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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 343 records · Page 19Linked to original sources
PubMed1993

The cystic fibrosis gene and its product CFTR.

Cystic fibrosis is the commonest, fatal, inherited disease of caucasian populations occurring with a frequency of 1 in 2000 live births. The CF gene spans about 230 kb of genomic DNA and encodes a protein of 1480 amino acids named the cystic fibrosis transmembrane conductance regulator (CFTR). The primary sequence predicts that CFTR is an ABC type protein with twelve transmembrane spans, two nucleotide binding domains and a cytoplasmic regulatory domain. CFTR functions as a cyclic AMP-regulated, low conductance, chloride channel in epithelial cells, but other roles are possible. Failure of the CFTR channel in CF reduces epithelial salt and water secretion, leading to a dehydration of epithelial surfaces which initiates the pathology of the disease.

Chloride Channels↗
PubMed1993

Physical mapping shows close linkage between the alpha-galactosidase A gene (GLA) and the DXS178 locus.

X-linked agammaglobulinaemia (XLA) is an inherited disorder characterised by a lack of circulating B-cells and antibodies. While the gene involved in XLA has not yet been identified, the locus for the disorder is tightly linked to the polymorphic marker DXS178, which maps to Xq22. Fabry disease is an X-linked recessive disorder caused by a deficiency in the lysosomal enzyme alpha-galactosidase A. The gene encoding this enzyme has been characterized and also maps to Xq22. Using pulsed field gel electrophoresis we have constructed a long-range restriction map that shows that the alpha-galactosidase A gene (GLA) and DXS178 lie no more than 140 kb apart on a stretch of DNA containing a number of putative CpG islands. We have also isolated yeast artificial chromosome (YAC) clones that confirm this physical linkage. The localisation of DXS178 near the alpha-galactosidase A gene will facilitate carrier detection in Fabry families using restriction fragment length polymorphism (RFLP) analysis. The identification of a number of CpG islands near DXS178 also provides candidate locations for the gene responsible for XLA.

Agammaglobulinemia↗
PubMed1993

Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain.

The frequency of two common disease-associated mutations in the arylsulphatase A (ASA) gene, and of a mutation causing ASA pseudodeficiency, have been established in metachromatic leukodystrophy patients diagnosed in our laboratory. A total of 37 mutant genes have been analysed. The G-->A change destroying the splice donor site of exon 2 is generally associated with more severe disease and was found in 43.2% of mutant ASA genes. The C-->T transition causing a proline to leucine substitution at position 426 in exon 8 (P426-->L) is associated with later onset disease, and was found in 16.2% of mutant genes. The A-->G transition leading to loss of a polyadenylation signal associated with ASA pseudodeficiency was present at a frequency of 7.5% in the patients and heterozygotes studied.

Adenosine↗
PubMed1993

Loperamide abolishes exercise-induced orocecal liquid transit acceleration.

Previous work in our laboratory has found that mild physical activity accelerates mouth-to-large intestinal transit of lactulose in a mixed liquid meal. Because loperamide is commonly used as an antidiarrheal agent, we wondered if it would blunt the orocecal transit acceleration provoked by mild exercise. We investigated this equation in 12 healthy persons by comparing orocolonic liquid transit at rest and in mild exercise. Each subject ingested 8 mg loperamide 1 hr prior to study under both resting and exercise conditions. With loperamide treatment, exercise (walking at 5.6 km/hr) failed to hasten increased H2 excretion (mean transit time 72 +/- 12 min at rest, 90 +/- 15 min in exercise; P = NS). This result contrasts sharply with previously reported controls: loperamide completely abolished exercise-induced orocecal transit acceleration (-23 +/- 5 min in controls; +18 +/- 13 min with loperamide; P < 0.05). Compared with these same controls, resting transit was not significantly slowed by the drug, while transit in exercise was retarded (64 +/- 5 min in controls, 90 +/- 15 min with loperamide; P = 0.06). Loperamide left unchanged the heart rate and oxygen uptake rises associated with exercise. In summary, by showing that loperamide blocks an exercise effect on the upper gut, these results suggest that the drug might prove effective in treating some gut symptoms induced by physical activity.

