To investigate potential trophic actions of extracellular ATP in human astrocytes, we have examined mitogenic signaling by purinergic receptors in cultures prepared from first trimester rostral central nervous system tissue. We found that ATP and ATPgammaS, a hydrolysis-resistant analog, stimulated DNA synthesis, thereby indicating that P2 purinergic receptors can stimulate mitogenic signaling in these cells. In addition, ATP activated a mitogen-activated protein kinase (MAPK) termed ERK (extracellular signal-regulated protein kinase), a key component of signal transduction pathways involved in cellular proliferation and differentiation. The activation of MAPK was mediated at least in part by P2 purinergic receptors, because a P2 purinoceptor antagonist, suramin, inhibited the ATP-evoked stimulation by 50%, whereas a P1 purinergic-receptor antagonist, 8-(para-sulfonphenyl)-theophylline, was without effect. In contrast to rat astrocytes, adenosine/P1 purinergic-receptor agonists, 2-chloroadenosine and 5'-N-ethylcarboxyamidoadenosine, stimulated MAPK activity and DNA synthesis in human astrocytes. A selective inhibitor of protein kinase C, Ro 31-8220, blocked the ability of ATP and adenosine analogs to stimulate MAPK, thereby indicating that protein kinase C is upstream of MAPK in both P2- and P1-receptor signaling pathways. An inhibitor of the MAPK activator MEK, PD 098059, effectively blocked ATP- and 2-chloroadenosine-induced DNA synthesis, thereby indicating that the ERK/MAPK cascade mediates mitogenic signaling by P2 and P1 purinergic receptors in human fetal astrocytes. These findings suggest a role for P1 and P2 purinergic receptors in the proliferation of human fetal astrocytes.

Adenosine Triphosphate↗

PubMed1998

Impact of alcohol on the histological and clinical progression of hepatitis C infection.

In patients infected with the hepatitis C virus (HCV), 20% to 30% will progress to cirrhosis in over two to three decades. Viral and host factors that are important in the clinical and histologic progression of HCV infection are not entirely certain. It has been suggested that liver disease is worse in alcoholics infected with HCV. In the present retrospective study, we examined the effect of moderate alcohol intake on the histologic and clinical progression of HCV infection and assessed whether other variables such as gender, length of exposure, mode of exposure, HCV RNA levels, and ferritin levels also independently impacted disease progression. Liver biopsies were analyzed for the degree of fibrosis, presence of cirrhosis, and histologic activity by using the Histologic Activity Index of Knodell. Patients were divided into two groups based on whether their alcohol intake was significant or not significant. Significant alcohol intake was defined as > 40 g alcohol/day in women and > 60 g of alcohol/day in men for > 5 years. Groups were further divided based on the decades of exposure to HCV. There was no difference in the age or length of exposure to HCV in the alcohol and the alcohol-free group. HCV RNA serum levels, ferritin levels, and viral genotypes were similar in both groups. There was a two- to threefold greater risk of liver cirrhosis and decompensated liver disease in the alcohol group. Also, the rate to which subjects developed cirrhosis was faster in the alcohol group with 58% being cirrhotic by the second decade as opposed to 10% being cirrhotic in the nonalcohol group by the second decade. The histologic and clinical acceleration of liver disease was independent of the mode of exposure or sex. In summary, alcohol intake is an independent risk factor in the clinical and histologic progression of HCV infection.

Adult↗

PubMed1998

Which terminally ill cancer patients receive hospice in-patient care?

The objective of this study was to investigate which terminally ill cancer patients receive in-patient care in hospices and other specialist palliative care in-patient units. An interview survey was made of family or others who knew about the last year of life of a random sample of people who died in 1990. Twenty district health authorities from a range of inner city, outer urban and rural settings took part. Although self-selected, districts were nationally representative in terms of social characteristics and on many indicators of health service provision and usage. Interviews were obtained for 2074 cancer deaths out of a random sample of 2915, a 71% response rate. 342 had been admitted to a total of 31 different hospices. Using logistic regression analysis five factors were found to independently predict hospice in-patient care: having pain in the last year of life, having constipation, being dependent on others for help with activities of daily living for between one and six months before death, having breast cancer, and being under the age of 85 years. A third of patients with all five factors were admitted, compared with no patients with none of these factors. It was found that symptom severity, age, dependency level and site of cancer played a role in determining hospice admission but have limited predictive value. Admission seems to be governed more by chance than by need. Further research is needed to identify which patients benefit most from in-patient care in hospices and other specialist palliative care units as the present arrangements appear to be both inequitable and insupportable.

Adult↗

PubMed1998

Weighing in on diabetes risk.

