y fluorescence in situ hybridization). In female pts with a male donor (MF group), donor genotype were identified by sex chromosome detection using FISH methodology. IF and FISH methods were applied in situ on the same filter, and amounts of MFB and PP cells are expressed as the percentage of all cells on the filter. In all, 70 samples from 46 pts were obtained 1-122 months after allo-SCT. The total MFB density (MFB(TOT)) was higher in allo-SCT pts compared with healthy individuals and auto-SCT pts and increased by time after transplantation (P<0.001). In MF recipients, this increase proved to be due to a significant (P<0.001) and gradual elevation of donor-derived MFB (MFB(XY)), whereas recipient-derived MFB (MFB(XX)) did not vary over time. Clinical ocular GvHD correlated with MFB(XY)/MFB(TOT) ratio (P=0.034), whereas no association between MFB(TOT) or MFB(XY) systemic GvHD was observed. In the MF group (n=25), both MFB(XY) and MFB(XX) were detected on 28 of the 37 imprints (76%). In pts >36 months post transplant, on 11/12 imprints, a median of 9.4% (1.4-39%) MFB(XY) and 3.6% (0-11%) MFB(XX) was found. In one patient, 1.6% MFB(XY) were detected at 3 weeks post transplant. PP cells (6-24n), exclusively of recipient origin, were found to a median of 0.6% (0-37%). The PP cell density differed significantly (P<0.001) between time intervals, with a maximum 8.9% (0-35%) of all cells at 3-12 months. No correlation between PP cells and GvHD (ocular or systemic) was observed. The MFB has been indicated as a culprit in chronic inflammation and fibrosis. The observation that MFB(XY)/MFB(TOT) ratio correlated with ocular GvHD suggests a role of donor MFB in GvHD pathogenesis. The constant finding of recipient-derived MFB(XX) cells many years after transplant in pts with 100% donor hematopoiesis indicates that there is a non-hematopoietic differentiation route to MFB. The origin and role of PP cells after allo-SCT remains obscure.

Vertical Banded Gastroplasty with Adjustable Silicone Band: Preliminary Experience.

A series of ten patients operated on with vertical banded gastroplasty (VBG) with an adjustable silicone band at the outlet is presented. The loss of body weight and complication rate is evaluated. Preoperative mean excess overweight of the patients was 94% and mean BMI was 42.6. The loss of body weight at one year's follow-up was 38 kg or 59% of excess weight. Complications were one case of infection at the subcutaneous injection port and one case of a nonfatal pulmonary embolus. The results so far are thus comparable with VBG with a conventional fixed band, but the adjustable band actually simplifies the operative procedure since no exact calibration of the collar size is necessary at the time of surgery and should diminish the need for reoperations due to misalignment of collar size. The possibility of better weight control in the long-term perspective remains to be proven.

Gastric Banding for Morbid Obesity: Initial Experience with a New Adjustable Band.

A new adjustable gastric band was developed, consisting of a silicone balloon connected to a subcutaneous port In a closed system. The stoma diameter can be regulated within an extensive range (0-40 mm). The diameter is adjusted individually for each patient and weight loss can therefore be controlled and optimized. We evaluated the application of this new gastric banding procedure in terms of technical feasibility, complication rate and weight loss, and also the relationship between weight loss and pouch volume. Between January 1987 and April 1990 two preliminary studies of 18 and 24 patients respectively were carried out. In the first group there were technical problems resulting in insufficient weight loss. We therefore changed the procedure. In the second group the system thereafter worked as expected. In the second group mean preoperative weight was 132 kg, mean excess weight 60 kg, and mean BMI 45. The mean follow-up was in 21 months. At follow-up mean weight was 91 kg, mean weight loss 41 kg, and mean BMI 31. The mean postoperative stay was 6.0 days. Pouch volume and stoma diameter were followed by regular ondoscopy. There was a distinct relationship between pouch volume and weight loss-the smaller the volume the greater the weight loss.

A Gastric Band with Adjustable Inner Diameter for Obesity Surgery: Preliminary Studies.

Gastric banding for morbid obesity is theoretically an attractive method, since it is easily reversible, does not require opening of the stomach or intestines, and is associated with a very low surgical risk. The disadvantage is the high rate of reoperation because of the difficulty to obtain an optimal stoma diameter. This led us to develop a new gastric balloon band in which it is possible to regulate the inner diameter between 0 and 40 mm. In this study of the technical properties, we have investigated the inner pressure of the band during filling, the breaking point of the balloon when overfilling, the strength of the band and finally the degree of diffusion through the system. We found that there is no pressure with filling up to 10 ml. The band is thus a low pressure system. It can be filled with five times its normal volume before breaking. A pressure of 300 mmHg can be applied inside the system without breaking it. Finally, when the system was filled with soya oil, there was no detectable diffusion through the system in a one-year trial. These findings are consistent with our preset specifications. Clinical trials have therefore been started.

