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Biomedical subjects

A N Smith

Publications and source records attributed to A N Smith.

At least 37 records · Page 2Linked to original sources
PubMed1998

A search for type 1 diabetes susceptibility genes in families from the United Kingdom.

Genetic analysis of a mouse model of major histocompatability complex (MHC)-associated autoimmune type 1 (insulin-dependent) diabetes mellitus (IDDM) has shown that the disease is caused by a combination of a major effect at the MHC and at least ten other susceptibility loci elsewhere in the genome. A genome-wide scan of 93 affected sibpair families (ASP) from the UK (UK93) indicated a similar genetic basis for human type 1 diabetes, with the major genetic component at the MHC locus (IDDM1) explaining 34% of the familial clustering of the disease (lambda(s)=2.5; refs 3,4). In the present report, we have analysed a further 263 multiplex families from the same population (UK263) to provide a total UK data set of 356 ASP families (UK356). Only four regions of the genome outside IDDM1/MHC, which was still the only major locus detected, were not excluded at lambda(s)=3 and lod=-2, of which two showed evidence of linkage: chromosome 10p13-p11 (maximum lod score (MLS)=4.7, P=3x10(-6), lambda(s)=1.56) and chromosome 16q22-16q24 (MLS=3.4, P=6.5x10(-5), lambda(s)=1.6). These and other novel regions, including chromosome 14q12-q21 and chromosome 19p13-19q13, could potentially harbour disease loci but confirmation and fine mapping cannot be pursued effectively using conventional linkage analysis. Instead, more powerful linkage disequilibrium-based and haplotype mapping approaches must be used; such data is already emerging for several type 1 diabetes loci detected initially by linkage.

Adolescent↗
PubMed1998

Tyler asbestos workers: mortality experience in a cohort exposed to amosite.

OBJECTIVES: To examine the causes of death among 1130 former workers of a plant in Tyler, Texas dedicated to the manufacture of asbestos pipe insulation materials. This cohort is important and unusual because it used amosite as the only asbestiform mineral in the production process. High level exposure of such a specific type was documented through industrial hygiene surveys in the plant. METHODS: Deaths were ascertained through various sources including data tapes from the Texas Department of Health and the national death index files. As many death certificates as possible were secured (304/315) and cause of death assigned. After select exclusions, 222 death certificates were used in the analysis. Causes of death were compared with age, race, and sex specific mortalities for the United States population with a commercial software package (OCMAP Version 2.0). RESULTS: There was an excess of deaths from respiratory cancer including the bronchus, trachea, and lung (standardised mortality ratio (SMR) 277 with 95% confidence interval (95% CI) 193 to 385). Four pleural mesotheliomas and two peritoneal mesotheliomas were identified. The analysis also showed an increasing risk of respiratory malignancy with increased duration of exposure including a significant excess of total deaths from respiratory cancer with less than six months of work at the plant (SMR 268 with 95% CI 172 to 399). CONCLUSIONS: The importance of the cohort lies with the pure amosite exposure which took place in the plant and the extended period of latency which has followed. The death certificate analysis indicates the pathogenicity of amosite, the predominant commercial amphibole used in the United States. These data confirm a link between amosite asbestos and respiratory malignancy as well as mesothelioma.

Adult↗
PubMed1997

Bile duct brushings cytology: potential pitfalls in diagnosis.

Bile duct brushings (BDB) are the method of choice for pathological diagnosis of malignancy of the hepatobiliary system in our institution. We examined results of the cytological assessment of 267 BDB and compared them with biopsies, which were available in 131 cases. Sensitivity of BDB for diagnosis of malignancy was 44% and specificity 100%, in keeping with the experience of others. The review of "false-negative cases" reveals four main reasons for the relatively modest sensitivity of BDB in diagnosis of malignancy: poor sampling, lack of diagnostic criteria for dysplasia-carcinoma in situ, difficulties in recognition of special tumor types, and underestimating the significance of the smear background. After a critical review and with regard to these issues, the sensitivity of BDB in our series could have been improved to 78%. We conclude that BDB can give a confident and definitive diagnosis of malignancy, which can be relied upon without a tissue biopsy. A negative result does not exclude malignancy.

