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PubMedDate not supplied

Gallbladder function before and after fundoplication.

No study has reported an association between gastroesophageal reflux disease (GERD) or its therapies and gallbladder function. We compared pre- and postoperative gallbladder function in patients undergoing fundoplication to determine the following: (1) whether patients with chronic GERD have preexisting gallbladder motor dysfunction; (2) whether medical or surgical therapy alters gallbladder function; and (3) whether division of the hepatic branch of the anterior vagus nerve is detrimental to gallbladder motility. Nineteen patients with documented GERD consented to a preoperative cholecystokinin-stimulated technetium hepatobiliary (CCK-HIDA) scan to quantify the gallbladder ejection fraction (GBEF). All patients underwent laparoscopic Nissen fundoplication. One month after fundoplication, 12 patients completed a repeat CCK-HIDA scan for determination of GBEF, with comparison to the preoperative GBEF. Among patients with preoperative GERD, 11 (58%) of 19 met the scintigraphic criteria for gallbladder dysfunction (GBEF <35%), which is a ratio comparable to that in patients undergoing a CCK-HIDA scan for presumed biliary dyskinesia during the same time period (31 [60%] of 53; P = NS, chi-square test) and exceeds the rate of abnormal GBEF reported in healthy volunteers (3%). Six of seven patients with a low preoperative GBEF who underwent repeat evaluation postoperatively had normalization of the GBEF (P < 0.05, paired t-test). In the 12 patients who underwent postoperative CCK-HIDA scanning, there was no association between preservation or division of the hepatic branch of the anterior vagus nerve and postoperative gallbladder dysfunction (P = NS, chi-square test). Unexpectedly, 58% of patients with GERD demonstrated gallbladder motor dysfunction prior to fundoplication, with improvement to normal occurring in most of those studied postoperatively. These data support controlled trials to determine the effect of chronic GERD and antisecretory therapy on gallbladder and global gastrointestinal smooth muscle function. Preservation of the hepatic branch of the anterior vagus nerve during fundoplication offered no clear benefit with regard to early postoperative gallbladder function.

Adult↗

PubMed2006

Hypophosphatemia: an evidence-based approach to its clinical consequences and management.

Optimal cellular function is dependent on maintenance of a normal serum phosphorus concentration. Serum phosphorus concentration is affected by several determinants, the most important of which is regulation of phosphorus reabsorption by the kidney. The majority of this reabsorption (80%) occurs in the proximal tubule and is mediated by an isoform of the sodium-phosphate cotransporter (NaPi-II). Parathyroid hormone, via a variety of intracellular signaling cascades leading to NaPi-IIa internalization and downregulation, is the main regulator of renal phosphate reabsorption. Shift of phosphorus from extracellular to intracellular compartments, decreased gastrointestinal absorption, and increased urinary losses, are the primary mechanisms of hypophosphatemia, which affects approximately 2% of hospitalized patients. Hypophosphatemia has been implicated as a cause of rhabdomyolysis, respiratory failure, hemolysis and left ventricular dysfunction. With the exception of ventilated patients, there is little evidence that moderate hypophosphatemia has significant clinical consequences in humans, and aggressive intravenous phosphate replacement is unnecessary. By contrast, patients with severe hypophosphatemia should be treated. Intravenous repletion may be considered, especially for patients who have clinical sequelae of hypophosphatemia.

Cardiomyopathies↗

PubMed2003

Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction.

1. Peroxisome proliferator activated receptor gamma (PPARgamma) has been implicated in several cellular pathways assumed to beneficially affect heart failure progression. In contrast, population-based studies demonstrate an increased incidence of heart failure in patients treated with PPARgamma agonists. Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice. 2. Mice were treated with placebo or pioglitazone (20 mg x kg(-1) by gavage) from week 1 to week 6 after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at weeks 1, 3, and 6. 3. Over 6 weeks, there was no difference in mortality (placebo 12%, pioglitazone 10%). Echocardiography showed significant left ventricular dilatation in animals with MI (week 6, end-systolic area, placebo sham 9.6+/-1.3 vs placebo MI 14.4+/-2.5 mm(2)). However, there was no difference between the placebo and pioglitazone groups (week 6, end-systolic area, pioglitazone MI 14.8+/-2.9 mm(2), P=NS vs placebo). 4. Moreover, there were no changes in metabolic parameters, inflammation, and collagen deposition. Endothelial function in the aorta was not changed by PPARgamma activation. 5. In conclusion, PPARgamma activation did not adversely affect left ventricular remodeling and survival in mice with chronic MI. However, we were also not able to identify a protective effect of pioglitazone.

