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Biomedical subjects

P Smith

Publications and source records attributed to P Smith.

At least 235 records · Page 13Linked to original sources

The effect of wind speed and direction on the distribution of sewage-associated bacteria.

A study of the relationship between wind and the distribution of sewage-associated bacteria was undertaken at a location where the sewage was discharged into the sea adjacent to the mouth of a river. The numbers of presumptive Escherichia coli were determined in 149 sea-water samples taken from three locations at distances of 1.9, 2.4 and 4.3 km from the outfall. On each sampling occasion, data on the wind speed and direction in the 3 h prior to collection of the samples were also collected. Analysis of these data demonstrated a significant role for wind speed and direction. With respect to wind direction, the numbers of presumptive E. coli present in a sample were significantly higher when the sample site lay downwind of the outfall. Wind speed was shown to have an influence on the numbers of presumptive E. coli only when the sample site was downwind of the outfall. In an analysis of 61 samples, an inverse correlation (r2 = 0.73) between salinity and log presumptive E. coli numbers was demonstrated. These data demonstrate that wind speed and direction at the time of sampling significantly influence the numbers of presumptive E. coli detected in any sea-water sample. It is argued that failure to pay sufficient attention to these parameters in the design of monitoring programmes may result in the generation of data that could provide a seriously distorted picture of the microbiological status of a water body.

Colony Count, Microbial↗

Oral anticoagulants are effective long-term after acute myocardial infarction.

Three long-term studies on oral anticoagulation, the Sixty Plus trial, the WARIS study, and the ASPECT trial all meet the methodological requirements for modern stand alone clinical trials: large number of patients, double-blinded, placebo-controlled design, and intention to treat analysis. All demonstrate significant reduction in recurrent myocardial infarction, and all show reduction in the risk of total stroke. The WARIS study, however, is the only study demonstrating efficacy in terms of statistically significant reduction of all-cause mortality. These findings are confirmed by a recent meta-analysis. The overall benefit of oral anticoagulation after myocardial infarction suggests avoidance of 4-26 events per 100 patients treated for 2-3 years. Given the results from the trials applying the most adequate control of anticoagulation, avoidance of 10-14 events per 100 patients treated seems to be a realistic benefit. Provided there is sound management of the anticoagulant therapy, especially employment of suitable control methods, the incidence of bleeding may be kept at a low level.

Administration, Oral↗

Functional capacity of fetal zone cells of the baboon fetal adrenal gland: a major source of alpha-inhibin.

We have shown that ACTH receptor mRNA expression and steroidogenesis were increased in the transitional zone and decreased in the fetal zone of the baboon fetal adrenal in the second half of gestation. Thus, we proposed that there is a divergence in ACTH receptor-mediated zone-specific steroidogenesis within the fetal adrenal during mid to late gestation. We have also demonstrated that fetal serum alpha-inhibin levels decline with advancing development. It is possible, therefore, that the alpha subunit of inhibin provides a good marker of fetal zone cellular function and that the changes in circulating fetal alpha-inhibin with advancing pregnancy reflect ontogenetic changes in fetal adrenal cortical zone-specific cell function. However, it remains to be determined whether the fetal adrenal is a major source of circulating alpha-inhibin in the fetus and whether alpha-inhibin is expressed in the fetal, definitive, and/or transitional zones. Therefore, the current study compared fetal serum alpha-inhibin levels with immunocytochemical localization of alpha-inhibin in baboon fetal adrenals obtained on Days 60 (early), 100 (mid), and 165 or 182 (late) of gestation (term averages Day 184) from animals untreated or treated with betamethasone, which we previously demonstrated suppressed fetal pituitary ACTH and adrenal weight. Fetal serum alpha-inhibin levels (mean +/- SE) were greater (p < 0.05) at mid (5863 +/- 730 microliter eq/ml) than at late (3246 +/- 379) gestation and were reduced (p < 0. 05) by betamethasone. The inhibin alpha subunit was expressed in abundant quantities in the fetal adrenal cortex, but not in medulla, throughout gestation. At mid and late gestation, alpha-inhibin was expressed throughout the fetal adrenal cortex but most intensely in the innermost area of fetal zone cells. By late gestation, the fetal adrenal exhibited a gradient of alpha-inhibin expression. Thus, the outermost definitive zone cells were devoid of alpha-inhibin, the transitional zone exhibited a relatively low alpha-inhibin content, and fetal zone cells continued to exhibit extensive expression of alpha-inhibin. Betamethasone diminished the intensity of alpha-inhibin expression throughout the fetal adrenal cortex. These results indicate that the fetal adrenal fetal zone is a significant source of circulating alpha-inhibin in the baboon fetus and that alpha-inhibin provides a good marker to study the developmental regulation of fetal zone-specific adrenocortical function.

