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Biomedical subjects

A Brady

Publications and source records attributed to A Brady.

At least 19 recordsLinked to original sources
PubMed2003

Prevalence of urinary catheterization in UK nursing homes.

A postal questionnaire survey was undertaken in registered nursing homes in three different health districts in England: Gloucestershire, North Staffordshire and Leeds. Nursing homes may be registered as general nursing or mental health homes. If homes also have provision for residential beds these are defined as dual registered homes. Overall, 9% (438/4900) of residents, with an equal male:female split, had urinary catheters. There was no significant difference in the overall urinary catheterization rate in the three districts (P=0.9). There was a wide range of urinary catheterization prevalence between homes, with some homes of all three categories having no catheterized residents and several with a prevalence of over 40%. The wide range of prevalence may be due to differences in residents' underlying medical conditions or to differences in attitudes towards urinary catheterization by nursing home staff. Almost all homes (114/124, 92%) stated they had an infection control policy, but 31% (38/124) did not have a written policy on urinary catheter care. In view of the potential for morbidity, infection control policies should include a section on the care of urinary catheters and this should form part of the continuing training of nursing home staff.

Aged↗
PubMed2003

The effects of KT3-671, a new angiotensin II (AT 1) receptor blocker in mild to moderate hypertension.

AIMS: To compare the antihypertensive effect, and tolerability and safety of once daily doses of KT3-671 with that of placebo in patients with mild to moderate uncomplicated essential hypertension. METHODS: A randomised, multicentre, double blind, parallel-group comparison of KT3-671 with placebo. Hypertensive patients [Ambulatory Blood Pressure Monitoring (ABPM), mean daytime DBP > 90 mmHg, Office sitting mean DBP 95-114 after a 7-28 day washout period] entered a 2-week, single blind, run-in phase. Patients eligible for the double-blind phase were randomised to receive KT3-671 40 mg, 80 mg, 160 mg or placebo once daily over 4 weeks. The primary end-point was trough mean sitting office DBP. The study had 90% power to detect a 5 mmHg change between treatments and placebo at the 5% level of significance. The secondary end-points were 24 hour, daytime and night time mean ABPM. RESULTS: Office DBP was significantly lower with KT3-671 40 mg but not the other 2 dosage groups (-3.2; 95% CL -6.1 : -0.3 P < 0.03). Office SBP was significantly reduced with all dosage groups (40 mg -5.9, 95% CL -11 : -0.9; 80 mg -4.9, 95% CL -9.9 : 0.1 and 160 mg -5.7, 95% CL -10.8 : -0.7 P < 0.05). All doses of KT3-671 reduced systolic and diastolic ABPM. The number of patients with treatment related adverse events were comparable to placebo (38.8% KT3-671 vs 32.8% placebo). There was some evidence of a dose-response relationship with fall in nocturnal ABPM. CONCLUSIONS: Oral KT3-671 was well tolerated. KT3-671 reduced office systolic BP at all doses and diastolic BP at some of the doses. Due to greater precision and power, the falls in mean ambulatory systolic and diastolic pressure were all significantly lower than placebo.

Adult↗
PubMed2000

A purpose built MRSA cohort unit.

The control of hospital-acquired infection, in particular methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge. Our hospital has established a purpose built 11-bed cohort unit with on-site rehabilitation for care of patients colonized with MRSA, in an attempt to improve their quality of care. Prior to the opening of this unit a number of concerns were voiced and the aim of this study was to address these. First, to establish if patient cohorting reduces the likelihood of successful decolonization, second, to evaluate the risk of staff colonization, and finally to see if successful environmental control of MRSA is possible.A patient database was established detailing patient demographics, infection rates, eradication and reacquisition rates. Staff screening was performed weekly, at the start of a period of duty. Sixty environmental sites were screened before unit opening, at 48h, six weeks and at six months. There were 88 admissions in the first six months; 62 patients were colonized with MRSA, and 26 patients (10 surgical, 16 medical) had MRSA infections. Twenty-three of 88 patients (26%) were successfully decolonized, which compares favourably with an eradication rate of 20% for the rest of the hospital. Twenty staff members participated in weekly screening. Five staff members colonized with MRSA were detected and all were successfully decolonized. Environmental control was achieved with a combination of a daily detergent clean and a once weekly clean with phenolic disinfectant. Our preliminary data suggest that, despite cohorting patients colonized with MRSA, with proper education and supervised cleaning protocols, it is possible to control environmental MRSA load, successfully decolonize patients and limit the risk of staff colonization.

