International spinal cord injury bowel function basic data set (Version 2.0).

STUDY DESIGN: International expert working group. OBJECTIVES: To revise the International Spinal Cord Injury (SCI) Bowel Function Basic Data Set as a standardized format for the collecting and reporting of a minimal amount of information on bowel function in clinical practice and research. SETTING: Working group appointed by the American Spinal injury association (ASIA) and the International Spinal Cord Society (ISCoS). METHODS: The draft prepared by the working group was reviewed by the International SCI Data Set Committee and later by members of the ISCoS Executive and Scientific Committees and the ASIA board. The revised data set was posted on the ASIA and ISCoS websites for 1 month to allow further comments and suggestions. Changes resulting from a Delphi process among experts in children with SCI were included. Members of ISCoS Executive and Scientific Committees and the ASIA board made a final review and approved the data set. RESULTS: The International SCI Bowel Function Basic Data Set (Version 2.0) consists of the following 16 items: date of data collection, gastrointestinal and anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, defecation method and bowel-care procedures, average time required for defecation, frequency of defecation, uneasiness, headache or perspiration during defecation, digital stimulation or evacuation of the anorectum, frequency of fecal incontinence, flatus incontinence, need to wear pad or plug, oral laxatives and prokinetics, anti-diarrheal agents, perianal problems, abdominal pain and discomfort and the neurogenic bowel dysfunction score. CONCLUSION: The International SCI Bowel Function Basic Data Set (Version 2.0) has been developed.

Greatly increased prevalence of esophageal dysmotility observed in persons with spinal cord injury.

The effects of spinal cord injury (SCI) on esophageal motility are largely unknown. Furthermore, due to the complete or partial loss of sensory innervation to the upper gastrointestinal tract, a symptom-based diagnosis of esophageal dysmotility is problematic in the SCI population. To determine the prevalence and characterize the type of motility disorders observed in persons with chronic SCI compared with that of able-bodied (AB) controls based on esophageal pressure topography isometrics acquired by high-resolution manometry and categorized by application of the Chicago Classification. High-resolution manometry of the esophagus was performed in 39 individuals: 14 AB, 12 with paraplegia (level of injury between T4-T12) and 13 with tetraplegia (level of injury between C5-C7). A catheter containing multiple pressure sensors arranged at 360° was introduced into the esophagi of subjects at a distance that allowed visualization of both the upper esophageal sphincters (UES) and lower esophageal sphincters (LES). After a period to acquire pressures at baseline, subjects were asked to perform 10 wet swallows with 5-mL boluses of isotonic saline while esophageal pressure and impedance were being recorded. No significant differences were noted for gender, age, or body mass index between AB and SCI groups. Twenty-one of 25 (84%) subjects with SCI had at least one motility abnormality: 12% with Type II achalasia, 4% with Type III achalasia, 20% with esophagogastric junction outflow obstruction, 4% with the hypercontractile esophagus, and 48% with peristaltic abnormalities (weak peristalsis with small or large defects or frequent failed peristalsis). In contrast, only 7% (1 out of 14) of the AB subjects had any type of esophageal motility disorder. Despite the lack of subjective complaints and clinical awareness, esophageal dysmotility appears to be a highly prevalent condition in persons with SCI. The use of new and improved techniques, as well as a more stringent classification system, permitted the identification of the presence of nonspecific motility disorders in almost all SCI subjects, including four individuals who were previously undiagnosed with achalasia. Future work in persons with SCI is required to clarify the clinical impact of this observation and to study potential associations between esophageal dysmotility, gastroesophageal reflux disease, and pulmonary function. An increased awareness of esophageal dysfunction in the SCI population may lead to the development of new clinical guidelines for the diagnosis, prevention, and treatment of these largely unrecognized disorders.

SmartPill technology provides safe and effective assessment of gastrointestinal function in persons with spinal cord injury.

