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Biomedical subjects

G Neale

Publications and source records attributed to G Neale.

At least 19 recordsLinked to original sources

Reducing risks in gastroenterological practice.

Eighty five malpractice claims against gastroenterologists have been analysed. Thirty seven (44%) arose from adverse events as a result of endoscopy and 48 (56%) from clinical practice. In 31 (84%) of the endoscopy cases (including all 13 endoscopic retrograde cholangiopancreatographies) there seemed to be significant fault. In nine cases the procedure was not clearly indicated and in 10 recognition and treatment of the adverse event was delayed. In no case had the patient given adequate informed consent. Diagnostic error was responsible for most of the claims related to clinical practice (31 of 48) of which 13 were indefensible. Failure to obtain an adequate history (17 cases) and insufficient awareness of disorders of the small intense (12 cases) were major factors. In 26 cases a key investigation was not performed. Seventeen claims were related to management or treatment but only one of these cases was difficult to defend. Overall, there was evidence of serious fault in 50% of claims. Greater care in selecting patients for endoscopic procedures and in providing postprocedural care would have eliminated the basis of more than half the claims arising from endoscopy. There would have been few claims if properly informed consent had been obtained. Over-ready acceptance of the diagnosis of a functional disorder (for example, irritable bowel, dyspepsia) was the usual cause of delays in diagnosis.

Clinical Competence

Nutritional aspects of dissimilatory sulfate reduction in the human large intestine.

In contrast to other anaerobic ecosystems, such as marine and estuarine sediments, there is a lack of information on the nutritional requirements of human gut sulfate-reducing bacteria (SRB). Various substrates stimulated sulfate reduction in mixed culture, including short-chain fatty acids and other organic acids, alcohols, and amino acids (but not sugars or aromatic compounds). However, the use of sodium molybdate as a specific inhibitor of sulfate reduction caused an accumulation of ethanol and malonate only, and reduced the rate of utilization of lactate. This indicates the importance of these electron donors for sulfate reduction. Since ethanol and lactate are primarily utilized by members of the Desulfovibrio genus, the results suggest a physiologically important role for this group. Experiments with two strains of Desulfovibrio desulfuricans isolated from human feces demonstrated that both were able to reduce sulfite, thiosulfate or nitrate in the absence of sulfate. In addition, one strain (DsvUC1) was able to grow by fermentative metabolism, although the second strain (DsvFD1) showed more restricted fermentative growth. The data indicate that desulfovibrios are ecologically the most significant group of SRB in the human colon, and that colonic isolates belonging to this genus are versatile, in terms of both the electron acceptors and donors that they are able to utilize.

Acetates

Acquired intestinal aganglionosis and circulating autoantibodies without neoplasia or other neural involvement.

The clinical course, diagnosis, and treatment of 2 patients with acquired intestinal aganglionosis without other neurological involvement or neoplasia are described. They initially presented with constipation and abdominal pain in late childhood. They were found to have enteric ganglionitis with a loss of neurons together with vacuolated nerve cells surrounded by CD3- and CD4-positive T lymphocytes. This process initially affected only the colon but later the entire gastrointestinal tract was involved in 1 patient. Associated with this process there were circulating immunoglobulin G class enteric neuronal antibodies in high titer (1:5000-8000). The staining of central nervous system neuronal nuclei and Western blotting indicated the presence of antineuronal nuclear protein antibodies of the ANNA-1 (anti-Hu) type usually associated with paraneoplastic sensory neuropathy. However, the reaction pattern in enteric neurons was quite different with strong reaction to perikarya and only weak staining of nuclear antigens.

Adolescent

Radionuclide studies in intestinal transplantation. Diagnosis of rejection and assessment of permeability.

Three patients who received intestinal allografts were studied using two distinct radionuclide investigations. In the first, 111In or 99mTc-labeled leukocyte scanning was performed to assist in the diagnosis of rejection. It was able to demonstrate the occurrence of rejection in the transplanted intestine, and the response to antirejection therapy. In 1 case, the abnormality on the scan preceded the histological confirmation of rejection. The second technique studied mucosal integrity by serial 51Cr-EDTA/14C-mannitol permeability tests. These studies demonstrated the initial marked impairment and the slow return to normal function of the intestinal mucosal barrier. In 1 patient, this occurred by 91 days; in another, it took 232 days. A single assay performed in the third patient at the time of allograft rejection was also abnormal. Both radionuclide tests were helpful in the care of these complicated cases.

Adult

Home enteral tube feeding in East Anglia.