Adult↗
PubMed1993

Butter in the initial treatment of hot tar burns.

Hot tar adheres to skin and produces burns of variable depth. Removal of the tar is not essential but it improves patient comfort and allows early assessment of the underlying tissue damage. Butter is readily available and is an effective method of removing the adherent tar.

Accidents, Occupational↗
PubMed1993

Effect of opiate and beta-adrenergic blockers on the gut transit response to mild exercise.

Acute mild exercise accelerates transit of material through the gastrointestinal tract via mechanisms that remain entirely unknown. Because exercise increases peripheral sympathetic drive, and can increase circulating opioids, in this study we examined the role that naloxone and propranolol-dependent pathways play in accelerating orocecal transit in exercise. Transit was determined in 11 subjects by H2 detection after ingestion of 0.36 g/kg lactulose in a 240 kcal, 250 ml liquid meal; the exercise was mild walking at 5.6 km/hr. Under naloxone treatment (0.4 mg intravenous bolus followed by infusion at 40 micrograms/kg/hr) transit acceleration in mild exercise was apparent: transit time (mean +/- SE) was 87 +/- 7 min at rest, 63 +/- 5 min in exercise (p < 0.05), a result identical to that seen in previous studies not involving drugs. In contrast, propranolol treatment (160 mg/day) accelerated the resting transit rate to equal the rate during exercise (65 +/- 6 vs. 60 +/- 4 min; p = NS). Under both conditions, exercise elevated oxygen consumption and heart rate, although propranolol predictably produced relative bradycardia at rest and exercise. These results suggest that mild exercise accelerates upper gut transit via an opiate-independent effect that, for gut propulsive motility, yields results similar to beta-adrenergic blockade.

Administration, Oral↗
PubMed1993

Missense mutations in the arylsulphatase A genes of metachromatic leukodystrophy patients.

Novel predicted disease-causing mutations have been defined in three patients with metachromatic leukodystrophy (MLD). The first new mutation is a C-->A change at base 884 in exon 5 of the arylsulphatase A (ASA) gene causing a serine to tyrosine substitution at position 295 of the protein (S295Y). A late-infantile MLD patient was found to be homozygous for this mutation. The second mutation is a G-->A substitution at nucleotide 1144 in exon 7, that causes a glutamic acid to lysine substitution at amino acid 382 (E382K). A juvenile MLD patients was found to be homozygous for this mutation. Finally an adult MLD patient has been shown to be heterozygous for two novel point mutations in exon 3. These are both C-->T changes at position 635 and 671 that result in alanine to valine substitutions at amino acids 212 (A212V) and 224 (A224V) of the ASA protein.

Adult↗
PubMed1993

Expression of the cystic fibrosis gene in human foetal tissues.

In order to examine the onset of the cystic fibrosis (CF) disease process, the expression of the cystic fibrosis gene (CFTR) has been examined in mid-trimester human foetal tissues by in situ hybridization. CFTR mRNA was detected in the epithelia of pancreatic ducts, small intestine, colon, genital ducts, lung and trachea. The majority of these sites of CFTR expression in the foetus are similar to those seen in adult tissues. However, epithelia of the lung, that contain very little CFTR mRNA in the adult, express high levels of CFTR mRNA in the foetus. Since the lung is the major site of pathology and morbidity in CF these findings have implications for treatment.

Cystic Fibrosis↗
PubMed1993

Abnormal mRNA splicing resulting from three different mutations in the CFTR gene.

