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Biomedical subjects

C Harvey

Publications and source records attributed to C Harvey.

At least 19 recordsLinked to original sources
PubMed2000

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.

Adult↗
PubMed2000

Effects on protein kinase C and gene expression in a human mast cell line, HMC-1, following microwave exposure.

We used a resonant cavity which delivered a continuous wave exposure at 864.3 MHz at an average specific absorption rate (SAR) of 7 W/kg to determine non-thermal biological effects of microwave exposure. A human mast cell line, HMC-1, was used as the biological target. Cells were given three exposures each of 20-min duration daily for 7 days. The temperature of the cell culture medium during the exposure fell to 26.5 degrees C. Effects were seen on localization of protein kinase C, and expression of three genes of 588 screened. The affected genes included the proto-oncogene c-kit, the transcription factor Nucleoside diphosphate kinase B and the apoptosis-associated gene DAD-1. Stress response genes were variably upregulated. No significant effect on morphology or on F-actin distribution was detected. We conclude that low-power microwave exposure may act on HMC-1 cells by altering gene expression via a mechanism involving activation of protein kinase C, and at temperatures well below those known to induce a heat shock response.

Actins↗
PubMed2000

Americans' view of cancer.

This paper presents the concept of the town hall meeting and discusses how it can be used as a forum for those who have been touched by cancer. It can be a platform for people to express their views about cancer, not only in the community but also nationally. Empowerment is the hallmark of a town hall meeting. Those who are in leadership positions in health care and elected officials and community leaders are given the opportunity to hear the opinions of people who represent a broad-based constituency of individuals affected by cancer. The idea of holding a town hall meeting was first introduced in the cancer community by the National Coalition for Cancer Survivorship NCCS) as a means of identifying issues, exchanging information and considering creative solutions to problems. The first town hall meeting was held in 1994 in conjunction with the NCCS annual assembly. Since then, utilizing the guidelines set forth by the NCCS, 30 or more town hall meetings have been held across the United States. Cancer survivors have, by and large, been responsible for garnering the necessary support for conducting a town hall in their local area. Organizations such as the American Cancer Society, the Leukemia Society of America, hospitals, clinics, pharmaceutical and healthcare companies and also noncancer groups, such as the YMCA, churches, and radio/T.V. stations, join with the cancer survivors in organizing the meeting, planning related displays, and advertising the event. In 1998, seven town hall meetings were sponsored jointly by OnCare and NCCS in advance and support of the upcoming THE MARCH- Coming Together To Conquer Cancer, a national rally held in Washington, D.C. in September 1998. Attendees at the meetings included not only cancer survivors and their families, but also healthcare professionals, local and state legislators, community leaders and the media. Results of the 1998 town hall meetings are discussed and compared with the topics identified during the meetings held in 1994-1996. Town hall participants were outspoken about what is needed in America if cancer is truly to become the nation's healthcare priority. They are asking for equal access to quality care, increases in financial backing for research, and more support for cancer advocacy efforts. Benefits of holding town hall meetings are identified.

Health Services Accessibility↗
PubMed2000

Perceived need for mental health care, findings from the Australian National Survey of Mental Health and Well-being.

BACKGROUND: The Australian National Survey of Mental Health and Well-being was designed to detect and describe psychiatric morbidity, associated disability, service use and perceived need for care. The survey employed a single-phase interview methodology, delivering a field questionnaire to a clustered probability sample of 10,641 Australians. Perceived need was sampled with an instrument designed for this survey, the Perceived Need for Care Questionnaire (PNCQ). This questionnaire gathers information about five categories of perceived need, assigning each to one of four levels of perceived need. Reliability and validity studies showed satisfactory performance of the instrument. METHODS: Perceived need for mental health care in the Australian population has been analysed using PNCQ data, relating this to diagnostic and service utilization data from the above survey. RESULTS: The survey findings indicate that an estimated 13.8% of the Australian population have perceived need for mental health care. Those who met interview criteria for a psychiatric diagnosis and also expressed perceived need make up 9.9% of the population. An estimated 11.0% of the population are cases of untreated prevalence, a minority (3.6% of the population) of whom expressed perceived need for mental health care. Among persons using services, those without a psychiatric diagnosis based on interview criteria (4.4% of the population), showed high levels of perceived met need. CONCLUSIONS: The overall rate of perceived need found by this methodology lies between those found in the USA and Canada. The findings suggest that service use in the absence of diagnosis elicited by survey questionnaires may often represent successful intervention. In the survey, untreated prevalence was commonly not accompanied by perceived need for mental health care.