STUDY DESIGN: Spinal cord injury (SCI) results in gastrointestinal (GI) complications, including gastroesophageal reflux disease and constipation, but much of the data is based on older technology. OBJECTIVE: GI transit times were determined in subjects with SCI using a new device called a SmartPill. Our principal goal was to assess whether this new technology can be applied in persons with SCI. METHODS: SCI and age- and gender-matched able-bodied (AB) control subjects not taking proton pump inhibitors were studied. Following an 8-h overnight fast, subjects consumed 120 g EggBeaters (60 kcal), two slices of white bread (120 kcal) and 30 g strawberry jam (74 kcal). A pH calibrated SmartPill capsule was swallowed with 8 ounces of water, after which subjects fasted for an additional 6 h prior to consuming an Ensure Plus nutrition shake (350 kcal). Subjects remained fasted for an additional 2 h, after which time they resumed their regular diets. RESULTS: Twenty subjects with SCI and 10 AB control subjects were studied. Data are expressed as mean±s.d. Comparing the group with SCI to the AB control group, gastric emptying time (GET), colonic transit time (CTT) and whole gut transit time (WGTT) were prolonged (GET: 10.6±7.2 vs 3.5±1.0 h, P<0.01; CTT: 52.3±42.9 vs 14.2±7.6 h, P=0.01; WGTT: 3.3±2.5 vs 1.0±0.7 days, P<0.01). No complications or side effects were reported. CONCLUSION: Our results indicate that the SmartPill technology is a safe, non-invasive assessment technique that provides valid diagnostic information in persons with SCI.

Genetic structure in large, continuous mammal populations: the example of brown bears in northwestern Eurasia.

Knowledge of population structure and genetic diversity and the spatio-temporal demographic processes affecting populations is crucial for effective wildlife preservation, yet these factors are still poorly understood for organisms with large continuous ranges. Available population genetic data reveal that widespread mammals have for the most part only been carefully studied at the local population scale, which is insufficient for understanding population processes at larger scales. Here, we provide data on population structure, genetic diversity and gene flow in a brown bear population inhabiting the large territory of northwestern Eurasia. Analysis of 17 microsatellite loci indicated significant population substructure, consisting of four genetic groups. While three genetic clusters were confined to small geographical areas-located in Estonia, southern Finland and Leningrad oblast, Russia-the fourth cluster spanned a very large area broadly falling between northern Finland and the Arkhangelsk and Kirov oblasts of Russia. Thus, the data indicate a complex pattern where a fraction of the population exhibits large-scale gene flow that is unparalleled by other wild mammals studied to date, while the remainder of the population appears to have been structured by a combination of demographic history and landscape barriers. These results based on nuclear data are generally in good agreement with evidence previously derived using mitochondrial markers, and taken together, these markers provide complementary information about female-specific and population-level processes. Moreover, this study conveys information about spatial processes occurring over multiple generations that cannot be readily gained using other approaches, e.g. telemetry.

A prospective assessment of renal impairment after preparation for colonoscopy: oral sodium phosphate appears to be safe in well-hydrated subjects with normal renal status.

BACKGROUND: The outcome of colonoscopy is highly dependent upon the quality of bowel cleansing prior to the procedure. Oral sodium phosphate solutions (OSPS) or preparations containing polyethylene glycol (PEG) are generally employed. However, the safety of administering OSPS prior to colonoscopy has been questioned because of the potential for renal failure. AIM: To compare rates of renal failure after OSPS and PEG in a randomized, prospective trial and to assess the quality of colonoscopy after these two bowel preparations. METHODS: Subjects with eGFR >or= 60 ml/min/1.73 m(2) and expressed willingness to adhere to hydration recommendations were randomized to OSPS or PEG solutions. Renal function was assessed 1 week prior to, immediately prior to, and 1 week after colonoscopy. RESULTS: No subject had acute kidney failure after OSPS or PEG. OSPS was associated with significant increases in the serum phosphate and sodium levels and significant decreases in the calcium and potassium levels. These values returned to normal limits in all subjects by 1 week after colonoscopy. The quality of colonic cleansing was superior after OSPS than after PEG (Ottawa score 2.5 +/- 2.2 vs. 3.5 +/- 2.3, respectively, P < 0.05). The detection of one or more adenomatous polyps was higher after OSPS than after PEG. CONCLUSIONS: Renal failure was not detected after the use of OSPS for colonoscopy preparation in subjects with recently documented normal renal function who were able to consume the required amounts of water after each dose. However, based on the number of subjects studied, the theoretical risk of this complication is still between 0 and 6.3%. Thus, it is appreciated that only a very large prospective trial would have yielded a more accurate estimate of the likelihood of renal compromise after OSPS. Despite this caveat, OSPS has advantages over PEG in terms of the adequacy of colonic visualization and the number of polyps detected.

Clinical trial: the efficacy and safety of routine bowel cleansing agents for elective colonoscopy in persons with spinal cord injury - a randomized prospective single-blind study.