Why the Operation I Prefer is Adjustable Gastric Banding.

The author discusses why he performs adjustable gastric banding. Advantages cited are simplicity, and ability to control weight loss by adjusting stomal diameter

Meal-induced thermogenesis in obese patients before and after weight reduction.

The purpose of this study was to find out whether human obesity is associated with a diminished meal-induced thermogenesis and, if so, to what extent this response is influenced by weight reduction. Ten obese subjects (body mass index 42 +/- 2) and 10 age- and sex-matched non-obese volunteers were studied with continuous indirect calorimetry in the basal state and after the ingestion of a standardized test meal. Six obese subjects (body mass index 44 +/- 2) were examined on two occasions, once before and once after gastric banding and an average weight reduction of 18 +/- 3 kg. Basal oxygen uptake and energy expenditure were 30% (P less than 0.001) greater in the obese subjects compared to non-obese controls. After the meal, pulmonary oxygen uptake and energy expenditure increased rapidly and reached a relatively constant level after 60 min; for pulmonary oxygen uptake the average rise above basal was less in the obese (17.7 +/- 1.6%) than the non-obese (27.8 +/- 1.9%, P less than 0.001); the increase in energy expenditure was 18.5 +/- 1.7% in obese and 30.8 +/- 2.1% in non-obese subjects (P less than 0.001). After weight reduction, oxygen uptake and energy expenditure in the basal state were 20% lower (P less than 0.05) than before weight reduction. The average post-prandial increase in oxygen uptake was greater after weight reduction (24.8 +/- 2.0%) than before (16.7 +/- 1.6%, P less than 0.001). Corresponding values for energy expenditure were 27.2 +/- 2.2 and 18.2 +/- 2.2% (P less than 0.001). It is concluded that: (1) the thermogenic response to a mixed meal is lower in obese compared to non-obese individuals; and, (2) this impaired response is partly normalized after weight reduction. These findings suggest that a diminished meal-induced thermogenesis is a secondary phenomenon rather than a primary pathogenic factor in human obesity.

Neurotensin-like immunoreactivity in plasma after fat intake in normal and obese subjects and after jejunoileal bypass.

The plasma concentration of neurotensin-like immunoreactivity (p-NTLI) was measured after oral intake of fat in (a) healthy non-obese volunteers, (b) grossly obese but otherwise healthy persons, and (c) patients who had undergone jejunoileal bypass because of gross obesity. In addition, p-NTLI was measured after intravenous infusion of fat in healthy non-obese volunteers. Basal p-NTLI levels were significantly higher in the patients with bypass than in the obese group. After oral intake of fat, the increase in p-NTLI was much greater and more sustained in the bypass group than in the two other groups. The type of bypass (end-to-end, end-to-side or biliointestinal) and the time after the operation did not correlate with the p-NTLI response. Intravenous infusion of fat evoked no increase in p-NTLI. To produce a rise in p-NTLI level, therefore, the fat does not have to be absorbed and hematogenously distributed to the N-cells (neurotensin-storing cells). This observation may suggest that direct contact between chyme and the N-cells, or local neural or hormonal factors, are required to stimulate release of NTLI. The authors suggest that increase in the postprandial release of neurotensin may promote the diarrhoea after bypass operations, and possibly has other physiologic effects in such patients.

Experiences with antireflux valves in jejunoileal bypass surgery.

Intussusception valves were created in the small intestine of jejunoileal bypass-operated dogs and patients with the intention to prevent reflux of chyme into the excluded intestinal loop and thereby increase weight loss. In the dogs the valves were shown to withstand a pressure of at least 100 cm of water. All patients with end-to-side bypass were at X-ray examination found to have sufficient valves whereas only four of fourteen with end-to-end bypass, where the defunctionalized loop was implanted into the cecum, had tight valves. During five years of observation no significant difference in weight loss was seen between the patients with valves and control groups without valves. It is concluded that reflux of chyme only plays a minor role for weight loss after jejunoileal bypass for obesity.

The effect of clindamycin on the intestinal flora in patients with enteric hyperoxaluria.

