PubMed Health⌕ Search

Biomedical subjects

C Brooks

Publications and source records attributed to C Brooks.

At least 19 recordsLinked to original sources
PubMed2003

Management of women who test positive for high-risk types of human papillomavirus: the HART study.

BACKGROUND: Certain types of human papillomavirus (HPV) are the primary cause of almost all cervical cancers. HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology. We aimed to compare the detection rate and positive predictive values of HPV assay with cytology and to determine the best management strategy for HPV-positive women. METHODS: We did a multicentre screening study of 11085 women aged 30-60 years. Women with borderline cytology and women positive for high-risk HPV with negative cytology were randomised to immediate colposcopy or to surveillance by repeat HPV testing, cytology, and colposcopy at 12 months. FINDINGS: HPV testing was more sensitive than borderline or worse cytology (97.1% vs 76.6%, p=0.002) but less specific (93.3% vs 95.8%, p<0.0001) for detecting CIN2+. Of 825 randomised women, surveillance at 12 months was as effective as immediate colposcopy. In women positive for HPV at baseline, who had surveillance, 73 (45%) of 164 women with negative cytology and eight (35%) of 23 women with borderline cytology were HPV negative at 6-12 months. No CIN2+ was found in these women, nor in women with an initial negative HPV test with borderline (n=211) or mild (32) cytology. INTERPRETATION: HPV testing could be used for primary screening in women older than 30 years, with cytology used to triage HPV-positive women. HPV-positive women with normal or borderline cytology (about 6% of screened women) could be managed by repeat testing after 12 months. This approach could potentially improve detection rates of CIN2+ without increasing the colposcopy referral rate.

Adult↗
PubMed2002

Quantitative and functional differences in CD8+ lymphocyte responses in resolved acute and chronic hepatitis C virus infection.

CD8+ T lymphocyte responses are important in the clearance of viral infections. In chronic infections they may contribute to pathogenesis. To investigate the role of CD8+ T lymphocyte responses in viral clearance and chronic hepatitis C we have compared hepatitis C virus (HCV) specific cytotoxicity and interferon-gamma (IFN-gamma) production in patients with resolved-acute, and chronic HCV infection. CD8+ T cell responses to a panel of 13 HCV T cell peptide epitopes were studied using Elispot assays of IFN-gamma production and chromium release cytotoxicity assays. Responses of seven patients with resolved acute HCV infection were compared with those of 14 chronically infected patients. HCV-specific cytotoxicity differentiated the two populations of patients. The majority (71%) of patients with resolved acute infection tested positive to 42% of relevant peptides compared with the minority (28%) of patients with chronic hepatitis C (P=0.03) who responded to only 8% of relevant peptides (P=0.0009). In contrast, HCV-specific IFN-gamma production was detected in 86% of patients with either resolved or chronic infection in response to 42% and 35%, respectively, of relevant peptides tested (not significant). In patients with chronic infection the magnitude of the HCV-specific IFN-gamma production was inversely correlated to viral load (R2=0.52; P=0.042). Failure to clear HCV infection may be attributable to the presence of noncytolytic IFN-gamma producing CD8+ T lymphocytes in chronically infected patients. However these CD8+ T cells may play a beneficial role in contributing to the control of viral load in chronic hepatitis C.

Acute Disease↗
PubMed2002

No evidence of mutations in the CACNA1S gene in the UK malignant hyperthermia population.

BACKGROUND: Malignant hyperthermia (MH) is an inherited, potentially fatal, pharmocogenetic disorder triggered by certain anaesthetic agents. In light of the reported genetic heterogeneity for the disorder and the recent introduction of DNA testing guidelines for the trait, we have assessed the role of the CACNA1S gene in MH susceptibility in UK patients. Linkage to this locus has previously been demonstrated in several European MH families. METHODS AND RESULTS: We screened 200 unrelated MH-susceptible individuals for known CACNA1S mutations. With the aim to characterize further novel mutations at this locus, functionally relevant regions of the gene were also sequenced in 10 unrelated individuals from families where the involvement of other MH susceptibility loci was unlikely. No sequence variations were detected in any of the patients investigated. CONCLUSIONS: Defects in CACNA1S are not a major cause of MH in the UK population. Diagnostic screening of this gene is unlikely to be of value to UK MH patients in the near future.

