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Biomedical subjects

S J Williams

Publications and source records attributed to S J Williams.

At least 55 records · Page 3Linked to original sources

Quantitative competitive polymerase chain reaction: analysis of amplified products of the HIV-1 gag gene by capillary electrophoresis with laser-induced fluorescence detection.

A quantitative competitive polymerase chain reaction (PCR) assay for the detection and quantification of HIV-1 has been developed using capillary electrophoresis. Separation of the PCR products is carried out in coated capillaries filled with replaceable linear polyacrylamide, and detection is performed using laser-induced fluorescence. The quantitative capabilities of this assay are described. We show results from analysis of a noninfectious plasmid encoding the HIV genome and integrated proviral DNA. Potential applications of this assay are discussed.

Cell Line↗

Fast capillary electrophoresis-laser induced fluorescence analysis of ligase chain reaction products: human mitochondrial DNA point mutations causing Leber's hereditary optic neuropathy.

High speed capillary electrophoresis-laser-induced fluorescence (CE-LIF) has been used to separate and detect point mutations using the ligase chain reaction (LCR). The method utilizes short capillary columns (7.5 cm effective length) and fields of 400 V/cm to analyze DNA-ethidium bromide complexes using an He/Ne laser. The method was first demonstrated with a commercially available kit for LCR based on a lacI gene fragment inserted in a Bluescript II phagemid. LCR-CE-LIF was then applied to detect point mutations in human mitochondrial DNA, resulting in Leber's hereditary optic neuropathy (LHON). Three severe mutations were analyzed in which the original base is substituted by a thymidine base at positions 3460, 11778 and 14459. Appropriate primers were designed with polyT tails for length discrimination of pooled samples. Successful detection of mutated samples was achieved, with appropriate correction for small amounts of nonspecific ligated product. The method is rapid, easy to implement, and automatable.

Base Sequence↗

Measuring health status? A review of the sickness impact and functional limitations profiles.

Recent years have witnessed a growing interest in the measurement of health status. One of the most well-known health status instruments is the Sickness Impact Profile (SIP). This paper examines the nature, development and testing of the SIP (and its UK equivalent the FLP). The practical merits of these instruments are explained, and some cautionary remarks are offered about their limitations.

Evaluation Studies as Topic↗

The 'limits' of medicalization?: modern medicine and the lay populace in 'late' modernity.

Taking as its point of departure the medicalization thesis and its limitations, this paper provides a critical discussion of certain more recent theoretical perspectives on life in contemporary society, and their relevance for understanding the relationship between modern medicine and the lay populace. In particular, attention is paid to the contours and existential parameters of life in 'late' modernity in terms of the following four key themes: (i) modernity as a 'reflexive' social order, (ii) 'risk' and the dialectic of scientific and social rationality; (iii) the "mediation' of contemporary experience; and (iv) lay 're-skilling' and the 'life political' agenda. On the basis of this, it is argued that far from being simply passive and dependent, a 'critical distance' is beginning to emerge between modern medicine and the lay populace; a situation which resonates with broader social trends and currents within society at large.

Aged↗

The end of the road? Lay views on a pain-relief clinic.

Studies of the lay evaluation of pain-relief clinics are rare, particularly in the U.K. Hence, in an attempt to rectify this lacuna, this paper reports the findings of a small-scale qualitative study which charts the vicissitudes of hope and despair of attenders at pain-relief clinics in London. In doing so, we demonstrate the complex interplay between peoples' pain careers, their styles of adjustment, socio-demographic characteristics, and their evaluations of medical treatment. Sadly, for many of these patients, this was the end of the road and their last hope of finding relief. Unfortunately, however, the overarching feeling was of medicine having "failed" them. The paper concludes with a discussion of these findings and some suggestions for possible future research in this area.

Adaptation, Psychological↗

Laser palliation of inoperable malignant dysphagia: initial and at death.

BACKGROUND: Nd: YAG laser therapy has been shown to be highly effective in the palliation of dysphagia due to inoperable esophageal malignancy. However, the duration of response and the degree of palliation present at death have not been adequately addressed. METHODS: Seventy consecutive patients with inoperable malignant dysphagia (mean age, 70 years; 48 men, 22 women) underwent palliative laser therapy. Dysphagia was assessed on a 5-point scale (0, normal; 4, complete dysphagia) before and after laser therapy and within 2 weeks of death. RESULTS: Ninety-six percent of patients were palliated initially (70% successful, 26% partial). Mean swallowing score improved from 2.3 to 1.1 (p < 0.001) with a mean of 1.9 initial treatment sessions. Swallowing score remained improved in the last two weeks of life at a mean of 1.7 (p < 0.001). Seventy-three percent of patients were palliated at death (36% successful, 37% partial); median survival was six months. The mean total number of laser sessions was 3.4, with a mean time interval between laser sessions of 27.2 days. Complications included one perforation (1.4%) resulting in death. CONCLUSION: Endoscopic laser therapy provides safe and effective initial palliation of inoperable malignant dysphagia. In the majority of patients the palliation is maintained until death.