Bile Duct Neoplasms↗
PubMed1997

Rectal hypersensitivity in the irritable bowel syndrome.

Studies of rectal sensory thresholds and compliance in patients with the irritable bowel syndrome have produced conflicting results though there is persistent evidence of rectal hypersensitivity particularly in those with diarrhoea-predominant symptoms. This study examined rectal sensation and compliance in 31 patients with constipation-predominant irritable bowel syndrome (mean age 41 years, 27 female) and 17 healthy volunteers (mean age 45 years, 17 female). A rectal balloon was inflated with fluid at a constant rate and the volume and intrarectal pressure at sensory threshold was recorded. The volumes at first (129 +/- 8 vs 229 +/- 24 ml, P < 0.001 Mann-Whitney-U test), constant (159 +/- 12 vs 286 +/- 21, P < 0.001) and maximum tolerated sensation (290 +/- 13 vs 509 +/- 19, P < 0.001) were all significantly less in the irritable bowel group. There was no significant difference in intrarectal pressures at any of these volumes (29.0 +/- 2.2 cmH2O vs 29.0 +/- 2.5, 35.0 +/- 2.5 vs 34.0 +/- 2.8, 71 +/- 2.5 vs 65.0 +/- 3.0 respectively). Rectal compliance was significantly less in the irritable bowel group (3.6 +/- 0.2 ml/cmH2O vs 8.7 +/- 0.4, P < 0.001). Twenty two patients complained of abdominal pain on balloon inflation, mimicking that experienced as part of their symptoms. Patients with constipation-predominant irritable bowel syndrome have rectal hypersensitivity and reduced compliance.

Adult↗
PubMed1997

A survey of routine head CT protocols in Australia.

The choice of scanning protocol in CT will affect the dose delivered to the patient. A nationwide survey of CT operators was carried out in Australia in 1994 to determine the variation in routine head CT protocols. Only 29% of respondents used the supraorbitomeatal (SOM) baseline and thus avoided scanning the eyes. At 74% of sites, the routine protocol included scans both before and after injection of contrast. However, the post-contrast protocol differed from that used in the pre-contrast series in a number of cases. Where 5 mm thick slices were used, the mAs was 16% higher than for 10 mm thick slices. Increased awareness of the influence of baseline, slice thickness/spacing and accompanying exposure factors on patient dose may lead to greater standardization of head CT scanning protocols.

Adult↗
PubMed1996

A regulatory element in intron 1 of the cystic fibrosis transmembrane conductance regulator gene.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene exhibits a tightly regulated pattern of expression in human epithelial cells. The mechanism of this regulation is complex and is likely to involve a number of genetic elements that effect temporal and spatial expression. To date none of the elements that have been identified in the CFTR promoter regulate tissue-specific expression. We have identified a putative regulatory element within the first intron of the CFTR gene at 181+10kb. The region containing this element was first identified as a DNase I hypersensitive site that was present in cells that express the CFTR gene but absent from cells not transcribing CFTR. In vitro analysis of binding of proteins to this region of DNA sequence by gel mobility shift assays and DNase I footprinting revealed that some proteins that are only present in CFTR-expressing cells bound to specific elements, and other proteins that bound to adjacent elements were present in all epithelial cells irrespective of their CFTR expression status. When assayed in transient expression systems in a cell line expressing CFTR endogenously, this DNA sequence augmented reporter gene expression through activation of the CFTR promoter but had no effect in nonexpressing cells.

Base Sequence↗
PubMed1996

Use of HIV-1 specific immunoglobulin G3 as a serological marker of vertical transmission.