Enteric hyperoxaluria is due to increased absorption of oxalate, especially in the colon. However, this mechanism is not fully understood. Little is also known about the composition of the intestinal flora in these patients. Eleven patients with hyperoxaluria (greater than 0.45 mmol/24 h) after jejunoileal bypass were therefore studied under surgical ward conditions for 5 days. The patients were maintained on a constant diet. During days 3, 4, and 5 clindamycin (Dalacina), 1.8 g/24 h, was given parenterally in three divided doses. All patients had hyperoxaluria, with a mean oxalate absorption of 0.94 +/- 0.09 mmol/24 h (+/- SEM). No significant disturbances in the colonic microflora were found. The degree of hyperoxaluria did not change during clindamycin administration, in spite of a significant decrease in the number of anaerobic bacteria. Our patients with enteric hyperoxaluria seem to have a normal colonic microflora. The degree of hyperoxaluria did not seem to be related to changes in the intestinal anaerobic flora.

A roentgenological study of the small intestine after different intestinal bypass operations for treatment of morbid obesity.

Twenty-nine patients who had undergone four different types of jejunoileal bypass for obesity were examined roentgenologically after ingestion of barium contrast. Functional intestinal length, blind loop reflux and speed of contrast through the small intestine were recorded. Weight loss was not correlated to any of the mentioned parameters or to operative method. Length of functioning intestine increased and speed of contrast decreased with time after surgery.

An oral amino acid loading test before and after intestinal bypass operation for morbid obesity.

Blood samples were taken from six overweight women after an overnight fast on three different occasions, before an jejunoileal bypass operation and 1 and 6 months after the operation. The preoperative levels of several plasma free amino acids were significantly elevated, e.g. leucine, isoleucine, valine, lysine, phenylalanine, tyrosine, proline and glutamic acid. One month after the operation all indispensable plasma amino acid concentrations had fallen, in particular the levels of the branched-chain amino acids (BCAA), lysine and tryptophan. Among the dispensable amino acids, plasma tyrosine, arginine and ornithine concentrations were significantly reduced. No further changes of significance were observed in samples taken 5 months later. A close correlation was observed between the plasma levels of retinol-binding protein (RBP) and thyroxine-binding prealbumin (TBPA). One month after the operation the levels of RBP and TBPA had fallen slightly in two subjects and substantially in one subject. A test diet, containing crystalline amino acids, glucose and fat emulsion was given before operation and twice after the operation. Plasma amino acid changes were studied for a period of 2 hours after the meal. The increases in plasma levels following the test meal were lower for many amino acids after the operation. A linear correlation was found between the postprandial increases in BCAA concentrations and the levels of RBP and TBPA. By using complete, carefully defined diets in loading tests, it should be possible to screen for glucose tolerance and amino acid and lipid malabsorption.

Magnesium deficiency following jejunoileal bypass operations for obesity.

Skeletal muscle biopsies, blood samples, and 24-hour urines, before and after magnesium infusions, were obtained from 12 patients who had undergone jejuno-ileal bypass surgery several years earlier, selected for probable magnesium deficiency on the basis of repeated hypomagnesemia. The patients retained significant amounts of the infused magnesium, and exhibited elevation of low skeletal muscle magnesium and potassium, with concomitant decreases of muscle sodium and chloride. These changes were accompanied by increased urinary calcium and sodium and decreased urinary phosphorus excretion.

Serum carotene, vitamin A, retinol-binding protein and lipoproteins before and after jejunoileal bypass surgery.

The plasma vitamin A and carotene transport in 45 obese patients was examined before and at various times after bypass surgery. The serum levels of lipoproteins, carotene, vitamin A and retinol-binding protein (RBP) were monitored and compared to those of healthy controls. LDL-cholesterol levels were decreased by 40 per cent (P less than 0.001) within the first year after surgery and remained low thereafter. The reduction of serum carotene (from a mean of 64 to 17 micrograms/dl) was rapid and constant. This change was observed already within 1-2 weeks post-surgery. The serum concentrations of carotene and LDL-cholesterol were highly correlated (r = 0.74). The concentrations of vitamin A and RBP were normal before the operation and remained so until 30 months after surgery, when slight reductions were observed compared to the control values [46 +/- 28 vs 66 +/- 11 micrograms/dl for vitamin A (P less than 0.01) and 32 +/- 8 vs 41 +/- 6 mg/l for RBP (P less than 0.01)]. No overt signs of vitamin A deficiency were observed. The mechanisms by which carotene (but not vitamin A) decreases so rapidly after bypass surgery cannot be explained by the decreased LDL levels.