Adult↗
PubMed2000

Psychotic disorders in urban areas: an overview of the Study on Low Prevalence Disorders.

OBJECTIVE: This paper reports on a study designed within the framework of the National Survey of Mental Health and Wellbeing to: estimate the prevalence of psychoses in urban areas of Australia; identify profiles of symptomatology, impairments and disabilities; collect information on services received and needed; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses. METHOD: The study was conducted over four areas in the Australian Capital Territory, Queensland, Victoria and Western Australia, as a two-phase survey: (i) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997; and (ii) interviews with a stratified random sample (n=980) of the screen-positive individuals (n=3800) using a standardised instrument. RESULTS: The point prevalence (1 month) of psychotic disorders in the urban population aged 18-64 is in the range of 4-7 per 1000 with a weighted mean of 4.7 per 1000. People with psychotic disorders experience high rates of functional impairments and disability, decreased quality of life, persistent symptoms, substance-use comorbidity and frequent side effects of medication. Although the utilisation of hospital-based and community mental health services, as well as of public and non-governmental helping agencies, is high, the majority live in extreme social isolation and adverse socioeconomic circumstances. Among the many unmet needs, the limited availability of community-based rehabilitation, supported accommodation and employment opportunities is particularly prominent. CONCLUSIONS: The so-called 'low-prevalence' psychotic disorders represent a major and complex public health problem, associated with heavy personal and social costs. There is a need for a broad programmatic approach, involving various sectors of the community, to tackle the multiple dimensions of clinical disorder, personal functioning and socioeconomic environment that influence the course and outcome of psychosis and ultimately determine the effectiveness of service-based intervention.

Activities of Daily Living↗
PubMed2000

Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial.

OBJECTIVE: Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. RESEARCH DESIGN AND METHODS: A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs), joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study. Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. RESULTS: Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT, and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. CONCLUSIONS: Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear.

Adult↗
PubMed2000

Do practice-based preventive child health services affect the use of hospitals? A cross-sectional study of hospital use by children in east London.

BACKGROUND: Acute paediatric admissions have risen steadily over the past 20 years. During the same period, practice-based child health clinics have increased, although provision is less common in areas of deprivation where hospital use is greatest. AIM: To investigate the contribution of practice-based, preventive child health services to rates of hospital utilisation in children under five years of age. METHOD: A cross-sectional retrospective study examining practice variations in paediatric acute admissions, outpatient referrals, and accident and emergency (A&E) department attendances in the East London and the City Health authority, including all 164 practices in the inner-city boroughs of Hackney, Newham, Tower Hamlets, and the City of London. The main outcome measures were practice-based paediatric hospital attendance rates, for discrete age and sex bands, for the year to 31 March 1996. RESULTS: Hospital use varied with age and sex, with the rates being highest for the youngest children and for boys. The median A&E attendance rate (including reattendances) for boys up to one year of age was 897 per thousand children per practice. In east London, 62% of practices are registered for child health surveillance and 71% provide a child health clinic. Practice approval for child health surveillance, and the provision of child health clinics, did not account for differences between practices in hospital use, but proportionally greater health visiting hours were significantly related to lower rates of emergency hospital admission by young children. Multivariate analyses revealed that up to 23% of the variation between practice admission rates could be explained by health visiting hours. CONCLUSIONS: We found significant associations between the amount of health visiting time available to the practice population and rates of acute admission and outpatient referral among children up to five years of age. These findings suggest that increasing health visitor provision could contribute to lower paediatric emergency admission and outpatient referral rates. A small change would have a significant effect, particularly among the youngest children, given that during the study year 10,000 children under two years of age in east London were either admitted or referred to hospital.