Calcium Channels, L-Type↗
PubMed2000

Pharmacologic response of a controlled-release PLGA formulation for the alpha-melanocyte stimulating hormone analog, Melanotan-I.

PURPOSE: The objective of this study was to evaluate in vitro and in vivo the melanogenic activity of one-month duration Melanotan-I (MT-I) implants prepared using poly (D,L lactide-co-glycolide) polymer. METHODS: The biological activity of the samples of MT-I released in vitro from the non-irradiated or gamma irradiated implants was measured using a frog skin bioassay. The effect of MT-I on skin pigmentation was measured using a Chroma meter (reflectometer) after subcutaneous administration of implants containing 4 mg MT-I to guinea pigs. Eumelanin, the black/brown melanin pigment, was quantified in skin biopsies as pyrrole-2, 3, 5-tricarboxylic acid using HPLC. RESULTS: The MT-I released in vitro from implants after 24 hours exhibited 100% melanotropic activity in frog skins compared to an identical concentration of a freshly prepared MT-I standard. The reflectance readings demonstrated a prolonged skin darkening for up to three months as evidenced by the decrease in the luminance values from 0 to -4.82. A 2.5-fold increase in eumelanin levels was observed after one month and the increased pigmentation lasted for 3 months. CONCLUSIONS: The melanogenic response to MT-I implants persisted for three months and the increase in pigmentation, especially the increased eumelanin levels, could provide protection from ultraviolet radiation.

Animals↗
PubMed2000

Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-alpha-MSH in humans.

Seven normal volunteers (six males and one female) with tanning skin types III or IV (Fitzpatrick scale) were given 10 daily subcutaneous injections of a superpotent synthetic analog of alpha-melanocyte stimulating hormone (alpha-MSH) over two weeks. This agent, [Nle4-D-Phe7]alpha-MSH, also called Melanotan-I (MT-I), was administered at a dose of 0.16 mg/kg/day (Monday-Friday), over a two week period. Tanning was measured serially using computerized light reflectance. This regimen induced tanning at 3 of 8 anatomic sites including the face, neck and forearm by comparison of baseline to (1) the end of the daily dosing period, (day 14), and (2) one week later, (day 21). Shave biopsies of the forearm taken at baseline and day 21 were analyzed by high performance liquid chromatography for eumelanin content which was measured as the permanganate oxidation product, pyrrole-2,3,5-tricarboxylic acid or PTCA. Pheomelanin content was measured as the hydroiodic acid digestion product, aminohydroxyphenylalanine (AHP). Eumelanin was also measured in the forehead skin samples of three subjects. The HPLC results show that mean (+/- SD) baseline eumelanin (PTCA) levels in forehead skin (n = 3) averaged 1.38 (+/- 0.87) ng/mg of wet skin tissue weight. Higher mean baseline levels of PTCA were detected in forearm skin (2.06 +/- 0.28 ng/mg wet weight, n = 7). One week after MT-I treatments ended, there was a mean (SD) 49% (+/- 17.6%) increase in forehead skin PTCA levels compared to baseline (P = 0.019, n = 3, by paired sample T-test). The mean (SD) increase in forearm skin PTCA levels was 98% (+/- 25.4%) over the same period (P = 0.003). In contrast, forearm pheomelanin expression following MT-I treatment did not significantly change from baseline. Overall, the MT-I regimen increased the eumelanin: pheomelanin ratio in forearm skin from 51:1 at baseline to 86:1 following MT-I (P = 0.054 by paired sample T-test). These results show that the tanning induced by MT-I in the face and forearm is associated with a significant increase in the eumelanin content of the human skin.

Adult↗
PubMed2000

Proneness to eating disorders: weightlifters compared to exercisers.

Previous findings were confirmed suggesting that weightlifters may be more prone to eating disorders than are casual exercisers. 25 weightlifters' mean eating disorder score was significantly higher than that of 25 casual exercisers when contrasted for practical difference.

