Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection

The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M. avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M. avium (chi2 test, P < .001). M. avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M. avium strain causing infection was detected.     

Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation

The macrophage mannose receptor, a pattern recognition molecule and component of innate immunity, mediates binding and phagocytosis of Pneumocystis carinii and likely represents an important clearance mechanism in the lungs of immunocompetent hosts. The purpose of this study was to examine the ability of alveolar macrophages from HIV-infected individuals to bind and phagocytose P. carinii, and to investigate the role of the macrophage mannose receptor in mediating this interaction. Compared with healthy individuals, alveolar macrophage phagocytosis of P. carinii from HIV+ persons was reduced up to 74% (P = 0.02), primarily reflecting a reduction in the number of organisms associated with each macrophage (P = 0.019). Furthermore, macrophages from HIV+ individuals demonstrated up to an 80% (P < 0.05) reduction in mannose receptor surface expression and endocytosis. Mannose receptor affinity was unaltered, and mRNA levels were modestly reduced (P < 0.05). Cells from HIV+ individuals with CD4(+) counts < 200 cells/mm3 (representing individuals at high clinical risk for P. carinii pneumonia) demonstrated the lowest levels of P. carinii phagocytosis and mannose receptor endocytosis. In vitro HIV infection of alveolar macrophages from healthy individuals reduced mannose receptor endocytosis to 53.2% (P < 0.05) and P. carinii binding and phagocytosis to 67.4% (P < 0.05) of control. Our studies suggest that HIV infection may alter innate immunity in the lungs, and that impaired alveolar macrophage mannose receptor-mediated binding and phagocytosis of P. carinii may contribute to the susceptibility of HIV-infected individuals to this opportunistic pulmonary pathogen.     

The care of HIV-infected adults in the United States. HIV Cost and Services Utilization Study Consortium

BACKGROUND AND METHODS: In order to elucidate the medical care of patients with human immunodeficiency virus (HIV) infection in the United States, we randomly sampled HIV-infected adults receiving medical care in the contiguous United States at a facility other than military, prison, or emergency department facility during the first two months of 1996. We interviewed 76 percent of 4042 patients selected from among the patients receiving care from 145 providers in 28 metropolitan areas and 51 providers in 25 rural areas. RESULTS: During the first two months of 1996, an estimated 231,400 HIV-infected adults (95 percent confidence interval, 162,800 to 300,000) received care. Fifty-nine percent had the acquired immunodeficiency syndrome according to the case definition of the Centers for Disease Control and Prevention, and 91 percent had CD4+ cell counts of less than 500 per cubic millimeter. Eleven percent were 50 years of age or older, 23 percent were women, 33 percent were black, and 49 percent were men who had had sex with men. Forty-six percent had incomes of less than $10,000 per year, 68 percent had public health insurance or no insurance, and 30 percent received care at teaching institutions. The estimated annual direct expenditures for the care of the patients seen during the first two months of 1996 were $5.1 billion; the expenditures for the estimated 335,000 HIV-infected adults seen at least as often as every six months were $6.7 billion, which is about $20,000 per patient per year. CONCLUSIONS: In this national survey we found that most HIV-infected adults who were receiving medical care had advanced disease. The patient population was disproportionately male, black, and poor. Many Americans with diagnosed or undiagnosed HIV infection are not receiving medical care at least as often as every six months. The total cost of medical care for HIV-infected Americans accounts for less than 1 percent of all direct personal health expenditures in the United States.     

Hospital admissions of HIV-infected patients from 1988 to 1992 in Maryland

To determine how the patterns of inpatient hospital care for HIV-infected patients have evolved in recent years, we analyzed data obtained from a statewide hospital discharge database from Maryland for the years 1988, 1990, and 1992. For each of these years, we compared demography, diagnoses, lengths of stay, use of the intensive care unit, third-party payer, and hospital charges (inflation-adjusted to 1992 dollars). HIV-infected patients accounted for 0.42% of all Maryland's hospital admissions in 1988, 0.68% in 1990, and 1.1% in 1992, with progressively more women and African-Americans hospitalized. Average lengths of stay fell from 11.7 days (1988) to 10.7 days (1990) and 9.5 days (1992) (p < 0.0001). Average charges per admission fell from $11,634 (1988) to $9,938 (1990) and $8,618 (1992) (p < 0.0001). Medicare or Medicaid paid for 50.9% of hospital admissions in 1988, 56.8% in 1990, and 66.8% in 1992 (p < 0.001). In-hospital mortality rates (7.8% in 1988, 7.9% in 1990, and 7.7% in 1992; p = 0.783) were stable, as was severity of illness. P. carinii pneumonia (PCP) was the most common principal diagnosis, but it declined in prevalence from 13.6% in 1988 to 9.1% in 1992 (p < 0.0001). Principal diagnoses of other opportunistic infections remained stable (8.0% in 1988, 9.9% in 1990, 8.6% in 1992; p = 0.90), as did other nonopportunistic infections (32.8% in 1988, 27.2% in 1990, and 30.0% in 1992; p = 0.16). Non-PCP pneumonias increased from 7.6% (1988) to 10.2% (1992) (p < 0.0001). Substance abuse as a principal or secondary diagnosis increased from 30.9% (1988) to 34.3% (1992) (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Changing patterns of HIV transmission and better targeting for intervention strategies