BACKGROUND: As difficulty with evacuation is a common occurrence in individuals with spinal cord injury, preparation prior to colonoscopy may be suboptimal and, perhaps, more hazardous. AIM: To assess the safety and efficacy of bowel cleansing regimens in persons with spinal cord injury. METHODS: Randomized, prospective, single blind study comparing polyethylene glycol (PEG), oral sodium phosphosoda (OSPS) and combination of both for colonic preparation prior to colonoscopy in subjects with spinal cord injury. RESULTS: Thirty six subjects with eGFR > or =60 mL/min/1.73 m(2) were randomized to PEG or OSPS or PEG+OSPS. Regardless of bowel preparation employed, >73% of subjects had unacceptable colonic cleansing. No subject in the OSPS preparation group demonstrated a decrease in eGFR or an increase in serum creatinine concentration from the baseline. OSPS and PEG+OSPS preparations caused a transient change in serum potassium, phosphate and calcium concentrations, but no change in electrolytes was noted in the PEG group. CONCLUSIONS: Neither OSPS alone, PEG alone nor their combination was sufficient to prepare adequately the bowel for colonoscopy in most patients with spinal cord injury. However, administration of OSPS and/or PEG appears to be safe in the spinal cord injury population, provided adequate hydration is provided.

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol.

BACKGROUND: Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS). AIM: To evaluate whether OSPS is associated with changes in renal function. METHODS: A chart review performed on 311 patients who had colonoscopy at the James J. Peters VA Medical Centre prepared with either OSPS (n = 157) or polyethylene glycol (PEG) (n = 154). Patients had a baseline serum creatinine or=50% increase above their baseline creatinine was similar (OSPS vs. PEG, 5% vs. 3%, P = 0.77). CONCLUSIONS: Oral sodium phosphate solution was associated with a slight increase in serum creatinine, which was not clinically significant. Renal toxicity from OSPS appears to be minimal when used in patients with serum creatinine value <1.5 mg/dL.

Application of summary receiver operating characteristics (sROC) analysis to diagnostic clinical testing.

Summary receiver operating characteristics (sROC) analysis is a recently developed statistical technique that can be applied to meta-analysis of diagnostic tests. This technique can overcome some of the limitations associated with pooling the sensitivities and specificities of published studies. The sROC curve is initially constructed by plotting the sensitivity (true positivity) and false positivity (1 - specificity) of each study. After mathematical manipulation of the true and false positivities, linear regression is performed to calculate the slope and y-intercept. These coefficients are then entered into the sROC equation to generate the sROC curve. There are three commonly used methods to assess the accuracy of the test: the exact area under the curve (AUC) for the sROC function, the homogeneous AUC, and the index Q*. Statistical formulas can compare these values from different diagnostic tests. With the introduction of sROC software and better understanding of this method, the application of sROC analysis should continue to increase.

Torsion and infarction of an accessory liver lobe.

Accessory lobes of the liver (ALL) may be congenital or acquired and are usually of no clinical significance. Torsions of the ALL are exceedingly rare and most are incidental findings at laparotomy, autopsy and in the course of investigation radiological investigations. A total of 17 infant and adult cases have been described previously in the medical literature. Most cases described since 1925 have been diagnosed at laparotomy, we report the 18th case of torsion of the accessory lobe of the liver in an elderly female which, despite all radiological interventions, required laparoscopy for diagnosis. We conclude that torsion of the accessory lobes of the liver is a rare finding; radiological imaging does not reveal the diagnosis and most are found at laparotomy. Laparoscopy may aid in the diagnosis of torsion of accessory liver lobes. If pain persists, we advocate the use surgical intervention with or without cholecystectomy.

Recent concepts in the management of bowel problems after spinal cord injury.

Bowel problems after SCI can be debilitating. Colonic inertia as a result of decreased parasympathetic (S2-4) stimulation of the left colon and rectosigmoid seems to be the principal abnormality accounting for DWE. The conventional measures used for decades have poor results in many people. Neostigmine, an anticholinesterase inhibitor, appears to be a more physiological agent for these individuals. The combination of neostigmine + glycopyrrolate infusion has shown encouraging results after intravenous administration and studies are under way to assess the efficacy of neostigmine by other routes.

Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover.