Adult↗
PubMed1999

Child death reviews: a gold mine for injury prevention and control.

OBJECTIVES: The purpose of this study was to demonstrate how child death review teams can be used to prevent future deaths through retrospective, multiagency case analysis and recommendations for educational programs and policy change. METHODS: A listing of all deaths to persons ages 21 years and younger in Philadelphia that occurred in 1995 was compiled by the Philadelphia Interdisciplinary Youth Fatality Review Team (PIYFRT), a multiagency, multidisciplinary, community based group created in 1993 with the mission to prevent future deaths through review, analysis, and initiation of corrective actions. Data were collected on demographic variables, as well as the circumstantial variables on injuries such as weapon type, alcohol and drug use, and contact with the criminal justice system, among others. Each case was reviewed thoroughly to determine whether or not the death was preventable. Selected injury related death cases were analyzed further by demographic and circumstantial variables. RESULTS: In 1995, 607 children ages 21 years and younger died in Philadelphia from natural causes (61.6%), unintentional injuries (16.3%), homicide (18.6%), suicide (2.3%), and undetermined causes (1.2%). More than a third (37.2%) of all deaths were considered preventable. Of the injury deaths (n=224), 95% were judged to be preventable. Preventable fire/burn injury deaths (n=29) were associated with lack of a smoke detector, nonsupervision of children, and faulty home appliances. Violent deaths were associated with substance abuse, gang involvement, chronic truancy, academic failure, and access to weapons. CONCLUSIONS: Relevant policies for these preventable or intervenable deaths are discussed such as use of non-battery powered smoke detectors.

Adolescent↗
PubMed1998

Radiofrequency catheter ablation versus medical therapy for initial treatment of supraventricular tachycardia and its impact on quality of life and healthcare costs.

We prospectively compared the impact on quality of life and cost effectiveness between ablation and medication as an initial strategy for patients with paroxysmal supraventricular tachycardia (SVT). Seventy-nine consecutive patients with newly documented paroxysmal SVT were treated with either ablation or medication. Health surveys (SF-36 and disease-specific questions) were obtained at baseline and after 12 months of follow up. Cost of health care utilization for the 6 months before and after treatment were measured. Both medication and ablation improved quality of life. However, ablation improved quality of life in more general health categories than medication. At follow up, ablation was associated with significantly improved quality of life in the bodily pain (63+/-24 vs 81+/-20, p <0.005), general health (69+/-21 vs 79+/-21, p <0.05), vitality (55+/-21 vs 66+/-22, p <0.05), and role emotion (78+/-36 vs 94+/-17, p <0.05) categories when compared with medication. Although both medication and ablation decreased frequency of disease-specific symptoms, ablation resulted in complete amelioration of symptoms in more patients (33% vs 74%). Potential long-term costs were similar for medication and ablation. In conclusion, ablation improves health-related quality of life to a greater extent, and in more aspects of general and disease-specific health than medication.

Activities of Daily Living↗
PubMed1998

Safety and efficacy of hydrogen peroxide plasma sterilization for repeated use of electrophysiology catheters.

OBJECTIVES: The purpose of this study was to evaluate a new technique for sterilizing nonlumen electrophysiology catheters that uses hydrogen peroxide gas plasma. BACKGROUND: The reuse of electrophysiology catheters may potentially result in a significant cost savings. While ethylene oxide sterilization appears to be safe and effective from a clinical standpoint, toxic ethylene oxide residuals, which exceed Food and Drug Administration standards, have been reported. METHODS: Ten nonlumen electrophysiology catheters were extensively evaluated. Each catheter was used five times and resterilized after each use with hydrogen peroxide gas plasma. Tests for sterility, mechanical and electrical integrity, chemical residuals and standard and electron microscopic inspection were performed. RESULTS: Loss of electrical integrity or mechanical integrity was not observed in any catheter. No evidence of microbial contamination was found. Surface integrity was preserved except for one ablation catheter that exhibited fraying of the insulation at the insulation-electrode interface. Surface inspection using standard magnification and electron microscopy revealed no significant change in surface characteristics associated with the sterilization process. Hydrogen peroxide was the only chemical residual noted, with an average concentration of 0.22% by weight, which is within accepted American Association for the Advancement of Medical Instrumentation limits. The cost for a standard electrophysiology catheter ranges from $200 to $800, and one sterilization cycle costs $10. If electrophysiology catheters are used five times, resterilization could potentially result in a savings of $2,000 per catheter, or $9,000 for five ablation procedures. CONCLUSIONS: Hydrogen peroxide gas plasma sterilization may provide a cost-effective means of sterilizing nonlumen electrophysiology catheters without the problem of potentially harmful chemical residuals. However, careful visual inspection of catheters, particularly at the insulation-electrode interface, is required if catheter reuse is performed.

