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PubMed2000

Interventions for deliberately altering blood pressure in acute stroke.

BACKGROUND: It is unclear whether hypertension should be treated after acute stroke, and some have hypothesised that blood pressure should be increased to improve cerebral perfusion. OBJECTIVES: The objective of this review was to assess the effect of lowering or elevating blood pressure in people with acute stroke, and the effect of different vasoactive drugs on blood pressure in acute stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, the Ottawa Stroke Trials Registry (1994), Medline (from 1965), Embase (from 1981), ISI, and existing review articles. We contacted researchers in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised trials of interventions that aimed to alter blood pressure in patients within two weeks of acute ischaemic or haemorrhagic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria and assessed trial quality. Two reviewers extracted the data. MAIN RESULTS: Three trials involving 133 people were included. The trials tested the following vasodilators: nimodipine (66 people), nicardipine (five people), captopril (three people) and clonidine (two people). Oral calcium channel blockers (nimodipine, nicardipine) reduced systolic blood pressure (weighted mean difference 10.9mmHg, 95% confidence interval 2.0 to 19.7), diastolic blood pressure (weighted mean difference 9.5mmHg, 95% confidence interval 4.0 to 15.1) and heart rate (weighted mean difference 4.7 beats per minute, 95% confidence interval 0.2 to 9.2) at 48 hours. The greatest fall in blood pressure over the first 24 hours was shown in patients given the highest dose of nimodipine. The relationship between change in blood pressure and clinical outcome was not clear. There was not enough information to assess the effect of drugs other than calcium channel blockers. No studies of interventions to raise blood pressure were found. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the effect of altering blood pressure after acute stroke. Although oral calcium channel blockers appear to reduce blood pressure following acute stroke, the balance of benefit and risk remains unclear.

Blood Pressure↗
PubMed2005

Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria.

BACKGROUND: Chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP) are inexpensive drugs, but treatment failure is a problem. Combination therapy may reduce treatment failure. CQ or AQ plus SP are affordable options of combination treatment, but there is debate about their effectiveness. OBJECTIVES: To assess the combination of CQ or AQ plus SP compared with SP alone for first-line treatment of uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1981 to April 2005), African Index Medicus (1993 to 1998), and reference lists. We also contacted researchers at relevant organizations and a pharmaceutical company. SELECTION CRITERIA: Randomized controlled trials in adults or children with uncomplicated Plasmodium falciparum malaria were eligible for inclusion. The main outcomes of interest were total and clinical failure at day 28 follow up and serious adverse events. DATA COLLECTION AND ANALYSIS: Two people independently applied the inclusion criteria. One author extracted data and another checked them independently. We used relative risk (RR) and 95% confidence intervals (CI). MAIN RESULTS: Twelve trials (2107 participants) met the inclusion criteria. A meta-analysis of five AQ trials (461 participants) showed a statistically significant reduction in total failure at day 28 with the combination therapy (RR 0.64, 95% CI 0.46 to 0.91), and meta-analysis of three trials (384 participants) showed a significant reduction in clinical failure at day 28 (RR 0.23, 95% CI 0.11 to 0.49). The statistical significance in the total failure analysis was sensitive to losses to follow up. Data from two CQ trials showed no advantage for total failure with combination therapy at day 28. There was no evidence from the included trials of serious adverse events. AUTHORS' CONCLUSIONS: The evidence base is not strong enough to support firm conclusions. The available evidence suggests that AQ plus SP can achieve less treatment failure than SP, but this might depend on existing levels of parasite resistance to the individual drugs.

Adult↗
PubMed2000

Vasoactive drugs for acute stroke.

