Lipid accumulation in jejunal and colonic mucosa following chronic cholestyramine (Questran) feeding

The hypolipidemic agent, cholestyramine (Questran), when fed to rats inhibits intestinal absorption of cholesterol and triglycerides and causes significant epithelial cell damage in both small and large intestine. In this study, we report significant accumulation of lipids in the mucosal layer of both jejunum and colon in rats administered 2% cholestyramine for a four-week period, when compared to a control group maintained on regular chow. The total lipid increment with cholestyramine was 4.7-fold in the jejunum and 3.7-fold in the colon. The triglyceride fraction increased substantially in the small but not the large intestine. Relative phospholipid levels decreased in the treated jejunum but not in the colon. The biochemical data were reflected in morphological evidence of lipid-laden enterocytes obtained by light and transmission electron microscopy. Since cholestyramine has been shown to sequester 99.8% of micellar phospholipidin vitro, it is concluded that the presence of cholestyramine in the intestinal lumen may interefere with phospholipid availability for chylomicron synthesis and serosal lipid exit from the epithelium. This unusual deposition of lipid within the mucosal layer may also be correlated with the known cocarcinogenic effect of this resin in experimentally induced intestinal cancer.Supported by USDA grants 82CRCR 1071 and 82 CRCR 1001.     

Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy

Gastric emptying was studied with a double radioisotopic method in 12 patients with insulin-dependent diabetes mellitus complicated by autonomic neuropathy and in 22 control subjects. In the diabetics, the acute and chronic effects of oral domperidone on gastric emptying, symptoms of gastroparesis, and glycemic control were assessed. Gastric emptying of solid and liquid was slower in diabetics than controls (P<0.001). Acute administration of domperidone increased the rate of both solid and liquid emptying (P<0.005). Domperidone was most effective in those patients with the greatest delay in gastric emptying. After chronic administration (35–51 days), domperidone had no significant effect on solid emptying (P>0.05), but was still effective in increasing liquid emptying (P<0.025). Symptoms of gastroparesis were less after domperidone (P<0.001).Dr. M. Horowitz was supported by a grant from the National Health and Medical Research Council of Australia.     

Cellular Immune Functions, Endorphins, and Alcohol Consumption in Males

The effects of alcohol abuse on cellular immune functions were measured by various levels of alcohol use in adult men. Total lifelong abstainers were used as controls. Previous abusers, current abusers, and patients with alcoholic cirrhosis or pancreatitis were age-matched to controls. T-lymphocyte mitogenesis stimulated by phytohemagglutinin and concanavalin A was generally reduced in peripheral blood lymphocytes of current and previous alcohol consumers, although the decrease was not statistically significant. B-cell mitogenesis stimulated by pokeweed mitogen was not changed by previous alcohol consumption. The number of T-cells was not changed by either previous or current alcohol abuse. T-helper cells were significantly increased and T-suppressor cells increased only in the patients with alcoholic cirrhosis or pancreatitis. The percentage of T-lymphocytes with T-suppressor characteristics in controls was 27% while in alcoholic cirrhosis or pancreatitis subjects it was 16%. Plasma corticosteroid levels were significantly increased in people currently consuming alcohol (12.1 +/- 1.1 mg/dl) compared to controls (7.7 +/- 1.1). The corticosteroid levels were also higher in previous alcohol abusers although not statistically significant. Plasma endorphin levels were increased by severe alcohol abuse in the patients with cirrhosis or pancreatitis to 25.03 +/- 6.74 from 11.85 +/- 2.48 pg/ml in controls.     

Relationship between enteral glucose load and adaptive mucosal growth in the small bowel

Infusion of hyperosmolar glucose solutions into small bowel will prevent mucosal atrophy or stimulate mucosal growth in rats otherwise maintained on total parenteral nutrition (TPN). It is not certain whether this growth effect is related to the osmolarity of the solution or its total molecular load. Therefore, various concentrations of glucose and sodium salt solutions were studied for comparative effects on growth of small bowel mucosa. Male Sprague-Dawley rats (240 g) were maintained on TPN and infused continuously with either glucose or sodium chloride (2 and 0.6 ml/hr) or sodium sulfate (0.6 ml/hr) via a catheter placed in the mid-small intestine. Concentrations of infusion solutions ranged in osmotic pressure from 300 to 1500 mosmol/liter. Controls were TPN rats without infusion of any solution. Over a seven-day period, TPN rats receiving mid-gut infusions of 300 mosM saline gained 18.4 g in body weight. In TPN rats receiving mid-gut infusions of progressively greater concentrations of glucose, the additional total kilocalories per day resulted in greater body weight gain compared with the saline controls. After seven days, rats were killed, the small bowel removed, and divided into eight equal segments (segment 1, duodenum; segment 8, terminal ileum). Segment weight, mucosal weight, DNA, and protein concentration per segment were measured. Mid-gut infusions of 900 and 1500 mosM glucose solutions progressively increased mucosal mass in segments downstream from the site of infusion compared with 300 mosM glucose in water or 600 mosM glucose in saline which did not differ from any of the salt solutions or TPN alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Ethanol on Reproduction and Arterial Hypertension in Spontaneously Hypertensive and Normotensive Rats: a Preliminary Communication