Adrenal Cortex↗

Promoting physical activity in general practice: should prescribed exercise be free?

In the UK there are numerous schemes whereby general practitioners can prescribe exercise programmes, usually based in leisure centres. Of the factors that discourage adherence to such programmes in the USA, cost has proved important. We collected demographic and questionnaire data from 152 inner-London patients (108 women, 44 men) before they started an exercise programme on a National Health Service prescription, and analysed the results according to whether they dropped out of the programme (78%) or not. Use of logistic regression revealed only one previous barrier to exercise, 'not knowing about local exercise facilities', as a significant positive determinant of adherence (adjusted odds ratio 3.51, 95% confidence interval, 1.04 to 11.86). For 'lack of money' patients were more likely to drop out of the programme (adjusted odds ratio 0.25, 95% CI 0.07-0.85). The very low cost of participation in this scheme, did not encourage adherence, particularly by those who had cited 'lack of money' as a previous barrier. The case of making prescribed exercise free or even low-cost remains unproven.

Adolescent↗

Identifying the concerns of informal carers in palliative care.

The purpose of this preliminary study was to identify the perceived support needs of informal carers (families and friends) of cancer patients receiving palliative care in the community. Changes in policy mean that increasing numbers of palliative care patients receive the majority of their care at home. This potentially places heavy demands on families and friends. Thirty-nine informal carers were recruited from two areas in southern England. Data were obtained on psychological morbidity (General Health Questionnaire), and caregiving burden (Carer Strain Index), and a semistructured interview was used to elicit data on perceptions of caring. Results indicate that 33 (84%) reported above normal levels of psychological distress and 16 (41%) experienced high levels of strain related to caregiving. Younger age and being female were found to be correlated with psychological morbidity and strain. Participants also reported life restrictions, emotional distress and limited support.

Adult↗

Low-bandwidth tele-ultrasound.

We examined the acceptability and diagnostic accuracy of dynamic ultrasound images transmitted at 128 kbit/s and 384 kbit/s. The gold standard was the direct recording of 200 ultrasound examinations on video-tape. The taped images were later transmitted at both 128 kbit/s and 384 kbit/s and recorded, resulting in three tapes for each case. Four observers viewed each tape individually. Ninety per cent of images transmitted at 384 kbit/s were rated as diagnostically acceptable compared with 32% of images transmitted at 128 kbit/s. Diagnostic agreement between tapes transmitted at 384 kbit/s and the gold standard was 85%, compared with 78% for 128 kbit/s transmissions. Observers were not satisfied with low-bandwidth transmission of ultrasound images despite adequate diagnostic accuracy. Dynamic ultrasound images transmitted at 384 kbit/s were viewed as both diagnostically acceptable and accurate.

Electronics↗

Effect of ipratropium bromide treatment on oxygen saturation and sleep quality in COPD.