The objective of the study was to indicate HIV infection in infants. The patients were part of a longitudinal cohort of 43 infants born to HIV seropositive mothers. A modified Genelavia EIA primarily directed against HIV envelope proteins was used. An alkaline phosphatase labelled IgG3 conjugate was substituted in place of the kit conjugate. HIV specific IgG3 clearance was optimal at 6 months, whilst HIV total antibody was reliable only from age 12 months onwards. At 6 months no detectable IgG3 were found in 91 per cent of uninfected infants where more of these infants had reduced their total HIV antibody titres at the same period. We confirm that HIV specific IgG3 measurement is a reliable and cost effective means of identifying HIV infected infants from 6 months of age onwards.

Biomarkers↗
PubMed1995

cAMP-activated chloride channels in a CFTR-transfected pancreatic adenocarcinoma-derived cell line, pANS6.

Pancreatic adenocarcinoma cell lines rarely express the CFTR gene, despite the high levels of CFTR protein that are present in primary pancreatic duct cells. We have attempted to generate a non-CF pancreatic adenocarcinoma cell line that stably produces high levels of CFTR mRNA and protein by transfecting a vector containing the CFTR cDNA, driven by a strong mammalian promoter, into the poorly differentiated pancreatic adenocarcinoma cell line, Panc-1. The pANS6 pancreatic duct cell line expresses substantial levels of CFTR mRNA, but little CFTR protein. Despite this we were able to detect low conductance chloride channels in 40% of patches, stimulated with cAMP, that have similar biophysical properties to CFTR.

Adenocarcinoma↗
PubMed1995

Characterization of DNASE I hypersensitive sites in the 120kb 5' to the CFTR gene.

The chromatin structure of 120kb of genomic DNA 5' to the CFTR gene has been analysed in a number of CFTR expressing and non-expressing cell types, including primary genital duct epithelial cells. Novel DNAse I hypersensitive sites have been observed at -79.5kb and -20.5kb 5' to the ATG translation start codon of the CFTR coding sequence. Neither of these sites appears to show strong correlation with CFTR expression in the cell types investigated, hence they are unlikely to reflect the sites of binding of the major CFTR tissue specific regulator(s). However, they may still play an important part in the complex series of events involved in the regulation of CFTR transcription.

Base Sequence↗
PubMed1995

Serological screening for sexually transmitted infections in pregnancy: is there any value in re-screening for HIV and syphilis at the time of delivery?

OBJECTIVE: The aim of this study was to assess the prevalence of syphilis, human immunodeficiency virus (HIV), and hepatitis B virus (HBV) infections in women at the time of delivery, and to determine the seroconversion rates for syphilis and HIV infections from initial booking visit to delivery. SETTING: The labour ward of a typical tertiary hospital in a developing country and serving an indigent African population. METHOD: Four hundred and eighteen women presenting in labour were randomly selected and informed consent obtained for serological testing for syphilis and HBV infections in umbilical cord blood samples. The specimens were then given a study number, the gestational ages recorded and anonymously tested for HIV infection. RESULTS: Of the 191 women who had antenatal care, 13 (6.8%) were HIV antibody positive at the initial "booking" visit. An additional 4 were found to be HIV antibody positive at the time of delivery resulting in a seroconversion rate of 2.2%. The seroconversion rate for syphilis at the time of delivery was 2.7%. Hepatitis B surface antigens were detected in only 2 women, one of whom was antigen positive. CONCLUSION: The high seroconversion rates for both syphilis and HIV infection in pregnancy justifies re-screening for these conditions in endemic areas such as ours.

Delivery, Obstetric↗
PubMed1995

Suprascapular neuropathy in a collegiate pitcher.