Animals↗

PubMed2004

Innate immunity of the gut: mucosal defense in health and disease.

The intestine is an important immune organ consisting of a complex cellular network, secreted peptides and proteins and other host defenses. Innate immunity plays a central role in intestinal immune defense against invading pathogens. It also serves as a bridge to the activation of the adaptive immune system. Pattern recognition molecules of microorganisms are an essential component for identifying invading pathogens. Toll-like receptors (TLRs), CARD15/NOD2 and scavenger receptors all serve as the pattern recognition receptors in the innate immune defense system. Secreted bactericidal peptides or defensins produced by the intestinal epithelia represent another crucial element of innate mucosal immune defense. Mutations in pattern recognition receptors and dysfunction of secretory bactericidal peptides may impair host immune defenses leading to an invasion of pathogens resulting in chronic inflammation of the gut. This review updates our current understanding of innate immunity of the gastrointestinal tract.

Humans↗

PubMed2003

Visceral afferent pathways and functional brain imaging.

The application of functional imaging to study painful sensations has generated considerable interest regarding insight into brain dysfunction that may be responsible for functional pain such as that suffered in patients with irritable bowel syndrome (IBS). This review provides a brief introduction to the development of brain science as it relates to pain processing and a snapshot of recent functional imaging results with somatic and visceral pain. Particular emphasis is placed on current hypotheses regarding dysfunction of the brain-gut axis in IBS patients. There are clear and interpretable differences in brain activation following somatic as compared with visceral noxious sensation. Noxious visceral distension, particularly of the lower gastrointestinal tract, activates regions associated with unpleasant affect and autonomic responses. Noxious somatic sensation, in contrast, activates regions associated with cognition and skeletomotor responses. Differences between IBS patients and control subjects, however, were far less clear and interpretable. While this is in part due to the newness of this field, it also reflects weaknesses inherent within the current understanding of IBS. Future use of functional imaging to examine IBS and other functional disorders will be more likely to succeed by describing clear theoretical and clinical endpoints.

Afferent Pathways↗

PubMed2005

Farnesyltransferase inhibitors in myelodysplastic syndrome.

The farnesyltransferase inhibitors (FTIs) are in active clinical development in a variety of human malignancies. The most promising activity to date has been demonstrated in patients with hematological malignancies, in particular acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In patients with MDS, two non-peptidomimetic agents, tipifarnib (Zarnestra, Johnson & Johnson, New Brunswick, NJ) and lonafarnib (Sarasar, Schering-Plough, Kenilworth, NJ) have been the most extensively studied. In both phase I and phase II trials, tipifarnib has demonstrated significant efficacy with overall response rates of 30%, with complete remissions in about 15%. Dose-limiting side effects have been primarily myelosuppression, although fatigue, neurotoxicity, and occasional renal dysfunction have required dose reductions. Lonafarnib in patients with MDS has also resulted in clinical responses in approximately 30%, including significant improvements in platelet counts. Lonafarnib has been associated with primarily diarrhea and other gastrointestinal toxicity, anorexia, and nausea, which has limited its efficacy. Clinical response correlation with documentation of inhibition of farnesyltransferase and/or evidence of decreased farnesylation of downstream protein targets has not been demonstrated with either agent. In addition, the presence of an activating Ras mutation has not predicted response to therapy with FTIs in MDS and AML. Despite this, significant clinical efficacy of the FTIs in MDS, on par with that of currently available chemotherapeutic agents, has been observed, leading to further development of this new class of drugs in MDS and AML.

Acute Disease↗

PubMedDate not supplied

Complications associated with the diagnostic, medical, and surgical management of portosystemic shunts.

