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At least 1,117 records · Page 62Linked to original sources

PubMed2000

The impact of protease inhibitor-containing highly active antiretroviral therapy on progression of HIV disease and its relationship to CD4 and viral load.

OBJECTIVE: To compare the rate of disease progression according to viral load and CD4 cell count in patients receiving or not receiving highly active antiretroviral therapy (HAART), defined as protease inhibitor-containing regimens. DESIGN: An observational study, with prospectively collected data. METHODS: All patients attending the HIV Outpatient clinic as of 1 January 1995 (n = 2083) were included. Follow-up was until the first AIDS-defining event or death. Associations between viral load or CD4 cell count and disease progression were assessed using a person-years approach. Event rates were compared using Poisson regression analysis; a multivariate model was used to assess the independent effects of CD4, viral load and treatment group on event rates and to consider interactions between these variables. RESULTS: The event rates increased with lower CD4 cell count and higher viral load for both treatment groups and were generally lower in the HAART group. In a multivariate analysis, lower CD4 cell counts and higher viral loads remained significantly associated with disease progression, irrespective of treatment group. However, the event rate was significantly lower for the HAART group compared with the control group (relative rate 0.53, P < 0.001). CONCLUSIONS: HAART-treated patients with high viral loads and CD4 cell counts experienced reduced disease progression compared with individuals with the same CD4 cell count and viral load not receiving HAART. Consequently, the short-term prognosis associated with viral load levels and CD4 cell counts may differ in patients on HAART. Whether this effect will be observed with non-protease-inhibitor-containing HAART is not known at this time.

Adolescent↗

PubMed2001

Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.

OBJECTIVE: To compare the clinical response among patients who initiate protease inhibitor therapies with different virological potency. DESIGN: We analysed patients who started indinavir, ritonavir or saquinavir hard gel capsule (hgc) as part of at least triple therapy during prospective follow-up within the EuroSIDA study. METHODS: Changes in plasma viral load (pVL) and CD4 cell count from baseline were compared between treatment groups. Time to new AIDS-defining events and death were compared in Kaplan--Meier models, and Cox models were established to further assess differences in clinical progression (new AIDS/death). Adjustment was made for differences in baseline parameters, in particular pVL, CD4 cell count, and region of Europe. RESULTS: A total of 2708 patients (median follow-up: 30 months) were included, of which 556 started ritonavir (21%), 1342 indinavir (50%), and 810 saquinavir hgc (30%). The three groups were fairly evenly balanced at baseline regarding CD4 count, previous diagnosis of AIDS and pVL, After 12 months, the median changes in CD4 cell count were 90, 96 and 74 x 10(6) cells/l, respectively;P < 0.001, the proportions of patients with pVL < 500 copies/ml were 47, 54 and 41%; P < 0.001, and the proportions with clinical progression were 11.9, 9.2 and 11.9%, respectively; P = 0.20 (log-rank test). In multivariate models the relative risk of clinical progression for indinavir compared with saquinavir hgc was: 0.77 (0.60--0.99); P = 0.043, and for ritonavir 0.83 (0.62--1.11); P = 0.20. CONCLUSIONS: Saquinavir hgc was associated with an inferior long-term clinical response relative to indinavir, which was consistent with the observed differences in virological and immunological responses.

Administration, Oral↗

PubMed2001

HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy.

OBJECTIVE: To determine if HIV-1 RNA and CD4 lymphocyte thresholds for the initiation of highly active antiretroviral therapy (HAART) are associated with clinical response to therapy. DESIGN: Observational cohort study. SETTING: Johns Hopkins Hospital HIV Clinic. PATIENTS: HIV-infected adults. INTERVENTION: Patients initiating HAART (n = 530) were compared with concurrent patients who did not receive HAART (n = 484). MAIN OUTCOME MEASURE: Progression to a new AIDS-defining illness or death. RESULTS: The average duration of follow-up for the cohort was 22 months. HAART resulted in decreased disease progression among persons with fewer than, but not more than, 200 x 10(6) CD4 lymphocytes/l prior to treatment. Among persons receiving HAART, plasma HIV-1 RNA level prior to therapy was not associated with HIV disease progression within CD4 T-lymphocyte count strata. In a Cox multivariate proportional hazards model that adjusted for age, sex, race, prior opportunistic infection, and CD4 T lymphocytes, < or = 200 x 10(6) CD4 lymphocytes/l was the strongest predictor of disease progression. HIV-1 RNA level prior to starting HAART of < 5000 copies/ml, 5001-55 000 copies/ml, or > 55 000 copies/ml was not associated with disease progression on therapy, particularly among persons with > 200 x 10(6) CD4 lymphocytes/l. There was no sex difference in disease progression on treatment. CONCLUSIONS: Our data suggest that current guidelines for initiating HAART should place greater emphasis on CD4 lymphocyte than HIV-1 RNA level for both men and women. Further longitudinal follow-up will be needed to better ascertain whether HAART initiated at > 200 x 10(6) CD4 lymphocytes/l is effective in slowing disease progression.