A healthy, 20-year-old, highly competitive collegiate baseball pitcher developed vague pain and soreness in the dominant posterior shoulder with live pitching. The symptoms intensified, and, after a particularly poor starting performance, the athlete presented for physical examination. Examination revealed visible atrophy of the infraspinatus muscle and decreased strength in external rotation and abduction. Magnetic Resonance Imaging was inconclusive. Electromyographic examination revealed decreased suprascapular nerve conduction to the infraspinatus muscle. Our diagnosis was entrapment neuropathy from traction on the suprascapular nerve at the spinoglenoid notch, causing delayed conduction to the infraspinatus muscle. We took a conservative approach of shoulder rehabilitation and activity modification, which resulted in the athlete returning to a highly competitive level without further problems, despite the remaining atrophy and muscle weakness. Examination of injuries to the shoulder complex, especially in athletes involved in repetitive overhead motions, should take suprascapular neuropathy into consideration.

Journal Article↗
PubMed1994

Obstructive defaecation and slow transit constipation: the proctographic parameters.

Twenty-two patients with functional obstructive defaecation were compared with seven patients with slow transit constipation using isotope proctography. The obstructive defaecation patients were unable to perform a complete rectal evacuation (% of the activity evacuated: 54%). The defaecation time in this group was prolonged (120 s) with a lower defaecation rate (0.5%/s) compared with the slow transit constipation subjects (32 s and 1.8%/s). The anorectal angle (ARA) on straining did not change in the obstructive defaecation patients but became more obtuse in the slow transit constipation subjects (P < 0.02). The pelvic floor (PF) descent on straining and evacuation was greater in obstructive defaecation patients compared with the slow transit constipation ones (P < 0.01). Obstructive defaecation is characterised by prolonged defaecation and reduced defaecation rate compared with slow transit constipation. Obstructive defaecation patients present with more acute ARAs on straining, and abnormal perineal descent in contrast to the slow transit constipation ones.

Adult↗
PubMed1994

Effects of biofeedback on obstructive defecation--reconditioning of the defecation reflex?

Twenty two patients with obstructive defecation were recruited for relaxation training by domiciliary self regulatory biofeedback. Each patient served as his or her own control for anorectal and proctographic assessments. Biofeedback training improved the obstructive symptoms of the patients and showed significant change in various parameters related to the obstructive defecation syndrome. As examined by isotope dynamic proctography: the defecation rate (% of evacuation/defecation time) was significantly increased (p < 0.05), the anorectal angles at rest and during attempted defecation were made more obtuse (p < 0.05), and the pelvic floor movements were made more dynamic on voluntary contraction of the anal sphincter (p < 0.03). The external anal sphincter electromyographic voltage recorded during defecation was significantly reduced (p < 0.0005) as was the surface anal plug electromyographic electrode voltage (p < 0.0001), which was associated with a greatly reduced anismus index (p < 0.0001). The rectal sensation was improved (p < 0.05), concomitantly. Biofeedback thus improves the defecation act in patients suffering from inappropriate contraction of the pelvic floor and sphincter musculature. Furthermore, this study has shown that biofeedback objectively influences the defecation reflex leading to an improved quality of higher control of bowel function.

Adult↗
PubMed1994

Significance of the thickness of the anal sphincters with age and its relevance in faecal incontinence.

BACKGROUND: Ultrasonographic studies in healthy volunteers showed that the external anal sphincter (EAS) and internal anal sphincter (IAS) thicknesses were inversely related at rest. The functional importance of the two sphincters in continence control was demonstrated in the relationship between the sum of the thicknesses of the two sphincters and the anal canal resting pressure. The aims of the present study were to assess the morphometric appearance of the anal sphincters by endosonography in faecally incontinent patients and to contrast this with that of older healthy subjects. METHODS: Twenty-eight female patients with neurogenic faecal incontinence (FI) were studied. An older group of 7 healthy women, aged 41-75 years, and a young group of 11 nulliparous healthy women, aged 20-23 years, served as control groups. Anal endosonography was performed with a radial rotating endoprobe, with the subject in the left lateral position. Conventional anal manometry was performed in all subjects. RESULTS: The EAS in the FI group was thicker than the EAS in the old (p < 0.04) but did not differ from the EAS in the young. The IAS thickness in the FI group did not differ from that in the older group. In both these groups the IAS was thicker than in the young women (p < 0.01). The anal pressures in the FI group were reduced compared with the normal groups (p < 0.04). There was a direct relationship between the two sphincters in FI (p < 0.001). CONCLUSIONS: The increased thickness of the IAS in the FI group does not seem to compensate for function and results in a failure of the sphincter mechanism to maintain continence, whereas in healthy elderly subjects the increased IAS thickness appears to be compensatory and important for continence control.

