Different effects of vertical banded gastroplasty and Roux-en-Y gastric bypass on meal inhibition of ghrelin secretion in morbidly obese patients.

A decrease in ghrelin plasma levels in morbidly obese patients subjected to bariatric surgery has been considered to help increase body weight loss. Contradictory results have been described after Roux-en-Y gastric bypass (RYGBP), and no study to date has compared RYGBP and vertical banded gastroplasty (VBG), the two main operations performed in the United States. We investigated the effects of RYGBP (10 patients) and VBG (12 patients) on basal and postmeal ghrelin plasma levels in 22 morbidly obese patients (20 F and 2 M), mean age 42.1 +/- 3.7 years, mean weight 115 +/- 3.9 kg, mean body mass index (BMI) 43.5 +/- 1.7. Before surgery and after a 20% reduction in BMI, ghrelin concentrations (pg/mL; radioimmunoassay [RIA], DRG Diagnostics, Germany) were measured in all patients 45 min before and for 3 h after a standard liquid meal (Osmolite RTH solution, 500 mL, 504 kcal). The results were expressed as mean +/- SD. Differences between times and groups were evaluated by Student's t-test and one-way analysis of variance (ANOVA). We found that basal ghrelin plasma levels were reduced after RYGBP (to 73.1 +/- 6 pg/mL, p < .05) but increased after VBG (to 172 +/- 26 pg/mL, p < .0009). After a standard liquid meal, ghrelin plasma levels decreased significantly over 1 h in VBG patients, whereas they remained unchanged in RYGBP patients. Since these results were obtained under the same metabolic and anthropometric conditions, we conclude that RYGBP acts through permanent inhibition of ghrelin secretion, whereas VBG merely restores the mechanisms of ghrelin regulation by nutrients.

Vertical banded gastroplasty modifies plasma ghrelin secretion in obese patients.

BACKGROUND: Restrictive bariatric surgery causes weight loss through substantial decline of appetite with satiety after meals. Reduction of plasma ghrelin levels after Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding could contribute to these effects, although contradictory results have been reported. The only restrictive operation still not yet investigated is vertical banded gastroplasty (VBG). We studied the effects of VBG on basal plasma ghrelin levels and meal-mediated inhibition. METHODS: 12 morbidly obese patients, 11 female and 1 male, were studied before and after VBG, when the BMI fell by 20%. The control group consisted of 6 lean volunteers. Active ghrelin was determined by RIA after overnight fasting and after the administration of a liquid meal. RESULTS: Obese patients preoperatively had significantly lower basal plasma ghrelin levels than lean volunteers, and the meal did not inhibit ghrelin secretion. After VBG and 20% BMI loss, basal plasma ghrelin levels increased and the reduction caused by a meal recovered. CONCLUSIONS: Weight loss caused by VBG is associated with higher plasma ghrelin levels in obese patients. The operation restores the normal adaptation of the A- cells of the stomach to a meal.

Metastatic melanoma of the gallbladder.

A 38-year-old man arrived at our clinic with symptoms and investigation results (U.S. scan and MR) suggestive of acute calculous cholecystitis. He gave a past history of excision of a stage I melanoma of the shoulder. Metastatic disease was suspected following measurement of CA 19.9 levels and the CT scan. The patient underwent laparotomy and cholecystectomy; pathological examination confirmed the presence of a malignant melanoma metastatic lesion of the gallbladder.

The mechanisms of blood vessel closure in humans by the application of ultrasonic energy.

BACKGROUND: The use of the ultrasonically activated scalpel (UAS) for vessel closure has attained widespread acceptance in many surgical fields. The aim of our study was to investigate the electron microscopic changes to the blood vessels after the application of UAS. METHODS: We collected 10 arterial and 10 venous segments from vessels that had previously been closed by UAS during abdominal operations. The samples were then prepared for ultramicroscopic analysis. Pathological changes in the lumen and the three wall layers of the blood vessel were examined under scanning and transmission electron microscopy. RESULTS: All of the vessel segments showed similar changes: the presence of a blood clot, endothelial cell condensation, coagulative necrosis of the wall, and charring of the vessel at its tip. The edge of the cut vessel were closed by the coagulation bond, which was tied up by collagen fibrils escaped from denaturation. CONCLUSION: When ultrasonic energy is applied to tissues, it changes their structure so as to make a new extracellular matrix.