Adolescent↗

PubMed2003

Mortality and progression to AIDS after starting highly active antiretroviral therapy.

OBJECTIVES: To examine survival and progression to AIDS among HIV-infected patients after starting highly active antiretroviral therapy (HAART). METHODS: The study population consisted of 3724 patients from the ATHENA observational cohort who initiated HAART. We considered progression to either an AIDS-defining disease or death, distinguishing HIV-related and non-related (including therapy-related) deaths. A time-dependent multivariate hazards model was fitted to the patient data and 5-year survival probabilities under various therapy scenarios estimated. RESULTS: A total of 459 patients developed AIDS and 346 died during 12 503 person-years of follow-up. HIV-related mortality decreased from 3.8 to 0.7 per 100 person-years between 1996 and 2000 whereas non-HIV-related mortality did not change (0.4 and 0.9, respectively, P = 0.25). For asymptomatic and symptomatic therapy naive patients younger than 50 years with CD4 counts above 10 x 10(6) and 150 x 10(6) cells/l, respectively, predicted 5-year survival probabilities were above 90% when HAART was used continuously. This limit was 450 x 10(6) cells/l when HAART was used during 20 weeks in each 24 week-period of follow-up, and 110 x 10(6) cells/l when patients delayed initiation of HAART for 1 year after becoming eligible for treatment. CONCLUSIONS: Survival probabilities were high among HIV-infected patients initiating HAART at an early stage of infection. The best therapy strategy is therefore to start HAART at this stage of infection. However, deferring HAART in patients with high CD4 cell counts may be clinically more appropriate given toxicity and adherence problems. The lack of any change in non-HIV-related mortality suggests that toxicity has not yet become a major risk factor for death.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Relationship between postoperative anemia and cardiac morbidity in high-risk vascular patients in the intensive care unit.

OBJECTIVE: To determine if postoperative anemia is associated with postoperative myocardial ischemia and morbid cardiac events DESIGN: Case control study. SETTING: Postanesthesia care unit and surgical intensive care unit. PATIENTS: A total of 27 high-risk patients undergoing infra-inguinal arterial bypass procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After informed consent, patients were continuously monitored by ambulatory electrocardiographic recorders from the evening before surgery up to 80 hrs during the postoperative period. Myocardial ischemia was defined as > or = 1 mm of horizontal or downsloping ST depression or > or = 2 mm ST segment elevation persisting for at least 60 secs on the ambulatory electrocardiogram. Morbid cardiac events were defined as: cardiac death, myocardial infarction, unstable angina, and ischemic pulmonary edema. Using a receiver operating characteristic curve, a hematocrit of 28% was determined to be the best threshold hematocrit value below which morbid cardiac events were most likely to occur. Statistical significance between hematocrit and cardiac outcome was determined by Fisher's exact test where appropriate. Thirteen of 27 patients had a hematocrit < 28%. Of these 13 patients, ten demonstrated postoperative myocardial ischemia and six sustained a morbid cardiac event. Of 14 patients with a hematocrit > or = 28%, two displayed myocardial ischemia and none sustained a morbid cardiac event. A hematocrit of < 28% was significantly associated with myocardial ischemia (p = .001) and morbid cardiac events (p = .0058). No significant differences in baseline heart rate and heart rate at the onset of myocardial ischemia were noted between the anemic and nonanemic patients. CONCLUSIONS: This study suggests that postoperative anemia may play a role in postoperative myocardial ischemia and cardiac morbidity.

Aged↗

PubMed1984

The effect of advanced life support and sophisticated hospital systems on motor vehicle mortality.

