PubMed Health⌕ Search

Biomedical subjects

R Snowden

Publications and source records attributed to R Snowden.

At least 19 recordsLinked to original sources
PubMed1999

Personal hormone monitoring for contraception.

OBJECTIVE: To determine the effectiveness and acceptability of personal hormone monitoring for contraception. DESIGN: A large prospective study was carried out on personal hormone monitoring for contraception when used with abstinence during the identified fertile days. SETTING: Three country study under the auspices of the departments of Obstetrics and Gynaecology of the Universities of Birmingham, Dublin and Dusseldorf SUBJECTS: Seven hundred and ten women, median age 30, were recruited from the general population. They were required to have regular menstrual cycles (23-35 days) and to be delaying their next pregnancy. INTERVENTIONS: Personal hormone monitoring consists of a hand held monitor and disposable test sticks which measure changes in urinary concentrations of oestrone-3-glucuronide and luteinising hormone. An algorithm estimated the fertile days which were displayed by a red light. OUTCOME MEASURES AND RESULTS: One hundred and sixty two pregnancies occurred in 7209 cycles of use, of which 67 were method related pregnancies. The 13 cycle life-table method pregnancy rate (95 per cent CI) was 12. 1 per cent (9.3-14.8). The system allowed analysis of the effect of changes to the algorithm to modify the defined fertile period. As a result the algorithm was changed to increase the median warning of the luteinising hormone surge to six days. With the revised algorithm, half of the method pregnancies would have been prevented giving a calculated method pregnancy rate of 6.2 per cent (4.2-8.3) and method efficacy of 93.8 per cent. The continuation rate after 13 cycles was 78 per cent. CONCLUSION: Personal hormone monitoring proved simple to use and will be of value to women who do not want to use other methods of contraception.

Adolescent↗
PubMed1997

Susceptibility of different subsets of immature thymocytes to apoptosis.

In the present study the susceptibility of different subsets of immature rat thymocytes to undergo apoptosis was examined. Unfractionated rat thymocytes were negatively enriched into immature double positive (CD4+ CD8+), immature single positive (CD4- CD8+ CD3-) and triple negative (CD4- CD8- CD3-) thymocytes. These enriched subsets of immature thymocytes were then exposed to various apoptotic stimuli such as dexamethasone, etoposide and thapsigargin which readily induced apoptosis in unfractionated rat thymocytes. We found that the double positive thymocytes and their precursor cells, i.e. the single positive immature thymocytes, were equally sensitive to apoptosis after treatment with the apoptotic stimuli. In sharp contrast, the early migrants or precursor-containing thymocytes which are triple negative have a lower spontaneous apoptosis rate and were relatively resistant to all the apoptotic stimuli. These findings showed a breakpoint in thymocyte sensitivity to apoptosis which occurs after the onset of CD8 expression, suggesting that susceptibility of thymocytes to apoptosis is developmentally regulated.

Animals↗
PubMed1996

Differential effects of staurosporine analogues on cell cycle, growth and viability in A549 cells.

Staurosporine is a potent but non-specific kinase inhibitor. It has served as synthetic template for a variety of analogues, the indolocarbazoles, UCN-01 and CGP 41251, and the bisindolylmaleimides, Ro 31-8220 and GF 109203X, were investigated as growth inhibitors of human-derived A549 human lung adenocarcinoma cells. They were compared with respect to (1) effect on the cell cycle, (2) time dependency of growth arrest and (3) cytotoxic potency. Cells were exposed for 1, 2 and 4 days, or for 6, 12 and 24 h in the case of cycle-synchronised cells, to staurosporine analogues at concentrations at which they inhibited growth by 80% after 4 day exposure. Staurosporine and UCN-01 retarded cells in G0/1, and CGP 41251 appeared to inhibit cell growth without cell cycle specificity. Ro 31-8220 slowed progression of synchronised cells through the cycle; over a longer time period it induced a weak block in G2/M. GF 109203X induced potent G2/M arrest in synchronised cells. This was not so apparent in asynchronous cells, which by day 4 were slowed in G0/1 instead. Growth arrest induced by these inhibitors was more potent after incubation for 4 rather than 2 days. Incubation for 1 day followed by maintenance in drug-free medium for 3 days was sufficient to exert some cytostasis. The differences between cytotoxic and cytostatic concentrations, the former measured by release from cells of lactate dehydrogenase, were 15 000-fold for staurosporine, 300-fold for UCN-01, approximately 400-fold for CGP 41251, 25-fold for Ro 31-8220 and approximately 4-fold for GF 109203X. The results show that PKC-selective staurosporine analogues differ with respect to the mechanisms by which they interfere with the cell cycle. The necessity of long-term exposure for effective growth inhibition and the considerable margin between cytostatic and acute cytotoxic indolocarbazole concentrations are findings which might influence the planning and interpretation of clinical trials of these kinase inhibitors.

