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Biomedical subjects

S M Gabe

Publications and source records attributed to S M Gabe.

14 recordsLinked to original sources
PubMed2006

Survival and dependence on home parenteral nutrition: experience over a 25-year period in a UK referral centre.

BACKGROUND: Home parenteral nutrition (HPN) is the standard treatment for severe intestinal failure in the United Kingdom. AIM: To review long-term survival and ongoing HPN dependence of patients receiving HPN treated at a specialist UK referral centre. METHODS: Medical records of patients commenced on HPN between 1979 and 2003 were reviewed retrospectively. Regression analysis was employed to identify factors associated with poor prognosis. RESULTS: Case notes of 188 patients were reviewed. Overall probability of survival was 86%, 77%, 73% and 71% at 1, 3, 5 and 10 years after starting treatment. In multivariate analysis, association was seen between mechanism of intestinal failure and survival: short bowel syndrome associated with a favourable prognosis, and intestinal dysfunction, dysmotility and obstruction with poorer prognoses. There was an association between increasing age and poor prognosis, but increased mortality was also seen in the youngest age groups. Only 9% of deaths were due to complications of HPN. Continued HPN dependence was 89%, 87%, 84% and 84% at 1, 3, 5 and 10 years in survivors. CONCLUSIONS: Long-term survival of patients receiving HPN remains better than that reported after intestinal transplantation. Mortality predominantly relates to underlying disease rather than complications of HPN.

Adolescent↗
PubMed2006

A pilot study investigating a novel subcutaneously implanted pre-cellularised scaffold for tissue engineering of intestinal mucosa.

Tissue engineering of the small intestine offers an alternative to long-term intravenous nutrition and transplantation in patients with intestinal failure. Initial work, although encouraging, is limited by the volume of neonatal tissue required to produce a small neomucosal cyst. Our novel approach is to implant tubular poly-lactide-co-glycolide (PGLA) foam scaffolds subcutaneously. The aim of this study was to investigate whether these scaffolds would support growth of intestinal neomucosa. PGLA scaffolds were implanted subcutaneously into 8 Lewis rats; after 5 weeks, 'organoid units' were injected into the lumens. Tissue was assessed histologically after harvesting and quantitative immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGF-R2), fibroblast growth factor basic (bFGF) and fibroblast growth factor receptor 2 (FGF-R2). At 4 weeks post organoid unit implantation, clearly recognisable mucosa and submucosa was present on the luminal surface of the scaffold. Densities of VEGF and VEGF-R2 positive cells increased with time post organoid unit implantation. This pilot study demonstrates that it is possible to tissue engineer small intestinal neomucosa using subcutaneously implanted PLGA scaffolds. The yield of the process compares favourably to the published literature. Further work is required to optimise the technique.

Animals↗
PubMed2006

Nutrition and management of enterocutaneous fistula.

BACKGROUND: The management of enterocutaneous fistula is challenging, with significant associated morbidity and mortality. This article reviews treatment, with emphasis on the provision and optimal route of nutritional support. METHODS: Relevant articles were identified using Medline searches. Secondary articles were identified from the reference lists of key papers. RESULTS AND CONCLUSION: Management of enterocutaneous fistula should initially concentrate on correction of fluid and electrolyte imbalances, drainage of collections, treatment of sepsis and control of fistula output. The routine use of somatostatin infusion and somatostatin analogues remains controversial; although there are data suggesting reduced time to fistula closure, there is little evidence of increased probability of spontaneous closure. Malnutrition is common and adequate nutritional provision is essential, enteral where possible, although supplemental parenteral nutrition is often required for high-output small bowel fistulas. The role of immunonutrition is unknown. Surgical repair should be attempted when spontaneous fistula closure does not occur, but it should be delayed for at least 3 months.

Cutaneous Fistula↗
PubMed2006

Prolonged maintenance of neointestine using subcutaneously implanted tubular scaffolds in a rat model.

