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Biomedical subjects

R Yates

Publications and source records attributed to R Yates.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pharmacokinetics of two multiple-dosing regimens of D0870 in human immunodeficiency virus-positive patients: a phase I study.

D0870 is a triazole with a broad antifungal spectrum, and it has been shown to have both in vitro and in vivo activities against wild-type and fluconazole-resistant strains of Candida albicans. Twenty-two human immunodeficiency virus (HIV)-positive male subjects were enrolled in an open, nonrandomized trial investigating the pharmacokinetics of two different dosing regimens of D0870 and assessing the safety of multiple oral doses of D0870 in HIV-positive subjects and their ability to tolerate multiple oral doses. Nine subjects received an initial loading dose of 50 mg, followed by four once-daily maintenance doses of 10 mg. A further nine subjects received an initial 200-mg loading dose followed by four daily maintenance doses of 25 mg. All subjects were fasting. A single loading dose of 50 mg of D0870 resulted in a mean maximum concentration in serum (Cmax) of 107 +/- 32 ng/ml. Concentrations in plasma were maintained by the 10-mg once-daily dosing regimen as seen by the similar values of the area under the concentration-time curve from 0 to 24 h following dosing on days 1 and 5 and a mean accumulation ratio close to unity (0.90). The terminal plasma half-life of D0870 in plasma following dosing on day 5 ranged from 23 to 85 h (mean, 49 h). A single loading dose of 200 mg of D0870 resulted in a Cmax of 431 +/- 186 ng/ml. Concentrations in plasma were again maintained by the 25-mg daily dosing regimen, with the mean accumulation ratio being close to unity (1.17). The terminal half-life of D0870 in plasma following dosing on day 5 of phase II of the study ranged from 34 to 137 h (mean, 71 h). In addition, the concentrations achieved in the plasma of these HIV-positive subjects were similar to the values predicted from simulations based on data derived from normal, healthy subjects. D0870 was well tolerated. No serious adverse events were experienced during the course of the study, and all volunteers completed the trial. A total of 15 adverse events were reported, but none were considered to be related to the administration of D0870 and all had resolved by the end of the trial. No changes in the hematology, clinical chemistry, or urinalysis parameters were considered to be related to dosing with D0870. No clinically significant changes in the electrocardiogram parameters were noted during the trial. The data generated in this trial support further investigation of these regimens with HIV-positive subjects with fluconazole-susceptible or -resistant oropharyngeal candidosis.

Adolescent↗
PubMed1998

Endocarditis as the first presentation of AIDS in infancy.

A two month old Ugandan boy underwent surgery for an obstructive right ventricular vegetation associated with disseminated Staphylococcus aureus infection. Both the child and his mother subsequently tested positive for HIV infection. Very little is know about the incidence of endocarditis in paediatric patients with AIDS. To our knowledge this is the first case reported of disseminated S aureus infection associated with endocarditis and an obstructing vegetation in an HIV positive infant with a structurally normal heart. The initial signs and symptoms for endocarditis were atypical, a reflection of the overwhelming infection in an immunocompromised patient. Severe infections may have an atypical presentation in immunosuppressed patients. AIDS needs to be considered in these patients, especially if they come from populations with endemic HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1998

Complications of modified Blalock-Taussig shunts mimicking pulmonary disease.

The modified Blalock-Taussig shunt is commonly performed as early palliation in cyanotic congenital heart disease. To highlight unusual diagnostic problems in such patients, two cases are reported in whom shunt complications were initially diagnosed as lobar pneumonia and tuberculosis, respectively. The children, an 8 month old boy and a 3 year old boy, had false aneurysm secondary to infection of the graft and dilatation of the left pulmonary artery caused by blood flow through the shunt, respectively.

Cardiac Surgical Procedures↗
PubMed1997

The comparative effect of acidified sodium chlorite and chlorhexidine mouthrinses on plaque regrowth and salivary bacterial counts.