STUDY OBJECTIVES: Patients with COPD are at risk of experiencing a deterioration in arterial oxygen saturation (SaO2) during sleep, which is generally most pronounced during rapid eye movement (REM) sleep. Increased cholinergic tone has been suggested as a contributing factor to this decrease in SaO2. Therefore, we investigated whether 4-week treatment with ipratropium bromide inhalation solution 0.02% (qid) could improve sleep characteristics in COPD. DESIGN: Randomized, placebo-controlled, double-blind, two-arm parallel study of 4 weeks of treatment with ipratropium bromide solution or placebo. SETTING: Multicenter investigation. PATIENTS: Thirty-six patients with moderate-to-severe COPD (FEV1 < 65% of predicted). MEASUREMENTS AND RESULTS: Evaluation included polysomnographic, pulmonary function, and subjective quality of sleep (visual analog scale [VAS]) assessments. It was found that 4 week of treatment with ipratropium bromide solution in patients with COPD led to the following: (1) a significant (p = 0.05) improvement in mean nocturnal SaO2 with the more severe the nocturnal desaturation, the greater the improvement in SaO2; (2) significant (p = 0.03) improvement in perceived sleep quality (VAS: 5.5 +/- 0.5 after placebo; 7.2 +/- 0.5 after ipratropium); (3) a significant (p = 0.05) increase in REM sleep time (48.6 +/- 6.3 min after placebo; 66.5 +/- 6.4 min after ipratropium) with no effect on other sleep stages or total sleep time; and (4) a significant (p = 0.01) increase in pre-sleep FVC and flow rate at 50% of the vital capacity. CONCLUSIONS: These findings demonstrate that ipratropium bromide therapy can improve sleep SaO2 as well as sleep quality in patients with moderate-to-severe COPD.

Adult↗

Populations of granulosa cells in small follicles of the sheep ovary.

The aim of this study in sheep ovaries was to determine the total number of granulosa cells in primordial follicles and at subsequent stages of growth to early antrum formation. The second aim was to examine the interrelationships among the total number of granulosa cells in the follicles, the number of granulosa cells in the section through the oocyte nucleolus, and the diameter of the oocyte. A third aim was to examine whether proliferating cell nuclear antigen labelling occurred in flattened granulosa cells in primordial follicles or was confined to follicles containing cuboidal granulosa cells. The follicles were classified using the section through the oocyte nucleolus by the configuration of granulosa cells around the oocyte as type 1 (primordial), type 1a (transitory), type 2 (primary), type 3 (small preantral), type 4 (large preantral), and type 5 (small antral). In type 1 follicles, the number of granulosa cells and oocyte diameter were highly variable in both fetal and adult ovaries. Each type of follicle was significantly different from the others (all P < 0.05) with respect to oocyte diameter, number of granulosa cells in the section through the oocyte nucleolus and total number of granulosa cells. Follicles classified as type 2, 3, 4 or 5 each corresponded to two doublings of the total granulosa cell population. The relationships between oocyte diameter and the number of granulosa cells (that is, in the section through the oocyte nucleous or total population per follicle) could all be described by the regression equation loge chi = a + b loge gamma with the correlation coefficients R always > 0.93. For each pair of variables the slopes (b) for each type of follicle were not different from the overall slope for all types of follicle pooled. Immunostaining for proliferating cell nuclear antigen was observed in granulosa cells in type 1 follicles, as well as in the other types of follicle. These findings indicate that 'flattened' granulosa cells in type 1 follicles express an essential nuclear protein involved in cell proliferation before assuming the cuboidal shape. Thus, when considering factors that regulate specific phases of early follicular growth, it is important to consider: (i) the follicle classification system used; (ii) the animal model studied; (iii) whether type 1 follicles are all quiescent; and (iv) the likelihood that each follicle type represents more than one doubling of the population of granulosa cells.

Animals↗

Stem cell factor and c-kit gene expression and protein localization in the sheep ovary during fetal development.