Aged↗

Endoscopic laser division of an esophageal web in a child.

The authors report the first successful endoscopic laser division of a congenital esophageal web in a child in whom dilatation had failed. Laser lysis is minimally invasive and should be attempted before surgery is considered.

Dilatation↗

Determinants of non-compliance and attrition in the elderly.

BACKGROUND: This report identifies demographic and health-related baseline factors associated with non-compliance and attrition in elderly subjects participating in a preventive intervention study over a 4-year follow-up period. METHODS: The Cox proportional hazards model and polychotomous logistic regression were used to evaluate time to clinic assessment non-compliance and type of non-participation. RESULTS: Of 1785 subjects, 35.6 percent were non-compliant during follow-up which meant they were eligible to participate at the time they were contacted but would not or could not return for an assessment. Refusals due to a lack of continuing interest or being too busy,and those citing health problems constituted the major subgroups of non-compliers. Death, unable to contact, and ineligible due to disenrollment or moving away accounted for nearly 20 percent. Four-year compliance was achieved by 44.4 percent of the participants. Time to non-compliance was significantly shorter with older age, lower annual income, poorer personal health ranking, and, to a marginal extent, depression. Lower annual income was associated with all reasons for non-participation including disenrollment or moving. Other factors correlated with specific types of nonparticipation. CONCLUSIONS: These results can be useful in designing more effective cohort maintenance strategies. Greater resources may be allocated to subgroups who are less likely to continue.

Aged↗

Medical staff leadership: a national panel survey.

Dramatic change in health care has challenged traditional medical staff governance and leadership. The role of medical staff leaders, particularly the chief of staff, and of the medical executive committee is explored through a national panel survey.

Decision Making, Organizational↗

Endoscopic laser therapy for watermelon stomach.

Eleven patients (nine females, two males) with anaemia due to acute and chronic gastrointestinal blood loss were found to have gastric antral vascular ectasia (watermelon stomach). Nine patients were transfusion-dependent, receiving a mean of 13.1 units over a mean period of 12.3 months. All patients received neodymium:yttrium-aluminium-garnet laser coagulation with a median of 3.0 treatment sessions. Post-treatment transfusion needs were abolished in six patients and minimal in two patients during a mean follow up of 27.3 months (range 12-60 months). Overall there was a mean reduction in transfusion requirement with treatment from 2.5 units per month to 0.4 units per month (P < 0.02). Mean pretreatment haemoglobin improved from 7.7 to 11.9 g/dL after treatment (P < 0.001). No complications occurred. Laser coagulation is safe and effective treatment for anaemia due to watermelon stomach and should be considered as first line therapy.

Aged↗

Comparison of three faecal occult blood tests in the detection of colorectal neoplasia.

METHODS AND AIMS: For the detection of colorectal neoplasia, 192 consecutive patients had colonoscopy to evaluate the sensitivity and specificity of three faecal occult blood tests (FOBT). Of 160 evaluable patients (96 female, mean age 51.9), 21 patients (13.1%) had adenomas and three patients (1.9%) had colorectal carcinoma. RESULTS: When comparing all three faecal occult blood tests for the detection of colorectal neoplasia, the sensitivity of Monohaem (43.8%) was superior to both Hemoccult II (25%) and to BM-Test colon albumin (25%). The specificity of Monohaem (94.6%) was greater than both Hemoccult II (88%) and BM-Test colon albumin (89%). Using McNemar's test, Monohaem was a more accurate FOBT than Hemoccult II and BM-Test albumin (p < 0.05). In the 21 patients with adenomatous polyps, FOBT sensitivity seemed to be dependent on polyp size, but not polyp site. CONCLUSIONS: Monohaem, a feacal occult blood test that uses a monoclonal antibody that is specific for human haemoglobin, is a more accurate test in the detection of colorectal neoplasia and should possibly be used in colorectal cancer screening programmes.

Adenoma↗

Spinal projection neurons to the laterodorsal pontine tegmental nucleus: relationship to preganglionic neurons and nitric oxide synthase.