Adenocarcinoma↗
PubMed1996

Regulation of P-glycoprotein 1 and 2 gene expression and protein activity in two MCF-7/Dox cell line subclones.

The MCF-7 doxorubicin-resistant cell line MCF-7/Dox has been used extensively for studies of the multidrug resistance phenomenon. Using fluorescence-activated cell sorting (FACS), these cells were separated into two populations on the basis of rhodamine 123 (R123) accumulation. We designated these as low P-glycoprotein (LP-gp) and high P-gp (HP-gp) cells on the basis of their P-gp content. Using the reverse transcriptase polymerase chain reaction technique controlled by homologous internal standards, we analysed levels of MDR1 and MDR2 mRNA in each cell type. LP-gp and HP-gp cells had MDR1 mRNA levels of 2.17 +/- 0.17 and 6.65 +/- 2.29 amol ng-1 total RNA respectively, compared with 0.00088 +/- 0.00005 amol ng-1 in wild-type MCF-7 cells (MCF-7/WT). MCF-7/WT cells additionally contained 0.023 +/- 0.016 amol ng-1 of MDR2 mRNA, which was unchanged in LP-gp cells, but lower than in HP-gp cells, which contained 0.42 +/- 0.08 amol ng-1. Both LP-gp and HP-gp cells contained increased copies of the MDR1 gene. However, the degree of gene amplification did not correlate with the changes in MDR1 mRNA levels, indicating further regulatory levels of gene expression. The level of P-gp detected by MRK 16 correlated with R123 accumulation. HP-gp cells expressed a 10-fold higher level of P-gp1 than LP-gp cells. However, there was only a 3-fold increase in MDR1 mRNA level in HP-gp cells compared with LP-gp cells. These data suggest that some regulation of P-gp1 expression also occurred at the post-translational level. Phosphorylation of P-gp by protein kinase C (PKC)-alpha is necessary for its activity. Our analysis of PKC-alpha, 0 and epsilon isozyme levels, and subcellular distribution, shows a co-regulation of expression with P-gp, suggesting a necessary role for PKC in P-gp regulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Alterations in the cell cycle of mouse cumulus granulosa cells during expansion and mucification in vivo and in vitro.