OBJECTIVE: To establish the profile of patients receiving home enteral tube feeding (HETF) in East Anglia, to assess the adequacy of care, and to consider the causes and implications of differences in the geographic prevalence of HETF. DESIGN: A 1-year prospective study. SETTING: Eight independently funded districts within East Anglia. SUBJECTS: Basic clinical data were available from 234 patients, 191 of which were tube-fed in the same district as that which initiated treatment, with detailed data obtained from 126. OUTCOME MEASURES: Prevalence, complications in relation to the dietetic support available, and standards of care in relation to those set in the reports of the King's Fund and the British Association of Parenteral and Enteral Nutrition. RESULTS: The patients, who were usually elderly subjects or children, had severe disabilities: 40% were unable to walk: 39% were unable to speak; and 20% were housebound. In all cases enteral tube feeding had been initiated in hospital but in this survey we found inadequate training for home care in 23%, inadequate support and follow-up in 20%, inadequate equipment in 41%, uncertainties regarding organisation, and various clinical problems such as feed regurgitation, in 22%, aspiration pneumonia in 13% , which occasionally led to hospitalization (4%), and frequent but usually minor peristomal problems in patients with gastrostomies. There was a direct correlation between the prevalence of HETF (which varied fourfold between districts) and the number of NHS dieticians per head of population; and in inverse correlation with respect to requests by patients for more support (r = 0.97), complaints of blocked tubes (r = 0.82) and the need for hospital help. CONCLUSION: HETF provides an important form of support to a small group of severely disabled patients. There are important differences between districts in the prevalence of HETF which may be related to variation in local expertise and available support staff. The standards of care did not always conform to those set in the King's Fund report and BAPEN report on Enteral and Parenteral Nutrition in the community.

Adolescent

Clinical analysis of 100 medicolegal cases.

OBJECTIVE: To find the reasons for legal claims against hospital doctors. DESIGN: Prospective analysis of requests for medical opinion submitted by solicitors during 1984-93 on legal claims against hospital doctors. SUBJECTS: 100 successive cases: 98 from the United Kingdom and two from the Republic of Ireland. MAIN OUTCOME MEASURES: Principal underlying causes of claims. RESULTS: In 44 cases there was no serious clinical error. Of the 56 cases of clinical fault, seven were a failure of communication by doctors, 15 were an isolated error in otherwise good clinical management, 21 were errors that might not have occurred with better control of clinical practice (doctors exceeding their competence, poor clinical judgment, and poor teamwork), and 13 were major errors due to carelessness or incompetence. In 34 cases there was evidence of clinical fault that might escape clinical audit and medicolegal processes. Most of these legal claims have been or are likely to be withdrawn: only five plaintiffs have settled out of court, and 11 are pursuing their actions. CONCLUSIONS: To reduce the incidence of errors, hospital doctors should consult colleagues about difficult cases and specialists should maintain a broad interest in disease. The NHS clinical complaints procedure should be extended to cover potential claims, and serious cases should be subject to independent external assessment by experienced consultants.

Clinical Competence

Impaired IgA response to Giardia heat shock antigen in children with persistent diarrhoea and giardiasis.

The serum antibody response in Gambian children with persistent diarrhoea and giardiasis has been studied. Total serum IgG, IgA, and IgM concentrations were increased in these patients as compared with controls from the same area. Determination of the concentrations of Giardia specific antibodies by enzyme linked immuno adsorbent assay (ELISA), however, revealed that only IgM was raised while those of IgA and IgG were similar to the controls. Analysis of the antigenic determinants of the IgG and IgA responses by immunoblotting showed that patients with chronic infection unlike those who clear the infection have no IgA response to a 57 kDa Giardia heat shock antigen. The association of high concentrations of Giardia specific IgM, low concentrations of Giardia specific IgA and IgG and inability to clear the infection suggests that the switch from an IgM to an IgG or IgA response is inefficient.

Animals

Persistent diarrhea and malnutrition--the impact of treatment on small bowel structure and permeability.

Previous studies using dual sugar permeability tests suggested that damage to the small intestinal mucosa plays an important part in the development of persistent diarrhea in The Gambia. The present study has extended these findings by examining the effect of nutritional rehabilitation on intestinal permeability and mucosal morphology. Intestinal permeability, measured by lactulose:mannitol (L:M) absorption, and mucosal structure, measured by a quantitative, computerised morphologic technique, were evaluated in 20 children before and after such treatment. L:M ratios were high on admission, (0.66 +/- 0.36) and, despite some temporary improvement, did not significantly improve (0.49 +/- 0.30) following rehabilitation for one month. The changes in L:M ratio were largely due to an increase in lactulose absorption, showing that the small intestinal mucosa becomes more "leaky" as a result of nutritional rehabilitation. Although no correlation was found between measures of intestinal permeability and mucosal morphology, nutritional restitution was associated with a significant increase in size of the mucosal crypt cell compartment, but not in villous epithelial volumes during the same period. It is necessary to establish, by further prospective studies, the interval required for full restitution of small intestinal structure and function during treatment for persistent diarrhea.