The region of the rat sacral parasympathetic nucleus (SPN) contains distinct subpopulations of neurons that project supraspinally or are preganglionic neurons. Some preganglionic neurons in the SPN serve as the motor outflow for urinary bladder contraction; other neurons in the SPN project to regions of the rostral pons that subserve micturition reflexes. Previous studies utilizing immunohistochemistry or staining for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) have demonstrated that numerous neurons in the SPN contain nitric oxide synthase (NOS), the enzyme for nitric oxide synthesis. Thus, the objectives of this study were to determine 1) the distribution of neurons in the region of the SPN that project to the laterodorsal tegmentum (LDT) of the pons, 2) whether spinal neurons projecting to a peripheral autonomic ganglion also project to the LDT, and 3) whether NOS or NADPH-d is present in LDT projection neurons. Preganglionic neurons were identified by injecting the retrograde tracer fluorogold (FG) into the major pelvic ganglion (MPG). Supraspinally projecting neurons were identified by injecting the retrograde tracer fast blue (FB) into the LDT. Numerous FB-labeled neurons were present in the ipsi- and contralateral SPN and were immediately dorsal to FG-labeled preganglionic neurons. Neurons containing both tracers were not observed. Approximately 20% of preganglionic neurons, but no LDT projection neurons, were reactive for NOS and NADPH-d. These data suggest that the region of the SPN is a site for distinct subpopulations of neurons that project to the LDT and to the MPG and that NOS is contained in some preganglionic neurons, but is not a marker for LDT projection neurons.

Amidines↗

Interferon alfa for chronic active hepatitis B. Long term follow-up of 62 patients: outcomes and predictors of response.

OBJECTIVE: To evaluate the response to treatment with interferon alfa and the long term outcome of patients with chronic active hepatitis B. METHODS: Sixty-two patients with chronic active hepatitis B (43 males, 19 females; age range, 10-67 years) who were treated with interferon alfa at Westmead Hospital between 1984 and 1992 were followed up (mean period of follow-up, 44 months). Thirty-nine patients were treated with interferon alfa-2a and 23 with interferon alfa-2b for a mean of 22.5 weeks. Interferon was given three times a week with a dose range of 3-21 million U. We evaluated pretreatment predictors of response (patient's age, sex, ethnic origin, presence of cirrhosis, serum levels of alanine aminotransferase [ALT] and hepatitis B virus DNA [HBV-DNA]) and the effect of dose and type of interferon. RESULTS: Nine patients had a complete response to treatment with interferon alfa (loss of hepatitis B surface antigen), 26 had a partial response (permanently HBV-DNA negative, hepatitis B e antigen to anti-hepatitis Be seroconversion), eight had a transient response and 19 had no response. All patients with a complete response had normal ALT levels at last follow-up. Histological evidence of hepatic inflammation was significantly reduced in responders. A high pretreatment ALT level and a low HBV-DNA titre were both positive predictors of a favourable response. We found no significant difference in the response to different types of interferon or to high or low dose regimens, or in the responses of patients with cirrhosis. CONCLUSION: Treatment with interferon alfa was associated with prolonged suppression of HBV replication in over half these patients and 14% appear to have been cured of the infection. Suppression of HBV replication is associated with sustained abatement of liver disease.

Adult↗

Parasympathetic preganglionic neurons in the spinal cord involved in uterine innervation are cholinergic and nitric oxide-containing.

BACKGROUND: The purpose of this study was to elucidate parasympathetic preganglionic neurons in the spinal cord that project axons in pathways to the uterus and to reveal their neurotransmitter phenotype. METHODS: "Uterine-related" neurons were identified by using a combination of retrograde axonal tracers: (1) Fluorogold injected into the ganglia of termination of preganglionic fibers, and (2) a transganglionic axonal tracer (pseudorabies virus) injected into the uterus. Immunohistochemistry was used to reveal virus-labeled neurons and their neurotransmitter marker. RESULTS: Double-labeled (Fluorogold+pseudorabies virus) "uterine" preganglionic neurons were identified in the sacral parasympathetic nucleus of the rat lumbosacral spinal cord. Subpopulations of neurons in the sacral parasympathetic nucleus were shown to be immunoreactive for choline acetyltransferase or nitric oxide synthase. Double-staining immunohistochemistry (for pseudorabies virus+neurotransmitter enzyme) revealed that some of the uterine-related preganglionic neurons were cholinergic and some nitric oxide synthase-containing. CONCLUSIONS: These results demonstrate a subpopulation of preganglionic parasympathetic neurons in the sacral parasympathetic nucleus that are involved in uterine innervation. In addition, both acetylcholine and nitric oxide could be used to modify activity in the postganglionic neurons, which directly innervate the uterus.