The cell cycle characteristics of mouse cumulus granulosa cells were determined before, during and following their expansion and mucification in vivo and in vitro. Cumulus-oocyte complexes (COC) were recovered from ovarian follicles or oviducts of prepubertal mice previously injected with pregnant mare serum gonadotrophin (PMSG) or a mixture of PMSG and human chorionic gonadotrophin (PMSG+hCG) to synchronize follicle differentiation and ovulation. Cell cycle parameters were determined by monitoring DNA content of cumulus cell nuclei, collected under rigorously controlled conditions, by flow cytometry. The proportion of cumulus cells in three cell cycle-related populations (G0/G1; S; G2/M) was calculated before and after exposure to various experimental conditions in vivo or in vitro. About 30% of cumulus cells recovered from undifferentiated (compact) COC isolated 43-45 h after PMSG injections were in S phase and 63% were in G0/G1 (2C DNA content). Less than 10% of the cells were in the G2/M population. Cell cycle profiles of cumulus cells recovered from mucified COC (oviducal) after PMSG+hCG-induced ovulation varied markedly from those collected before hCG injection and were characterized by the relative absence of S-phase cells and an increased proportion of cells in G0/G1. Cell cycle profiles of cumulus cells collected from mucified COC recovered from mouse ovarian follicles before ovulation (9-10 h after hCG) were also characterized by loss of S-phase cells and an increased G0/G1 population. Results suggest that changes in cell cycle parameters in vivo are primarily mediated in response to physiological changes that occur in the intrafollicular environment initiated by the ovulatory stimulus. A similar lack of S-phase cells was observed in mucified cumulus cells collected 24 h after exposure in vitro of compact COC to dibutyryl cyclic adenosine monophosphate (DBcAMP), follicle-stimulating hormone or epidermal growth factor (EGF). Additionally, the proportion of cumulus cells in G2/M was enhanced in COC exposed to DBcAMP, suggesting that cell division was inhibited under these conditions. Thus, both the G1-->S-phase and G2-->M-phase transitions in the cell cycle appear to be amenable to physiological regulation. Time course studies revealed dose-dependent changes in morphology occurred within 6 h of exposure in vitro of COC to EGF or DBcAMP. Results suggest that the disappearance of the S-phase population is a consequence of a decline in the number of cells beginning DNA synthesis and exit of cells from the S phase following completion of DNA synthesis. Furthermore, loss of proliferative activity in cumulus cells appears to be closely associated with COC expansion and mucification, whether induced under physiological conditions in vivo or in response to a range of hormonal stimuli in vitro. The observations indicate that several signal-transducing pathways mediate changes in cell cycle parameters during cumulus cell differentiation.

Animals↗
PubMed1989

Perspectives of physicians in Sri Lanka on periodic abstinence.

Since physicians strongly influence both national family planning policy and individuals' contraceptive choice, a survey was conducted to learn about the perspectives of Sri Lankan physicians (n-100) regarding periodic abstinence methods of family planning (PA). Female doctors (28% of the sample) were twice as likely to have ever provided PA advice to their clients as their male counterparts. Providers of PA were more likely to have ever personally used this form of contraception than PA non-providers. Regardless of PA provider status, all physicians most frequently recommended pills, injectables and IUDs to their clients. They had very good knowledge of the temperature method. The scientific foundation of this method is studied in medical school, suggesting that if the other modern methods (Billings and sympto-thermal) were incorporated into medical school curricula, physicians might be more willing to discuss, refer or provide other modern, scientific forms of PA to their clients.

Attitude of Health Personnel↗
PubMed1988

The effect of sodium chromate pretreatment on mercuric chloride-induced nephrotoxicity.

Sodium chromate (20 mg/kg, s.c.), which in male rats inflicted necrotic damage mainly in the P1 region (proximal part of the proximal convoluted tubules), protected against proximal tubular necrosis induced by 0.5 or 3.0 mg Hg2+/kg in the P2 (distal part of the proximal convoluted tubules) and P3 (pars recta part of the proximal tubules) regions. Histochemical staining for mercury indicated that chromate increased mercury deposition in those cells of the P1 region which were unaffected by chromate (had intact brush border) but did not decrease mercury deposition in the most severely affected P3 region. Chromate pretreatment actually increased mercury deposition in the kidneys of animals killed 24 h after the injection of 0.5 mg Hg2+. The protective effect was mutual. Cellular proliferation and fibrosis observed 4-5 days after chromate were prevented by injecting 0.5 mg Hg2+/kg 3 days after chromate treatment.

Animals↗
PubMed1987

Use of sodium restriction and enalapril in persons with moderate to severe hypertension.

One hundred and seventy-four patients who were receiving drug therapy for hypertension were asked to restrict their sodium intake for three months. At the end of that time their drug therapy was replaced with enalapril and the dose of the drug "titrated" to obtain a diastolic blood pressure of less than 90 mmHg. Sodium restriction caused a small fall in blood pressure and could be used as sole therapy in only 6% of patients. Enalapril therapy was instituted without problems and control of blood pressure below 90 mmHg was achieved in 62% of persons with monotherapy. The number of tablets of enalapril that were taken was reduced from 5.9 to 2.7; in most patients these were taken once a day. There were few side-effects and no depression of white cell count, no proteinuria and no deterioration of renal function. Seventy-six per cent of patients preferred the new regimen either because they felt better than with their previous therapy (52%) or because of the more simple regimen (24%). Enalapril was an effective, well tolerated antihypertensive agent and potentially has a major role to play in the management of patients with high blood pressure.