BACKGROUND: It is unclear whether blood pressure should be managed after acute stroke and if so whether it is best to reduce or increase blood pressure. OBJECTIVES: The objective of this review was to assess the effect of lowering or elevating blood pressure in people with acute stroke, and the effect of different vasoactive drugs on blood pressure in acute stroke. SEARCH STRATEGY: We searched the Cochrane Library (1999 Issue 1) using the CDSR and the CCTR databases, MEDLINE (from 1966), EMBASE (from 1980), BIDS ISI (Science Citation Index from 1981), and existing review articles. We contacted researchers in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised trials of interventions that would be expected, on pharmacological grounds, to alter blood pressure in patients within two weeks of the onset of acute ischaemic or haemorrhagic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the trial inclusion criteria, assessed trial quality, and extracted the data. MAIN RESULTS: Sixty five trials were identified involving in excess of 11,500 patients; a further 5 trials are ongoing. Data were obtained for 32 trials (5,368 patients). Significant imbalances in baseline blood pressure were present across trials of intravenous calcium channel blockers and prostacyclin. Major imbalances in baseline blood pressure between treatment and control groups have made the interpretation of these results difficult. Intravenous calcium channel blockers (CCBs) and oral CCBs significantly lowered late blood pressure as compared to controls. (systolic/diastolic BP): iv CCBs -8.2/-6.7 mm Hg (95% CI -12.6 to -3.8)/ (95% CI -9.2 to -4.3); oral CCBs -3.2/-2.1 mm Hg (95% CI -5.0 to -1.3)/ (95% CI -3.0 to -1.0). Beta blockers significantly lowered late diastolic blood pressure but not significantly late systolic blood pressure; -5.0/-4.5 mm Hg (95% CI -10.2 to 0.4)/(95% CI -7.8 to -1.15). Angiotensin converting enzyme inhibitors and prostacyclin non-significantly reduced late BP as compared to the controls by -5.4/-3.0 mm Hg (95% CI -16.5 to 5.8)/(95% CI -11.1 to 5.0) and -7.4/-3.9 mmHg (95% CI -15.6 to 0.2)/(95% CI -8.1 to 0.4) respectively. Magnesium, naftidrofuryl and piracetam had no significant effect on blood pressure. Oral CCBs and beta blockers each significantly reduced late heart rate (beats per minute (bpm)): CCBs -2.8 bpm (95%CI -3.9 to -1.7); beta blockers -9.3 bpm (95% CI -12.0 to -6.6). Prostacyclin significantly increased late heart rate by +5.6 bpm (95% CI 0.8 to 10.4). None of the drug classes significantly altered outcome apart from beta blockers and streptokinase which increased early case fatality (odds ratio 1.77, 95%CI, 1.05 to 3.00) and 2.27 (95% CI 1.4 to 3.67). REVIEWER'S CONCLUSIONS: There is not enough evidence reliably to evaluate the effect of altering blood pressure on outcome after acute stroke. CCBs, beta blockers, and probably ACE-inhibitors, prostacyclin and nitric oxide, each lowered BP during the acute phase of stroke. In contrast, magnesium, naftidrofuryl and piracetam had little or no effect on BP.

Administration, Oral↗
PubMed2006

Reading aids for adults with low vision.

BACKGROUND: The purpose of low vision rehabilitation is to allow people to resume or to continue to perform daily living tasks, reading being one of the most important. This is achieved by providing appropriate optical devices and special training in the use of residual vision and low vision aids, which range from simple optical magnifiers to high power video magnifiers. OBJECTIVES: The objective of this review was to assess the effects of reading aids for adults with low vision. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library, MEDLINE, EMBASE, SIGLE, LILACS, IndMed to July 2006 and the reference lists of relevant articles. We used the Science Citation Index to find articles that cited the included studies and contacted investigators and manufacturers of low vision aids. We handsearched the British Journal of Visual Impairment from 1983 to 1999 and the Journal of Visual Impairment and Blindness from 1976 to 1991. SELECTION CRITERIA: This review included randomised and quasi-randomised trials in which any device or aid used for reading had been compared to another device or aid in people aged 16 or over with low vision as defined by the study investigators. DATA COLLECTION AND ANALYSIS: Each author independently assessed trial quality and extracted data. MAIN RESULTS: Eight small studies with a cross-over design (221 people overall) and one three parallel-arm study (243 participants) were included in the review. The cross-over studies evaluated various types of aids. The quality of the studies was unclear in most cases, especially concerning carry-over or period effects. In one study on 20 participants head-mounted electronic devices (four types) were worse than optical devices. We could not find any differences in comparisons among electronic devices when pooling 23 participants of two small studies. One study on 10 people found that overlay coloured filters were no better than a clear filter. A parallel-arm study including 243 patients with age-related macular degeneration found that custom or standard prism spectacles are not different from conventional near spectacles, but the estimated difference was not precise. AUTHORS' CONCLUSIONS: Further research is needed on the comparison of different types of low vision aids. It will be also necessary to delineate patient's characteristics that predict performance with costly electronic devices as well as their sustained use in the long term compared to simpler and cheaper optical devices.