Acetylcholine↗

Nitric oxide, an enteric nonadrenergic-noncholinergic relaxant transmitter: evidence using phosphodiesterase V and nitric oxide synthase inhibition.

1. The effects of NG-nitro-L-arginine (L-NOARG), a nitric oxide synthase inhibitor, and SK&F 96231, a phosphodiesterase type V inhibitor, on electrical field stimulated (EFS) nonadrenergic noncholinergic (NANC) relaxations of rat fundal strips, guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, and guinea-pig taenia caeci were investigated. 2. Reproducible repeated control random EFS frequency-response curves were obtained for all three tissues. 3. Depending on the frequency of stimulation, L-NOARG (10(-4)-5 x 10(-3) M) caused either a complete or partial inhibition of the NANC-induced relaxations of the rat fundal strips and the guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea-pig taenia caeci. The inhibitory action of L-NOARG was partially or totally reversed, depending on the tissue, by L-arginine (5 x 10(-3) M). 4. SK&F 96231 (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation of both the size and duration of the EFS-induced NANC relaxant response of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea-pig taenia caeci. 5. Zaprinast, another phosphodiesterase type V inhibitor (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation of the NANC relaxant responses to EFS of rat fundal strips. 6. SK&F 96231 and zaprinast alone (10(-6)-10(-4) M) caused a concentration-dependent relaxation of the agonist-induced tone of all three tissues with the maximum degree of relaxation found to be in the order stomach < ileum < caecum. This is the reverse order for ability of SK&F 96231 to potentiate relaxant responses to EFS. 7. These results suggest NO is involved in the NANC nerve-mediated relaxation of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not the guinea-pig taenia caeci.

Animals↗

Identifying depressive symptoms among elderly Medicare HMO enrollees.

Increasing attention has been devoted to the urgent need for identifying depressive symptomatology at the primary care point of contact for older individuals to prevent more serious disease and potential negative behavioral outcomes. Delivering medical care services in a system that is sensitive to the symptoms of depression may lead to greater cost-effectiveness and improved quality of life. This paper examines the correlates of depression in a random sample of 1800 Medicare beneficiaries enrolled in a risk-sharing HMO. Ten percent of the total sample reported a high degree of depressive symptoms, as measured by the CES-D score. The prevalence of depressive symptoms was significantly higher for those who were not married, reported less well-developed social support networks, had low perceived ability to control future health, or had poorer health status. Depressive symptoms were also associated with a greater number of physician office visits and higher ambulatory charges, although no significant relationship was found for inpatient use or total charges. Practical approaches to monitoring depressive symptomatology at the primary care level in an HMO are suggested.

Aged↗

Changes in health behaviors of older adults: the San Diego Medicare Preventive Health Project.

BACKGROUND: This study presents behavioral outcomes at 1-year follow-up from a preventive services intervention trial with Medicare beneficiaries. METHODS: The health promotion package consisted of goal setting and counseling based on a health risk appraisal and a series of eight educational sessions. All subjects completed a health risk appraisal questionnaire immediately prior to the intervention and 1 year later; this served as the dependent measure. RESULTS: Results indicated that there were significant, positive changes in intervention subjects in activity level and selected nutrition behaviors relative to control subjects. The strengths and weaknesses of a broad-based approach to intervention are discussed.

Aged↗

Item non-response to lifestyle assessment in an elderly cohort.

BACKGROUND: Greater attention is being paid to data quality in surveys of older age groups. In this paper patterns of item non-response are examined in a health risk appraisal instrument administered to an elderly cohort participating in a randomized preventive intervention study. METHODS: The association between demographic and health status factors with the number of non-responses out of 174 items was examined at baseline and at the 12-month follow-up on 1791 subjects. RESULTS: Overall, non-response decreased from baseline to 12 months. The pattern was consistent across the seven major components of the questionnaire. Univariate analyses at baseline found that item non-response increased significantly (P < 0.05) with age, being female, being unmarried, lower annual income, less education, and poorer personal health ranking. Polychotomous logistic regression identified age and personal health ranking as statistically significant at both baseline and 12-month follow-up assessments after controlling for all other factors. In addition, education was significant at baseline. CONCLUSIONS: These results help to identify subgroups of elderly participants who contribute to non-random patterns of missing data.

Aged↗