A mileage population death index (MPDI) was devised to compare the death rate from motor vehicle trauma in Florida counties. The MPDI was defined as the average death rate per one hundred million miles driven divided by the population of the particular county X 10(5). The resultant MPDI was correlated with the presence in a county of basic life support only and advanced life support. In addition, counties with large metropolitan hospitals which might possibly classify as Level I institutions were compared with other counties. A low MPDI was found to be highly correlated with the presence of an ALS system (p = 0.001). Counties with hospitals which might qualify as Level I also had a significantly lower MPDI (p = 0.04). We conclude that the presence of advanced life support and a sophisticated hospital is correlated with a significantly lower motor vehicle mortality.

Accidents, Traffic↗

PubMed1995

Hamster to rat kidney xenotransplantation. Effects of FK 506, cyclophosphamide, organ perfusion, and complement inhibition.

Hamster to rat renal xenotransplantation was performed with recipient nephrectomies. Recipients were treated beginning on day 0 with continuous FK 506 monotherapy, a 7-day or open-ended monotherapeutic course of cyclophosphamide (CP), and the two drug regimens combined. CP alone (10 mg/kg/day) prevented a xenospecific antibody response and tripled median survival of the kidney (defined as recipient death) from 6 (control) to 18.5 days whereas FK 506 alone had no effect. The drugs in combination were no better than CP alone (15 days) unless the 5-day course of CP was given at a higher dose (15 mg/kg) and started 3 days preoperatively (79 days). In further experiments, adjuvant measures were added to the minimally effective FK 506/7-day CP regimen which gave a median survival of only 15 days. In the most successful modification, intraoperative antibody depletion by the temporary transplantation of third party hamster liver or en bloc kidneys increased median survival from 15 to 34 and 48 days, respectively. An intraoperative i.v. dose administration of the anticomplement drug K76 instead of antibody depletion increased survival to 26 days. Although the events of kidney rejection were similar to those of heart xenografts and partially forestalled by the antibody inhibiting CP treatment, or by antibody depletion, survival for > 100 days was accomplished in only 5 of 86 treated animals. The poorer survival previously reported with cardiac xenotransplantation is largely explained by the life support requirement of the kidneys. Renal failure was responsible for almost all deaths before 60 days, and subnormal renal failure was a pervasive adverse factor thereafter, frequently caused by pyelonephritis which is suspected to have had an immunologic etiology.

Animals↗

PubMed1996

Combination therapy with ZDV + DDI versus ZDV + DDC in patients with progression of HIV-infection under treatment with ZDV.

HIV-seropositive patients (n = 67) who had tolerated zidovudine for at least 24 weeks and deteriorated clinically or immunologically within 12 weeks prior to study entry were allocated in an alternating manner to didanosine chewable tablets (400 mg/day) plus zidovudine (500 mg/day) or dideoxicytidine capsules (2.25 mg/day) plus zidovudine (500 mg/day). The combination of didanosine and zidovudine resulted in a more pronounced increase of CD4 cells over time compared to the combination of dideoxicytidine with zidovudine (p < 0.002). The increase of CD4 cells was almost exclusively due to patients with more than 100 CD4 cells/microliters. Clinical end points (death, AIDS-defining disease, CDC IV event) were less frequent under didanosine plus zidovudine but failed to reach statistical significance (p = 0.07). For didanosine plus zidovudine the median time on medication during study was shorter (63% vs. 100%, p < 0.05) and the number of patients discontinuing medication prematurely due to side effects was higher (59% vs. 30%, p < 0.02). The present study favors the combination of didanosine and zidovudine in patients deteriorating while receiving zidovudine for > 24 weeks in respect to the time course of the CD4 cells. In this small sized study, there seemed to be fewer clinical events in patients on the didanosine combination compared to the combination with dideoxicytidine; however, this trend failed to reach statistical significance and needs therefore to be substantiated by larger studies. However, the lower compliance of the patients may hamper the efficacy of didanosine.

Adult↗

PubMed1996

Switching from zidovudine to didanosine in patients with symptomatic HIV infection and disease progression. ddI Iberian Study Group.

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).

AIDS-Related Complex↗

PubMed2006

Population-based analysis of meningococcal disease mortality in the United States: 1990-2002.