Acidified sodium chlorite (ASC) is recognised as a highly potent, broad spectrum antimicrobial system that has been successfully developed for uses in veterinary, food processing and medical device fields. The current studies aimed to investigate the persistence of antimicrobial action and plaque inhibitory properties of 3 ASC mouthrinses by comparison with positive control, chlorhexidine 0.12%, and placebo control, water, rinses. Both studies were randomised, double-blind, cross-over 5-cell designs balanced for carryover. The 1st study involved 15 healthy subjects who immediately before and at 30, 60, 180, 300 and 420 min after rinsing provided 2 ml saliva samples. The samples were immediately processed for total anaerobic bacterial counts recorded after 96 h incubation. Washout periods were a minimum of 3 days. The second study involved 20 healthy subjects who on day 1 of each study were rendered plaque free, suspended normal oral hygiene methods and commenced rinsing twice daily with the allocated rinse. On day 5, plaque was scored by index and area after disclosing with erythrosin. Washout periods were 2 1/2 days. The 3 ASC and chlorhexidine rinses produced similar reductions in salivary bacterial counts which remained significantly below the placebo control to 7 h. There were no significant differences between ASC and chlorhexidine rinses except at 30 and 60 min when significantly greater reductions were produced by 2 ASC rinses compared to the chlorhexidine rinse. Plaque indices and areas were considerably and significantly lower with the ASC and chlorhexidine rinses compared to the placebo rinse. There were no significant differences between plaque scores for the 3 ASC rinses and the chlorhexidine rinse, although for 2 ASC rinses plaque scores were lower than for the chlorhexidine rinse. The results indicate that the 3 ASC rinses have equivalent plaque inhibitory action to chlorhexidine as a rinse. Similar to chlorhexidine, the plaque inhibitory action of the rinses appears to be derived from a persistence of antimicrobial action in the mouth.

Anti-Infective Agents, Local↗
PubMed1997

The neonatal consequences and neonatal cost of reducing the number of embryos transferred following IVF.

This clinical audit project examined the effects of change of policy between 1990 and 1993 transferring an average two (maximum three for particular cases) embryos to women undergoing IVF in the West of Scotland programme. All women who achieved clinical pregnancy in 1990 (92 women) and 1993 (93 women) as a result of the IVF programme were included in the study. The hospital records of women via the programme were analysed. The results of the study showed that there was a significant reduction in the rate of multiple pregnancy, preterm birth and low birth weight babies in the 1993 group (new policy). The cost of neonatal intensive care in 1993 for babies born following IVF was about nine times lower than that in 1990 (old policy). This study concluded that a policy of transferring two embryos (or three for particular cases) to women in an IVF programme, had improved the perinatal outcome and reduced the cost of the neonatal service for those babies.

Chi-Square Distribution↗
PubMed1997

The effect of transmission bandwidth on diagnostic accuracy in remote fetal ultrasound scanning.

Six subspecialists with considerable experience in fetal ultrasound viewed a selection of pre-recorded ultrasound scans. Scans from 18 patients recorded on VHS video-tape were supplied from five centres in the UK and Ireland, each made on a high-resolution ultrasound machine by an experienced sonologist at a referral centre. Each observer viewed the scans on a large display monitor in an individual viewing booth. The scans were viewed in random order, at randomly selected bandwidths. Observers, who were blinded to both recording and bandwidth, assessed the technical quality on a five-point Likert scale. They also recorded their diagnosis. The six observers each carried out 32 viewing sessions, which gave a total of 192 viewings. There was no significant difference in the perceived technical quality of the scans between the two bandwidths used (P = 0.09). Of the 84 recordings transmitted at 1920 kbit/s, 71 (85%) were diagnosed correctly or 'half correctly' and 13 (15%) were misdiagnosed. Of the 95 recordings transmitted at 384 kbit/s, 66 (69%) were diagnosed correctly or 'half correctly' and 29 (31%) were misdiagnosed. This difference was significant (P = 0.03). The results indicate that although there were no perceived differences in technical quality between recordings transmitted at 384 or 1920 kbit/s, diagnostic accuracy was marginally worse at the lower bandwidth. This suggests that the higher bandwidth conveys more detail and information to the observer, which in turn enables more accurate diagnosis. However, further work is required before a definitive choice can be made about the optimum transmission bandwidth for remote fetal ultrasound studies.

Female↗
PubMed1995

Phosphatidylserine decarboxylase 2 of Saccharomyces cerevisiáe. Cloning and mapping of the gene, heterologous expression, and creation of the null allele.

