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Biomedical subjects

S Meredith

Publications and source records attributed to S Meredith.

At least 19 recordsLinked to original sources
PubMed2004

Decision-making about hormone replacement therapy by women in England and Scotland.

OBJECTIVE: The aim of this study was to explore women's decision-making about the balance of risks and benefits of taking hormone replacement therapy (HRT) based on the latest evidence from the Women's Health Initiative (WHI) trial of combined HRT. METHODS: Women aged 50-69 years, who were eligible for the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) trial, were invited to participate in one of eight focus groups. Participants were asked to discuss their views about taking HRT based on the latest international evidence. RESULTS AND CONCLUSIONS: Eighty-two women participated overall. Qualitative content analysis was applied to the discussion transcripts. Women regarded the decisions they make about taking HRT as highly personal, and, for women currently taking HRT, the overwhelming reason for continuation was perceived improvement in quality of life regardless of either the risks or the benefits in the longer term.

Aged↗
PubMed2001

Antipsychotics and the risk of sudden cardiac death.

BACKGROUND: Case reports link antipsychotic drugs with sudden cardiac deaths, which is consistent with dose-related electrophysiologic effects. Because this association has not been confirmed in controlled studies, we conducted a retrospective cohort study in Tennessee Medicaid enrollees, which included many antipsychotic users; there were also computer files describing medication use and comorbidity. The study was conducted before the introduction of risperidone and, thus, did not include the newer atypical agents. METHODS: The cohort included 481,744 persons with 1,282,996 person-years of follow-up. This included 26,749 person-years for current moderate-dose antipsychotic use (>100-mg thioridazine equivalents), 31,864 person-years for current low-dose antipsychotic use, 37,881 person-years for use in the past year only, and 1 186,501 person-years for no use. The cohort had 1487 confirmed sudden cardiac deaths; from these, we calculated multivariate rate ratios adjusted for potential confounding factors. RESULTS: When current moderate-dose antipsychotic use was compared with nonuse, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3.22; P<.001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P=.003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P<.001) use. Among cohort members with severe cardiovascular disease, current moderate-dose users had a 3.53-fold (95% confidence interval, 1.66-7.51) increased rate relative to comparable nonusers ( P<.001), resulting in 367 additional deaths per 10,000 person-years of follow-up. CONCLUSIONS: Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Although the study data cannot demonstrate causality, they suggest that the potential adverse cardiac effects of antipsychotics should be considered in clinical practice, particularly for patients with cardiovascular disease.

Adolescent↗
PubMed2001

Possible medication errors in home healthcare patients.

OBJECTIVE: To determine the frequency of possible medication errors in a population of older home healthcare patients according to expert panel objective criteria. DESIGN: A cross-sectional survey. SETTING: Two of the largest urban home healthcare agencies in the United States. PARTICIPANTS: Home healthcare patients age 65 and older admitted to selected offices of these agencies between October 1996 and September 1998. MEASUREMENTS: We used two sets of consensus-based expert panel criteria to define possible medication errors. The Home Health Criteria identify patients with patterns of medication use and signs and symptoms that indicate sufficient likelihood of a medication-related problem to warrant reevaluating the patient. The Beers criteria identify medications that experts have deemed generally inappropriate for older patients. RESULTS: The 6,718 study subjects took a median of five drugs; 19% were taking nine or more medications. A possible medication error was identified for 19% of patients according to Home Health Criteria, 17% according to the Beers criteria, and 30% according to either. Possible errors increased linearly with number of medications taken. When patients taking one to three medications were compared with those taking nine or more drugs, the percentages with possible errors were, respectively, 10% and 32% for the Home Health Criteria, 8% and 32% for the Beers criteria, and 16% and 50% for both. CONCLUSION: Nearly one-third of the home healthcare patients surveyed had evidence of a potential medication problem or were taking a drug considered inappropriate for older people. More-effective methods are needed to improve medication use in this vulnerable population.