BACKGROUND: Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in the United States. Approximately 10-15% of meningococcal patients died despite antimicrobial therapies. METHODS: We used vital records to assess meningococcal disease mortality in the United States during 1990-2002. Meningococcal cases were defined as reported deaths with recorded International Classification of Diseases, 9th revision (ICD-9) codes 036.0-036.9 or ICD-10 codes A39.0-A39.9. Denominator data were obtained from population estimates published by the U.S. Census Bureau. We analyzed the effects of age, sex, race/ethnicity and season of the year on meningococcal disease mortality. RESULTS: We identified 3335 meningococcal deaths. Both the crude and age-adjusted mortality rates were 0.10 death per 100,000 population per year (95% confidence interval, 0.09-0.10). Fifty-eight percent of deaths occurred among persons younger than 25 years old. Mortality was elevated in infants, young adults (15-24 years old), and older adults (older than 74 years old). Mortality rates in African-Americans were 1.45 and 3.32 times higher than mortality rates in whites and Asians/Pacific Islanders, respectively. Mortality caused by meningococcal disease rose in winter months and declined during the summer. Observed mortality rates increased from 1990 to 1997 and decreased from 1997 to 2002. CONCLUSIONS: Meningococcal disease continues to be an important, vaccine-preventable cause of death in the United States. Vaccination and other disease prevention efforts should be augmented for higher risk groups. Meningococcal mortality data can be used to assess the effectiveness of these efforts.

Adolescent↗

PubMed2004

Microvascular dysfunction in angiographically normal or mildly diseased coronary arteries predicts adverse cardiovascular long-term outcome.

OBJECTIVE: To study the role of coronary flow reserve for the prediction of long-term cardiovascular event rate. DESIGN: Observational, longitudinal. SETTING: Single-center, coronary vasomotor testing at university hospital. PARTICIPANTS: One hundred and twenty patients with angiographically normal or minimally diseased coronary vessel. METHODS: Coronary flow reserve was assessed by intracoronary Doppler and quantitative coronary angiography. Cardiovascular events during follow-up (6.5+/-3 years, range 14-125 months) were defined as sudden death, myocardial infarction, unstable angina, ischemic stroke or the need for revascularization by percutaneous transluminal coronary angioplasty or coronary as well as peripheral bypass surgery. RESULTS: Reduced coronary flow reserve was significantly associated with a poor long-term outcome: cardiovascular events occurred in seven (18%) patients in the lowest tertile of coronary flow reserve compared with four patients in the middle tertile (10%) and two patients in the upper tertile (5%) (P=0.019 by Kaplan-Meier analysis). The multivariate Cox proportional hazard model revealed coronary flow reserve as an independent predictor of prognosis (P=0.017) in addition to angiographic evidence of atherosclerosis (P=0.047) and arterial hypertension (P=0.013). CONCLUSIONS: Coronary flow reserve in normal to mildly diseased arteries is an independent predictor of long-term prognosis of atherosclerosis within the next decade.

Adult↗

PubMed2005

Selective drug taking during combination antiretroviral therapy in an unselected clinic population.

OBJECTIVES: Multidrug therapy is necessary to achieve sustained viral suppression. Discordant adherence to individual components of a multidrug regimen may lead to adverse outcomes. METHODS: Antiretroviral-naive patients initiating therapy from 1997 through 2002 were included. Adherence for each antiretroviral was determined using pharmacy refill data. Selective drug taking was defined as > or =5% difference in adherence between 2 components of an antiretroviral regimen lasting at least 60 days. RESULTS: A total of 322 of 415 patients (78%) met inclusion criteria. Selective drug taking occurred in 47 of 322 patients (15%) and on 51 of 438 regimens (12%). Factors associated with selective drug taking were lower baseline CD4 lymphocyte count (adjusted odds ratio [AOR]: 1.3, 95% CI: 1.1 to 1.6 per 100 cell/microL decrease); 3 times daily dosing schedule (AOR: 4.1, 95% CI: 1.1 to 15.5); and the presence of significant adverse drug events (AOR: 2.9, 95% CI: 1.3 to 6.4). Regimens containing a fixed-dose combination dosage form were less likely to have selective drug taking (AOR: 0.5, 95% CI: 0.2 to 0.99). Outcomes independently associated with selective drug taking included earlier progression to a new AIDS-defining illness or death (hazard ratio: 2.3, 95% CI: 1.2 to 4.5). CONCLUSIONS: Selective drug taking was relatively common among patients taking combination antiretroviral therapy. The factor most closely associated with selective drug taking was the presence of an adverse drug event. Clinical outcomes appeared worse in patients with selective drug taking.

Adult↗

PubMed2007

Antiretroviral therapy interruption guided by CD4 cell counts and plasma HIV-1 RNA levels in chronically HIV-1-infected patients.