The aim of this study was to investigate stem cell factor and c-kit gene expression and protein localization in the mesonephros and ovary of sheep fetuses at different days of gestation, using RNA in situ hybridization and immunohistochemical procedures. At days 24 and 26 of gestation, stem cell factor mRNA and protein were present in cells throughout the developing gonad and mesonephros. From day 28 to day 40 of gestation, stem cell factor mRNA and protein became increasingly localized to the cortical region of the ovary, where most germ cells were present as actively proliferating oogonia. From day 40 to day 90 of gestation, stem cell factor mRNA and protein localization were confined mainly to the ovarian cortex. Moreover, within the cortical region, stem cell factor mRNA was low or absent where follicles were first forming and highest in the outer ovarian cortex, where germ cells were undergoing mitosis or the early stages of meiosis. In contrast, stem cell factor protein was present in newly forming follicles, as well as in mitotic and meiotic germ cells, which is consistent with the presence of both membrane-bound and soluble forms of this ligand. However, by day 90 of gestation, both stem cell factor mRNA and protein were observed in the granulosa cells of most (> 90%) primordial follicles. C-kit mRNA and protein were observed from day 24 of gestation in both germ cells and somatic cells but, with increasing gestational age, preferentially in germ cells (for example, pre-meiotic germ cells and both isolated oocytes and follicle-enclosed oocytes). C-kit protein, but not mRNA, was also observed in germ cells that were undergoing meiosis. The results indicate that the cells containing stem cell factor mRNA within the ovary up to day 90 of gestation originated from the gonadal blastema and from cells that migrated from the mesonephros before day 28 of gestation. Since stem cell factor mRNA was absent in both mesonephric cells migrating after day 28 of gestation and in regions where follicles were first forming, it is suggested that these later migrating mesonephric cells are the progenitors of the granulosa cells in the first forming follicles. In conclusion, during follicle formation, c-kit mRNA is localized to germ cells whereas c-kit, together with stem cell factor protein, is localized to both germ cells and somatic cells, consistent with the hypothesis that the presence of this receptor-ligand pair is essential to prevent apoptosis.

Animals↗

Paraproteins and monoclonal expansion of CD3+CD8+ CD56-CD57+ T lymphocytes in a patient with HIV infection.

An expansion of CD8+ lymphocytes associated with a monoclonal rearrangement of the T-cell receptor gamma locus was found in a woman with HIV-1 infection. A subpopulation of HIV-positive patients display an unusual response to HIV infection characterized by a persistent marked CD8+ lymphocytosis, the presence of which appears to be associated with an improved long-term prognosis. This condition is thought to represent a florid immune response to an ongoing viral infection which may be HIV itself, and suggests that monoclonal proliferation of CD8+ lymphocytes does not imply the presence of an underlying malignant process.

Antigens, CD↗

Clinical impact of quality assurance in an organized cervical screening program.

BACKGROUND: We have studied whether clinical monitoring of an established population register based cervical screening program could reduce the number of cervical cancer cases and if drawbacks in the coverage could be detected. METHOD: A total of 123 consecutive cervical cancer cases were studied. A retrospective study of five years was followed by five prospective years after the introduction of increased efforts to find previously neglected low-grade positive smears. Cervical cancer incidence, histology, stage, and early mortality were related to smear history. RESULTS: The absence of cancer cases with neglected positive smears was a major reason for a 50 percent lower incidence of squamous cancers in the prospective period. Rapid onset interval cancers were few. Older women, never invited to the program, accounted for the majority of the advanced or aggressive cases in the former period. However, serious post-screening cancers remained common among women who had not had smears taken regularly up to the age of sixty, whereas there was little morbidity in women who had a regular smear to that age. CONCLUSION: This organized screening program is a versatile tool in identifying women at risk. To attain effectiveness it needs, however, active monitoring of the smear history and a mechanism to ascertain that all women have participated well beyond the age of fifty before being left out of the program.

Adult↗

The use of dexamethasone in women with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled, randomised trial. Dexiprom Study Group.