Anti-Bacterial Agents

para-amino benzoic acid in the assessment of completeness of 24-hour urine collections from hospital outpatients and the effect of impaired renal function.

Eighteen (29%) of 24-h urine collections made by 63 hospital outpatients attending a gastroenterology clinic were incomplete, as judged by 24 h urine recovery of an oral marker, para-amino benzoic acid (PABA), despite more than the usual efforts to obtain complete collections. Incomplete collections contained significantly less sodium, urea and total nitrogen than full collections. Average outputs were 134 mmol and 103 mmol per day for sodium (P less than 0.02); 301 mmol and 223 mmol for urea (P less than 0.001); and 10.1 g and 8.3 g nitrogen (P less than 0.01) in the complete and incomplete collections respectively. In renal outpatients with a plasma creatinine in excess of 125 mumol per litre, urine recoveries of PABA were reduced, but within the expected range in renal patients whose plasma creatinine was normal.

4-Aminobenzoic Acid

Chronic diarrhea and malnutrition--histology of the small intestinal lesion.

The purpose of this study was to quantitate the jejunal lesion in Gambian children with chronic diarrhea-malnutrition syndrome. There were 40 subjects (20 male, 20 female) with a mean age of 19.7 months. All were severely malnourished, with marasmus in 30, marasmic kwashiorkor in 9, and kwashiorkor in 1. Of subjects tested, 70% were anergic to intradermal challenge with either purified protein derivative or candidin. Jejunal biopsies, performed on every subject after admission to hospital, were studied by computerised image analysis and immunocytochemistry. A spectrum of mucosal changes that varied from "normal" to "flat" was seen. Mucosae with "normal" architecture revealed infiltration of villous epithelium by small lymphocytes, while crypt hypertrophy was invariably present. At the other extreme, the surface epithelium of flat mucosae was less severely infiltrated, although heavy lymphoid infiltrates persisted within crypt epithelium. Immunohistochemical studies revealed that most intraepithelial lymphocytes were of the CD8 + phenotype. Mucosal morphology did not relate to clinical, biochemical, or anthropometric data for each child. These findings are consistent with an intestinal reaction to some environmental antigen (dietary, microbial, or both) of the cell-mediated type. This interpretation is strengthened by the expression of major histocompatibility class 2D locus alloantigens on crypt epithelial cells in the absence of gut-reactive autoantibodies.

Biopsy

The treatment of persistent diarrhoea and malnutrition: long-term effects of in-patient rehabilitation.

This study aimed to characterise the clinical condition of Gambian children presenting with persistent diarrhoea and severe protein energy malnutrition and to evaluate the effects of short term in-patient treatment in terms of long-term outcome. Twenty-two children (aged 6 to 36 months) with persistent diarrhoea (greater than or equal to four loose stools/day for more than two weeks) and severe malnutrition (weight-for-height less than 75% of the National Center for Health Statistics median value) were assessed prior to in-patient treatment for three weeks with antibiotics and high nutrient-density milk. Initial assessment included biochemical and immunological status together with stool microbiology. Criteria for discharge--cessation of diarrhoea for five consecutive days and steady weight gain--were met in all subjects within four weeks. Progress was assessed clinically and anthropometrically at weekly intervals and 6 and 12 months following discharge. Results showed a steady improvement in growth during the period of in-patient treatment. Continuing improvement in weight-for-age and mid-upper arm circumference was observed after 6 and 12 months and weight-for-height continued to improve up to 6 months but fell back by 12 months. This study has demonstrated that, in the treatment of persistent diarrhoea in the tropics, relatively short periods of in-patient rehabilitation, whilst leading to a resolution of diarrhoeal symptoms and weight gain in the short term, do not lead to complete recovery. Persistent diarrhoea and malnutrition are likely to recur when the child returns to his village.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry

Prevalence and treatment of giardiasis in chronic diarrhoea and malnutrition.

To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished children without diarrhoea were giardia positive. Twenty-three children with chronic diarrhoea were reinvestigated after treatment with metronidazole; giardia was found in 11 of them. These results show that giardia is highly prevalent in children with chronic diarrhoea and malnutrition and that the infection does not respond to standard therapeutic measures.

Animals