Aged↗
PubMed2000

Uterine contraction patterns and fertility in early postpartum ewes.

Three experiments were conducted to determine: (1) the direction of uterine contractions in Days 32 and 52 postpartum ewes (Experiment 1); (2) the effect of PGF(2alpha) on direction of uterine contractions (Experiment 2); and (3) the effect of PGF(2alpha) on fertility rates in Day 32 postpartum ewes (Experiment 3). In Experiment 1, non-lambing (>90 days postpartum) and lambing ewes (day of lambing=Day 0) received medroxyprogesterone acetate (MAP) vaginal sponges for 8 days and 500 IU of eCG at sponge withdrawal (Days 30 or 50 postpartum). At the time of eCG injection, ewes were divided into the following groups: (1) non-lambing (control; n=29); (2) Day 32 postpartum dry (n=15) and lactating (n=16); and (3) Day 52 postpartum dry (n=14) and lactating (n=16). At estrus or 60h post-eCG, the uterus was exteriorized through a mid-ventral incision, and the origin and direction of uterine contractions were recorded for 10min. In Experiment 2, ewes received MAP sponges on Day 16 postpartum followed by 500 IU of eCG on day of sponge removal (Day 30). At estrus, the ewes were divided into the following treatments: (1) two injections of saline 4h apart (n=10) and (2) 12.5mg of PGF(2alpha) followed by another 12.5mg 4h later (n=7). After the second injection, ewes were laparotomized and uterine contractions were counted. In Experiment 3, estrus was induced in postpartum ewes, and ewes were mated to two rams, then received the same two treatments as described in Experiment 2 (ram+saline; n=32 and ram+PGF(2alpha); n=28). Two days following mating, ewes were laparotomized and the oviducts flushed for recovery of ova. In Experiment 1, lactational status had no effect, therefore, the data were pooled. Control ewes had a greater percentage (p<0.05) of uterine contractions (69%) moving towards the oviducts than did Day 32 (8%) or Day 52 (43%) ewes. In Experiment 2, PGF(2alpha) treatment increased the proportion of contractions (p<0.05) moving toward the oviducts (controls 16%, PGF(2alpha) 42%). Number of PGF(2alpha)-treated ewes (Experiment 3) with fertilized ova were not significantly different from the control ewes (5/32 versus 2/28; respectively). In conclusion, it can be said that the direction of uterine contractions moving toward the oviducts increased as the postpartum interval progressed or if they received PGF(2alpha) injection. PGF(2alpha) treatment did not improve fertility rates in Day 32 postpartum ewes.

Journal Article↗
PubMed2000

Long-term supplementation with melatonin delays reproductive senescence in rats, without an effect on number of primordial follicles.

The primary objective of the present experiment was to determine if lifelong supplementation with melatonin delayed reproductive senescence through decreased loss of ovarian primordial follicles. Holtzman rats were divided into three treatments on Day 10 after pupping (Day 0 = day of pupping). Treatment 1 pups had access to water, whereas Treatment 2 and 3 pups had access to water containing 10 microg/ml melatonin only at night (Treatment 2) or continuously (Treatment 3). Estrous cycles and weights of pups were monitored at selected times during the experiment; ovaries were removed for histology at 75 and 380 days of age. Vaginal opening in Treatment 2 was delayed (P <.01) compared with Treatments 1 and 3, but there was no difference (P > 0.05) among treatments in percentage of normal length estrous cycles from vaginal opening to 75 days of age. There were fewer (P < 0.001) abnormal-length estrous cycles from 180 to 380 days of age in Treatment 2 as compared with Treatments 1 or 3. There was no effect of treatment (P > 0.05) on number of primordial follicles. In conclusion, nighttime, but not continuous supplementation with melatonin, delayed puberty and reproductive senescence without any effect on number of primordial follicles.

Aging↗
PubMed2000

Classification of small type B/C follicles as primordial follicles in mature rats.