Ethanol consumption and spontaneous (essential) hypertension are important fetal and maternal risk factors. Alone, they contribute to embryopathy (fetal alcohol syndrome) or maternal organ pathology and fetal loss in hypertensive pregnancies. Combined, the effects of ethanol consumption on the progress of a hypertensive pregnancy have not been adequately investigated. In the present study, groups of O-A strain genetic hypertensive (SHR: groups 1 and 2) and Wistar-Kyoto normotensive (WKY: groups 3 and 4) pregnant rats were given 20 ml/kg of distilled water by gavage to serve as controls [groups 1 (SHR) and 3 (WKY)] or 3.2 g/kg of ethanol [groups 2 (SHR) and 4 (WKY)] from days 6 to 15 of gestation. During acclimation, hypertension developed in SHR rats (WKY pressures were 105 to 114 mm Hg; SHR pressures were 137 to 148 mm Hg). From day 6 to 15 of gestation, ethanol-consuming rats (groups 2 and 4) had higher arterial pressures than controls (groups 1 and 3). Pregnant SHR rats given ethanol did not experience a prebirthing hypotension. On gestation day 20, most offspring (84%, group 2; 86%, group 4) of alcoholic dams were dead or malformed. Intrauterine growth retardation occurred in group 4. Hydrocephalus, microphthalmia, and mild hydronephrosis and hydroureter were common in live offspring of group 2 dams. Hydronephrosis and hydroureter were increased in group 4 pups. Variant cranial ossification was noted in group 2 and 4 pups. These preliminary data suggest an altered hypertensive response during pregnancy in alcohol-consuming rats and confirm the embryopathic effects of relatively high levels of ethanol consumed during the critical period of organogenesis in two additional strains of rats.     

Outcome of ankle arthrodesis in posttraumatic arthritis

Background:

Ankle arthrodesis is still a gold standard salvage procedure for the management of ankle arthritis. There are several functional and mechanical benefits of ankle arthrodesis, which make it a viable surgical procedure in the management of ankle arthritis. The functional outcomes following ankle arthrodesis are not very well known. The purpose of this study was to perform a clinical and radiographic evaluation of ankle arthrodesis in posttraumatic arthritis performed using Charnley''s compression device.

Materials and Methods:

Between January 2006 and December 2009 a functional assessment of 15 patients (10 males and 5 females) who had undergone ankle arthrodesis for posttraumatic arthritis and/or avascular necrosis (AVN) talus (n=6), malunited bimalleolar fracture (n=4), distal tibial plafond fractures (n=3), medial malleoli nonunion (n=2). All the patients were assessed clinically and radiologically after an average followup of 2 years 8 months (range 1–5.7 years).

Results:

All patients had sound ankylosis and no complications related to the surgery. Scoring the patients with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot scale, we found that 11 of the 15 had excellent results, two had good, and two showed fair results. They were all returned to their preinjury activities.

Conclusion:

We conclude that, the ankle arthrodesis can still be considered as a standard procedure in ankle arthritis. On the basis of these results, patients should be counseled that an ankle fusion will help to relieve pain and to improve overall function. Still, one should keep in mind that it is a salvage procedure that will cause persistent alterations in gait with a potential for deterioration due to the development of subtalar arthritis.     

Fear of Cancer Recurrence after Curative Pancreatectomy: A Cross-sectional Study in Survivors of Pancreatic and Periampullary Tumors

Background

Fear of disease recurrence is well documented among cancer survivors, but its significance among patients treated for solid pancreatic and periampullary neoplasms is unknown despite the known risk of recurrence associated with these tumors. We hypothesized that fear of cancer recurrence (FCR) represents a common source of psychosocial distress in this population and sought to characterize subgroups for whom FCR might represent a target for intervention to improve quality of life.

Methods

We conducted a cross-sectional study of FCR in patients who were disease-free after potentially curative pancreatectomy for ductal or periampullary adenocarcinoma or pancreatic neuroendocrine tumor. We assessed seven discrete dimensions of FCR using the Fear of Recurrence Inventory and evaluated quality of life and psychosocial distress using the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire and the Hospital Anxiety and Depression Scale.

Results

Of 354 eligible patients, 240 (68?%) participated in the study a median of 48?months after potentially curative pancreatectomy. An FCR severity score indicative of frequent fearful thoughts, emotional disturbance and functional impairment was identified in 37, 28, and 35?% of patients with pancreatic adenocarcinoma, nonpancreatic periampullary adenocarcinoma, and pancreatic neuroendocrine tumor, respectively. Anxiety (P?<?0.001) and low quality of life (P?=?0.028) were independently associated with a clinically significant level of FCR, but histopathologic diagnosis and clinicopathologic markers of prognosis were not.

Conclusions

FCR represents a significant concern for one-third of patients after curative surgery for a pancreatic or periampullary tumor, regardless of their actual likelihood of recurrence or disease-related death.     

Interferon‐gamma inhibits healing post scald burn injury

Impaired healing after severe burns remains a reason for prolonged hospitalization, opportunistic infections, and debilitating scarring. Interferon‐gamma (IFN‐γ) is an important immune regulator that has been shown to inhibit collagen synthesis by fibroblasts, resulting in delayed healing in incision wounds. To determine whether IFN‐γ plays similar roles in the healing process after severe burn, we induced scald injury in mice deficient or sufficient in IFN‐γ and examined local responses. In the absence of IFN‐γ, scalded areas healed faster. This was associated with attenuated local inflammatory responses, enhanced reepithelialization, increased proliferation of keratinocytes in reepithelialized leading edges, and up‐regulation of growth factors in burned skin areas. Furthermore, angiogenesis and myofibroblast formation commenced and terminated earlier in IFN‐γ^–/– mice compared with wild type (WT) controls. Our observations demonstrate that inhibition of IFN‐γ results in accelerated healing after burn injury by dampening excessive inflammation and facilitating reepithelialization, collagen deposition, and wound contraction.