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Birth Weight↗

PubMed1998

Social environment and substance misuse: a study of ethnic variations among inner London adolescents.

OBJECTIVES: To explore ethnic variations in drug, tobacco and alcohol use and their correlation with other factors which operate through peer, familial and religious influences. DESIGN: Semi-structured interviews with 132 12-13-year-old young people from four ethnic groups attending secondary schools in two inner London boroughs and a follow-up interview completed approximately 17 months later. RESULTS: The data was analysed using chi-square and McNemar tests. Familial, religious and peer influence closely correlated with ethnicity. Bangladeshi young people showed lower levels of peer and higher levels of religious and familial involvement and lower levels of substance use. White young people reported higher levels of peer, lower levels of religious and familial involvement, and a higher level of substance use. Black African and Black Caribbean young people lay between the two extremes. CONCLUSION: The findings suggest that young people with lower levels of familial and religious influence, or higher levels of peer influence, have higher levels of substance consumption than other young people. Health education initiatives need to promote personal decision-making skills within the context of the young people's individual culture. Cultural diversity should be recognised within local health education needs assessment.

Adolescent↗

PubMed1998

Variations by age in symptoms and dependency levels experienced by people in the last year of life, as reported by surviving family, friends and officials.

OBJECTIVE: To explore the relationships between age, reported symptoms and dependency in the last year of life in those dying from cancer and in those dying from other causes. DESIGN: Secondary analysis of data from the Regional Study of Care for the Dying, a retrospective interview survey of deaths in 1990 in 20 nationally representative English health districts. There were 2061 cancer deaths and 1469 non-cancer deaths (sudden deaths were excluded). MAIN RESULTS: In cancer patients, the mean number of symptoms reported to have been experienced in the last year of life decreased with age (from 8.29 in those aged <65 to 7.79 in those aged 65 -74, 7.37 in those aged 75-84 and 7.42 in those aged 85 and older), while the number of symptoms reported to have lasted more than 6 months increased (2.93, 3.15, 3.24 and 3.52). In both cancer and non-cancer patients the proportion of symptoms reported to have been 'very distressing' decreased with age (cancer, 45, 43, 40 and 35%; non-cancer, 39, 38, 34 and 27%). In non-cancer patients the mean number of self-care tasks the deceased had needed help with increased substantially with age (2.23, 2.50, 3.04 and 3.95); in cancer patients the mean level was higher and there was no age gradient (3.89, 3.94, 3.83 and 4.1). The prevalence of dependency on most of the seven self-care tasks in cancer patients was comparable with or higher than that in the older and most restricted non-cancer patients. CONCLUSION: Younger cancer patients are more likely than older cancer patients to need help with relieving distressing symptoms. However, some elderly patients were reported to have had very distressing symptoms, and these patients should not be excluded from specialist palliative care services on the basis of their age. Cancer patients did not show increased dependency with age, indicating the importance of community health and social services being appropriate for and accessible by cancer patients of all ages.

Age Distribution↗

PubMed1998

The contracting round: achieving health gain or financial balance?

In the 1991 National Health Service reforms, health authorities became responsible for the health of their resident population, and they contract for health services from NHS providers - trusts and primary care services. A case study in Camden and Islington, an inner London health district, during 1996-1997 shows that contracting was directed more towards achieving financial balance than health objectives. Reasons include the inflationary effect of competition within an internal market, the power of administrators in decision-making within the health authority, and lack of adequate financial accounting in the NHS to relate costs to health outcomes. The introduction of programme budgets for districts would provide more cost-effective use of the nation's resources.

Budgets↗

PubMed1998

Acute infectious encephalitis complicated by neuroleptic malignant syndrome.

Explore the source record for details and available documents.

Adolescent↗

PubMed1998

Case managed residential care for homeless addicted veterans. Results of a true experiment.

OBJECTIVES: The effectiveness of case-managed residential care (CMRC) in reducing substance abuse, increasing employment, decreasing homelessness, and improving health was examined. METHODS: A five-year prospective experiment included 358 homeless addicted male veterans 3, 6, and 9 months during their enrollment and at 12, 18, and 24 months after the completion of the experimental case-managed residential care program. The customary control condition was a 21-day hospital program with referral to community services. RESULTS: The experimental group averaged 3.4 months in transitional residential care with ongoing and follow-up case management for a total of up to 1 year of treatment. The experimental group showed significant improvement compared with the control group on the Medical, Alcohol, Employment, and Housing measures during the 2-year period. An examination of the time trends indicated that these group differences tended to occur during the treatment year, however, and to diminish during the follow-up year. CONCLUSIONS: Within groups, significant improvements were observed with time from baseline to all posttests on the four major outcomes. We learned, however, that veterans had access to and used significant amounts of services even without the special case-managed residential care program. This partially may account for improvements in the control group and may have muted the differences between groups.