BACKGROUND: Pancreatic fibrosis is a characteristic feature of chronic pancreatic injury and is thought to result from a change in the balance between synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies suggest that activated pancreatic stellate cells (PSCs) play a central role in pancreatic fibrogenesis via increased synthesis of ECM proteins. However, the role of these cells in ECM protein degradation has not been fully elucidated. AIMS: To determine: (i) whether PSCs secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and, if so (ii) whether MMP and TIMP secretion by PSCs is altered in response to known PSC activating factors such as tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1), interleukin 6 (IL-6), ethanol, and acetaldehyde. METHODS: Cultured rat PSCs (n=3-5 separate cell preparations) were incubated at 37 degrees C for 24 hours with serum free culture medium containing TNF-alpha (5-25 U/ml), TGF-beta1 (0.5-1 ng/ml), IL-6 (0.001-10 ng/ml), ethanol (10-50 mM), or acetaldehyde (150-200 micro M), or no additions (controls). Medium from control cells was examined for the presence of MMPs by zymography using a 10% polyacrylamide-0.1% gelatin gel. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine gene expression of MMP9 and the tissue inhibitors of metalloproteinases TIMP1 and TIMP2. Western blotting was used to identify a specific MMP, MMP2 (a gelatinase that digests basement membrane collagen and the dominant MMP observed on zymography) and a specific TIMP, TIMP2. Reverse zymography was used to examine functional TIMPs in PSC secretions. The effect of TNF-alpha, TGF-beta1, and IL-6 on MMP2 secretion was assessed by densitometry of western blots. The effect of ethanol and acetaldehyde on MMP2 and TIMP2 secretion was also assessed by this method. RESULTS: Zymography revealed that PSCs secrete a number of MMPs including proteinases with molecular weights consistent with MMP2, MMP9, and MMP13. RT-PCR demonstrated the presence of mRNA for metalloproteinase inhibitors TIMP1 and TIMP2 in PSCs while reverse zymography revealed the presence of functional TIMP2 in PSC secretions. MMP2 secretion by PSCs was significantly increased by TGF-beta1 and IL-6, but was not affected by TNF-alpha. Ethanol and acetaldehyde induced secretion of both MMP2 and TIMP2 by PSCs. CONCLUSIONS: Pancreatic stellate cells have the capacity to synthesise a number of matrix metalloproteinases, including MMP2, MMP9, and MMP13 and their inhibitors TIMP1 and TIMP2. MMP2 secretion by PSCs is significantly increased on exposure to the proinflammatory cytokines TGF-beta1 and IL-6. Both ethanol and its metabolite acetaldehyde increase MMP2 as well as TIMP2 secretion by PSCs. IMPLICATION: The role of pancreatic stellate cells in extracellular matrix formation and fibrogenesis may be related to their capacity to regulate the degradation as well as the synthesis of extracellular matrix proteins.

Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis.

BACKGROUND: It is now generally accepted that chronic pancreatic injury and fibrosis may result from repeated episodes of acute pancreatic necroinflammation (the necrosis-fibrosis sequence). Recent studies suggest that pancreatic stellate cells (PSCs), when activated, may play an important role in the development of pancreatic fibrosis. Factors that may influence PSC activation during pancreatic necroinflammation include cytokines known to be important in the pathogenesis of acute pancreatitis, such as tumour necrosis factor alpha (TNF-alpha), and the interleukins 1, 6, and 10 (IL-1, IL-6, and IL-10). AIM: To determine the effects of these cytokines on PSC activation, as assessed by cell proliferation, alpha smooth muscle actin (alpha-SMA) expression, and collagen synthesis. METHODS: Cultured rat PSCs were incubated with cytokines for 24 hours. Cell proliferation was assessed by measuring (3)H thymidine incorporation into cellular DNA, alpha-SMA expression by western blotting, and collagen synthesis by incorporation of (14)C proline into collagenase sensitive protein. mRNA levels for procollagen alpha(1)(1) in PSCs were determined by northern and dot blotting methods. RESULTS: Expression of alpha-SMA by PSCs was increased on exposure to each of the cytokines used in the study. Stellate cell proliferation was stimulated by TNF-alpha but inhibited by IL-6, while IL-1 and IL-10 had no effect on PSC proliferation. Collagen synthesis by PSCs was stimulated by TNF-alpha and IL-10, inhibited in response to IL-6, and unaltered by IL-1. Changes in collagen protein synthesis in response to TNF-alpha, IL-10, and IL-6 were not regulated at the mRNA level in the cells. CONCLUSION: This study has demonstrated that PSCs have the capacity to respond to cytokines known to be upregulated during acute pancreatitis. Persistent activation of PSCs by cytokines during acute pancreatitis may be a factor involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis.