OBJECTIVE: To assess whether administration of dexamethasone in women with preterm premature rupture of membranes (PPROM) has an effect on the prevalence of maternal sepsis, neonatal respiratory distress syndrome (RDS), perinatal mortality and neonatal sepsis in a developing country. SETTING: Six public hospitals in South Africa that deal mainly with indigent women. METHOD: A multicentre, double-blind, placebo-controlled, randomised trial was performed on women with PPROM and fetuses of 28-34 weeks' gestation or clinically estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown. Women were randomised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart. All women received amoxycillin and metronidazole and were managed expectantly. Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial. OUTCOME MEASURES: The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis. The outcome measures for infants were perinatal death, RDS, mechanical ventilation, necrotising enterocolitis, and neonatal infection within 72 hours. RESULTS: One hundred and two women who delivered 105 babies were randomised to the dexamethasone group and 102 women who delivered 103 babies, to the placebo group. The groups were well balanced with regard to clinical features. There was a trend towards fewer perinatal deaths in the dexamethasone group: 4 compared with 10 (P = 0.16, odds ratio 0.37, 95% confidence intervals 0.09-1.34). A subanalysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths; 1 death in the dexamethasone group and 7 in the placebo group, P = 0.047 (Fisher's exact test). No woman in either group developed severe sepsis, and the incidence of sepsis in the women did not differ significantly. Eleven infants in each group developed sepsis. CONCLUSION: This is the first randomised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo, where all women received prophylactic antibiotics concomitantly with the corticosteroids. A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone. There was no increased risk of infection in the women or their infants where dexamethasone was administered. Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries.

Anti-Inflammatory Agents↗

Control of early ovarian follicular development.

Early follicular growth refers to the development of an ovarian follicle from the primordial to early antral phase. In sheep and cows these phases of growth can be classified by the configuration of granulosal cells in the largest cross-section of the follicle as types 1 (primordial), 1a (transitory) 2 (primary), 3 and 4 (preantral) and 5 (early antral). Follicles classified as type 1 may be highly variable within each species with respect to number of granulosal cells and diameter of oocyte. Much of the variation in granulosal cell composition of type 1 follicles may occur at formation and this may account for the variability in granulosal cell composition throughout subsequent stages of growth. There appear to be important differences among species (for example sheep and cattle) in the number and function of granulosal cells relative to the diameter of the oocyte during the initiation of follicular growth. There is evidence that most, if not all, of the growth phases from types 1 to 5 are gonadotrophin-independent and that follicles develop in a hierarchical manner. In sheep, cows and pigs, numerous growth factor, growth factor receptor and gonadotrophin receptor mRNAs and peptides (for example c-kit, stem cell factor, GDF-9, beta B and beta A activin/inhibin subunit, alpha inhibin subunit, follistatin, FGF-2, EGF, EGF-R, TGF beta 1,2 and 3 FSH-R and LH-R) are expressed in a phase of growth (for example types 1-5)-specific and cell-specific manner. However, the roles of many of these factors remain to be determined.

Animals↗

Temporal patterns of physical activity in Olympic dinghy racing.

BACKGROUND: The objective of the present study was to determine the temporal patterns of physical activity in four classes of Olympic racing dinghy. METHODS EXPERIMENTAL DESIGN: Descriptive. SETTING: A field (on-water) study. PARTICIPANTS: Nineteen elite New Zealand sailors (fifteen male and four female). INTERVENTION: Not applicable. MEASURES: The temporal pattern (duration and frequency) and nature of the physical activities of each sailor during each leg of simulated races were recorded on video tape and subsequently systematically quantified and categorised using notational analysis. The accumulated percentage of total leg time spent sitting (upright or leaning backwards), hiking (upright or fully extended) whilst trimming and whilst pumping the mainsheet and for the time spent on rig adjustments, tacking and gybing were calculated for both up-wind and off-wind sailing. RESULTS: When sailing up-wind, the most time was spent hiking upright (average 29-66% of total leg time) while trimming the mainsheet. During off-wind sailing, sailors spent the most time sitting upright while trimming the mainsheet (average 29-55% total leg time). Hiking upright while trimming the mainsheet was executed the greatest number of times (average 15.8-23.9) when sailing up-wind and sitting upright while trimming was executed the most times (average 3.5-7.4) when sailing off-wind. The most lengthy continuous activity was hiking upright while trimming the mainsheet when sailing up-wind (9-18 seconds) and sitting upright while trimming the mainsheet when sailing off-wind (17-34 seconds). CONCLUSIONS: The most physically demanding aspect of Olympic yacht racing is hiking. It occurs for the majority of up-wind legs when the wind starts to exceed approximately 8 knots. The only respite that the sailor gets from hiking is during tacking, rig adjustments or sitting in-board for brief periods when the wind is low. Sustained hiking tends to last for no more than approximately 20 seconds before the sailor changes to either a more extended or more upright hiking posture. The physical demands during off-wind sailing are generally less, except for a greater requirement for power in the arms and shoulders to pump the mainsheet in order to assist the dinghy in accelerating down waves. The findings of the present study are directly applicable to the design of sailing specific physical conditioning programmes for Olympic class sailors.