We considered the HIV population of our area, comparing demographic characteristics between 2 consecutive 6-year periods to assess the current patterns of HIV transmission. All HIV-positive patients referred to our hospital from January 1985 to December 1996 were included in the study and were classified into 2 periods: A (January 1985 to December 1990) and B (anuary 1991 to December 1996). The variables analysed were: sex, age at first visit, HIV risk category. A total of 4284 HIV subjects were observed, 2306 in period A vs 1978 in period B (P=ns). Males were 76.3% vs 75.2% (P=ns). Mean age for males was 27.4 vs 32.4 years (P < 0.001) and for females 25.4 vs 30.1 years (P < 0.001). Intravenous drug users (IVDUs) were 88.4% vs 65.4% (P < 0.001), 'heterosexuals' 14.3% vs 24.8% (P < 0.001), 'men who have sex with men' 2.4% vs 4.8% (P < 0.001). Mean age by the main risk groups was: IVDUs 25.9 vs 29.7 years (P < 0.001); heterosexuals 30.4 vs 36 years (P=0.007); 'men who have sex with men' 35 vs 35 years. In conclusion, our study confirms the emerging role of heterosexuals in the current HIV epidemic. People older than teenagers seem to have misperceived their own risk of HIV infection, given the increase in the mean age occurred in the most recent years. This trend suggests the need for prevention strategies focusing more on heterosexual transmission and older people.     

Current results of endoscopic sphincterotomy for lithiasis of the common bile duct

Between January 1989 and June 1990, endoscopic sphincterotomy was performed in 308 consecutive patients with common bile duct stones (mean age: 74 years). Complete clearance of common bile duct was achieved at the first attempt in 65% of cases. This rate was significantly related to the size and the number of biliary stones. The success rate reached 97 percent after repeated endoscopic sessions (127 patients), mechanical lithotripsy (20 patients), extracorporeal or intracorporeal lithotripsy (18 and 11 patients, respectively). During the month following the endoscopic sphincterotomy, 39 patients (13%) developed one or more complications and 11 patients (3.7%) died. The complication rate was related to the time elapsed between biliary opacification and endoscopic sphincterotomy (P = 0.04) and between endoscopic sphincterotomy and total common bile duct clearance (P = 0.0007). No patient younger than 75 years died, but death occurred in 4.5% of the patients older than 75 years. Thirty patients (10%) developed endoscopic sphincterotomy-related complications. Cholangitis and bleeding were the most frequent complications (4 and 2%, respectively). Cholangitis occurred more frequently among the patients older than 75 (P < 0.05) or when transhepatic guided endoscopic sphincterotomy or intracorporeal lithotripsy was used (P < 0.005). Cholangitis led to death in 2 patients, 86 and 87 years old (0.7%). Endoscopic sphincterotomy related complications developed within 48 hours in all but 4 patients (2 patients with pancreatitis and 2 patients with cholecystitis).     

Beta 2-microglobulin as a predictor of death in HIV-infected women from Kigali, Rwanda