Antihypertensive Agents↗
PubMed1987

The effects of treatment with selenite before and after the administration of [75Se]selenite on the exhalation of [75Se]dimethylselenide.

The exhalation of dimethylselenium, as indicated by the respiratory loss of 75Se from injected Na75SeO3, depends not only on the dose, but also on previous exposure. Three days pretreatment with 1.2 mumol/100 g unlabelled selenite increased exhalation of 75Se from 0.1 or 1.2 mumol/100 g Na2 75SeO3 and decreased the retention of 75Se in blood and liver from the higher dose. Similarly the injection of 1.2 mumol/100 g unlabelled selenite 24 h after the last of 3 daily doses of 1.2 mumol/100 g labelled selenite increased the exhalation of 75Se in the following 24 h period. Thus, pre-exposure to selenium increased the exhalation of 75Se by making a higher proportion of the newly injected dose accessible for methylation. The exhaled dimethylselenide, however, is not derived solely from the injected dose, since in pretreated animals, it is possible to demonstrate exchange between injected and deposited selenium.

Animals↗
PubMed1987

Intestinal uptake and retention of copper in the suckling rat, Rattus rattus--IV. Mechanisms of intestinal copper accumulation.

Copper-67, administered either parenterally or via the maternal milk, accumulates principally in the intestine and liver of the 6-day-old pup. Most of the 67Cu in the soluble fraction of the intestine is associated with the heterogeneous Cu-complex, which is located predominantly in the ileum. The rates of uptake and loss of 67Cu in the liver and intestine indicate that enterohepatic circulation of Cu in the neonate is appreciable. Whilst the concentration of Cu in the bile of the 13-day-old pup is high (16-fold greater than that in the adult male rat), translocation of Cu from both the liver and duodenum to the ileum probably occurs via the blood, rather than by the reabsorption of biliary Cu. Although the Cu-complex normally seems to be retained within the distal intestine until the enterocytes are desquamated, Cu in this form is utilized when the Cu-intake of the neonate is restricted.

Animals↗
PubMed1987

Effect of carvedilol and metoprolol on blood pressure, blood flow, and vascular resistance.

Carvedilol and metoprolol were given for 4 weeks in a double-blind study to patients with essential hypertension. The effects on blood pressure were measured and hemodynamic alterations were assessed by forearm venous plethysmography before and after chronic administration, and 2 h after an acute dose before and during chronic therapy. Carvedilol (50 mg/day) reduced supine and erect blood pressure, and pulse rate similar to the reduction with metoprolol (100 mg b.i.d.). There was a tendency for forearm blood flow to rise and for forearm resistance to fall with both drugs. When administered acutely, there was no fall in pulse rate with carvedilol compared to the fall with metoprolol when on placebo or active therapy. The blood pressure fall with acute administration was similar with both drugs when not on treatment, but when on chronic therapy, there was no fall with metoprolol but a marked fall with carvedilol. In this circumstance, vascular resistance rose with metoprolol but not with carvedilol. No effect of either drug on a modified cold presser test was observed. Both drugs were well tolerated and there were no significant side effects except for an excessive fall in blood pressure in one patient on carvedilol. Plasma renin activity (PRA) fell with both drugs and there was a tendency for both plasma potassium and plasma uric acid to rise. Carvedilol was well tolerated and reduced blood pressure successfully.

Adrenergic beta-Antagonists↗
PubMed1986

Compliance and the elderly hypertensive.