Adult↗
PubMed2001

Strategies for integrating primary health services in middle- and low-income countries: effects on performance, costs and patient outcomes.

BACKGROUND: Integration of primary health care is change to bring together inputs, organisation, management and delivery of particular service functions. Integration has been promoted in the health sector to improve the efficiency of health care delivery. The need for integration arose from perceptions that services were fragmented when delivered through separate vertical programmes. Integration is relevant to the health system at various levels, and this review is concerned with integration at the point of delivery. OBJECTIVES: To assess the effects of strategies to integrate primary health care services on producing a more coherent product and improving health care delivery and health status, in relation to service cost, outputs, impact and user acceptability. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register (August 2000), MEDLINE (1966 to September 2000), EMBASE (1988 to September 2000), Socio Files (1974 to September 2000), Popline (1970 to September 2000), HealthStar (1975 to September 2000), Cinahl (1982 to September 2000); Cab Health (1972 to 1999), International Bibliography of the Social Sciences (1970 to 1999), and reference lists of articles. We also searched the Internet and World Health Organization (WHO) library database, hand searched relevant WHO publications and contacted experts in the field. SELECTION CRITERIA: Randomised trials, controlled before and after studies, and interrupted time series analyses of integration strategies in primary health care services. Health services in high-income countries were excluded. The primary outcomes were service outputs: productivity and coverage, impact, user acceptability and unit cost. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Four studies were included. There was no consistent pattern of benefit. Integration had a clear positive effect on the outputs in only one study; in another it had similar effects to vertical programme delivery but greater effect than the control group. In the other two studies integration resulted in negative outputs in comparison with vertical programmes, although in one of these integration performed better than the control group. REVIEWER'S CONCLUSIONS: Few studies of good quality, large and with rigorous study design have been carried out to investigate the evidence to support integration as a style of service delivery. In fact, some studies found greater effects for vertical health care delivery. Policy makers and planners considering integration could introduce strategies, using rigorous study design, to allow further evaluation and increase the base of studies from which to draw evidence.

Clinical Trials as Topic↗
PubMed2006

Strategies for integrating primary health services in middle- and low-income countries at the point of delivery.

