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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 631 records · Page 35Linked to original sources
PubMed1995

Chromosome 11q13 markers and D-type cyclins in breast cancer.

One in six primary human breast cancers has DNA amplification centered on the cyclin D1 gene (CCND1) on chromosome 11q13. This genetic abnormality is preferentially associated with estrogen-receptor positive tumors and may define a sub-class of patients with an adverse prognosis. Although CCND1 has the credentials of a cellular oncogene, being a target for chromosomal translocation and retroviral integration, the 11q13 amplicon encompasses several other markers and CCND1 is not the only candidate for the key gene on the amplified DNA. To assess their relative importance, we have constructed a physical map of the amplified DNA and compared the extent and frequency of amplification across the region. Since it is likely that the gene providing the selective force for amplification will be expressed at elevated levels, we have also examined expression of both RNA and protein. By these criteria, cyclin D1 remains the strongest candidate for the key oncogene on the amplicon and we are currently investigating the functional consequences of its over-expression.

Breast Neoplasms↗
PubMed1995

Fish odour syndrome: verification of carrier detection test.

An oral trimethylamine challenge test has been used to confirm the heterozygous status of patients with 'fish-odour syndrome'. By measuring the percentage of total urinary trimethylamine-related material excreted as the N-oxide, no discrimination could be made between obligate heterozygotes (parents of 'fish-odour syndrome' patients) (n = 15; 96 +/- 2%, range 92-98%) and control individuals (parents of unaffected children) (n = 16; 96 +/- 2%, range 93-99%) on a normal diet. However, after ingesting a trimethylamine load (600 mg base) the obligate heterozygotes were clearly distinguishable (76 +/- 3%, range 71-79%) from controls (95 +/- 2%, range 91-99%) (t-test; p <0.001). One of a hundred apparently normal volunteers who were subsequently challenged with trimethylamine had a N-oxidation capacity which fell within the range found among the obligate heterozygotes.

Adult↗
PubMed1995

Characteristics of cloned cerebrovascular endothelial cells following infection with Theiler's virus. I. Acute infection.

The present study describes the replication of Theiler's virus in cloned cerebrovascular endothelial cells (CVE) isolated from strains of mice that are either susceptible or resistant to Theiler's virus-induced demyelination (TVID). CVE isolated from all strains of mice were equally permissive to Theiler's virus infection. Interferon-gamma and tumor necrosis factor-alpha were found to inhibit the replication of Theiler's virus in CVE. A correlation between susceptibility to demyelination and the ability of Theiler's virus to induce MHC Class I on CVE was demonstrated.

Acute Disease↗
PubMed1995

Characteristics of cloned cerebrovascular endothelial cells following infection with Theiler's virus. II. Persistent infection.

Cloned cerebrovascular endothelial cells (CVE) persistently infected with Theiler's virus (PI-CVE) have been established and characterized. The CVE were derived from strains of mice that are susceptible (SJL/J and CBA) and resistant (BALB/c) to Theiler's virus-induced demyelination (TVID). The cells were persistently infected with either the BeAn or GDVII strains of Theiler's virus in vitro and studied at various passage levels for infectious virus, viral antigen and the expression of major histocompatibility complex (MHC) Class I and II antigens. The virus replicated to lower titers than in acutely infected CVE and appeared to be more cell-associated. Flow cytometric analysis revealed that 18-39% of the PI-CVE contained viral antigen. Persistently infected CVE derived from SJL/J and CBA mice expressed high levels of MHC Class I, whereas BALB/c PI-CVE did not. MHC Class II was upregulated by IFN-gamma in SJL/J PI-CVE albeit at a slightly lower level than in uninfected CVE. In addition, the PI-CVE demonstrated increased levels of mRNA for IL-1 beta when compared to uninfected CVE.

Animals↗
PubMed1995

The effects of running and meditation on beta-endorphin, corticotropin-releasing hormone and cortisol in plasma, and on mood.