Tissue-engineered small intestine offers a possible alternative to long-term parenteral nutrition or intestinal transplantation in patients with short bowel syndrome. The aim of this study was to investigate the prolonged development of neointestine grown on subcutaneously implanted scaffolds. Tubular polylactide-coglycolide (PLGA) scaffolds were implanted into adult Lewis rats. Four weeks after scaffold implantation, a suspension of organoid units was delivered to the lumen of each scaffold. Organoid units were manufactured from small intestine harvested from neonatal Lewis rats by partial digestion using collagenase and dispase. Scaffolds were removed at 4, 8, and 12 weeks after organoid unit implantation, processed to paraffin, and sectioned. Hematoxylin and eosin staining demonstrated well-developed and well-differentiated intestinal mucosa and a vascularised submucosa within the scaffolds at 4, 8, and 12 weeks. Appearances were similar to native small intestine. Immunohistochemistry performed using primary antibody against proliferating cell nuclear antigen, a marker for cellular proliferation, demonstrated positively staining cells within the mucosa and submucosa at all time points. In the mucosal layer these positively staining cells were found primarily in the crypts. These findings show that neointestinal mucosa can be maintained for at least 12 weeks on a subcutaneous PLGA scaffold, and the presence of actively proliferating cells at 12 weeks suggests potential for further development beyond this.

Animals↗
PubMed2006

Parenteral nutrition: ethical and legal considerations.

Parenteral nutrition is an expensive therapeutic modality that is used to treat patients with intestinal failure. The benefit it offers in terms of life prolongation needs to be weighed against its risks and burdens. Through the use of descriptive clinical vignettes, this article illustrates the ethical and legal principles that underpin decisions to administer and, more importantly, to withhold or withdraw parenteral nutrition.

Bioethical Issues↗
PubMed2004

An 11-year experience of enterocutaneous fistula.

BACKGROUND: Enterocutaneous fistula has traditionally been associated with substantial morbidity and mortality, related to fluid, electrolyte and metabolic disturbance, sepsis and malnutrition. METHODS: A retrospective review of enterocutaneous fistula in 277 consecutive patients treated over an 11-year period in a major tertiary referral centre was undertaken to evaluate current management practice and outcome. RESULTS: Most fistulas occurred secondary to abdominal surgery, and a high proportion (52.7 per cent) occurred in association with inflammatory bowel disease. A low rate of spontaneous healing was observed (19.9 per cent). The healing rate after definitive fistula surgery was 82.0 per cent, although more than one attempt was required to achieve surgical closure in some patients. Definitive fistula resection resulted in a mortality rate of 3.0 per cent. In addition, one patient died after laparotomy for intra-abdominal sepsis and an additional 24 patients died from complications of fistulation, giving an overall fistula-related mortality rate of 10.8 per cent. CONCLUSION: Early recognition and control of sepsis, management of fluid and electrolyte imbalances, meticulous wound care and nutritional support appear to reduce the mortality rate, and allow spontaneous fistula closure in some patients. Definitive surgical management is performed only after restitution of normal physiology, usually after at least 6 months.

Adolescent↗
PubMed2000

A prospective study of gastric mucosal ischaemia in paracetamol-induced acute liver failure.

OBJECTIVE: To evaluate the time course of changes in the gastric mucosal pH (pHi) and the gastric mucosal to arterial CO2 gap (CO2 gap) following paracetamol-induced acute liver failure and to relate these variables to the severity of illness. DESIGN: Clinical prospective study. SETTING: A liver intensive care unit in a university teaching hospital. PATIENTS: Twenty-three patients with paracetamol-induced acute liver failure. INTERVENTIONS: Gastric tonometer placement. MEASUREMENTS AND MAIN RESULTS: Daily assessment of pHi and CO2 gap, the systemic organ failure assessment (SOFA) score for up to 9 days post-paracetamol ingestion. Both pHi and CO2 gap were within the normal range on entry into the study. The CO2 gap showed increases from the normal range on days 5-7 post-ingestion (P<0.01) and increases from study entry on days 4, 7, and 8 post-ingestion (P< 0.01). The pHi showed decreases from the normal range on days 4, 6, 7 and 9 post-ingestion (P< 0.01) and decreases from study entry on days 4, 5, 7, and 9 post-ingestion (P<0.01). There was no correlation found between pHi, CO2 gap, and the SOFA score. CONCLUSIONS: Paracetamol-induced acute liver failure is associated with increases in the CO2 gap and decreases in pHi between 4 to 9 days post-paracetamol ingestion. This may reflect changes in mesenteric blood flow related to hepatic regeneration. These changes may be in part responsible for some of the morbidity seen with this condition.

Acetaminophen↗
PubMed1998

The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans.