Anti-Infective Agents, Local↗
PubMed1998

Endovascular treatment of renal artery thrombosis caused by umbilical artery catheterization.

Renal arterial thrombosis, usually in association with aortic thrombosis, has been reported as a result of prolonged neonatal umbilical artery catheterization. A case of renal artery thrombosis attributable to umbilical artery catheterization, resulting in malignant renovascular hypertension, in a 15-day-old neonate, treated by catheter-directed thrombolysis through the involuting umbilical artery, was studied. Resolution of systemic hypertension and partial return of right renal function followed rapid thrombus dissolution.

Catheterization↗
PubMed1998

Indicators for drug and therapeutics committees.

AIMS: This study describes development and field testing of a set of indicators for drug and therapeutics committees (DTCs) in hospitals. It was intended that these indicators should be accessible, useful and relevant in the Australian setting. METHODS: Candidate indicators were written following consultation and data collection. A framework of outcome, impact and process indicators was based on DTC goals, objectives and strategies. The candidate indicators were field tested over a 2 month period in teaching, city non-teaching, rural and private hospitals. The field tests provided response data for each indicator and evaluation of the indicators against criteria for accessibility, relevance, usefulness, clarity and resource utilisation. Consensus on which indicators to accept, modify or reject was reached at a workshop of stakeholders and experts, taking account of the field test results. RESULTS: Thirty-five candidate indicators were tested in 16 hospitals. Twenty-two had a response from >80% of sites, 23 had a mean relevance rating >3.5, 19 had a mean usefulness rating >3.5, 27 were correctly interpreted by > 90% of sites and 25 could be collected in an acceptable time. The most acceptable indicators required least data collection or provided data deemed useful for purposes other than the field test. At the consensus workshop 13 indicators were accepted with no or minor change, nine were accepted after major modification and eight were discarded. It was recommended that a further five indicators should be merged or subsumed into one indicator. CONCLUSIONS: This study has developed and field tested a set of indicators for DTCs in Australia. The indicators have been taken up enthusiastically as a first attempt to monitor DTC performance but require ongoing validation and development to ensure continuing relevance and usefulness.

Australia↗
PubMed1998

Effect of long-term olive oil dietary intervention on postprandial triacylglycerol and factor VII metabolism.

Although the beneficial effects of Mediterranean-type diets, which are rich in olive oil, a good source of monounsaturated fatty acids (MUFAs), are generally accepted, little is known about the effects of long-term dietary MUFA intake on postprandial lipoprotein metabolism and hemostasis. This study used a single-blind, randomized, crossover design to investigate the relative effects of a long-term dietary olive oil intervention and a control [saturated fatty acid (SFA)-enriched] diet on postprandial triacylglycerol metabolism and factor VII activity. The postprandial response to a standard test meal was investigated in 23 healthy men who adhered to both diets for 8 wk. cis-MUFAs were successfully substituted for SFAs in the MUFA diet without affecting total dietary fat or energy intakes. The long-term dietary MUFA intervention significantly reduced plasma and LDL-cholesterol concentrations (P = 0.01). Postprandial triacylglycerol concentrations were significantly greater in the early postprandial period after the MUFA diet (P = 0.003). Postprandial factor VII activation and the concentration of the factor VII antigen were significantly lower after the MUFA diet (P = 0.04 and P = 0.006, respectively). This study showed that isoenergetic substitution of MUFAs for SFAs reduces plasma cholesterol and reduces the degree of postprandial factor VII activation. The alterations in the postprandial triacylglycerol response suggest a greater rate of dietary fat absorption and postprandial triacylglycerol metabolism after a diet rich in MUFAs. This study presents new insights into the biochemical basis of the beneficial effects associated with long-term dietary MUFA consumption, which may explain the lower rates of coronary mortality in Mediterranean regions.