In the present study, follicles were classified according to the morphology of their granulosa cells. Type B follicles contained only flattened granulosa cells; type B/C follicles had a mixture of flattened and cuboidal granulosa cells in a single layer, and type C follicles had a single layer of cuboidal granulosa cells. The primary objectives of the study were to determine whether 5-bromo-2-deoxyuridine incorporation into type B/C follicles was a marker for initiation of growth and how long type B/C follicles could remain at the same stage before transformation to type C follicles. Female Holtzman rats received bromo-deoxyuridine for 7 days. After the infusion (day minipumps were removed = day 0), rats were ovariectomized on days 0 (n = 9), 30 (n = 8), 90 (n = 8) and 150 (n = 9). The numbers of type B, B/C and C follicles within one ovary were determined using modified fractionator counting. Analysis over all times demonstrated that there were more (P < 0.0001) type B/C (941 +/- 61 per ovary) than type C (140 +/- 18 per ovary) or type B (159 +/- 19 per ovary) follicles. The numbers of type B and type C follicles did not differ from each other at any time. Only one of 34 rats evaluated had bromo-deoxyuridine-labelled type B follicles. On day 150, 57% of the bromo-deoxyuridine-labelled type B/C follicles remained from day 0. It is concluded that (1) DNA synthesis in granulosa cells of type B/C follicles is not a reliable indicator of impending growth; and (2) type B and type B/C follicles are both components of the pool of primordial follicles.

Analysis of Variance↗
PubMed1999

Mapping the major interaction between binding protein and Ig light chains to sites within the variable domain.

Newly synthesized Ig chains are known to interact in vivo with the binding protein (BiP), a major peptide-binding chaperone in the endoplasmic reticulum. The predominant interactions between the light chain and BiP are observed early in the folding pathway, when the light chain is either completely reduced, or has only one disulfide bond. In this study, we describe the in vitro reconstitution of BiP binding to the variable domain of light chains (VL). Binding of deliberately unfolded VL was dramatically more avid than that of folded VL, mimicking the interaction in vivo. Furthermore, VL binding was inhibited by addition of ATP, was competed with excess unlabeled VL, and was demonstrated with several different VL proteins. Using this assay, peptides derived from the VL sequence were tested experimentally for their ability to bind BiP. Four peptides from both beta sheets of VL were shown to bind BiP specifically, two with significantly higher affinity. As few as these two peptide sites, one from each beta sheet of VL, are sufficient to explain the association of BiP with the entire light chain. These results suggest how BiP directs the folding of Ig in vivo and how it may be used in shaping the B cell repertoire.

Animals↗
PubMed1999

Single-section counting error when distinguishing between primordial and early primary follicles in sections of rat ovary of different thickness.

UNLABELLED: The number of primordial follicles within an ovary is frequently determined by counting 5, 7 or 10 microns thick sections and multiplying by the fraction of sections counted and a correction factor to adjust for duplicate counts. The objectives of the present study were: (i) to evaluate the accuracy of the correction factor developed by Abercrombie (1946); (ii) to evaluate the accuracy of the classification of primordial follicles from single tissue sections; and (iii) to determine the incorporation rate of 5-bromo-2-deoxyuridine into primordial follicles. In Expt 1, rat ovaries were sectioned at a thickness of 5, 7 or 10 microns. Primordial follicles were counted and classified across ten adjacent ovarian sections. The percentage of primordial follicles from single sections that were counted twice was 10, 9 and 2% in 5, 7 and 10 microns sections, respectively. This was lower than predicted by Abercrombie's method. The major error in counting from single sections was classification of early primary follicles as primordial follicles (55, 33 and 3% in 5, 7 and 10 microns sections, respectively). In Expt 2, a mean of 12 +/- 7% of primordial follicles incorporated 5-bromo-2-deoxyuridine after infusion for 7 days (four of seven rats had no labelled primordial follicles). IN CONCLUSION: (i) Abercrombie's correction factor should not be used for adjusting counts of follicles; (ii) evaluation of primordial follicles from single sections gives inaccurate counts and incorrect classification is of greater importance than duplicate counting, particularly in thinner sections; (iii) for evaluation of the number of follicles, 10 microns is the optimal thickness; and (iv) primordial follicles incorporated 5-bromo-2-deoxyuridine infrequently.