The relations between three hormones of the hypothalamic-pituitary-adrenocortical (HPA) axis, beta-endorphin (beta-EP), corticotropin-releasing hormone (CRH) and cortisol, and mood change were examined in 11 elite runners and 12 highly trained mediators matched in age, sex, and personality. Despite metabolic differences between running and meditation, we predicted that mood change after these activities would be similar when associated with similar hormonal change. Compared to pre-test and control values, mood was elevated after both activities but not significantly different between the two groups at post-test. There were significant elevations of beta-EP and CRH after running and of CRH after meditation, but no significant differences in CRH increases between groups. CRH was correlated with positive mood changes after running and mediation. Cortisol levels were generally high but erratic in both groups. We conclude that positive affect is associated with plasma CRH immunoreactivity which itself is significantly associated with circulating beta-EP supporting a role for CRH in the release of beta-EP. Increased CRH immunoreactivity following meditation indicates, however, that physical exercise is not an essential requirement for CRH release.

Adult↗
PubMed1995

The elective use of oxytocin infusion during labour in nulliparous women using epidural analgesia: a randomised double-blind placebo-controlled trial.

The obstetric outcome following the elective use of oxytocin infusion was determined in a randomised, double-blind placebo-controlled trial. 93 nulliparous women in a London hospital, who had requested epidural analgesia in labour (</= 6 cm.), were given an infusion of oxytocin (n = 46) or placebo (n = 47). The initial epidural dose was 15 ml of 0.125% bupivacaine, followed by an infusion at 10 ml per h, with 15 ml top-ups if required. When oxytocin was used electively there was a reduction in the length of the first stage of labour from 696 min to 578 min, (P < 0.05) even though more than half of the control group (53%) required oxytocin augmentation. There was no significant difference between the number of operative deliveries (34 [74%] vs 35 [74%]). The rotational delivery rate was less in the study group (2 [4%] vs 5 [11%]), though this did not reach significance. There were no adverse effects on the fetus, as judged by cord pH measurement, Apgar score, admission to the special care baby unit and neonatal jaundice. The prophylactic use of oxytocin in nulliparous women with epidurals reduces the length of the first stage of labour and appears to be safe. It does not reduce the operative delivery rate.

Journal Article↗
PubMed1995

A placental clock controlling the length of human pregnancy.

We report the existence of a 'placental clock', which is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women we have demonstrated that placental secretion of corticotropin-releasing hormone (CRH) is a marker of this process and that measurement of the maternal plasma CRH concentration as early as 16-20 weeks of gestation identifies groups of women who are destined to experience normal term, preterm or post-term delivery. Further, we report that the exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH binding protein in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at a time that coincides with the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans.

Biological Clocks↗
PubMed1995

Type I collagen biosynthesis by skin fibroblasts from patients with idiopathic juvenile osteoporosis.

1. Skin fibroblast lines were cultured from nine patients who had the features of idiopathic juvenile osteoporosis, six relatives, five unrelated control subjects and three unrelated patients with osteogenesis imperfecta type I. Some patients with idiopathic juvenile osteoporosis were adults whose previous osteoporosis was in remission. Two patients with idiopathic juvenile osteoporosis were siblings and one patient with idiopathic juvenile osteoporosis had a daughter with severe osteogenesis imperfecta (type III). 2. The ratio of type III to type I collagen, synthesized by fibroblasts, was increased in two of the patients with osteogenesis imperfecta type I and in the daughter with osteogenesis imperfecta type III, but was normal in all the other patients with idiopathic juvenile osteoporosis and the other relatives. 3. Radiolabelled collagen was digested by cyanogen bromide and separated on SDS-PAGE. Unreduced collagen peptides migrated normally, except those from both the two siblings with idiopathic juvenile osteoporosis. In these two lines, abnormal migration suggested the presence of collagen I mutations. 4. The secretion of synthesized collagen by these two idiopathic juvenile osteoporosis lines and two others was reduced to only 43-45% as compared with a line from a 13-year-old control subject, which was defined as 100%. The three osteogenesis imperfecta type I lines secreted 18-37%, the other five idiopathic juvenile osteoporosis lines secreted 57-75%, the relatives (including the daughter with severe osteogenesis imperfecta) secreted 49-115% and the controls secreted 69-102%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Idiopathic juvenile osteoporosis: experience of twenty-one patients.