Carrier State↗
PubMed1997

Behavioural and demographic characteristics of attenders at two genitourinary medicine clinics in England.

OBJECTIVES: To investigate how attenders with sexually transmitted disease (STD) differ from the general population with respect to sexual behaviour, and to identify which attenders at genitourinary medicine (GUM) clinics are at particular behavioural risk for acquiring STD. DESIGN: Multicentre cross sectional survey. SETTING: Two genitourinary medicine clinics, one in London and one in Sheffield SUBJECTS: 20,516 patients attending the two clinics over an 18 month period. MAIN OUTCOME MEASURES: Behavioural and demographic characteristics and clinical diagnoses were recorded for each patient. RESULTS: 8862 patients, in whom 12,506 diagnoses were made, were seen in the Sheffield clinic, and 11,654 patients, in whom 20,243 diagnoses were made, were seen in the London clinic. When compared with the reported results from a general population survey, there were higher proportions of clinic attenders reporting two or more sexual partners in the preceding 12 months (p < 0.001), and a higher proportion of males reporting homosexual contact (13% compared with 1%, p < 0.001). Only age and number of sexual partners in the past 12 months were significantly associated with acute STDs for each sex in each clinic. Acute STDs tended to occur with greater frequency in the younger age groups, peaking among 16-19 year olds, particularly among females. CONCLUSIONS: The results have confirmed that patients with STDs exhibit higher risk sexual behaviour than the general population, and have highlighted the problem of continuing high risk behaviour among younger attenders, particularly younger homosexual men. This study has demonstrated that among GUM clinic attenders age and number of sexual partners are key risk factors for the acquisition of an acute STD. The results of this survey also indicate, however, that half of the females and more than one quarter of males with acute STDs reported only one sexual partner in the past 12 months, suggesting that health education messages should point out that it is not only those who have multiple recent sexual partners, or who have recently changed sexual partner, that are at risk of STD, including HIV.

Adolescent↗
PubMed1997

Pain management guidelines: implications for managed care--a roundtable discussion.

One of the most important concerns of patients with cancer, particularly those with metastatic disease, is "Will I be in constant pain?" This is a similar concern voiced by patients with late-stage human immunodeficiency virus infection. The management of chronic pain has enormous implications on a patient's ability to function and on his or her quality of life. In June 1996, Medical Interface convened a panel of experts in Chicago to discuss pain management therapies, guidelines, and how these issues will affect, and be affected by, the managed care environment.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The squirrel monkey as an animal model of pelvic relaxation: an evaluation of a large breeding colony.

OBJECTIVE: Findings of pelvic relaxation have been reported in up to 50% of older adult female squirrel monkeys. To evaluate further the potential use of the squirrel monkey as an animal model of pelvic relaxation, we objectively observed and described the perineal findings of 160 adult females. The aim of this study was to examine the relationship of perineal findings to age and parity, factors thought to predispose women to pelvic relaxation. STUDY DESIGN: The urethra, cervix, and anterior and posterior segments of the vagina were evaluated. The degree of support loss at each site was documented. Genital measurements were obtained by previously reported methods. The findings were tested for association with elements of obstetric history, age, and subspecies. RESULTS: The females represented three subspecies and ranged from 3 to 17 years old with parities of 0 to 10. The proportion of females with normal support was inversely related to increasing parity and age. Although birth weights, frequency of dystocia at term, and requirement for cesarean section did not differ significantly between females with and without evidence of prolapse, animals with multiple sites of prolapse tended to have infants with higher birth weights. Animals without prolapse were significantly younger and less likely to have been delivered of a term infant (p < 0.001). Subspecies differences unrelated to age or parity were found for each of the genital measurements. Differences were also found between animals with normal perineal findings and those with findings of prolapse. Animals with prolapse had shorter perineal bodies (p < 0.001), greater genital hiatal ratios (p < 0.001), and wider genital hiatal measurements (p < 0.001). Females with abnormal pelvic findings were of increased parity (4.0 vs 1.6, p < 0.001) and age (9.4 vs 6.3 years, p < 0.001) compared with those normal pelvic findings. CONCLUSION: Analysis of genital prolapse in a large population of breeding squirrel monkeys demonstrated an association of loss of pelvic support with age and parity. A tendency for loss of support at multiple sites was associated with obstetric complications. These observations support continuing investigation into the nature and cause of spontaneous pelvic relaxation in this species and support the potential use of this nonhuman primate as an animal model.