Adult↗

PubMed1998

Comparison of performance and cost-effectiveness of direct fluorescent-antibody, ligase chain reaction, and PCR assays for verification of chlamydial enzyme immunoassay results for populations with a low to moderate prevalence of Chlamydia trachomatis infection.

Many laboratories use a commercial enzyme immunoassay (EIA) with verification testing to diagnose Chlamydia trachomatis infections in an effort to contain costs. This study was designed to compare the performance and cost-effectiveness of direct fluorescent-antibody assay (DFA), commercial PCR, and ligase chain reaction (LCR) for the verification of EIA results. Cervical specimens were screened by EIA. DFA, PCR, and LCR were compared as verification tests for EIA-reactive specimens and negative greyzone (NGZ) specimens at 50% below the cutoff value. These samples were also tested by in-house PCR, which was used in the analysis of verification results. A total of 477 (7%) of 6,571 samples were reactive or within the NGZ. EIA results with verification by DFA testing (EIA/DFA results) agreed with 93% of the true results compared with 97% for EIA/PCR results for one set of 242 samples; there was 97% agreement with true results for EIA/DFA results versus 95% for EIA/LCR results for another set of 235 samples. Ten samples were false positive by LCR. Time and costs were equivalent for EIA with the DFA, PCR, or LCR as the verification test but were two- to threefold greater for PCR or LCR alone than for EIA with verification. Since it is important to balance cost containment with public health objectives, DFA, PCR, and LCR as EIA verification tests for cervical samples offer acceptable sensitivities and specificities at reasonable cost for low- to moderate-risk populations and therefore can be extended to a broader spectrum of at-risk populations.

Adolescent↗

PubMed1998

A randomised controlled trial of postal versus interviewer administration of a questionnaire measuring satisfaction with, and use of, services received in the year before death.

STUDY OBJECTIVES: To develop a short form of an interview schedule used successfully in previous national surveys of care for the dying, and to investigate the effect of administering it by post on response rate, response bias and on the nature of responses to questions. DESIGN: Randomised controlled trial. SETTING: An inner London health authority. PARTICIPANTS: Informants (person registering death) of random sample of cancer deaths between June 1995 and July 1996. MAIN RESULTS: The shortened questionnaire (VOICES) has 158 questions. Response rate did not differ significantly between postal and interview groups (interview; 56% (69 of 123), postal: 52% (161 of 308). Responders in the two groups did not differ in terms of their sociodemographic characteristics. Postal questionnaires had significantly more missing data, particularly on questions about service provision and satisfaction with services. Responses to questions differed between the groups on 11 of 158 questions. Interview group respondents were more likely to give top ranking responses to questions on service satisfaction and symptom control. CONCLUSIONS: Postal questionnaires are an acceptable alternative to interviews in retrospective post-bereavement surveys of care for the dying, at least in terms of response rate and response bias. However, the increased costs of interview surveys need to be balanced against the fact that postal questionnaires result in more missing data, and possibly less reliable answers to some questions. Caution is needed in combining results from the two data collection methods as interview respondents gave more positive answers to some questions.

Adult↗

PubMed1998

Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model.

Effect of increasing blood viscosity during extreme hemodilution on capillary perfusion and tissue oxygenation was investigated in the awake hamster skinfold model. Two isovolemic hemodilution steps were performed with 6% Dextran 70 [molecular weight (MW) = 70,000] until systemic hematocrit (Hct) was reduced by 65%. A third step reduced Hct by 75% and was performed with the same solution [low viscosity (LV)] or a high-molecular-weight 6% Dextran 500 solution [MW = 500, 000, high viscosity (HV)]. Final plasma viscosities were 1.4 and 2.2 cP (baseline of 1.2 cP). Hct was reduced to 11.2 +/- 1.1% from 46.2 +/- 1.5% for LV and to 11.9 +/- 0.7% from 47.3 +/- 2.1% for HV. HV produced a greater mean arterial blood pressure than LV. Functional capillary density (FCD) was substantially higher after HV (85 +/- 12%) vs. LV (38 +/- 30%) vs. baseline (100%). PO2 levels measured with Pd-porphyrin phosphorescence microscopy were not statistically changed from baseline until after the third hemodilution step. Wall shear rate (WSR) decreased in arterioles and venules after LV and only in arterioles after HV. Wall shear stress (WSR x plasma viscosity) was substantially higher after HV vs. LV. Increased mean arterial pressure and shear stress-dependent release of endothelium-derived relaxing factor are possible mechanisms that improved arteriolar and venular blood flow and FCD after HV vs. LV exchange protocols.

Animals↗