In the control of chronic disease no therapeutic regimen is successful unless it is complied with. A number of studies have indicated that compliance with tablet-taking may be as low as 40%. Patients with hypertension are frequently on a number of different anti-hypertensive agents, and if they have other chronic disorders they may take as many as 10 different drugs and up to 40 tablets per day. It is therefore not surprising that compliance is poor. To achieve compliance requires education of the patient, reduction in the number of drugs and simplification of the drug regimen. Methyldopa was used in a crossover study on a once- or twice-daily basis. Blood pressure was measured at the same time each day 2 hours after the morning dose. Compliance was assessed by tablet count and by blood pressure control, which was better on once-a-day therapy. Over a 6-week period 95% of medication was taken on the once-daily compared with 84% on the twice-daily regimen. In a subsequent study atenolol once per day replaced propranolol given 3 times per day. Blood pressure was lower on atenolol and tablet compliance was 94% compared with 74% on thrice-daily propranolol therapy. In addition, many patients admitted not taking the midday dose. The effect of dietary advice was then monitored by 24-hour urine electrolytes. When advice was given superficially by the doctor, urine sodium fell from 186 mmol/day to 165 mmol/day. When seen on one occasion by a dietitian and given diet sheets, it fell from 182 to 135 mmol/day. When seen at repeated visits by the dietitian and the advice modified according to sodium excretion, urine sodium excretion fell from 188 to 83 mmol/day. Supplemental oral potassium is often given as antihypertensive medication and up to 6 tablets per day may be administered. Compliance decreased as the number of tablets increased. Compliance was 92% on 1 tablet, 83% on 2 tablets, 68% on 3 tablets, 75% on 4 tablets (usually taken as 2 tablets twice a day) and 58% when on 6 tablets per day. The compliance with diuretic-taking was 96%. When given amiloride/hydrochlorothiazide the compliance was 93% and this elevated plasma potassium more than high dose supplemental potassium. In a recent study people on 3 or more drugs for blood pressure control were placed on a low salt diet and their drugs replaced with enalapril.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

The dependence of biliary methylmercury secretion on liver GSH and ligandin.

The biliary secretion of methylmercury was investigated in male rats which were given i.p. 400 mumoles/kg azathioprine or 96 mumoles/kg benziodarone 2 hr after the i.v. injection of 5 mumoles/kg MeHgCl. A group of rats were given 400 mg/kg trans-stilbene oxide (TSO) for 4 days before treatment with 10 mumoles/kg MeHgCl. A common link between these three compounds is their interference with ligandin. Azathioprine is a competitive inhibitor of glutathione S-transferase, benziodarone is covalently bound to ligandin and TSO is an inducer of liver ligandin. Although only azathioprine depletes liver GSH stores, both azathioprine and benziodarone inhibited the biliary secretion of methylmercury. As there is published proof that the reaction of MeHg+ with GSH does not require enzymatic help, the inhibitory effect of azathioprine and benziodarone confirms the role of ligandin in the transport of methylmercury or its GSH complex. However, the biliary secretion of methylmercury was increased only slightly by TSO pretreatment, but when 2 hr after the injection of MeHgCl animals received 2 mmoles/kg GSH, secretion increased twice as much in TWO pretreated than in control rats. This indicates the dual dependance of biliary methylmercury secretion on liver GSH and ligandin.

Animals↗
PubMed1984

Pelvic infection: a comparison of the Dalkon shield and three other intrauterine devices.

A detailed analysis was undertaken of reports of possible pelvic infection in relation to the use of four commonly fitted intrauterine contraceptive devices during 1971 to 1978 in the United Kingdom. The four devices were the Dalkon shield, Lippes loops 3C and 2D, and the Gravigard (copper 7), and data used were those collected systematically through the UK intrauterine device research network. Prospective reports that the Dalkon shield was uniquely related to high levels of infection when compared with other intrauterine devices were not substantiated in this prospective study among 13 349 users. Though some factors such as social class and previous experience of abortion appeared to influence the rate of infection, the type of intrauterine device being worn did not appear to be a significant factor. Various methods of analysis were used including life table, regression, and discriminant analysis, using information relating to the type of intrauterine device worn, the characteristics of the user, the fitting centre, and the pattern of diagnosis and treatment of reported or suspected pelvic infection. The results of this study suggest that fears that the Dalkon shield may be associated with a higher incidence of pelvic infection than other intrauterine devices may have been unjustified.

Female↗