The features and outcome of 21 children (12 boys, nine girls) with idopathic juvenile osteoporosis (IJO) followed for up to 23 yr are described. The mean age of onset was 7 yr (range 1-13 yr) with no sex difference; the main presenting symptoms were long bone fractures, pain in the back and difficulty in walking. Typically, radiographs demonstrated compression of the vertebrae and metaphyses of the long bones; bone histology sometimes showed an excess of osteocytes associated with woven bone; routine biochemistry was normal for age; and with three exceptions no abnormalities of extracted dermal collagen or collagen synthesized by fibroblasts were detected. Where circulating vitamin D metabolites were measured they were within the normal range; and hip and spine bone mineral density (measured by DXA) was strikingly low. Five patients are still growing and two are currently untraceable. Of the remaining 14 who are now adults, 11 have substantially or completely recovered and three are disabled. Since spontaneous recovery occurs it remains impossible to assess the many forms of treatment given.

Age of Onset↗
PubMed1995

Phenotypic and pathologic evaluation of the myd mouse. A candidate model for facioscapulohumeral dystrophy.

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease of unknown pathogenesis which is characterized by weakness of the face and shoulder girdle. It is associated with a sensorineural hearing loss which may be subclinical. FSHD has been mapped to the distal most portion of 4q35, although the gene has not yet been identified. Distal 4q has homology with a region of mouse chromosome 8 to which a mouse mutant, myodystrophy (myd), has been mapped. Muscle from homozygotes for the myd mutation appears dystrophic, showing degenerating and regenerating fibers, inflammatory infiltrates, central nuclei, and variation in fiber size. Brainstem auditory evoked potentials reveal a sensorineural hearing loss in myd homozygotes. Based on the homologous genetic map locations, and the phenotypic syndrome of dystrophic muscle with sensorineural hearing loss, we suggest that myd represents an animal model for the human disease FSHD.

Animals↗
PubMed1995

Selecting an exposure lag period.

In epidemiology, there is an inclination to consider more credible the larger estimates of exposure effect. For example, higher relative risks or rate ratios are often emphasized as a criterion for choosing among various hypothesized exposure-lag values. An alternative criterion for this choice might be based on a goodness-of-fit measure. We present examples, based on hypothetical data, in which an exposure-lag parameter is estimated by trial and error fitting: we compare the behavior of the likelihood-ratio goodness-of-fit statistic obtained over the assigned values of the parameter with that of the relative risk. We show that there can be inconsistencies between the highest-estimate and likelihood-based goodness-of-fit criteria. Concern about the validity of the highest-estimate criterion prompts us to recommend that this criterion not be used for the estimation of exposure-weighting parameters, which should preferably be based on a priori biological knowledge or on goodness-of-fit criteria.

Case-Control Studies↗
PubMed1995

A model for technology assessment as applied to closed loop infusion systems. Technology Assessment Task Force of the Society of Critical Care Medicine.

OBJECTIVES: To test a model for the assessment of critical care technology on closed loop infusion control, a technology that is in its early stages of development and testing on human subjects. DATA SOURCES: A computer-assisted search of the English language literature and reviews of the gathered data by experts in the field of closed loop infusion control systems. STUDY SELECTION: Studies relating to closed loop infusion control that addressed one or more of the questions contained in our technology assessment template were analyzed. Study design was not a factor in article selection. However, the lack of well-designed clinical outcome studies was an important factor in determining our conclusions. DATA EXTRACTION: A focus person summarized the data from the selected studies that related to each of the assessment questions. The preliminary data summary developed by the focus person was further analyzed and refined by the task force. Experts in closed loop systems were then added to the group to review the summary provided by the task force. These experts' comments were considered by the task force and this final consensus report was developed. DATA SYNTHESIS: Closed loop system control is a technological concept that may be applicable to several aspects of critical care practice. This is a technology in the early stages of evolution and much more research and data are needed before its introduction into usual clinical practice. Furthermore, each specific application and each device for each application (e.g., nitroprusside infusion, ventilator adjustment), although based on the same technological concept, are sufficiently different in terms of hardware and computer algorithms to require independent validation studies. CONCLUSIONS: Closed loop infusion systems may have a role in critical care practice. However, for most applications, further development is required to move this technology from the innovation phase to the point where it can be evaluated so that its role in critical car practice can be defined. Each application of closed loop infusion systems must be independently validated by appropriately designed research studies. Users should be provided with the clinical parameters driving each closed loop system so that they can ensure that it agrees with their opinion of acceptable medical practice. Clinical researchers and leaders in industry should collaborate to perform the scientifically valid, outcome-based research that is necessary to evaluate the effect of this new technology. The original model we developed for technology assessment required the addition of several more questions to produce a complete analysis of an emerging technology. An emerging technology should be systematically assessed (using a model such as the model developed by the Society of Critical Care Medicine), before its introduction into clinical practice in order to provide a focus for human outcome validation trials and to minimize the possibility of widespread use of an unproven technology.