Anomalous vascular connections between the portal and systemic circulations can result in several profound alterations in normal physiology. In most cases the presenting clinical signs are referable to the nervous, gastrointestinal, and urinary systems. Medical management may help control the clinical signs, but only surgical redirection of the shunting blood back to the liver parenchyma can result in reversal of the hepatic atrophy and dysfunction that exists. This article describes the problems associated with the diagnostic, medical, and surgical management of animals with congenital portosystemic shunts.

Animals↗

PubMed1985

[Phase I trial of 4'-O-tetrahydropyranyl-doxorubicin (THP)--a multi-institutional cooperative study].

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Aged↗

PubMed1995

Liver transplantation in familial amyloidotic polyneuropathy. Follow-up of the first 20 Swedish patients.

Familial amyloidotic polyneuropathy (FAP) is an inherited fatal form of amyloidosis caused by mutant transthyretin. The disease is characterized by progressive peripheral and autonomic neuropathy. Most of the transthyretin is produced by the liver, and we have shown previously that the metabolic deficiency can be corrected by liver transplantation. In the present study, the clinical results from the first 20 patients who underwent liver transplantation for FAP in Sweden are evaluated. Three of the patients suffered from renal failure and underwent a simultaneous kidney transplantation. Fourteen of the 20 patients (70%) are alive 10-52 months after transplantation. The patients' nutritional status at the time of transplantation had a significant impact on mortality and morbidity (P < 0.007). Long-standing disease was another negative prognostic factor (P < 0.02). One year after transplantation, the nutritional status had improved (P < 0.02). Improvements were also noted in walking capacity and for gastrointestinal and urogenital symptoms. The results show that liver transplantation offers an effective means to treat patients with FAP. The procedure should preferably be performed before the nutritional status is poor and advanced organ dysfunction has developed.

Adult↗

PubMed1997

[Perineal injuries in wartime].

Perineal war wounds involve the anterior perineum or urogenital perineum and posterior perineum or ano-sphincteric perineum. They are rare in civilian practice and in war practice, as only a small and hidden surface of this anatomical region is exposed to damaging agents. An isolated wound of the perineum is rarely life-threatening, but always threatens the functional prognosis of these patients, who have a mean age less than 30 years. In war practice, these wounds are often associated with lesions of adjacent of sacral, buttock or abdomino-pelvic regions. This article is confined to perineal war wounds in men. Lesions of the urethra and anus and rectum, as well as lesions of the genital appendages and pelvic nerves, leave micturating, gastrointestinal and sexual sequelae, which are sometimes permanent. These sequelae must not be exacerbated during investigation and surgical repair, despite the unfavourable emergency context, associated lesions and the time required to repair them. The basic principles of surgical treatment remain urinary diversion by a large cystostomy tube for urogenital lesions, faecal diversion by terminal colostomy for ano-sphincteric lesions, conservative debridement of the margins of the anal or urethral wound, debridement and drainage of contaminated soft tissues and connective tissue spaces. First-line immediate suture of the urethra or edges of the anal wound must be considered according to the defect, and the septic and haemorrhagic context. When ideal repair cannot be performed, alignment over an urethral catheter, urethrostomy, fixation-identification of the urethral or anal extremities constitute intermediate procedures allowing secondary urological and proctological specialized procedures in these patients.

Abdominal Injuries↗

PubMed2004

Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects.

The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder to the absence of binge-eating. The present review also examines evidence of defects in signalling that differentiate these sub-types. The signalling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and alpha-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety. Adipose tissue provides signals about energy storage levels to the brain through leptin, adiponectin and resistin. Binge-eating has been related to a dysfunction in the ghrelin signalling system. Moreover, changes in gastric capacity are observed, and as gastric capacity is increased, so satiety signals arising from gastric and post-gastric cues are reduced. Understanding the host of neuropeptides and peptide hormones through which hunger and satiety operate should lead to novel therapeutic approaches for obesity; potential therapeutic strategies are highlighted.

Adipocytes↗

PubMed2000

COX-2 inhibitors.