Age Factors↗
PubMed1999

TP53 mutation and haplotype analysis of two large African American families.

Two large apparently unrelated African American families with a high incidence of breast cancer and other tumors characteristic of Li-Fraumeni breast sarcoma cancer family syndrome were studied. Mutation screening revealed that in both families the affected members carried a germline mutation of the TP53 gene at codon 133 (ATG--> ACG, M133T). In order to determine whether an ancestral haplotype was shared by these two families, polymorphic markers within and flanking the TP53 gene were studied. Haplotype analysis using five markers revealed an identical haplotype shared by the two families. Loss of heterozygosity at the TP53 locus in the probands' tumor tissues from each family was observed; in each case, the retained allele carried the common haplotype. The frequency of this haplotype in the general African American population is <0.003. This unique haplotype, combined with the rare TP53 mutation, suggests that these African American families share a common ancestry. This finding suggests that other African Americans may be carriers of this mutation and thus may be at risk of early-onset breast cancer or other cancers characteristic of the Li-Fraumeni breast sarcoma cancer family syndrome. The finding of recurring mutations in African Americans may facilitate carrier screening and identification in this population.

Alleles↗
PubMed1999

Imaging of tumour therapy responses by dynamic CT.

The objective of this study was to investigate whether functional CT with Patlak analysis could be used to demonstrate acute changes associated with radiotherapy. Patlak analysis yields fractional vascular volume and contrast clearance per unit volume (a measure of permeability). Four tumour types (prostate, bronchus, breast and cervix) were studied pre-radiotherapy and at 1-2 weeks and 6-12 weeks post-therapy. Significant rises in fractional vascular volume and contrast clearance were shown at 1-2 weeks. These indices were still significantly elevated at 6-12 weeks post-therapy. In the prostates perfusion values were also elevated reflecting a hyperemic response to radiotherapy. Dynamic CT with Patlak analysis can be used to measure important pathophysiological indices which may prove useful in assessing response to therapy of tumours.

Breast Neoplasms↗
PubMed1999

Prevalence of asthma and respiratory symptoms in south-central Durban, South Africa.

The prevalence of asthma and respiratory symptoms in south-central Durban, one of the most heavily polluted areas of South Africa, has been determined using a cross-sectional survey of 213 households in the communities of Merewent (97% Indians) and Austerville (98% coloreds). The study population consisted of 367 children (less than 17 years old) and 693 adults. About 10% of the children and 12% of adults reported doctor diagnosed asthma. The self-reported prevalence rates for wheezing (3740%) and attacks of shortness of breath with wheeze (16-28%) were much higher than that for doctor diagnosed asthma and common co-occurrence of the three symptoms is found. The prevalence rates for other respiratory symptoms include 33-35% for chronic cough, 31-32% for chronic phlegm, 44-50% for frequent blocked-runny nose, and 16-27% for sinusitis. Factors in the community that were associated with asthma, wheeze and shortness of breath with wheeze among the adult population included cigarette smoking, use of insecticides (coils and pump spray) and home ownership. An association between asthma among children and a number of household risk factors including dampness, carpet, pets or use of pesticides was not apparent in the community. Asthma prevalence was strongly correlated with missing of school by children (odds ratio (OR): 44; 95% confidence interval (CI): 13-141). The study serves to draw attention to a growing but neglected public health problem in urban areas of Africa.

Adolescent↗
PubMed1999

The utility of CT in imaging chest infections in HIV-negative patients.

This article focuses on the recent developments in CT imaging of chest infections in patients who are immunocompetent or immunosuppressed, but not infected with HIV. Although simple viral and bacterial infections predominate, more "exotic" infections are now being encountered. First, a re-emergence of mycobacterial disease has occurred. Second, a growing population of transplant recipients (i.e., lung, solid organ, and bone marrow) is susceptible to a wide range of pathogens. These trends are reflected in the forthcoming discussion. In particular, several important articles on immunosuppressed (HIV-negative) patients and on imaging fungal disease have been written within the past year.