Adult↗
PubMed1998

Identification of amino acid residues in the C-terminal tail of big endothelin-1 involved in processing to endothelin-1.

Big endothelin-1 (big ET-1) is converted to 21-amino acid residue endothelin-1 (ET-1) via a specific cleavage at Trp21-Val22 by endothelin converting enzyme (ECE). This conversion is an essential step to produce bioactive ET-1 and represents a regulatory site in the biosynthesis of this potent vasoconstrictor. ECE-1a, a unique membrane-bound enzyme, processes big ET-1 more efficiently than other big ET isoforms, which mainly differ in the C-terminal tail (residues 22-38). In this study, each of the highly conserved residues, Val22, Pro25, Pro30, Gly32, Leu33, and Gly34 were replaced with Ala in the preproendothelin-1 (PPET-1) cDNA using site-directed mutagenesis. The mutant and wild-type cDNAs were transiently transfected into Chinese hamster ovary cells along with ECE-1a cDNAs, and concentrations of the resulting recombinant peptides, ET-1 and big ET-1, in the transfection media were then measured. The concentration of immunoreactive ET-1 in the media from Val22, Pro25, Pro30, Gly32, and Leu33 mutant PPET-1-transfected cells was 4- to 6-fold lower than that of wild type and (Gly34-->Ala)PPET-1. Moreover, with the exception of Gly34 there was a corresponding increase in the concentrations of immunoreactive big ET-1 in the media from mutants. Similar results were obtained when His27, Val28, and Ser35 of big ET-1( )were substituted with the corresponding residues in big ET-2 and big ET-3. These findings suggest that the C-terminal tail has an important role in the intracellular processing of big ET-1 by ECE-1a. Herein we also report that a recombinant big ET-1 analog we previously generated and characterized, (Ala21)big ET-1, inhibits ECE-1a activity in a dose-dependent (K i=1 microM) and competitive manner.

Amino Acid Sequence↗
PubMed1998

What physicians should know about employment contracts.

If the contract does not provide the physician the right to amend or terminate the agreement--even when the employer has clearly breached the contract--the physician may have to choose between living with the present situation or suing for damages.

Contract Services↗
PubMed1997

Skin pigmentation and pharmacokinetics of melanotan-I in humans.

A comparative pharmacokinetic trial was performed with a superpotent synthetic melanotropic peptide, [Nle4-D-Phe7]-alpha-MSHi-13 (melanotan-I or MT-I) given by three routes of administration. Plasma levels were measured by RIA and tanning was quantiated using serial reflectometry. Doses of 0.16 mgkg-1 were administered intravenously (IV) and orally (PO), and doses from 0.08 to 0.21 mg kg-1 subcutaneously (SC), in a randomized crossover fashion to three male volunteers over five consecutive days for 2 weeks (ten doses). The results indicate that the SC dose is completely bioavailable compared to the IV dose. No detectable drug levels were observed following PO dosing. The plasma half-lives following SC dosing ranged from 0.07 to 0.79 h for the absorption phase and from 0.8 to 1.7 h for the beta-phase. Clearance ranged from 0.12 to 0.19 L kg-1 h-1 and 3.9% or less of the dose was recovered in the urine. Side-effects were minimal, consisting of occasional gastrointestinal upset and facial flushing. Significant tanning of the forehead, arms, and neck was noted following IV or SC dosing. This effect peaked at 1 week following drug administration but was still present 3 weeks after completing the ten-dose regimen. It is concluded that SC administration is an efficacious method of delivering melanotan-I.

Administration, Oral↗