Three different putative splicing mutations in the CFTR gene have been studied by analysing mRNA extracted from nasal epithelial cells harvested from patients with cystic fibrosis. Six patients were analysed, all of whom had classical symptoms of cystic fibrosis (CF). Two patients carried the 621 + 1G-->T mutation, 3 patients carried the 1717 - 1G-->A mutation and 1 patient carried the 1898 + 1G-->A mutation. All patients carried the delta F508 mutation on the other chromosome. Ten non-CF control subjects were also studied. The 621 + 1G-->T mutation resulted in activation of an alternative splice site within exon 4 in one patient and activation of this site or skipping of exon 4 in the other patient. The 1717 - 1G-->A mutation resulted in skipping of exon 11 in all 3 patients studied and the 1898 + 1G-->T mutation resulted in skipping of exon 12. These experiments demonstrate that these mutations do result in aberrant splicing of CFTR mRNA as predicted from the changes in genomic sequence.

Base Sequence↗
PubMed1993

Localization of expression of the cystic fibrosis gene in human pancreatic development.

Cystic fibrosis (CF) is a disease that affects the function of specialized epithelial cells within the lungs, gut, pancreas, sweat glands, and male genital ducts. Following the cloning of the CF gene, it is possible to examine tissue-specific expression of this gene. To investigate the onset of the CF disease process, expression of the CF gene in midtrimester human fetal tissues has been analyzed by in situ hybridization using antisense RNA probes. The major site of CF gene expression at this stage of development is in the pancreas. Within the pancreas, CF mRNA is seen to be largely restricted to the epithelium of intralobular and small interlobular ducts.

Cystic Fibrosis↗
PubMed1993

Nursing and medical staffing in neonatal units.

Organizational aspects of neonatal care were documented in a large scale national survey: these included the provision of cots, the nursing establishment, medical staffing and the use of nurses qualified in the specialty. Fifty-six unidentified neonatal units in England were contacted and information requested on staffing arrangements, policies and facilities. To gain an accurate picture, four representative units were selected in each health region: a regional centre, a sub-regional centre and two district units. Comparisons were made using data on cot provision, the nursing establishment set, the numbers of trained nurses and medical staffing in the target units. Large inter-unit differences were found and in many units the levels of staffing were found to be at lower levels than those recommended. The relationship between the nursing establishment and numbers of designated cots was examined using different models of staffing based on successive recommendations. The more recent the recommendation, the greater the discrepancy between the establishment in operation and that recommended. Large inter-unit variation was also found in the proportion of staff qualified in the specialty, ranging from 0% to 92% of qualified nurses in individual units. Overall 1544 (83%) trained nurses were working in the study units, of whom 820 (53%) were qualified in the specialty. Significant differences were found between the types of unit: regional and sub-regional units had a higher 'Qualified in Specialty' rate (50% and 49%) than district units (32%).(ABSTRACT TRUNCATED AT 250 WORDS)

England↗
PubMed1993

Gaucher's disease in the United Kingdom: screening non-Jewish patients for the two common mutations.

Twenty-six patients with Gaucher's disease diagnosed in the United Kingdom and two obligate carriers, all of non-Jewish origin, were screened for the two common disease causing mutations and two rarer mutations in the glucocerebrosidase gene. These mutations are referred to as N370S, L444P, Ins84G, and 1066 + 1G-->A, respectively. The results showed that out of 54 alleles screened, 26% were N370S, 35% were L444P, and the remaining 39% were rare or undefined. The results also showed a clear correlation between the presence of at least one N370S allele and mild disease.

Alleles↗
PubMed1993

Expression of the cystic fibrosis gene and the major pancreatic mucin gene, MUC1, in human ductal epithelial cells.

The main pathology of cystic fibrosis results from obstruction of ducts in several organs by mucous secretions. The cause of this obstruction remains unclear. We have examined expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and of the major pancreatic mucin, MUC1, in primary pancreatic duct and vas deferens epithelial cells, and in pancreatic duct cell lines. MUC1 is expressed at a high level in the primary ductal epithelial cells and at variable levels in different pancreatic adenocarcinoma cell lines. However, although the pancreatic duct is one of the sites in vivo where CFTR transcription is at its highest level, the majority of cell lines examined no longer express CFTR. Only one pancreatic duct cell line, Capan 1, expresses CFTR at a significant level; further, the level of expression is dependent on confluency. We have shown that salt stress alone is not sufficient to account for the build-up of mucous secretions in CF ducts.