Bacterial Infections↗
PubMed1998

Role of interleukin-12 in primary influenza virus infection.

The effect of endogenous interleukin-12 (IL-12) on the influenza virus immune response in BALB/c mice was evaluated. Following primary influenza virus infection, IL-12 mRNA and protein are detected in the lung, with live virus being required for cytokine induction. Endogenous IL-12 contributes to early NK cell-dependent gamma interferon (IFN-gamma) production (days 3 and 5) but not late T-cell-dependent IFN-gamma secretion (day 7). IL-12 contributes to the inhibition of early virus replication but is not required for virus clearance. IL-12 also modestly contributes to the activation of cytotoxic T lymphocytes. Thus, in this model of experimental influenza virus infection, endogenous IL-12 contributes primarily to the early development and activation of the innate immune response.

Animals↗
PubMed1998

Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells.

By means of differential RNA display, we have isolated a cDNA corresponding to transcripts that are down-regulated upon differentiation of the goblet cell-like HT-29-M6 human colon carcinoma cell line. These transcripts encode proteins originally identified as CROC-1 on the basis of their capacity to activate transcription of c-fos. We show that these proteins are similar in sequence, and in predicted secondary and tertiary structure, to the ubiquitin-conjugating enzymes, also known as E2. Despite the similarities, these proteins lack a critical cysteine residue essential for the catalytic activity of E2 enzymes and, in vitro, they do not conjugate or transfer ubiquitin to protein substrates. These proteins constitute a distinct subfamily within the E2 protein family and are highly conserved in phylogeny from yeasts to mammals. Therefore, we have designated them UEV (ubiquitin-conjugating E2 enzyme variant) proteins, defined as proteins similar in sequence and structure to the E2 ubiquitin-conjugating enzymes but lacking their enzymatic activity (HW/GDB-approved gene symbol, UBE2V). At least two human genes code for UEV proteins, and one of them, located on chromosome 20q13.2, is expressed as at least four isoforms, generated by alternative splicing. All human cell types analyzed expressed at least one of these isoforms. Constitutive expression of exogenous human UEV in HT-29-M6 cells inhibited their capacity to differentiate upon confluence and caused both the entry of a larger proportion of cells in the division cycle and an accumulation in G2-M. This was accompanied with a profound inhibition of the mitotic kinase, cdk1. These results suggest that UEV proteins are involved in the control of differentiation and could exert their effects by altering cell cycle distribution.

Amino Acid Sequence↗
PubMed1998

Role of neuropathy and high foot pressures in diabetic foot ulceration.