Cyclooxygenase-2 (COX-2) inhibitors constitute a new group of non-steroidal anti-inflammatory drugs (NSAIDs) which, at recommended doses, block prostaglandin production by cyclooxygenase-2, but not by cyclooxygenase-1. Two COX-2 inhibitors are currently available in Australia--celecoxib, which is taken twice daily, and rofecoxib, which is taken once daily. Both drugs act rapidly in providing pain relief and their anti-inflammatory analgesic effect in osteoarthritis and rheumatoid arthritis is equivalent to standard doses of non-selective NSAIDs. Celecoxib and rofecoxib show significantly lower incidences of gastrotoxicity (as measured by endoscopic studies and gastrointestinal ulcers and bleeds) than non-selective NSAIDs. There is Level 2 evidence that COX-2 inhibitors: reduce pain in classic pain models--third-molar extraction, dysmenorrhoea and after orthopaedic surgery; reduce pain and disability in osteoarthritis of the hip and knee; and reduce pain and disability in rheumatoid arthritis. Other adverse effects, such as interference with antihypertensive agents and the potential to produce renal dysfunction in patients with compromised renal function by COX-2 inhibitors, seem similar to those of non-selective NSAIDs.

Algorithms↗

PubMed1993

Immobility in the aged.

Bed rest has historically been used therapeutically in the management of many chronic maladies prevalent in elderly persons. Unfortunately, the deleterious consequences of immobility predispose elderly persons to significant functional decline and reduced quality of life. Prolonged inactivity reduces the physiologic reserve of most organ systems, particularly the musculoskeletal and cardiopulmonary systems. Consequently, muscle weakness, contracture formation, postural hypotension, and thrombogenic events are common in bed-bound patients. Fortunately, contemporary studies have dispelled the myth that inactivity fosters healing and have suggested techniques that may prevent immobility-induced dysfunction and ensure beneficial outcome in fragile and aging populations.

Aged↗

PubMed2006

Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis.

BACKGROUND: Randomised clinical trials have compared portosystemic shunting procedures with endoscopic therapy for variceal haemorrhage, but there is no consensus as to which approach is preferable. OBJECTIVES: To compare the effects of shunts (total surgical shunt (TS); distal spleno-renal shunts (DSRS) or transjugular intrahepatic porto-systemic shunts (TIPS) with endoscopic therapy (ET, sclerotherapy and/or banding) for prevention of variceal rebleeding in patients with cirrhosis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, conference proceedings, and the references of identified trials were searched (last search February 2004). Researchers in the field and in industry were contacted. SELECTION CRITERIA: Randomised clinical trials comparing TS, DSRS or TIPS with ET in patients who had recovered from a variceal haemorrhage and were known to be cirrhotic. DATA COLLECTION AND ANALYSIS: Data were collected to allow intention-to-treat analysis where possible. For each outcome, a pooled estimate of treatment effect (log hazard ratio for time to outcome, Peto odds ratio for binary outcomes, and differences in means for continuous outcomes) across trials was calculated. MAIN RESULTS: Twenty-two trials evaluating 1409 patients were included. All trials had problems of method. Shunt therapy compared with ET demonstrated significantly less rebleeding (OR 0.24, 95% CI 0.18 to 0.30) at the cost of significantly increased acute hepatic encephalopathy (OR 2.07, 95% CI 1.59 to 2.69) and chronic encephalopathy (OR 2.09, 95% CI 1.20 to 3.62). There were no significant differences regarding mortality (hazard ratio 1.00, 95% CI 0.82 to 1.21) and duration of in-patient stay (weighed mean difference 0.78 day, 95% CI -1.48 to 3.05). The proportion of patients with shunt occlusion or dysfunction was 3.1% (95% CI 0.4 to 10.7%) following TS (two trials), 7.8% (95% CI 3.8 to 13.9%) following DSRS (four trials), and 59% (range 18% to 72%) following TIPS (14 trials). AUTHORS' CONCLUSIONS: All shunts resulted in a significantly lower rebleeding rate at the expense of a higher incidence of encephalopathy. TIPS was complicated by a high incidence of shunt dysfunction. No survival advantage was demonstrated with any shunt.

Endoscopy↗

PubMed1993

Clinical, laboratory and prognostic features of congenital large intestinal motor dysfunction (pseudo-Hirschsprung's disease).