Adenocarcinoma↗
PubMed1993

Cost-effective management of pharyngocutaneous fistulas following laryngectomy.

A pharyngocutaneous fistula following a total laryngectomy is not an uncommon occurrence. The incidence of this serious complication ranges worldwide from 7.6 percent to 50 percent. It usually exacerbates post-operative morbidity and increases expense with prolonged hospitalization. This complication often requires additional operative procedures or if untreated may lead to a fatal complication such as carotid artery rupture. There are multiple predisposing factors leading to poor wound healing in this patient population. These factors include prior radiation therapy, chemotherapy, compromised nutrition, and associated surgical procedures including radical neck dissection. A treatment strategy for difficult fistulas with undermining is presented here. The cornerstones of this approach include opening the area large enough for packing and cleansing, diverting the copious pharyngeal secretions and providing an optimal wound environment through the use of an amorphous hydrogel dressing (Intrasite* Gel, Smith & Nephew United, Inc., Largo, FL). This treatment strategy led to complete and sustained healing when utilized by the authors in the following patients. It was successful even in heavily irradiated tissue with its severe changes of compromised vascularity, increased dermal fibrosis and epidermal thinning. The authors have found this technique a cost-effective alternative to secondary surgery, applicable in both the acute and home care settings.

Adult↗
PubMed1993

Perceived strategic and practical problems in the use of information technology for quality improvement in diabetes care in the United Kingdom.

Quality Assurance in Diabetes Care is a new aspect of our National Health Service Reforms linked to the publication of a Patient's Charter. If current pressures are maintained, most diabetics in UK will soon receive their diabetes care from their General Practitioner, often based in a Group Practice where structured care for chronic diseases is more easy to organise. Large inner cities like London have special problems not adequately addressed in resource allocation. Penetration of computers into General Practice is forecast in many areas to be approaching 100% within the next two years but few systems will be able to provide useful support for structured diabetes care. Organisational issues concerning treatment protocols, contracts for care, quality assessment and audit are daunting and will take time to agree and install. The British Diabetic Association and The Royal College of Physicians have a joint initiative in developing a National Audit Dataset for Diabetes Care which is compatible with WHO's DiabCare. Current information systems in hospital and community care are inadequate to monitor the St Vincent "End points" and it is unlikely that things will improve sufficiently quickly to either facilitate or document progress towards the St Vincent Objectives. The Government have not included diabetes in their strategic plans for the next five years. As a result, it seems unlikely that Diabetes Care in the UK will meet the St Vincent Objectives by 1995.

Age Factors↗
PubMed1993

Physicians' attitudes to the autopsy.

The overall autopsy rate (excluding coroner's autopsies) at a large teaching district general hospital over a four year period was 16.5%, but individual rates for ten general physicians varied from 5% to 35%. During this period, the mean autopsy rate for general medicine (14%) was significantly lower than rates for cardiology (21%), geriatrics (23%) and paediatrics (36%), but similar to general surgery (13%). Autopsies were widely perceived as being of benefit to education and research, but physicians were often unaware of their value for confirming the diagnosis and for clinical audit, and over-estimated their actual autopsy rates on average by 50%. High rates (18-30%) were associated with consultants who had a definite policy regarding autopsies and had made this clear to their junior staff. Low rates (6-10%) obtained where there was no consultant policy on autopsies, and were frequently attributed by the consultant physicians to failure by their junior staff. Physicians should be more aware of the value of autopsies, and should take responsibility for increasing and monitoring autopsy requests to improve clinical audit, quality assurance and medical education.

Attitude of Health Personnel↗