BACKGROUND: Strategies to integrate primary health care aim to bring together inputs, organisation, management and delivery of particular service functions to make them more efficient, and accessible to the service user. In some middle and low income countries, services have been fragmented by separate vertical programmes established to ensure delivery of particular technologies. We examined the effectiveness of integration strategies at the point of delivery. OBJECTIVES: To assess the effects of strategies to integrate primary health care services on producing a more coherent product and improving health care delivery and health status. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register (August 2005), MEDLINE (1966 to September 2005), EMBASE (1988 to 2005), Socio Files (1974 to September 2005), Popline (1970 to September 2005), HealthStar (1975 to September 2005), Cinahl (1982 to September 2005); Cab Health (1972 to 1999), International Bibliography of the Social Sciences (1970 to 1999), and reference lists of articles. We also searched the Internet and World Health Organization (WHO) library database, hand searched relevant WHO publications and contacted experts in the field. SELECTION CRITERIA: Randomised trials, controlled before and after studies, and interrupted time series analyses of integration strategies in primary health care services. Health services in high-income countries were excluded. The primary outcomes were indicators of health care delivery, user views on any measure of service coherence, and health status. We also sought information on comparative costs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study quality. MAIN RESULTS: Three cluster randomised trials and two controlled before and after studies were included, with three types of comparison: integration by adding on an additional component to an existing service (family planning); integrated services versus single special services (for sex workers); integrated delivery systems versus a vertical service (for family planning); and packages of enhanced primary child care services (integrated management of childhood illnesses) vs. routine child care. Interventions were complex and in some studies inputs varied substantially between comparison arms. Overall, no consistent pattern emerged. Only one study attempted to assess the user's view of the service provided. AUTHORS' CONCLUSIONS: Few studies of good quality, large and with rigorous study design have been carried out to investigate strategies to promote service integration in low and middle income countries. All describe the service supply side, and none examine or measure aspects of the demand side. Future studies must also assess the client's view, as this will influence uptake of integration strategies and their effectiveness on community health.

Child↗
PubMed2002

Advice on low-fat diets for obesity.

BACKGROUND: Overweight and obesity are global health problems contributing to an ever increasing noncommunicable disease burden. Calorie restriction can achieve short-term weight loss but the weight loss has not been shown to be sustainable in the long-term. An alternative approach to calorie restriction is to lower the fat content of the diet. However, the long-term effects of fat-restricted diets on weight loss have not been established. OBJECTIVES: To assess the effects of advice on low-fat diets as a means of achieving sustained weight loss, using all available randomised clinical trials. This review focused primarily on participants who were overweight or clinically obese and were dieting for the purpose of weight reduction. Since we were particularly interested in the ability of participants to sustain weight loss over a longer period of time, we focused on studies of 'free living' men and women who were given dietary advice rather than provision of food or money to purchase food. SEARCH STRATEGY: We searched the Cochrane Library (issue 2, 2001), MEDLINE (up to February 20002), and EMBASE (up to February 20002). We also searched the Science Citation Index (up to January 2001) and bibliographies of studies identified. Date of latest search: February 2002. SELECTION CRITERIA: Trials were included if they fulfilled the following criteria: 1) they were randomised controlled clinical trials of low-fat diets versus other weight-reducing diets, 2) the primary purpose of the study was weight loss, 3) participants were followed for at least six months, 4) the study participants were adults (18 years or older) who were overweight or obese (BMI >25 kg/m2) at baseline. Studies including pregnant women or patients with serious medical conditions were excluded. Two people independently applied the inclusion criteria to the studies identified. Disagreement was resolved by discussion or by intervention of a third party. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent reviewers and meta-analysis performed using a random effects model. Weighted mean differences of weight loss were calculated for treatment and control groups at 6, 12 and 18 months. MAIN RESULTS: Four studies were included at the six month follow-up, five studies at the 12 month follow-up and three studies at the 18 month follow-up. There was no significant difference in weight loss between the two groups at six months (WMD 1.7 kg, 95% CI -1.4 to 4.8 kg). The weighted sum of weight loss in the low fat group was -5.08 kg (95% CI -5.9 to -4.3 kg) and in the control group was -6.5 kg, (95% CI -7.3 to -5.7 kg). There was no significant difference in weight loss between the two groups at 12 months (WMD 1.1 kg, 95% CI -1.6 to 3.8 kg). The weighted sum of weight loss in the low fat group was -2.3 kg (95% CI -3.2 to -1.4 kg) and in the control group was -3.4 kg (95% CI -4.2 to -2.6 kg). There was no significant difference in weight loss between the two groups at 18 months (WMD 3.7 kg, 95% CI - 1.8 to 9.2). The weighted sum of weight loss in the control group was -2.3 kg (95% CI -3.5 to -1.2 kg) and in the low fat group there was a weight gain of 0.1 kg (95% CI -0.8 to 1 kg). There was significant heterogeneity in the results for weight loss at six months and 12 months. Apart from one study which showed a slight but statistically significant difference in total cholesterol in the low fat group at one year follow-up, there were no significant differences between the dietary groups for other outcome measures such as serum lipids, blood pressure and fasting plasma glucose. Studies measuring other factors such as perceived wellness and quality of life reported conflicting results. REVIEWER'S CONCLUSIONS: The review suggests that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people. Overall, participants lost slightly more weight on the control diets but this was not significantly different from the weight loss achieved through dietary fat restriction and was so small as to be clinically insignificant.