Algorithms↗
PubMed1995

Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha-interferon with steroid priming.

BACKGROUND: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pretreatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. METHODS: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. RESULTS: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. CONCLUSION: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.

Adult↗
PubMed1995

A double-blind, placebo controlled study of the effect of the specific histamine H1-receptor antagonist, terfenadine, in chronic severe asthma.

1. The characteristic changes seen in asthma are widely regarded as being caused by local mediator release in the airways, with histamine the first putative mediator in asthma to be identified. 2. We performed a double-blind, randomised, placebo-controlled crossover trial of the effect of 4 weeks treatment with terfenadine 120 mg twice daily in chronic severe asthma. 3. Forty-two subjects (20 male and 22 female) completed the 10 week study. 4. Terfenadine had no significant treatment effect on the primary efficacy variables measured. Mean (95% CI) measurements for terfenadine vs placebo treatment periods were 1.5 vs 1.5 (-0.3, 0.3) l for FEV1, 259 vs 260 (-42, 40) l min-1 for morning PEF and 0.8 vs 0.8 (-0.3, 0.3) for global symptom scores. 5. Bronchodilator use and sleep disturbance, the secondary efficacy variables studied, showed an improvement during terfenadine treatment but this only reached statistical significance for the number of times subjects awoke from sleep (P = 0.04). 6. There was a similar frequency of minor adverse effects reported during placebo (13.6%) and terfenadine (16.7%) treatments. 7. Addition of the potent and specific histamine H1-receptor antagonist terfenadine to maintenance asthma treatment had no significant therapeutic benefit in this group of chronic severe asthmatics.

Adult↗
PubMed1995

Role of re-screening of cervical smears in internal quality control.

AIMS: To investigate the use of rapid re-screening as a quality control method for previously screened cervical slides; to compare this method with 10% random re-screening and clinically indicated double screening. METHODS: Between June 1990 and December 1994, 117,890 negative smears were subjected to rapid re-screening. RESULTS: This study shows that rapid re-screening detects far greater numbers of false negative cases when compared with both 10% random re-screening and clinically indicated double screening, with no additional demand on human resources. The technique also identifies variation in the performance of screening personnel as an additional benefit. CONCLUSION: Rapid re-screening is an effective method of quality control. Although less sensitive, rapid re-screening should replace 10% random re-screening and selected re-screening as greater numbers of false negative results are detected while consuming less resources.

Cytological Techniques↗
PubMed1995

Relationship between MRI relaxation time and muscle fiber composition.

The relationship between nuclear magnetic resonance relaxation time obtained with magnetic resonance imaging (MRI) and muscle fiber composition of the lateral gastrocnemius was examined in 13 men. There was a positive correlation (r = 0.80, P < or = 0.001) between longitudinal relaxation time and the relative percentage of slow-twitch muscle fibers (type I). There was no relationship between transverse relaxation time and type I percentage (r = 0.17, P = 0.57). These results suggest that MRI longitudinal relaxation time can be used for the noninvasive estimation of muscle fiber composition in humans.

Adult↗