OBJECTIVE: High plantar foot pressures in association with peripheral neuropathy have been ascertained to be important risk factors for ulceration in the diabetic foot. Most studies investigating these parameters have been limited by their size and the homogeneity of study subjects. The objective of this study was therefore to ascertain the risk of ulceration associated with high foot pressures and peripheral neuropathy in a large and diverse diabetic population. RESEARCH DESIGN AND METHODS: We studied a cross-sectional group of 251 diabetic patients of Caucasian (group C) (n=121), black (group B) (n=36), and Hispanic (group H) (n=94) racial origins with an overall age of 58.5+/-12.5 years (range 20-83). There was an equal distribution of men and women across the entire study population. All patients underwent a complete medical history and lower extremity evaluation for neuropathy and foot pressures. Neuropathic parameters were dichotomized (0/1) into two high-risk variables: patients with a vibration perception threshold (VPT) > or =25 V were categorized as HiVPT (n=132) and those with Semmes-Weinstein monofilament tests > or =5.07 were classified as HiSWF (n=190). The mean dynamic foot pressures of three footsteps were measured using the F-scan mat system with patients walking without shoes. Maximum plantar pressures were dichotomized into a high-pressure variable (Pmax6) indicating those subjects with pressures > or =6 kg/cm2 (n=96). A total of 99 patients had a current or prior history of ulceration at baseline. RESULTS: Joint mobility was significantly greater in the Hispanic cohort compared with the other groups at the first metatarsal-phalangeal joint (C 67+/-23 degrees, B 69+/-23 degrees, H 82+/-23 degrees, P=0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21+/-8 degrees, B 26+/-7 degrees, H 27+/-11 degrees, P=0.000). Maximum plantar foot pressures were significantly higher in the Caucasian group (C 6.7+/-2.9 kg/cm2, B 5.7+/-2.8 kg/cm2, H 4.4+/-1.9 kg/cm2, P=0.000). Univariate logistic regression for Pmax6 on the history of ulceration yielded an odds ratio (OR) of 3.9 (P=0.000). For HiVPT, the OR was 11.7 (P=0.000), and for HiSWF the OR was 9.6 (P=0.000). Controlling for age, diabetes duration, sex, and race (all P < 0.05), multivariate logistic regression yielded the following significant associations with ulceration: Pmax6 (OR=2.1, P=0.002), HiVPT (OR=4.4, P=0.000), and HiSWF (OR=4.1, P=0.000). CONCLUSIONS: We conclude that both high foot pressures (> or =6 kg/cm2) and neuropathy are independently associated with ulceration in a diverse diabetic population, with the latter having the greater magnitude of effect. In black and Hispanic diabetic patients especially, joint mobility and plantar pressures are less predictive of ulceration than in Caucasians.

Adult↗
PubMed1997

Adaptation to capsaicin within and across days.

Subjects judged the time-course of the burn caused by 100 ppm capsaicin applied to the tongue on Day 1 and Day 5. On Days 2-4, they tasted hard candy containing capsaicin. Most subjects did not show adaptation within Day 1, but either plateaued after about 16 min or rose monotonically for the entire 34 min. Intensity was less on Day 5 and levelled off or declined for most subjects. Data were fit to a mathematical model of adaptation. Adaptation across days was accounted for by changes in the gains of the three processes.

Adaptation, Physiological↗
PubMed1996

Changes in liver core temperature during preservation and rewarming in human and porcine liver allografts.

Liver core temperature during organ procurement, storage, and rewarming has not been reported in human orthotopic liver transplantations (OLT). We have shown in the rat that optimal temperature for liver storage is not 4 degrees C but 0 degree C to 1 degree C. Therefore, a study was undertaken in humans and in pigs to determine the pattern of temperature change during OLT. The porcine studies were performed, because it was not possible to follow human grafts during the period that they were sterilely packaged. Temperature depression in humans was rapid during organ perfusion, remained stable during organ dissection, and decreased again slightly, when after excision, the organ was perfused again. Temperature depression during the period of perfusion with University of Wisconsin (UW) solution was curvilinear with the initial rapid temperature depression followed by a period of slower temperature depression. Volume perfused versus time was linear during these periods and the relationship between temperature depression and volume infused was curvilinear. At the time of packaging, 65 +/- 12 minutes after start of cold perfusion, the liver core temperature was 5.7 degrees C +/- 1.3 degrees C. Studies in the pig showed that it took 75 to 100 minutes for liver core temperature to decrease below 5 degrees C, and core temperature reached a plateau at 1 degree C at 195 +/- 75 minutes after packaging. During the rewarming period in humans, while vascular anastomoses were being constructed, there was a rapid linear increase in temperature from 0.8 degree C, when the graft was removed from the cold, to 17.2 degrees C +/- 3.1 degrees C at 45.5 +/- 4.4 minutes later, just before portal reperfusion commenced. These studies show that it takes only a short time to cool livers down to 10 degrees C, but after flushing is stopped, temperature depression is markedly reduced, and ideal temperatures are not reached before packaging. Rewarming of livers during performance of vascular anastomoses is rapid and reaches temperatures at which substantial hepatic metabolism is occurring.

Animals↗