Effects of warfarin on thrombosis of the jugular veins of rabbits induced by prolonged stasis.

We have studied the effects of warfarin pretreatment on blood coagulation tests, thrombosis and endothelial damage in the rabbit after 2 h of subsequent venous stasis. We found that 3 mg/kg warfarin significantly modified the results of prothrombin time, activated partial thromboplastin time and ProComplex tests. The incidence of thrombosis was not reduced by warfarin, but the weight of the thrombi were inversely related to the effects of the drug on blood coagulation. The endothelial cells showed some degree of damage. In conclusion, warfarin neither prevents endothelial damage nor reduces the incidence of thrombosis after venous stasis, but retards the growth of thrombi.

Paradoxical effects of intra-arterial administration of basic fibroblast growth factor on inflammatory angiogenesis in rats.

The authors studied the effects of basic fibroblast growth factor (b-FGF) on inflammatory angiogenesis in rats. In the corneal cauterization model b-FGF was given intra-arterially (i.a.) (carotid) and in the mesenteric window angiogenesis model, topically (i.e., intraperitoneally (i.p.)). The corneal cauterization was done under anaesthesia by topical application of silver nitrate. Mesenteric window angiogenesis was induced by injection of saline or b-FGF for four days. There were the same two groups of treatment in both models b-FGF 2.5 micrograms/kg/day or saline 1.2-5 ml/kg/day. The area of neovessels and the number of polymorphonuclear cells/field were considered for the corneal angiogenesis, the total length of neovessels was measured for the mesenteric window angiogenesis. The results were expressed as mean values (s.d.). When given i.a., b-FGF significantly reduced the number of polymorphonuclear cells three days after corneal cauterization (from 107 +/- 27 to 41.8 +/- 26, p < 0.01) and inhibited the area covered by neovessels (30 +/- 7.7% vs 51 +/- 20%, p < 0.01) after five days. In contrast, given through the extracellular space, it significantly stimulated the length of mesenteric window microvessels (169 +/- 60 mm vs 90 +/- 31 mm, p < 0.05). These results suggest that b-FGF stimulates inflammatory angiogenesis through interaction with extracellular matrix components, but inhibits it directly when given intra-arterially.

The effects of L-sulpiride on reflux oesophagitis.

Prokinetic drugs are commonly used for treatment of reflux oesophagitis. Although much data has been collected in clinical trials, their therapeutic effects are still uncertain. In this study the effects of L-sulpiride, if any, were examined when used to treat reflux oesophagitis in thirty patients. The patients were divided into two groups: a control group and a group given 25 mg t.i.v./day, p.o. of L-sulpiride for 30 days. They were treated as outpatients and had endoscopic, histological and ultrastructural examinations on the 30th and 60th days of treatment. It was found that the symptoms of patients with reflux oesophagitis were alleviated and the endoscopic and ultrastructural lesions of patients with minor oesophagitis were also decreased. In other patients, symptoms improved without resolution of the lesions. The authors conclude, therefore, that L-sulpiride would be appropriate treatment for Grade I cases.

Prevention and early diagnosis of cancer in the rectal stump of ulcerative colitis patients after colectomy and topical treatment.

Ulcerative colitis with malignant degeneration and dysplasia can be a precancerous lesion. Therefore, it is necessary to prevent or, at least to diagnose as early as possible any development toward neoplasia in the colon or rectum of the colitis patients. The only reliable guide for a risk of malignant tissue degeneration is dysplasia of the mucosa. A group of 31 patients was studied after total colectomy with ileorectal anastomosis and subsequent topical treatment with enemas containing sulphasalazine and corticosteroids. Two of these patients had mild rectal dysplasia before surgery, seen in a biopsy specimen obtained endoscopically. All the patients were followed for a long time after surgery, with endoscopy and microscopic and ultrastructural observation of rectal biopsy material taken from different sites in the mucosa, both from areas that looked dysplastic by endoscopy and from those that appeared normal. The two patients with presurgical dysplasia, when examined later, one 12 months and one 18 months after surgery, had no rectal dysplasia; the mucosal covering was moderately complete and the anastomosis was functioning. It is considered that to prevent development of cancer in the rectal stump, colectomy should always be followed by regular topical treatment and there should be a check-up at short intervals for early diagnosis of any premalignant areas that might develop. Regression of such lesion was observed to lesser degrees after continuous treatment with the topical medication.