Diet, Fat-Restricted↗
PubMed2004

Diazepam for treating tetanus.

BACKGROUND: Clinical management of the muscle spasms and rigidity of tetanus poses a difficult therapeutic problem to physicians everywhere, especially in resource poor countries. There are wide variations in therapeutic regimens commonly used in clinical practice due to uncertainties about effectiveness of conventional drugs. Diazepam compared to other drugs (eg phenobarbitone and chlorpromazine) may have advantages because of combined anticonvulsant, muscle relaxant, sedative and anxiolytic effects. OBJECTIVES: To compare diazepam to other drugs in treating the muscle spasms and rigidity of tetanus in children and adults. SEARCH STRATEGY: We searched the Cochrane Neonatal Group trials register (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003), LILACS (2003), CINAHL (October 2003), Science Citation Index, African Index Medicus, conference abstracts and reference lists of articles. We contacted researchers, experts and organizations working in the field and used personal communication. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials. DATA COLLECTION AND ANALYSIS: We independently identified eligible trials, assessed trial methodological quality and extracted data. MAIN RESULTS: Two studies met the inclusion criteria. Method of generation of allocation sequence, concealment of allocation and blinding were unclear in both studies. A total of 134 children were allocated to three treatment groups comprising diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and chlorpromazine and diazepam.Meta-analysis of in-hospital deaths indicates that children treated with diazepam alone had a better chance of survival than those treated with combination of phenobarbitone and chlorpromazine (Relative Risk for death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI -0.38 to -0.06). Giving diazepam alone, or supplementing conventional anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported in one study to be associated with a statistically significantly milder clinical course and shorter duration of hospitalization. REVIEWER'S CONCLUSIONS: Although there is evidence that diazepam alone compared with combination of phenobarbitone and chlorpromazine is more effective in treating tetanus, the small size, methodological limitations and lack of data on drug safety from available trials preclude definite conclusions to support change in current clinical practice. The application of the present evidence should be moderated by local needs and circumstances, pending the availability of more evidence. We recommend a large multicenter, randomized controlled trial which compares diazepam alone with combinations of other drugs (excluding diazepam).

Anticonvulsants↗
PubMed2005

Fluoroquinolones for treating tuberculosis.