Adult↗
PubMed1993

A regional audit of the investigation and treatment of colorectal and pelvic floor disorders (1984-1991).

The activities of a regional physiology unit established for the investigation of colorectal and pelvic floor physiology in health and disease in a clinically relevant setting has been audited and its evolution described over a period of eight years. Trends in surgical treatment of some of these disorders over the same period have also been documented in the Lothian Region. Although there has been little change in the number of patients investigated annually patterns of investigation appear to change. Sphincter manometry, proctometrography and somatosensory reflex measurements have remained the most frequently performed and useful investigations. Spinal stimulation studies increased transiently because of a collaborative investigation of bowel and bladder function in patients with spinal injuries. A considerable increase in surface EMG tests and dynamic proctography has occurred. These trends are thought to be related to interest in defining evacuation dysfunction of the rectum and related problems of the pelvic floor. Isotope proctography now rivals barium videoproctography; at the same time the use of manometric colonic motility studies has diminished. Anal ultrasonography has replaced sphincter mapping in the last year and is being applied to other aspects of anorectal pathology. The last 4 years have seen the introduction and increasing use of non-surgical therapeutic modalities for the treatment of faecal incontinence and constipation: reflex electronic sphincter stimulation, biofeedback and the use of a prokinetic agent to promote colonic motility. Concomitant changes in the surgery of constipation and reconstructive anorectal procedures have been observed. It is recommended that coloproctology units should have easy access to at least one such investigation laboratory within their catchment area together with appropriate auditing facilities.

Colonic Diseases↗
PubMed1993

Evaluation of isotope proctography in constipated subjects.

Twelve patients with longstanding constipation were examined by isotope proctography. Radio-labelled potato mash was inserted rectally to provoke the urge to defaecate and expulsive manoeuvres were recorded using a Gamma-camera. The method illustrated dynamic alterations in the anorectal angles (ARA) which became more acute on 'squeezing', less so on coughing and more obtuse on straining, and maximally so on evacuation. The pelvic floor (PF) movements were consistently upwards on squeezing, less so on coughing, downwards on straining, and maximally so on evacuation. A useful addition was the measurement of the completeness of evacuation and the time involved. The results were comparable to radiological videoproctography (P < 0.01), but the isotope method gave greater discrimination for both ARA and PF movement changes. It also allowed correlations to be made between the pelvic floor descent (P < 0.05) and anorectal angle changes (P < 0.01) with rectal evacuation.

Adult↗
PubMed1993

Anal endosonography in asymptomatic subjects.

The anal sphincter thickness was measured ultrasonographically in 30 asymptomatic subjects (13 male and 17 female: 23 young and 7 old). The internal anal sphincter (IAS) was measured at its thickest portion in the anal canal, its borders lying between the submucosa and the external and sphincter (EAS). The EAS was measured at the lowermost point in the anal canal, its borders being the IAS and the coccyx. The EAS was thicker in men than in women (p < 0.02). The IAS showed no difference with regard to gender. The EAS became thinner with age (p < 0.005), whereas the IAS appeared thicker with age (p < 0.0002). The EAS thickness correlated inversely with the IAS thickness (p < 0.001). Anorectal manometry showed a correlation between the anal canal resting pressure and the sum of the thickness of the two sphincters (p < 0.001). Thus, although the visualized thickness of the two sphincters vary, they do so proportionally, and their sum reflects their tonic activity.

Adult↗