[Acute hepatic failure and renal damage. Experimental and clinical studies]. / Insufficienza epatica acuta e danno renale. Rilievi sperimentali e clinici.

Renal damage in acute hepatic failure induced in the pig by means of an hepatic state, temporary or permanent devascularisation Amanita phalloides poisoning or orthotopic liver transplant proved of slight degree, particularly in animals treated with replacement therapy. In the cases of animals that died in acute hepatic coma, on the other hand, renal cortex ischaemia and marked medullary congestion were constant. Histologically, the damage consisted of slight tubular nephrosis; this was more apparent in the proximal tubules. Evaluation of renal damage in 38 patients with acute hepatic failure was more complicated owing to the variety of clinical conditions (level of coma, hypovolaemia, intensive care and hepatic assistance). Nevertheless, a clear relation was established between the degree of liver damage and blood creatinine and creatinine clearance values. All patients who died presented liver cell necrosis of over 75%, blood creatinine values of more than 2 mg/100 ml, and less than 50 ml/min clearance. Tubular nephrosis was the predominant lesion. It appeared that renal damage was primarily pre-renal. No signs of a true hepatorenal syndrome could be made out.

Transscleral contact cyclophotocoagulation with Nd:YAG laser CW: experimental study on rabbit eyes.

The authors suggest a new type of transscleral cyclophotocoagulation by using the Nd:YAG laser. This was done by bringing fibre optics into contact with the sclera. The study illustrates the macroscopic, histologic and scanning electron microscopic changes produced on the ciliary body of rabbit eyes with this technique. The actual possibility and the future prospect of applying this method to the human eye still remain to be investigated.

Pouch ileitis in excluded reservoir: an unusual complication of restorative proctocolectomy for ulcerative colitis.

One case of pouch ileitis after restorative proctocolectomy for ulcerative colitis is described. Diagnosis was made by endoscopy, histology and electron microscopy. The most prominent feature was intense inflammation of the mucosa and submucosa, with atrophy of the villi, and colonic metaplasia, occurring before closure of the loop ileostomy. The patient improved after a course of metronidazole therapy, but ileostomy closure was postponed. It appears that the ileum mucosa of patients with ulcerative colitis is highly prone to the development of inflammation and careful, regular follow-up is recommended.

Topical treatment of experimental skin lesions in rats: macroscopic, microscopic and scanning electron-microscopic evaluation of the healing process.

The effects of the topical antiseptic agents mercurochrome and silver nitrate and of sodium hyaluronate on the process of wound healing were assessed by macroscopic examination, light microscopy histology, electron microscopy and scanning electron microscopy of wounds made by cutting or by abrasion of the skin of rats. It was found that wounds treated with hyaluronic acid underwent longer periods of inflammation (proportional to the presence of mastocytes) and greater amounts of collagen deposition than wounds that were either untreated controls or treated with silver nitrate or mercurochrome, but this did not impede the formation in the early stages of healing of bridges of fibrin between the edges of the wounds.

Unusual technical procedures in reconstructive urological surgery.

Three successful technical procedures for the correction of complex defects of the urinary excretory pathway and the renal vessels are described. The authors emphasize their original technique which allowed kidney preservation and yielded good long-term results. They suggest that this conservative approach be used in more patients to avoid unnecessary nephrectomies.

The role of mast cells in wound healing.

Mast cells are known to participate in three phases of wound healing: the inflammatory reaction, angiogenesis and extracellular-matrix reabsorption. The inflammatory reaction is mediated by released histamine and arachidonic acid metabolites. Compound 48/80 and disodium-cromoglycate are both able to increase skin breaking strength shortly after wounding. Under light and electron microscopy we found that small, granule-poor, irregular mast cells (MLMC) accumulate in the wound. This suggests that the small MLMC (mucosal-like mast cells) migrate into the skin during wound healing, and that both CTMC (connective-tissue mast cells) and MLMC are involved in tissue repair. Moreover, there is some evidence that mast cells participate in angiogenesis, since heparin is able to stimulate endothelial-cell migration and proliferation in vitro, and protamine to inhibit these processes and also angiogenesis in vivo. When the effect of protamine on wound breaking strength was examined, we encountered a decrease which was not prevented by heparin administration. Further studies are needed to demonstrate that protamine is specifically involved in inhibiting heparin-mediated angiogenesis in wounded tissue. Finally, mast cells may play a role in the extracellular matrix remodelling, on the basis of in-vitro experiments (but there are still no in-vivo data).