Analysis of Variance↗
PubMed1998

Onchocerciasis.

Explore the source record for details and available documents.

Communicable Disease Control↗
PubMed1997

Timing of activation of primordial follicles in mature rats is only slightly affected by fetal stage at meiotic arrest.

The objective of this experiment was to test the production-line hypothesis by determining whether timing of activation of primordial follicles at different ages throughout the life of female rats was associated with embryonic age at meiotic arrest of their oogonia. Meiotic arrest of oogonia can occur at any time during mid to late gestation in rats. Pregnant rats received injections of 5-bromo-2'-deoxyuridine (BrdU) on either e17 (treatment 1) or on e19 (treatment 2) (e1 = embryonic day 1 [sperm-positive day 1]). Female offspring (pupping = Day 0) were killed at 30 (6/group), 100 (8/group), 180 (8/group) and 350 (7/group) days of age. Immunohistochemistry was used to determine which primordial follicles contained oocytes and pregranulosa cells that were undergoing DNA synthesis at the time of BrdU injection. The percentage of primordial and primary follicles labeled with BrdU was higher (p < 0.05) at all ages with e17 than with e19 injections. There was a significant (p < 0.001) treatment-by-age interaction in the number of BrdU-containing growing follicles. Growing follicles, however, were found at all ages from both e17 and e19 injections. It is concluded that gestational day of entry into meiotic arrest does influence age of activation of primordial follicles, but it is a minor effect.

Animals↗
PubMed1997

Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-(trifluoromethyl)-phenyl]5-methylisoxazole-4-carboxamide.

Many reports have cited coexpression of platelet-derived growth factor (PDGF) and its receptors by tumor cells or cells supporting tumor growth, suggesting both autocrine and paracrine mechanisms for PDGF-mediated tumor growth. We found that a small organic molecule, N-[4-(trifluoromethyl)phenyl] 5-methylisoxazole-4-carboxamide (SU101, leflunomide), inhibited PDGF-mediated signaling events, including receptor tyrosine phosphorylation, DNA synthesis, cell cycle progression, and cell proliferation. SU101 inhibited PDGF-stimulated tyrosine phosphorylation of PDGF receptor (PDGFR) beta in C6 (rat glioma) and NIH3T3 cells engineered to overexpress human PDGFRbeta (3T3-PDGFRbeta). SU101 blocked both PDGF- and epidermal growth factor (EGF)-stimulated DNA synthesis. Previously, this compound was shown to inhibit pyrimidine biosynthesis by interfering with the enzymatic activity of dihydroorotate dehydrogenase. In the current study, EGF-stimulated DNA synthesis was restored by the addition of saturating quantities of uridine, whereas PDGF-induced DNA synthesis was not, suggesting that the compound demonstrated some selectivity for the PDGFR pathway that was independent of pyrimidine biosynthesis. Selectivity was further demonstrated by the ability of the compound to block the entry of PDGF-stimulated cells into the S phase of the cell cycle, without affecting cell cycle progression of EGF-stimulated cells. In cell growth assays, SU101 selectively inhibited the growth of PDGFRbeta-expressing cell lines more efficiently than it inhibited the growth of PDGFRbeta-negative cell lines. SU101 inhibited the s.c., i.p., and intracerebral growth of a panel of cell lines including cells from glioma, ovarian, and prostate origin. In contrast, SU101 failed to inhibit the in vitro or s.c. growth of A431 and KB tumor cells, both of which express EGF receptor but not PDGFRbeta. SU101 also inhibited the growth of D1B and L1210 (murine leukemia) cells in syngeneic immunocompetent mice, without causing adverse effects on the immune response of the animals. In an i.p. model of tumor growth in syngeneic immunocompetent mice, SU101 prevented tumor growth and induced long-term survivors in animals implanted with 7TD1 (murine B-cell hybridoma) tumor cells. Because PDGFRbeta was detected on most of the tumor cell lines in which in vivo growth was inhibited by SU101, these data suggest that SU101 is an effective inhibitor of PDGF-driven tumor growth in vivo.