Age Factors↗
PubMed1995

The mutational spectrum in Waardenburg syndrome.

One hundred and thirty-four families or individuals with auditory-pigmentary syndromes such as Waardenburg syndrome (WS) or probable neurocristopathies were screened for mutations in the PAX3 and MITF genes. PAX3 mutations were found in 20/25 families with definite Type 1 WS and 1/2 with Type 3 WS, but in none of 23 with definite Type 2 WS or 36 with other neurocristopathies. The PAX3 mutations included substitutions of conserved amino acids in the paired domain or the homeodomain, splice-site mutations, nonsense mutations and frame-shifting insertions or deletions. No phenotype-genotype correlations were noted within WS1 families. With MITF, mutations likely to affect protein function were found in seven families, five of which had definite Type 2 WS. We conclude that Type 1 and Type 3 WS are allelic and are normally caused by loss of function mutations in PAX3; that Type 2 WS is heterogeneous, with about 20% of cases caused by mutations in MITF, and that individuals with auditory, pigmentary or neural crest syndromes which do not fit stringent definitions of Waardenburg syndrome are unlikely to have mutations in either the PAX3 or MITF genes. The molecular pathology of MITF/microphthalmia mutations appears to be different in humans and mice, with gene dosage having more significant effects in humans than in the mouse.

Amino Acid Sequence↗
PubMed1995

Antiestrogen inhibition of cell cycle progression in breast cancer cells in associated with inhibition of cyclin-dependent kinase activity and decreased retinoblastoma protein phosphorylation.

To define the mechanisms by which antiestrogens inhibit breast cancer cell proliferation, the effects of the antiestrogen ICI 182780 on G1 cyclins and their cyclin-dependent kinase (CDK) partners were investigated in MCF-7 cells. Inhibition of entry into S phase became evident 9 h after treatment, with the proportion of cells in S phase reaching a minimum by 24 h. ICI 182780 increased the proportion of the hypophosphorylated, growth inhibitory form of the retinoblastoma protein (pRB). This change began at 4-6 h, preceding effects on S phase. This suggests that there are early effects on the activities of CDKs that target pRB that are not merely a consequence of changes in cell cycle progression. The kinase activity of Cdk2 decreased to low levels at 18-24 h when changes in S phase and pRB phosphorylation were well advanced. An earlier effect was seen on kinase activity associated with immunoprecipitated cyclin D1, which was reduced approximately 40% by 12 h, with further decreases at 18-24 h. Cdk2 and Cdk4 protein levels remained constant over 24 h. Cyclin D1 messenger RNA and protein were down-regulated by ICI 182780 from 2 h, with levels halved at 8 h. ICI 182780 also increased the expression of the CDK inhibitors p27KIP1 and p21WAF1/CIP1 at later times. These observations are compatible with the hypothesis that antiestrogens block entry of cells into S phase and inhibit cell proliferation as the consequence of an early decline in pRB phosphorylation contributed to by reduced cyclin D1/Cdk4 activity. At later times, increased CDK inhibitor abundance may act to repress Cdk2 and Cdk4 activities, causing additional reductions in pRB phosphorylation, thus maintaining the antiestrogen blockade of cell cycle progression.

Breast Neoplasms↗
PubMed1994

Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis.