Differential diagnosis of Crohn's disease of the colon from ulcerative colitis: ultrastructure study with the scanning electron microscope.

Mucosal biopsies from patients with Crohn's disease and with ulcerative colitis were studied by scanning electron microscopy. Important abnormalities of the mucosal surface were found in both diseases. For Crohn's disease, the characteristic abnormality was loss of the regularity of the polygonal units, but with preservation of the mucosal integrity and of the normal mucosal design. For ulcerative colitis, the abnormalities were disorganization of the cells, signs of sloughing, and superficial erosions. Patients with Crohn's disease always had a significantly increased number of muciparous cells, while those with ulcerative colitis had obvious signs of decreased mucus production. The lesions of ulcerative colitis could be seen under the scanning electron microscope in mucosal areas that appeared normal endoscopically. We feel therefore that scanning electron microscopy of biopsy specimens from patients with inflammatory bowel diseases can be of great help in differential diagnosis.

The effects of oxygen free radicals on wound healing.

We have examined the effects of oxygen free radicals, generated by xenobiotics administration, ischaemia-reperfusion or sepsis, on the healing of skin or intestinal wounds in rats. We found that 5 days after operation there was a significant decrease in the wound breaking strength in rats treated with phenazine methosulfate, zymosan, ischaemia-reperfusion or retroperitoneal infection. These changes were specifically prevented by administration of superoxide-dismutase (SOD), aprotinin and (in some models) allopurinol. On the contrary, none of these measures was effective when a local trauma caused the decrease in breaking strength. Our results suggest that oxygen free radicals mediate the inhibition of wound healing following ischaemia-reperfusion and sepsis.

Prostaglandin cytoprotection in man: effectiveness of rosaprostol.

We studied the effect of a new prostaglandin analogue, 9-hydroxy-19,20-bis-norprostanoic acid (rosaprostol), on the duodenal mucosa of humans after administration of 40% ethanol. Eighteen healthy volunteers entered the study, which followed a blind cross-over design. At time 0 all the volunteers received rosaprostol or placebo; 5 minutes later, 40% ethanol (50 ml dose) was given. The mucosa was examined for lesions 3, 60 and 180 min later under endoscopy, light and scanning microscopy. It was found that: (i) 40% ethanol damaged the duodenum, with blood extravasation, inflammation and necrosis of the mucosa, (ii) rosaprostol significantly protected the mucosa 3 min after 40% ethanol, and (iii) the damage became worse after 3 h when placebo was given, whereas it was reduced after 1 h when PG was administered. The results suggest that PGs not only protect the mucosa against ethanol damage, but also stimulate its recovery.

Hyaluronic acid prevents oxygen free-radical damage to granulation tissue: a study in rats.

Oxygen free-radicals are known to impair wound healing after ischaemia-reperfusion or polymorphonuclear cell stimulation. Furthermore, they reduce the breaking strength of all recent wounds and might be a cause of wound leakage. This study was performed to evaluate whether or not hyaluronic acid can reduce the risk of wound impairment caused by free-radicals, in rats with abdominal sepsis, polymorphonuclear cell stimulation or cytochrome C function derangement produced by xenobiotics. Male Sprague-Dawley rats with open wounds received phenazine methosulfate or zimosan, or had abdominal sepsis to induce oxygen free-radical generation. There were three groups of treatment: hyaluronic acid cream, hyaluronic acid ethyl ester gel, and placebo. The reduction in wound size was measured from the 1st to the 11th postoperative day; biopsies were taken for histological evaluation. Every other day, a gentle debridement was performed in all the groups of animals. We found that hyaluronic acid and its ethyl ester derivative significantly improved the wound healing of rats subjected to an increased generation of oxygen free-radicals. It remains to be established whether or not hyaluronic acid acts as a scavenger of free-radicals.

Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing.

Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.