3T3 Cells↗
PubMed1996

Are healthcare workers in England and Wales at increased risk of tuberculosis?

OBJECTIVE: To determine whether healthcare workers in England and Wales are at increased risk of tuberculosis and to examine the frequency of drug resistance in this population. DESIGN: Comparison of notification rates by occupation obtained from national tuberculosis notification surveys in 1988 and 1993, with denominators from the 1991 census. SUBJECTS: People with notified tuberculosis in professional and associate professional occupations from the two surveys. MAIN OUTCOME MEASURES: Rates of notified tuberculosis in health professionals (mainly doctors) and health associate professionals (mainly nurses) compared with rates in other professional and associate professional occupations, adjusted for ethnic group, sex, and age. RESULTS: 119 cases of tuberculosis were identified in healthcare workers, including 61 nurses and 42 doctors. The crude notification rate in healthcare workers was 11.8 per 100,000 per year (95% confidence interval 9.8 to 14.1) compared with 3.3 per 100,000 per year (2.9 to 3.6) in other professional and associate professional occupations; rate ratios were higher (range 1.7 to 3.2) in all ethnic groups. The relative risk adjusted for ethnic group, sex, and age was 2.4 (95% confidence interval 2.0 to 3.0), slightly higher for health professionals (2.7 (1.9 to 3.8)) than for associate professionals (2.0 (1.5 to 2.6)). No multiple drug resistant strains of tuberculosis were identified in healthcare workers. CONCLUSIONS: Better detection and notification of cases of tuberculosis in healthcare workers may account for some of the apparent increased risk, but these findings imply that tuberculosis remains a hazard for healthcare workers and highlight the importance of ensuring that occupational health monitoring and protection workers are not neglected.

Disease Notification↗
PubMed1996

Embryonic survival in the uterus of ewes inseminated at the uterotubal junction on Day 32 post partum.

Experiments were conducted to determine 1) if pregnancy initiated on Day 32 post partum would be maintained until lambing, 2) if there is a difference in the ability of the previously gravid or nongravid uterine horn to maintain pregnancy, and 3) if season has an effect on embryo loss. Estrus was induced in ewes on Day 32 post partum. At estrus, ewes were inseminated surgically at the uterotubal junction and assigned to the following groups: 1) inseminated at estrus and laparotomized on Day 3 to collect embryos for determination of fertilization rate (C), 2) inseminated in the previously gravid uterine horn (PG), 3) inseminated in the previously nongravid uterine horn (NG), and 4) inseminated when both horns were previously gravid (BG). Ewes pregnant in the PG, NG and BG groups were allowed to lamb. Conception rate in Group C at embryo collection was 70%. Embryo loss, based on concentrations of progesterone at Day 18 post insemination, was 43, 19 and 18% in the BG, NG and PG group, respectively. The high embryo loss in Group BG occurred only during the breeding season. Only 24% of the ewes that had been inseminated lambed. This was due to the prepartum loss of embryos and fetuses (47, 48 and 33% in Group BG, NG and PG, respectively. In conclusion, the detrimental effects of the uterus on embryo survival was evident within 18 d post insemination in Group BG (breeding season), and embryo loss prior to lambing was high in all the treatment groups (both seasons).

Journal Article↗
PubMed1996

Occupational asthma: measures of frequency from four countries.