In this review we have evaluated the relationship between peroxisome proliferation and hepatocarcinogenesis. To do so, we identified all chemicals known to produce peroxisome proliferation and selected those for which there are data (on peroxisome proliferation and hepatocarcinogenesis) which meet certain criteria chosen to facilitate comparison of these phenomena. The summarised data and definition of the methodology used has been collected in appendices. These comparisons enabled us to evaluate the relationship between these phenomena using reliable data. As there is a good correlation between them, we further explored the mechanisms of action that have been proposed (direct genotoxic activity, production of hydrogen peroxide, cell proliferation and receptor activation). The relationship between these events in other species, including humans, was also reviewed and finally an overview of the assessment of human hazard is presented in section IX. Some of the first chemicals which were shown to produce peroxisome proliferation were also hepatocarcinogens whose carcinogenicity could not be readily explained by genotoxic activity. This raised the suggestion that the unusual phenomenon of peroxisome proliferation was intricately linked to the carcinogenic activity of these agents. Three questions have exercised the attention of regulatory, industrial and academic toxicology since then; are chemicals which elicit peroxisome proliferation in the liver actually a coherent class of chemical carcinogens?; does the early biological phenomenon of peroxisome proliferation have real predictive value for and mechanistic association with rodent carcinogenesis?; and what hazard/risk do these agents pose to humans that may be exposed to them? Whether peroxisome proliferators are indeed a discrete class of rodent carcinogens would appear to be the single, most important question. If so, then the assumptions and procedures relevant to human hazard and risk assessment should be applied to the class and should be essentially generic; if not, each chemical should be considered independently. Our critical analysis of the published data for over 70 agents which have been shown to possess intrinsic ability to induce peroxisome proliferation in the livers of rodents has led to the conclusion that there exists a strong correlation between peroxisome proliferation as n early effect in the liver and hepatocarcinogenicity in chronic exposure studies. An almost perfect correlation was observed between the induction of peroxisomes in the rodent liver and the eventual appearance of tumours following chronic exposure The few exceptions to this were largely explainable (section II).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Formation of N-methyl protoporphyrin in chemically-induced protoporphyria. Studies with a novel porphyrogenic agent.

1-[4-(3-Acetyl-2,4,6-trimethylphenyl)-2,6-cyclohexanedionyl]-O-eth yl propionaldehyde oxime (for short ATMP) is a novel porphyrogenic agent causing hepatic protoporphyria in the mouse. Mice given a single dose of the drug showed 24 h later a 70% inhibition of liver ferrochelatase and marked accumulation of protoporphyrin. These changes were not seen in similarly treated rats, guinea pigs, hamsters or chick embryos. A green pigment was isolated from the liver of mice treated with ATMP and identified by its electronic absorption spectrum and chromatographic properties on HPLC as N-methyl protoporphyrin. The ATMP pigment markedly inhibited the enzyme ferrochelatase in vitro, thus supporting its identification as N-methyl protoporphyrin. Two inhibitors of liver cytochrome P450, compound SKF 525-A and piperonyl butoxide, when given before ATMP, afforded protection against ATMP-induced porphyria and production of N-methyl protoporphyrin, suggesting a role of cytochrome P450 in the induction of the metabolic disorder. The most likely interpretation for these findings is therefore that ATMP is metabolized in the mouse to a reactive species, which in turn alkylates the haem moiety of liver cytochrome P450, thus producing N-methyl protoporphyrin. This inhibits ferrochelatase and, as a secondary response, protoporphyrin accumulates. This pathway of metabolism to the postulated reactive metabolite presumably does not occur to a significant extent in the other species examined and hence is the likely basis for the species difference in protoporphyria.

Animals↗
PubMed1993

A cry from the fringe.

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Attitude of Health Personnel↗
PubMed1988

Fluctuations in intra-ocular pressure with sleep: I. Time course of IOP increase after the onset of sleep.

Ten normal subjects slept over a series of four nights for time periods of 30 minutes, 1, 2 and 4 hours. Intra-ocular pressure (IOP) measurements were made using a non-contact tonometer before and after sleep. The subjects showed a significant increase in IOP of 3.45 mm Hg after 30 minutes of sleep and a further IOP increase thereafter to 6.41 mm Hg above baseline. Such increases in IOP after sleep in normal subjects suggest that glaucoma patients and those suspected of having glaucoma should be monitored overnight to assess their IOP control mechanisms.

Data Interpretation, Statistical↗