OBJECTIVE: We evaluated the safety of CD4 cell count and plasma HIV-1 RNA (pVL)-guided treatment interruptions (GTI) and determined predictors of duration of treatment interruption. METHODS: Chronically HIV-1-infected adults with sustained CD4 cell counts > 500 cells/microl and pVL < 50 copies/ml were randomly assigned to either continue with standard antiretroviral therapy (control group, n = 101) or to interrupt therapy aimed at maintaining CD4 cell counts > 350 cells/microl and pVL < 100,000 copies/ml (GTI group, n = 100). Both groups were followed for 2 years. RESULTS: There were no AIDS-defining illnesses or deaths in either group. Compared to controls, subjects interrupting therapy reduced treatment exposure by 67%, but suffered significantly more adverse events related to the intake of medication or to therapy interruption [relative hazard, 2.71; 95% confidence interval (CI), 1.64-4.49; P < 0.001), mainly due to an excess in mononucleosis-like symptoms. While GTI subjects demonstrated improvements in the psychosocial spheres of quality of life and pain reporting, GTI had no effect on the physical aspects of quality of life. Although both groups had a similar hazard for developing CD4 cell count < 200 cells/microl; at least 10% of subjects on GTI had CD4 cell counts < 350 cells/microl at every time point. Drug resistance mutations were detected in 36% of subjects but were selected de novo only in subjects interrupting non-nucleoside reverse transcriptase inhibitor therapy. Lower CD4 cell count nadir, higher set-point pVL and prior exposure to suboptimal regimens were all independent predictors of the need to reinitiate treatment. CONCLUSIONS: Overall, GTI were not as safe as continuing therapy. Despite achieving some improvements in quality of life, GTI did not reduce the overall rate of management-related adverse events.

Adult↗

PubMed2006

Very low level of microalbuminuria is associated with increased risk of death in subjects with cardiovascular or cerebrovascular diseases.

BACKGROUND: The original definition of microalbuminuria (20-200 microg min-1 or 15-150 microg min-1 overnight) is based on studies of patients with diabetes, in whom microalbuminuria was associated with increased risk of chronic renal failure. In a recent report an overnight urinary albumin excretion (UAE) above only 5 microg min-1 was strongly predictive of coronary heart disease and death in the general population. The aim of the present study was to investigate if this cut-off level also has prognostic value in a population with cardiovascular or cerebrovascular disease. METHODS AND RESULTS: In The Third Copenhagen City Heart Study in 1992-1994, 491 men and women aged 30-80 years with a history of coronary heart disease or stroke delivered a timed overnight urine sample. They were followed by registers with respect to vital status until 2004. During follow-up, 141 of the 491 participants died. The relative risk of death in subjects with UAE above 5 microg min-1 compared with subjects with lower UAE was 2.0 (1.4-2.8; P<0.001). It was unaffected [RR 1.9 (1.3-2.7); P<0.005] by adjustment for age, sex, blood pressure, diabetes, lipoproteins, renal creatinine clearance, smoking and body mass index. CONCLUSIONS: Subjects with cardiovascular or cerebrovascular disease have about 100% higher risk of death if microalbuminuria defined as UAE above 5 microg min-1 is present. Measurements of UAE should be included in the risk assessment in subjects with cardiovascular or cerebrovascular disease. This study supports the definition of microalbuminuria as UAE above 5 microg min-1.

Adult↗

PubMed2005

Increased risk of early virological failure in non-European HIV-1-infected patients in a Dutch cohort on highly active antiretroviral therapy.

OBJECTIVE: To compare early and late responses to highly active antiretroviral therapy (HAART) in European and non-European HIV-1 infected patients in a Dutch cohort. METHODS: We retrospectively analysed the response to HAART of 216 previously treatment-naive HIV-1-infected patients using the University Medical Centre Utrecht HIV database. African (n=51), Asian (n=7), and Central/South American (n=6) patients were classified as non-European, and others as European (n=152). Early failure was defined as a viral load that remained above 400 HIV-1 RNA copies/mL after 6 months of treatment with HAART. Late-phase failure was determined in patients who were successfully treated in the early phase and was defined as two consecutive viral load measurements above 400 copies/mL, a new AIDS-defining event or death. RESULTS: In the early phase, four of 152 (2.6%) European and eight of 64 (12.5%) non-European patients failed HAART. A significant increased risk of virological failure in the early phase of treatment was observed for non-Europeans as compared to Europeans (odds ratio 4.6; 95% confidence interval 1.1-20.2). Low serum drug levels in the absence of resistant virus were often seen at the time of early failure. No difference in late-phase failure was observed between the two groups (adjusted hazard ratio 0.6; 95% confidence interval 0.3-1.2). CONCLUSIONS: Non-European patients had a 4.6 times higher risk of virological failure than their European counterparts in the first 6 months of treatment with HAART. This failure seemed to be associated with low serum drug levels at the time of failure. However, if HAART was successful in the early phase, response rates in the late phase were similar for Europeans and non-Europeans.