Disease registers and surveillance schemes are not necessarily designed to measure incidence and prevalence, but their data can provide useful epidemiological insights. Their main functions are the detection and identification of hazards so that further cases can be prevented, and to provide a database for research to improve our understanding of the determinants and consequences of disease. Occupational asthma probably accounts for only a small proportion of adult asthma, of the order of 2-6% in the UK. On the other hand, asthma is very common and so thousands of people in the UK and in other western countries have asthma as a result of their work. The frequency of the disease in less developed countries is unknown but is potentially very large. Information on incidence is patchy but from Finland, where ascertainment is most complete, there are approximately 140 per million working people affected each year, and even there disease in the self-employed is probably missed. Data for the UK are limited to cases seen by specialist physicians and the best estimate is that the annual incidence of such cases is about 50 per million. Through internal comparisons and analysis it is possible to judge the extent to which variation in ascertainment and reporting have affected the frequency of reported disease, but so far it has not been possible to measure the underestimation due to persons with work-related symptoms not seeking medical attention or not being referred to a specialist.

Adolescent↗
PubMed1993

Reported incidence of occupational asthma in the United Kingdom, 1989-90.

STUDY OBJECTIVE: To estimate the incidence of occupational asthma seen by respiratory and occupational physicians in the UK in 1989 and 1990. DESIGN: New cases of occupational asthma were taken from a national reporting scheme, the Surveillance of Work-related and Occupational Respiratory Disease Project (SWORD). Estimates of the working population from the Labour Force Survey were used to calculate reported incidence by age group, sex, occupation, and region. SETTING: The SWORD project is a scheme for the reporting of new cases of work-related respiratory disease by thoracic and occupational physicians from throughout the UK which began in 1989. PATIENTS: In 1989 and 1990, of 4229 cases reported, 1085 (26%) were in patients with occupational asthma. MAIN RESULTS: Only half the reported cases were attributed to agents prescribed under the Industrial Injuries Scheme. There was considerable diversity in risk by occupation, with highest annual rates in welders, solderers, and electronic assemblers (175/million), laboratory workers (188/million), metal treaters (267/million), bakers (334/million), plastics workers (337/million), chemical processors (364/million), and spray painters (658/million). Crude rates in men were higher than in women, but rates within occupations were similar in both sexes. Rates of disease rose with age; adjustment for occupation increased the gradient. Regional differences were only partly explained by diversity of industry and were probably mainly due to variation in levels of ascertainment and reporting. CONCLUSIONS: Asthma is the most commonly reported occupational lung disease in the UK. The incidence in the general population is unknown, but it was estimated that the incidence of new cases seen by respiratory and occupational physicians was about three times that reported. High relative risks were found in a number of occupations in which effective control of the work environment is urgently required.

Adolescent↗
PubMed1992

Unilateral ovariectomy increases loss of primordial follicles and is associated with increased metestrous concentration of follicle-stimulating hormone in old rats.

The primary objective of these studies was to determine whether unilateral ovariectomy (ULO) would affect rate of loss of primordial follicles. In experiment 1, retired breeder rats, unilaterally ovariectomized and maintained on the experiment for 90 days after surgery, had fewer (p less than 0.01) primordial follicles per ovary than sham-operated controls of the same age. The purpose of experiment 2 was to determine whether time after ULO or age of rats was the critical factor necessary for increased loss of primordial follicles found after ULO in experiment 1. It was found that age was more important than time: when ULO was performed at 30 days of age, the number of primordial follicles did not decrease in ULO rats compared to controls (p greater than 0.05) before 250 days of age. Concentrations of FSH during metestrus were not greater (p greater than 0.05) in ULO rats than in controls until rats were 250 days old. There were also fewer (p less than 0.05) growing follicles per ovary in ULO than in sham-operated rats at 250 days of age. It is concluded that ULO can increase the loss of primordial follicles, but only in old rats (greater than or equal to 250 days of age).

Animals↗