BACKGROUND: Fluoroquinolones are sometimes used to treat multiple-drug-resistant and drug-sensitive tuberculosis. The effects of fluoroquinolones in tuberculosis regimens need to be assessed. OBJECTIVES: To assess fluoroquinolones as additional or substitute components to antituberculous drug regimens for drug-sensitive and drug-resistant tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), Science Citation Index (1940 to April 2005), and Russian database (1988 to April 2005). We also scanned reference lists of all identified studies and contacted researchers. SELECTION CRITERIA: Randomized controlled trials of antituberculous regimens containing fluoroquinolones in people diagnosed with bacteriologically positive (sputum smear or culture) pulmonary tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria, assessed methodological quality, and extracted data. We used relative risk (RR) for dichotomous data, weighted mean difference (WMD) for continuous data (both with 95% confidence intervals (CI)), and the random-effects model if we detected heterogeneity and appropriate to combine data. MAIN RESULTS: Ten trials (1178 participants) met the inclusion criteria. No statistically significant difference was found in trials substituting ciprofloxacin or ofloxacin for first-line drugs in relation to cure (89 participants, 2 trials), treatment failure (388 participants, 3 trials), or clinical or radiological improvement (216 participants, 2 trials). Substituting ciprofloxacin into first-line regimens in drug-sensitive tuberculosis led to a higher incidence of relapse (RR 7.17, 95% CI 1.33 to 38.58; 384 participants, 3 trials) and longer time to sputum culture conversion (WMD 0.50 months, 95% CI 0.18 to 0.82; 168 participants, 1 trial), although this was confined to HIV-positive participants. Adding or substituting levofloxacin to basic regimens in drug-resistant areas had no effect. A comparison of sparfloxacin versus ofloxacin added to regimens showed no statistically significant difference in cure (184 participants, 2 trials), treatment failure (149 participants, 2 trials), or total number of adverse events (253 participants, 3 trials). AUTHORS' CONCLUSIONS: Only ciprofloxacin, ofloxacin, levofloxacin, and sparfloxacin have been tested in randomized controlled trials for treating tuberculosis. We cannot recommend ciprofloxacin in treating tuberculosis. Trials of newer fluoroquinolones for treating tuberculosis are needed. No difference has been demonstrated between sparfloxacin and ofloxacin in drug-resistant tuberculosis.

Antitubercular Agents↗
PubMed2006

Vaccines for preventing malaria (SPf66).

BACKGROUND: A malaria vaccine is badly needed. SPf66 was one of the earliest vaccines developed. It is a synthetic peptide vaccine containing antigens from the blood stages of malaria linked together with an antigen from the sporozoite stage, and is targeted mainly against the blood (asexual) stages. OBJECTIVES: To assess the effect of SPf66 malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae, and P. ovale in preventing infection, disease, and death. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (September 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (1982 to September 2005), Science Citation Index (1981 to September 2005), and reference lists of articles. We also contacted organizations and researchers in the field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing SPf66 vaccine with placebo or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection (any species). DATA COLLECTION AND ANALYSIS: Two people independently assessed trial quality and extracted data, including adverse events. Results were expressed as relative risks (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten efficacy trials of SPf66 involving 9698 participants were included. Results with SPf66 in reducing new episodes of P. falciparum malaria were heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90 to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25; 1221 participants). In four trials in South America the number of first attacks with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807 participants). It did not reduce episodes of P. vivax malaria or admission to hospital with severe malaria. Trials have not indicated any serious adverse events with SPf66 vaccine. AUTHORS' CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

Humans↗
PubMedDate not supplied

Carbodiimide-based benzimidazole library method.

Using carbodiimide reagents [1,3-diisopropylcarbodiimide or N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)], we have developed a mild, generalized, one-pot method that delivers N-2-arylaminobenzimidazole esters from commercially available aryl isothiocyanates and o-phenylenediamines. Following saponification and acidifying, the benzimidazole acids were isolated in overall yields ranging from 75 to 88% from the starting aryl isothiocyanates. Nine benzimidazole acids were converted into a library consisting of 180 benzimidazole amides following EDC coupling with commercially available amines. The National Institute of General Medical Science will dispense these benzimidazole amides to academia groups for pilot scale biomedical studies. Using these mild conditions and environmentally safe reagents, we demonstrated that these pharmaceutically ornate heterocycles can also be constructed on solid support.

Amides↗
PubMed2000

Why does threonine, and not serine, function as the active site nucleophile in proteasomes?