Female↗

Endothelial selectins and alpha4 integrins regulate independent pathways of T lymphocyte recruitment in the pulmonary immune response.

The cell adhesion molecules (CAMs) required for T lymphocyte recruitment during pulmonary immune responses have not been defined. Our laboratories recently reported that intratracheal (IT) challenge of sensitized mice with SRBC induced prolonged expression of vascular P-selectin, E-selectin, and VCAM-1, particularly in areas of mononuclear leukocyte infiltration. A surge in the number of circulating T lymphocytes expressing selectin ligands preceded the peak accumulation of T cells in the lung. In addition, a significant percentage of the T cells recovered from the lung expressed selectin ligands as well. The current study demonstrates that cultured T lymphoblasts use both selectin ligands and alpha4 integrins to enter the airspace and interstitium during the response to SRBC. Fluorescently labeled T lymphoblasts, derived via activation on CD3 and growth in low dose IL-2, showed inflammation-specific recruitment into lungs harvested 24 h after cell infusion. Their flux paralleled the accumulation of host lymphocytes in the lung, with both peaking 2 to 4 days after SRBC challenge. Trafficking studies conducted over a 24-h period during peak lymphocyte accumulation in the lungs revealed preferential recruitment of labeled T lymphoblasts expressing P- and E-selectin ligands. In addition, mAb blockade of the alpha4 integrins and targeted deletion of an alpha(1,3)fucosyltransferase essential for selectin ligand synthesis each reduced labeled T lymphoblast trafficking to a significant degree. Furthermore, alpha4 integrin blockade reduced the trafficking of the selectin ligand-deficient cells into the airspace, confirming that its contribution is in part independent from the vascular selectins. These findings imply that both selectin ligands and alpha4 integrins participate in T lymphoblast recruitment during the pulmonary immune response to IT SRBC.

Animals↗

Performance indicators. All quiet on the front line.

Managers interviewed in hospital trusts, health authorities and regional offices believed performance indicators to be broadly helpful. But our study found evidence that the role of the current performance indicators is distinctly limited. The indicators are primarily used to highlight instances of exceptionally poor performance. Frontline staff, such as junior doctors, are often largely unaware of performance indicators. Performance indicators have led to misrepresentation and manipulation of data.

Attitude of Health Personnel↗

Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters.

The cell cycle-associated retinoblastoma protein (pRb) and p16 protein were demonstrated using immuno-histochemistry on paraffin sections from 192 cases of invasive breast carcinoma. Abnormal expression of pRb was defined as negative staining and was seen in 17% of tumours. Such abnormal expression was significantly more frequent in tumours with negative oestrogen receptor (ER) status. There was also a trend for tumours which were negative for pRb to be grade III ductal carcinomas. There was no association between p16 staining and any histopathological parameter, though, surprisingly, log-rank analysis showed that strong staining was associated with a poor outcome. There was a significant inverse relationship between pRb and p16 expression and a significant positive association between pRb and cyclin D1. In a Cox multivariate analysis, which included cyclin D1, neither pRb nor p16 was an independent predictor of patient outcome.

Breast Neoplasms↗