An implantable neuroprosthesis for restoring bladder and bowel control to patients with spinal cord injuries: a multicenter trial.

OBJECTIVE: To evaluate the safety and efficacy of an implanted neuroprosthesis for management of the neurogenic bladder and bowel in individuals with spinal cord injury (SCI). DESIGN: Prospective study comparing bladder and bowel control before and at 3, 6, and 12 months after implantation of the neuroprosthesis. SETTING: Six US hospitals specializing in treatment of SCI. PATIENTS: Twenty-three neurologically stable patients with complete suprasacral SCIs. INTERVENTION: Implantation of an externally controlled neuroprosthesis for stimulating the sacral nerves and posterior sacral rhizotomy. MAIN OUTCOME MEASURES: Ability to urinate more than 200mL on demand and a resulting postvoid residual volume of less than 50mL. RESULTS: At 1-year follow-up, 18 of 21 patients could urinate more than 200mL with the neuroprosthesis, and 15 of 21 had postvoid volumes less than 50mL (median, 15mL). Urinary tract infection, catheter use, reflex incontinence, anticholinergic drug use, and autonomic dysreflexia were substantially reduced. At 1-year follow-up, 15 of 17 patients reduced the time spent with bowel management. CONCLUSIONS: Neural stimulation and posterior rhizotomy is a safe and effective method of bladder and bowel management after suprasacral SCI.

Susceptibility to cerulein-induced pancreatitis in inducible nitric oxide synthase-deficient mice.

Production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been proposed as a pathogenic factor in acute pancreatitis, but its role has still not been fully examined. The present study explored the role of iNOS in cerulein-induced acute pancreatitis using iNOS-deficient mice. Twelve- to 14-week-old male mice (C57B1/6 and iNOS-deficient) were administered cerulein by intraperitoneal (i.p.) injection at hourly intervals for 7 hours and killed 24 hours later after the first dose. Pancreatic wet weight, pancreatic myeloperoxidase (MPO) activity, and levels of plasma nitrite and serum amylase were measured. In another experiment isosorbide dinitrate (an NO donor) was given by oral gavage every 6 hours for 24 hours beginning simultaneously with cerulein injections in iNOS-deficient mice. Cerulein administration dose-dependently increased pancreatic wet weight, myeloperoxidase activity, and levels of nitrite and amylase in C57B1/6 mice. These parameters (except nitrite levels) were significantly intensified in iNOS-deficient mice. At the dose employed, cerulein failed to increase nitrite levels in iNOS-deficient mice. The susceptibility to cerulein toxicity in iNOS-deficient mice was abolished by NO donor treatment. NO release from an iNOS source appears to play a protective role in cerulein-induced pancreatitis. At least in part, NO may prevent neutrophil accumulation after cerulein administration.

Reversal of the gastric effects of nicotine by nitric oxide donor treatment.

Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric mucosal injury in rats administered nicotine. A nicotine solution or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine.

Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells.

BACKGROUND & AIMS: Activated pancreatic stellate cells have recently been implicated in pancreatic fibrogenesis. This study examined the role of pancreatic stellate cells in alcoholic pancreatic fibrosis by determining whether these cells are activated by ethanol itself and, if so, whether such activation is caused by the metabolism of ethanol to acetaldehyde and/or the generation of oxidant stress within the cells. METHODS: Cultured rat pancreatic stellate cells were incubated with ethanol or acetaldehyde. Activation was assessed by cell proliferation, alpha-smooth muscle actin expression, and collagen synthesis. Alcohol dehydrogenase (ADH) activity in stellate cells and the influence of the ADH inhibitor 4-methylpyrazole (4MP) on the response of these cells to ethanol was assessed. Malondialdehyde levels were determined as an indicator of lipid peroxidation. The effect of the antioxidant vitamin E on the response of stellate cells to ethanol or acetaldehyde was also examined. RESULTS: Exposure to ethanol or acetaldehyde led to cell activation and intracellular lipid peroxidation. These changes were prevented by the antioxidant vitamin E. Stellate cells exhibited ethanol-inducible ADH activity. Inhibition of ADH by 4MP prevented ethanol-induced cell activation. CONCLUSIONS: Pancreatic stellate cells are activated on exposure to ethanol. This effect of ethanol is most likely mediated by its metabolism (via ADH) to acetaldehyde and the generation of oxidant stress within the cells.