Proteasomes belong to the N-terminal nucleophile group of amidases and function through a novel proteolytic mechanism, in which the hydroxyl group of the N-terminal threonines is the catalytic nucleophile. However, it is unclear why threonine has been conserved in all proteasomal active sites, because its replacement by a serine in proteasomes from the archaeon Thermoplasma acidophilum (T1S mutant) does not alter the rates of hydrolysis of Suc-LLVY-amc (Seemüller, E., Lupas, A., Stock, D., Lowe, J., Huber, R., and Baumeister, W. (1995) Science 268, 579-582) and other standard peptide amide substrates. However, we found that true peptide bonds in decapeptide libraries were cleaved by the T1S mutant 10-fold slower than by wild type (wt) proteasomes. In degrading proteins, the T1S proteasome was 3.5- to 6-fold slower than the wt, and this difference increased when proteolysis was stimulated using the proteasome-activating nucleotidase (PAN) ATPase complex. With mutant proteasomes, peptide bond cleavage appeared to be rate-limiting in protein breakdown, unlike with wt. Surprisingly, a peptide ester was hydrolyzed by both particles much faster than the corresponding amide, and the T1S mutant cleaved it faster than the wt. Moreover, the T1S mutant was inactivated by the ester inhibitor clasto-lactacystin-beta-lactone severalfold faster than the wt, but reacted with nonester irreversible inhibitors at similar rates. T1A and T1C mutants were completely inactive in all these assays. Thus, proteasomes lack additional active sites, and the N-terminal threonine evolved because it allows more efficient protein breakdown than serine.

Adenosine Triphosphatases↗
PubMed2006

The effect of number of births on women's mortality: systematic review of the evidence for women who have completed their childbearing.

Mortality in women who have completed their childbearing may increase with the number of births experienced because of maternal depletion or a trade-off between reproduction and mortality. We report a systematic review of the evidence on this association. We searched Medline, Embase, Popline, and the Science Citation Index for published and unpublished studies up to September 2003, and the book catalogues of relevant London libraries. Where necessary we also contacted authors for additional information. Mortality declined with increasing numbers of births in twelve historical cohorts, but in eight contemporary cohorts the highest mortality was seen in the nulliparous and in women with more than four births. All effects seen were small and there were few statistically significant results. Studies examining the relationship in other ways (such as by linear trends or by mean number of births by age at death) found inconsistent associations. We discuss methodological, social, and biological factors that may have affected these associations.

Aged↗
PubMedDate not supplied

Bibliography on AIDS-related bereavement and grief.

This annotated bibliography on AIDS-related bereavement and grief was compiled to address a steadily increasing population: survivors of persons who have died of AIDS. Bibliographical entries were located by searching printed indexes, including Cumulative Index to Nursing and Allied Health Literature, Hospital Literature Index, Index Medicus, International Nursing Index, Psychological Abstracts, Social Science Index, Social Work Abstracts, and Sociological Abstracts. Databases searched included ERIC (Department of Education), Med-Line (National Library of Medicine), and Psych-Lit (American Psychological Association). References cited at the end of each work were also checked. This bibliography includes publications of studies using the survey method of social research and the case-study approach. It also includes experiences of professionals personally affected by the loss of someone to AIDS, and informational articles and chapters. To be included in this bibliography the work must have dealt exclusively or largely with the topic of AIDS-related bereavement and grief, or it must have addressed some aspect of it not previously covered anywhere in the literature. The topic of AIDS-related bereavement and grief refers to the loss of someone to (or with, as is the case with suicide) Acquired Immune Deficiency Syndrome, and its psychological, emotional, physical, and social effects on the survivor(s). This bibliography does not include publications that deal with related topics such as thanatology, anticipatory grief and mourning, and mortality rates and trends. This work is meant to serve as a resource for professionals in a variety of fields (e.g., nursing, pastoral care, mental health, and social work) involved in social research, bereavement counseling, ministry, and group intervention. It can be useful as a literature search for students in a variety of disciplines and for the AIDS-bereaved themselves. The bibliography is accompanied by an overview of the current state of the literature and a summary of the areas still in need of research and publication.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Psychosocial factors related to adolescent smoking: a critical review of the literature.