The yeast Saccharomyces cerevisiae expresses two phosphatidylserine decarboxylase (PSD) activities which are responsible for conversion of phosphatidylserine to phosphatidylethanolamine, and either enzyme alone is sufficient for normal cellular growth. However, strains containing a PSD1 null allele and a mutation leading to loss of PSD2 activity (psd1-delta 1::TRP1 psd2) are auxotrophic for ethanolamine. This nutritional requirement was utilized to isolate the gene encoding the PSD2 enzyme by complementation. The PSD2 gene encodes a protein of 1138 amino acids with a predicted molecular mass of 130 kDa. The deduced amino acid sequence shows significant identity (34%) to a PSD-like sequence from Clostridium pasteurianum and the yeast PSD1 (19%) at the carboxyl end of the protein. Of particular interest is the presence of a sequence, GGST, which may be involved in post-translational processing and prosthetic group formation similar to other PSD enzymes. The PSD2 amino acid sequence also shows significant homology to the C2 regions of protein kinase C and synaptotagmin. Physical mapping experiments demonstrate that the PSD2 is located on chromosome 7. The PSD2 gene was heterologously expressed by infection of Sf-9 insect cells with recombinant baculovirus, resulting in a 10-fold increase in PSD activity. The null allele of PSD2 was introduced into yeast strains by one-step gene deletion/disruption with a HIS3 marker gene. Strains expressing wild type PSD1 and the psd2-delta 1::HIS3 allele show a small decrease in overall PSD activity, but no noticeable effect upon [3H]serine incorporation into aminophospholipids. Strains containing both the psd1-delta 1::TRP1 and psd2-delta 1::HIS3 null alleles, however, express no detectable PSD activity, are ethanolamine auxotrophs and show a severe deficit in the conversion of [3H]serine-labeled phosphatidylserine to phosphatidylethanolamine. These data indicate that the gene isolated is the structural gene for PSD2 and that the PSD1 and PSD2 enzymes account for all yeast PSD activity.

Alleles↗
PubMed1995

ARIMIDEX: a new oral, once-a-day aromatase inhibitor.

ARIMIDEX is a potent and selective aromatase inhibitor undergoing evaluation as a treatment for postmenopausal women with advanced breast cancer. Studies examining the pharmacology of ARIMIDEX were conducted in both animals and humans. In animals, ARIMIDEX elicits maximal aromatase suppressive activity at a dose of approx. 0.1 mg/kg, does not alter adrenal steroid hormone biosynthesis, and at a dose of 1 mg/kg, has no other pharmacologic effects other than aromatase inhibition. In this overview, the pharmacodynamic, pharmacokinetic, and safety profiles of single and multiple daily doses of ARIMIDEX are reported in humans. Daily doses of 1-10 mg of ARIMIDEX suppressed estradiol levels to the maximum degree measurable using sensitive estrogen assays. ARIMIDEX had no clinically significant effects on the response of cortisol and aldosterone to ACTH stimulation. Absorption of ARIMIDEX was rapid, with maximum plasma concentrations occurring within 2 h after oral administration. Plasma concentrations of ARIMIDEX rose with increasing doses of the drug. The elimination half-life of ARIMIDEX in humans ranged from 30 to 60 h. Consistent with the long plasma half-life, steady state plasma concentrations were 3-4-fold higher than plasma concentrations observed after single administration of 1, 3, 5, or 10 mg doses. Long term treatment of breast cancer patients with 10 mg/day has continued in 17 patients without an escape of estradiol suppression. Previously, these patients had received on average 2.6 systemic treatments for breast cancer and had significant metastatic disease. Three of the 17 patients continued ARIMIDEX treatment for 20 months and beyond. Given the number of previous treatments and tumor burden at the start of treatment, the response to ARIMIDEX treatment is encouraging. Phase III studies are now underway to assess the efficacy and safety of ARIMIDEX in the treatment of advanced breast cancer.

Administration, Oral↗
PubMed1993

A 6-month home usage trial of a 1% chlorhexidine toothpaste (1). Effects on plaque, gingivitis, calculus and toothstaining.

Research and development has been aimed towards the development of toothpastes for oral hygiene and gingival health benefits. The most effective antiplaque agent to date, chlorhexidine, is difficult to formulate into active toothpaste products. Despite some encouraging findings for experimental chlorhexidine toothpastes, there are to date no commercially available products. Based on positive findings from an experimental gingivitis study, this investigation evaluated 2 chlorhexidine toothpastes, one with fluoride, as adjuncts to oral hygiene. The study was a double-blind controlled, parallel, balanced group design, extending over 6 months. A total of 297 volunteers commenced the study after screening for a minimum acceptance level of gingivitis. At baseline, 6, 12 and 24 weeks, stain, gingival, bleeding and plaque indices were recorded, together with a calculus index at 6, 12 and 24 weeks. After a baseline prophylaxis, volunteers used the allocated product 2 x per day, with no other oral hygiene instructions given. Plaque, gingival and bleeding scores improved in all 3 groups, but to an overall significantly greater extent in the active groups. However, staining and calculus indices were significantly increased in the active compared to the control group. If the local side-effects of chlorhexidine are considered to be acceptable, these chlorhexidine toothpastes could be recommended for the same clinical applications as other chlorhexidine products. The apparent compatibility of fluoride with chlorhexidine in the one product may be pertinent to caries prevention.