Adult↗

PubMed1997

The Stockholm birth centre trial: maternal and infant outcome.

OBJECTIVE: To compare an in-hospital birth centre with standard maternity care regarding medical interventions and maternal and infant outcome. BACKGROUND: The birth centre care was characterised by comprehensive antenatal, intrapartum and postpartum care with the same team of midwives, restricted use of medical technology, and discharge within 24 h after birth. METHODS: Of 1860 women meeting low risk medical criteria in early pregnancy and interested in birth centre care, 928 were randomly allotted birth centre care and 932 standard maternity care. Data were collected mainly from hospital records, and analysis was by intention-to-treat. RESULTS: Of the women in the birth centre group, 13% were transferred antenatally and 19% intrapartum. No statistical differences were observed in maternal morbidity or in perinatal mortality, neonatal morbidity, Apgar score or infant admissions to neonatal care. Perinatal mortality, defined as intrauterine death after 22 weeks of gestation and infant death within seven days of birth, occurred in eight cases (0.9%) in the birth centre group and in two cases (0.2%) in the standard care group (OR 4.04, 95% CI 0.80 to 39.17; P = 0.11). Subgroup analysis showed that a larger proportion of first-born babies in the birth centre group (15.6%) were admitted for neonatal care than in the standard care group (9.5%) (P = 0.003), whereas the converse was the case for the newborns of multiparous women: 4.7% and 8.4%, respectively (P = 0.04). The overall rates of operative delivery (e.g. caesarean section, vacuum extraction and forceps), 11.1% in the birth centre group and 13.4% in the standard care group, did not differ statistically (P = 0.12), but obstetric analgesia, induction, augmentation of labour and electronic fetal monitoring were less frequently used in the birth centre group. Labour was 1 h longer in the birth centre group. CONCLUSION: Birth centre care was associated with less medical interventions than standard care without any statistically significant differences in health outcomes. However, the excess of perinatal deaths and of morbidity in primigravidas' infants in the birth centre group gives cause for concern and necessitates further studies.

Adult↗

PubMed1999

The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.

OBJECTIVE: To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo. DESIGN: A randomised placebo-controlled trial. SETTING: Two university teaching hospitals with level three neonatal intensive care units. POPULATION: Women in preterm labour with intact membranes between 23 and 30 weeks of gestation. METHODS: Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or peri-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group--6/19 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44-18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group. CONCLUSION: There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.

Adult↗

PubMed2005

Dopaminergic neurons in rat ventral midbrain cultures undergo selective apoptosis and form inclusions, but do not up-regulate iHSP70, following proteasomal inhibition.

Dysfunction of the ubiquitin-dependent protein degradation system, either at the level of the proteasome itself, or at the level of ubiquitination, may play a role in the pathogenesis of Parkinson's disease (PD) and other related neurodegenerative disorders. We have employed a cellular model of this dysfunction in which lactacystin or epoxomicin, selective pharmacological inhibitors of the proteasome, are applied to primary cultures of embryonic rat ventral midbrain. Proteasomal inhibition with either agent led to apoptotic death specifically within phenotypically defined tyrosine hydroxylase (TH)-positive dopaminergic neurons, with little or no apoptotic death induced in GABAergic neurons. Inhibition of the proteasome also led to the formation of ubiquitin and alpha-synuclein-positive cytoplasmic inclusions in TH-positive and TH-negative neurons. Inclusions were observed in viable as well as apoptotic neurons, and required new or ongoing transcription. Tyrosine hydroxylase immunolabeling was often present within the inclusions. Such mislocalization may lead to dysfunction of dopamine biosynthesis. Interestingly, dopaminergic neurons, unlike other neurons within these cultures or cultured cortical neurons, failed to induce the chaperone Hsp70 in response to proteasomal inhibition. This failure may explain in part the increased sensitivity of these neurons to proteasomal inhibitors.

Acetylcysteine↗