OBJECTIVE: To extend the analysis of psychosocial risk factors for smoking presented in the United States surgeon general's 1994 report on smoking and health, and to propose a theoretical frame of reference for understanding the development of smoking. DATA SOURCES: General Science Index, Medline, PsycLIT, Sociofile, Sociological Abstracts, and Smoking and Health. Holdings of the Addiction Research Foundation of Ontario Library as well as the authors' personal files. STUDY SELECTION: Reviewed literature focused on studies that examined the association of sociodemographic, environmental, behavioural, and personal variables with smoking. DATA SYNTHESIS: Adolescent smoking was associated with age, ethnicity, family structure, parental socioeconomic status, personal income, parental smoking, parental attitudes, sibling smoking, peer smoking, peer attitudes and norms, family environment, attachment to family and friends, school factors, risk behaviours, lifestyle, stress, depression/distress, self-esteem, attitudes, and health concerns. It is unclear whether adolescent smoking is related to other psychosocial variables. CONCLUSIONS: Attempts should be made to use common definitions of outcome and predictor variables. Analyses should include multivariate and bivariate models, with some attempt in the multivariate models to test specific hypotheses. Future research should be theory driven and consider the range of possible factors, such as social, personal, economic, environmental, biological, and physiological influences, that may influence smoking behaviour. The apparent inconsistencies in relationships between parental socioeconomic status and adolescent disposable income need to be resolved as does the underlying constructs for which socioeconomic status is a proxy.

Adolescent↗
PubMed1993

New human erg isoforms generated by alternative splicing are transcriptional activators.

The erg gene is a member of the ets gene family. ETS proteins have been shown to bind specifically the (GGA-A/T) motif and to transactivate via this consensus sequence. The human erg products exhibit approximately 70% homology with ETS proteins in their DNA-binding domain. We have isolated three erg cDNAs from a human fetal liver library. Two of them are different from the previously described erg-1 and erg-2 cDNAs (Rao et al., Science, 1987, 237, 635-639), in the middle of their coding sequence and in their 5' part where a novel initiation codon is introduced. These isoforms are generated by alternative RNA splicing from a single gene that leads to the inclusion or exclusion of different exon sequences. The three cDNAs expressed by an in vitro transcription-translation system direct the synthesis of proteins of approximately 38, 49 and 55 kDa. These in vitro erg products were tested for their DNA-binding activity by gel mobility-shift assays with different probes containing the ETS-specific binding site. The results indicated that all these erg isoforms are able to bind the ETS binding site in a specific manner. Our data using transient transfection assays indicate that erg protein isoforms function as transcriptional activators.

3T3 Cells↗
PubMed1996

Wavelets, adapted waveforms and de-noising.

This is a short summary of a talk given at the Frontier Science in EEG Symposium, Continuous Waveform Analysis, held on 9 October 1993 in New Orleans. We describe some new libraries of waveforms well-adapted to various numerical analysis and signal processing tasks. The main point is that by expanding a signal in a library of waveforms which are well-localized in both time and frequency, one can achieve both understanding of structure and efficiency in computation. We briefly cover the properties of the new "wavelet packet" and "localized trigonometric" libraries. The main focus will be applications of such libraries to the analysis of complicated transient signals: a feature extraction and data compression algorithm for speech signals which uses best-adapted time and frequency decompositions, and an adapted waveform analysis algorithm for removing fish noises from hydrophone recordings. These signals share many of the same properties as EEG traces, but with distinct features that are easier to characterize and detect.

Electricity↗
PubMed1989

OneSearch in a dental library: beyond MEDLINE.

MEDLINE, which includes the Index to Dental Literature, has been the database of choice for most search requests generated at Indiana University School of Dentistry. However, many requests extend beyond dentistry and the health sciences into the realms of business, education, psychology, law, and computer technology. For these requests, DIALOG's new OneSearch feature can be a simple and cost-effective mechanism for supplementing searches that would otherwise be confined to MEDLINE.

Dentistry↗