Prolonged ambulatory colonic manometric studies using endoclips.

BACKGROUND: It is difficult to study human colonic motility under physiologic conditions. An important limitation associated with prolonged colonic recording is the failure of the sensors to resist normal expulsive forces. METHOD: In this article we describe a method of endoscopically positioning a manometric catheter by using clips in conjunction with a solid-state catheter. With the use of a rotatable clip-fixing device loaded on to a colonoscope, the manometric catheter was clipped to the colonic mucosa. RESULTS: Recordings for up to 120 hours were obtained from 6 subjects without apparent migration of the catheter assembly. No complications were noted, the catheter does not interfere with defecation, and defecation does not result in its expulsion. CONCLUSION: The current technique will allow reliable ambulatory measurements over prolonged periods of time in relatively comfortable and unrestrained subjects. This technique should increase our understanding of normal and abnormal colonic motility.

Racial factors and the risk of chronic pancreatitis.

OBJECTIVE: It is unclear why some alcohol abusers develop alcoholic cirrhosis whereas others contract chronic pancreatitis. The aim of this study was to examine the importance of race as a risk factor for the development of chronic pancreatitis. METHODS: We compared the racial status of 1883 patients discharged with a first-listed diagnosis of two diseases strongly related to alcohol abuse: 433 patients with chronic pancreatitis (ICD 5771) and 1450 patients with alcoholic cirrhosis (ICD 5712). Information came from discharge statistics maintained by two acute care hospitals in New York City and one acute care hospital in Lisbon, Portugal. The study period included the years 1989-1996 in the US and 1989-1994 in Portugal. RESULTS: A total of 215 (50%) of the 433 chronic pancreatitis patients were black compared with 333 (23%) of the 1450 patients with alcoholic cirrhosis. When adjusted for sex and hospital site, patients with pancreatitis were significantly more likely to be black than patients with cirrhosis (odds ratio 2.5, 95% confidence interval 1.9-3.2, p < 0.001). CONCLUSIONS: In comparison with white patients, black patients are two to three times more likely to be hospitalized for chronic pancreatitis than alcoholic cirrhosis. This highly significant (p < 0.001) difference was observed in both men and women: in three different hospitals, and in two different countries. The explanation is unknown, but could be related to racial differences in diet, type or quantity of alcohol consumption, smoking, or ability to detoxify substances harmful to the liver or pancreas.

Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis.

BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress. AIMS: To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor beta (TGF-beta). METHODS: Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-beta. RESULTS: Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose related increase in cell counts as well as in the incorporation of 3H-thymidine into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-beta showed a dose dependent increase in alpha smooth muscle actin expression and increased collagen synthesis. In addition, TGF-beta increased the expression of PDGF receptors on stellate cells. CONCLUSIONS: Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-beta by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis.

Metabolism of ethanol by rat pancreatic acinar cells.

It has been postulated that ethanol-induced pancreatic injury may be mediated by the oxidation of ethanol within the pancreas with secondary toxic metabolic changes, but there is little evidence of pancreatic ethanol oxidation. The aims of this study were to determine whether pancreatic acinar cells metabolize significant amounts of ethanol and, if so, to compare their rate of ethanol oxidation to that of hepatocytes. Cultured rat pancreatic acinar cells and hepatocytes were incubated with 5 to 50 mmol/L carbon 14-labeled ethanol (25 dpm/nmol). Ethanol oxidation was calculated from the production of 14C-labeled acetate that was isolated by Dowex ion-exchange chromatography. Ethanol oxidation by pancreatic acinar cells was demonstrable at all ethanol concentrations tested. At an intoxicating ethanol concentration (50 mmol/L), 14C-labeled acetate production (227+/-20 nmol/10(6) cells/h) approached that of hepatocytes (337+/-61 nmol/10(6) cells/h). Phenanthroline (an inhibitor of classes I through III isoenzymes of alcohol dehydrogenase (ADH)) inhibited pancreatic ethanol oxidation by 90%, but 4-methylpyrazole (a class I and II ADH inhibitor), carbon monoxide (a cytochrome P450 inhibitor), and sodium azide (a catalase inhibitor) had no effect. This study has shown that pancreatic acinar cells oxidize significant amounts of ethanol. At intoxicating concentrations of ethanol, pancreatic acinar cell ethanol oxidation may have the potential to contribute to pancreatic cellular injury. The mechanism appears to involve the class III isoenzyme of ADH.