BACKGROUND & AIMS: The maintenance of the intestinal mucosal barrier may be energy dependent. Tacrolimus is a potent immunosuppressive drug that decreases mitochondrial adenosine triphosphate production and increases intestinal permeability in animals. METHODS: Twelve liver graft recipients receiving tacrolimus, 9 healthy volunteers, and 5 liver graft recipients not receiving immunosuppression underwent a combined absorption-permeability-mitochondrial function test using 5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O-methyl-D-glucose, 1 mg/kg 2-keto[1-13C]isocaproic acid ([13C]KICA), and 20 mg/kg L-leucine. The respiratory quotient and resting energy expenditure were measured by indirect calorimetry. Tacrolimus pharmacokinetic profiles and levels of endotoxin and IgM and IgG endotoxin core antibodies were determined. RESULTS: Tacrolimus inhibited the decarboxylation of [13C]KICA, the resting energy expenditure, and the respiratory quotient in an exposure-dependent manner, suggesting an inhibition of mitochondrial respiration. Tacrolimus inhibited intestinal absorptive capacity in an exposure-dependent manner. Tacrolimus-treated patients had an increased intestinal permeability and significantly higher endotoxin levels compared with healthy volunteers. CONCLUSIONS: Tacrolimus inhibits cellular energy production in humans at clinically relevant doses. This is associated with an increased intestinal permeability, endotoxemia, and an impaired intestinal absorptive capacity.

Adolescent↗
PubMed1996

Prospective randomized comparison of two different sized percutaneous endoscopically placed gastrostomy tubes.

We performed a prospective randomised study of two different sized percutaneous endoscopic gastrostomy (PEG) tubes to determine if tube size influenced the incidence of PEG-related complications. Patients were given prophylactic cefuroxime, if not already on antibiotics at the time of PEG insertion. Fifty-two PEGs were successfully placed, 26 in each group. Most patients who required a PEG had suffered a cerebrovascular event (82.7%). There were no procedure-related deaths. The mean ages (standard deviation) for the 12 and 20 French Gauge (FG) groups were 78.7 (8.9) and 73.9 (14.4) years, respectively, with no statistical difference. There were no significant differences in mortality (9 deaths in the 12 FG and 11 deaths in the 20 FG groups), number of peristomal infections (8 infections in the 12 FG and 12 infections in the 20 FG groups), episodes of leakage (12 leakages in the 12 FG and 17 leakages in the 20 FG groups) or tube blockage (2 blockage episodes in the 12 FG and 1 blockage episode in the 20 FG groups) between the two groups over a follow-up period of 190 days. The incidence of insertion- and feeding-related complications was thus not influenced by tube size. As the smaller PEG tubes were easier and less traumatic to insert we conclude that there are grounds for considering the more widespread use of the narrower diameter 12 FG PEG tubes.

Journal Article↗
PubMed1996

Lansoprazole, clarithromycin and metronidazole for seven days in Helicobacter pylori infection.

BACKGROUND: This study determines the efficacy and safety of a 1-week triple therapy regimen of lansoprazole, clarithromycin and metronidazole in an area with a high prevalence of pre-treatment metronidazole-resistant strains of Helicobacter pylori. METHODS: Seventy-five H. pylori positive patients with gastritis or duodenal ulcer were entered into an open study of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. H. pylori status was determined by CLOtest, histology, culture and by 13C-urea breath test (repeated > or = 28 days after treatment). RESULTS: Seventy-one patients completed the treatment and returned for follow-up. H. pylori was eradicated in 61 of 71 (86%) patients by per-protocol analysis, and in 61 of 75 (81%) patients by intention-to-treat analysis. H. pylori was eradicated in 12 of 16 (75%) patients with metronidazole-resistant strains compared with 22 of 24 (92%) in patients with metronidazole-sensitive strains of H. pylori (P = 0.14). Fourty-five patients reported at least one adverse event, and three patients stopped treatment due to them (two with headaches and one with diarrhoea). CONCLUSIONS: A 1-week course of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. eradicates H. pylori in up to 86% of patients. It is of proven benefit in patients with pre-treatment metronidazole-resistant strains of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMedDate not supplied

Referral patterns to a district general hospital gastroenterology outpatient clinic: implications for the 'two-week target'.

We defined the pattern and appropriateness of GPs' new-patient referrals to a large district general hospital gastroenterology department, and assessed the implications for workload in the context of the recently introduced 'two-week target'. Prospective data were collected on all new referrals over a two-month period and 426 new appointments were included, from which data were available on 390. Only six referrals were deemed inappropriate. Sixty-nine patients had a functional disorder, and GPs were less likely to diagnose this group at referral than the gastroenterologist was after the initial consultation. Nineteen per cent of all GP referrals were classified as urgent and 6% of these had a malignancy. Fifty per cent of patients with malignancy were not perceived as meriting an urgent referral by the GP Gastroenterology outpatient facilities are already overstretched and the implementation of the two-week target will add considerable strain to the current resources, with little gain in identifying malignancy.

Acute Disease↗