Adolescent↗
PubMed1992

Hormonal regulation of the growth and steroidogenic function of human granulosa cells.

The aim of this study was to assess development-related interactions between gonadotropins and insulin-like growth factor (IGF-I) on DNA synthesis and steroidogenesis in human granulosa cells. "Immature" granulosa cells were obtained from follicles during the late luteal phase or first half of the follicular phase; "mature" granulosa cells came from follicles during the second half of the follicular phase but before the midcycle LH surge; and granulosa-lutein cells were obtained as a by-product of in vitro fertilization. Granulosa cells were cultured for 96 h in serum-free medium 199 with and without LH or FSH, and in the presence and absence of IGF-I. The cell monolayers were then incubated with [3H]methyl thymidine to assess DNA synthesis. Spent culture medium was assayed for progesterone and estradiol content. Immature granulosa cells: Tritiated thymidine uptake in granulosa cell cultures from immature follicles were significantly increased by IGF-I. FSH was able to maintain or increase basal and IGF-I stimulated growth whereas LH had no effect. Basal progesterone production was low and not increased by either FSH or LH. However, treatment with FSH, but not LH, increased aromatase activity. Mature granulosa cells: IGF-I also stimulated thymidine uptake. However, whereas FSH either maintained or increased thymidine uptake by these cells, LH dose dependently suppressed thymidine uptake. This inhibitory action of LH was accentuated by the presence of IGF-I. Despite the inhibitory effect of LH on thymidine uptake, the gonadotropin markedly stimulated steroid production and the maximal steroidogenic response to LH was equivalent to 3-fold greater than that to FSH. Granulosa-lutein cells: Patterns of basal and IGF-I- and gonadotropin-stimulated steroid synthesis were similar to those observed for mature granulosa cells but steroid production rates were higher. Suppression of basal and IGF-I-stimulated thymidine uptake by LH was even more pronounced. These results suggest that the granulosa cell LH receptor, once expressed, negatively regulates cell growth and, simultaneously, positively regulates steroid synthesis. This development related event could be crucial to the mechanism whereby granulosa cells cease to divide and commence maximal rates of steroid synthesis in response to the LH surge.

Adult↗
PubMed1989

Uptake and stimulation-evoked release of tritiated neurotransmitters from slices of the rat rostral ventral medulla containing the nucleus raphe magnus: implications for pathways controlling nociception.

1. The rostral ventral medulla plays a central role in the integration of nociceptive control. 2. Slices of this area of the brainstem may be labelled with tritiated noradrenaline, dopamine, serotonin, GABA and choline. 3. Uptake was greatest for noradrenaline and dopamine, GABA was intermediate and serotonin and choline were poorly accumulated. 4. Conditions for the release of all transmitter candidates except acetylcholine were established using either potassium or electrical stimulation and release was proven to be calcium dependent. 5. Electrophysiological and microinjection data are at variance with the commonly assumed actions of noradrenaline and dopamine and can be rationalized by the presence of a GABA interneuron integrating nociceptive input to the nucleus raphe magnus.

Animals↗
PubMed1986

Light and electron microscopic studies of diet-induced hepatic changes in mice.

Adult mice were fed a choline-deficient ethionine enriched (CDE) diet for 24, 48 or 72 h. They were then fasted for 24 or 48 h prior to sacrifice. All tissues were studied by light and electron microscopy. Animals fed the CDE diet for 24 h exhibited cells with vacuolated cytoplasm, and the accumulation of lipid in these cells was clearly abnormal. Animals fed the CDE diet for 24 h and subsequently a regular diet for 48 h displayed normal hepatocytes, suggesting that the alterations at 24 h were reversible. Following 48 or 72 h of feeding the CDE diet, abundant lipid-laden cells were observed in the hepatic lobules, and at the electron microscope level these cells were undergoing frank degeneration. Evidence indicated that changes after 48 or 72 h were irreversible.

Animals↗