One hundred and forty-eight cases of congenital large intestinal motor dysfunction (pseudo-Hirschsprung's disease) were reported by members of the Japanese Society of Pediatric Surgeons during the past 20 years. The disorder was defined as a congenital, non-mechanical obstruction of the intestine with the presence of intramural ganglia in the terminal rectum. Intramural ganglia were abnormal in 77 cases, normal in 42, and could not be determined in 29. Of those with abnormal intramural ganglia, 54 had immature ganglia or hypoganglionosis (oligoganglionosis), 15 had neuronal intestinal dysplasia, and eight had a segmental anomaly. Of those with a normal myenteric plexus, 22 had chronic and twelve had suspected idiopathic intestinal pseudo-obstruction syndrome; eight had megacystis-microcolon-intestinal hypoperistalsis syndrome. While cases with both hypoganglionosis and normal intramural ganglia had normal acetylcholine esterase activity, a significantly greater number of patients with hypoganglionosis lacked normal rectoanal reflexes. Patients with hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction syndrome, and megalocystis-microcolon-intestinal hypoperistalsis syndrome had poor prognoses with an overall mortality of 36.9%. These findings indicate that congenital large intestinal motor dysfunction remains a serious disease of childhood.

Age of Onset↗

PubMed1994

Obstructing inflammatory fibroid polyp in pelvic ileal reservoir after restorative proctocolectomy in ulcerative colitis. Report of a case.

PURPOSE: This study was designed to describe clinical, endoscopic, and histopathologic features of an inflammatory fibroid polyp occurring in the pelvic ileal reservoir after restorative proctocolectomy in ulcerative colitis. METHOD: A case report describing the clinical course of such a patient is presented. RESULTS: Three years postoperatively, the patient developed diarrhea, anemia, weight loss of 10 kg, and symptoms of obstructed defecation. Ileoscopy showed pouchitis and a polypoid tumor filling the pouch. Biopsies revealed chronic inflammation without signs of malignancy. At laparotomy, a 5 cm x 3.5 cm x 3.5 cm submucosal, solid, circumscribed tumor was found within the pouch, and histopathologic examination yielded the diagnosis. The pelvic pouch was resected and replaced by a Brooke ileostomy. During 18 months of follow-up, the course has been uneventful. CONCLUSION: Inflammatory fibroid polyp is a rare, reactive, non-neoplastic lesion, which, for the first time, is reported in a pelvic ileal reservoir. It may cause pouch dysfunction. It is always benign but may masquerade as a malignant tumor.

Adult↗

PubMedDate not supplied

Autonomic influences on colorectal motility and pelvic surgery.

The nervous control of the motility of the human distal bowel was investigated by two physiological studies of electrical stimulation of sacral parasympathetic outflow in patients with high spinal injuries and in patients with intractable constipation following pelvic surgery. Identical and reproducible motility responses of the left colon, rectum, and anal sphincters were obtained by sequential electrical stimulation of anterior sacral roots S2, S3, and S4 in patients with spinal injury. S2 stimulation provoked isolated low-pressure colorectal contractions. S3 stimulation initiated frequency-dependent high-pressure colorectal motor activity which appeared peristaltic and was enhanced with repetitive stimuli. S4 stimulation increased colonic and rectal tone. Quantitative responses were maximal at the splenic flexure and rectum. Pelvic floor activity was stimulated in increasing magnitude from S2 to S4. These results of distal bowel motility were achieved by an implanted Brindley stimulator. A newer generation of externally active stimulators are envisaged for the control of lower bowel in fecal incontinence. Women with intractable constipation following hysterectomy had significantly increased rectal volume and compliance together with deficits of rectal sensory function. Following stimulation with Prostigmine (neostigmine) a colorectal motility gradient was paradoxically reversed in the patients following hysterectomy, thus constituting a functional obstruction. Denervation supersensitivity was demonstrable in 2 patients tested with carbachol provocation. These findings suggest dysfunction in the autonomic innervation of the hindgut in some patients following hysterectomy.

Adult↗

PubMed1998

Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation.

PURPOSE: There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. PATIENTS AND METHODS: Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. RESULTS: In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. CONCLUSIONS: In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.

Adult↗