OBJECTIVE: To determine if beta 2-microglobulin (beta 2M) predicts death among HIV-infected African women. DESIGN: Nested case-control study. SETTING: Kigali, Rwanda. PARTICIPANTS: Two hundred and five seroprevalent women known to be HIV-infected since 1986-1987; 67 of whom died of HIV disease (cases) and 138 were alive (controls) as of November 1991. In addition, 128 women who seroconverted between 1986 and 1991. MAIN OUTCOME MEASURES: HIV serology, clinical signs and symptoms of HIV disease, hematology variables, and beta 2M concentration. RESULTS: beta 2M concentration increased over time (P < 0.001) in the seroprevalent women and seroconvertors. The average rate of beta 2M increase in women who died was 0.5 compared with 0.3 mg/l/year in the vital, seroprevalent women (P = 0.07). The strongest independent predictors of death were the rate of change of beta 2M (mg/l/year) [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.7-6.8] and baseline beta 2M concentration (mg/l) [OR, 1.6; 95% CI, 1.2-2.1]. The rate of death for women with beta 2M concentration > or = 7.0 mg/l and a rate of change of beta 2M > or = 0.4 mg/l/year was 7.3 times higher than for women with beta 2M concentration < 7.0 mg/l and a rate of change of beta 2M of < 0.4 mg/l/year (95% CI, 3.1-17.2). The estimated median time from seroconversion to death assuming a constant rate of change of beta 2M was 10.6 years (95% CI, 9.9-11.2) for this cohort of HIV-infected women. CONCLUSIONS: Elevated beta 2M and a high rate of beta 2M increase were strongly associated with mortality among HIV-infected African women. Based on survival estimates using the rate of change of beta 2M, HIV-infected African women have similar survival compared with HIV-infected adults in the United States.     

Pneumocystis carinii pneumonia in HIV-negative immunocompromised adults

OBJECTIVES: To identify patient populations at risk of Pneumocystis carinii pneumonia (PCP) and assess the potential role of chemoprophylaxis. METHODS: Review of cases of PCP among patients admitted to a tertiary referral hospital in Sydney between January 1990 and April 1993. Cases were identified by indirect immunofluorescent antibody microscopy performed on respiratory tract specimens. RESULTS: Ninety-two episodes of PCP were diagnosed in 64 HIV-positive patients and 28 others. All HIV-negative patients had received corticosteroids combined with other immunosuppressive agents before the onset of PCP symptoms, which occurred within six months of immunosuppression. The group included nine of 150 kidney transplant recipients (6%) six of 138 liver transplant recipients (4.3%) and three of 25 patients with Wegener's granulomatosis (12%). Mortality associated with PCP in HIV-negative patients was significantly higher than in those who were HIV-positive (32% v. 8%, P < 0.005). CONCLUSION: Solid organ transplant recipients and individuals receiving treatment for Wegener's granulomatosis have a significant risk of developing PCP. Given the high mortality associated with this disease in HIV-negative patients, primary PCP chemoprophylaxis should be considered during the first six months of immunosuppression.     

Increasing social variation in birth outcomes in the Czech Republic after 1989

OBJECTIVES: This study investigated social variation in birth outcome in the Czech Republic after the political changes of 1989. METHODS: Routinely collected records on singleton live births in 1989, 1990, and 1991 (n = 380,633) and 1994, 1995, and 1996 (n = 286,907) were individually linked to death records. RESULTS: Mean birthweight fell from 3,323 g to 3,292 g (P < .001) between 1989 and 1991 and then increased to 3,353 g by 1996. The gap in mean birthweight between mothers with a primary education and those with a university education, adjusted for age, parity, and sex of infants, widened from 182 g (95% confidence interval [CI] = 169, 19) in 1989 to 256 g (95% CI = 240, 272) in 1996. Similar trends were found for preterm births. Postneonatal mortality declined most among the better educated and the married. The odds ratio for postneonatal death for infants of mothers with a primary (vs university) education, adjusted for birthweight, increased from 1.99 (95% CI = 1.52, 2.60) in 1989 through 1991 to 2.39 (95% CI = 1.55, 3.70) in 1994 through 1995. CONCLUSIONS: Despite general improvement in the indices of fetal growth and infant survival in the most recent years, social variation in birth outcome in the Czech Republic has increased.     

Long-term alterations in growth factor mRNA expression following seizures

Pneumocystis carinii pneumonia (PCP) is one of the most predominant opportunistic infectious diseases in patients with AIDS. Nested PCR has been described as a sensitive and specific tool for detecting P. carinii DNA in clinical specimens. Little is known about the correlation of positive PCR results and clinical evidence of PCP in patients with different forms of immunosuppression. One hundred and thirty-six sputum samples, 26 tracheal-bronchial aspirate samples, 35 bronchoalveolar lavage samples, and 11 lung biopsy samples from (i) human immunodeficiency virus (HIV)-infected patients with AIDS, (ii) immunocompromised patients with leukemia or lymphoma, and (iii) immunocompetent control patients were investigated by a nested PCR amplifying DNA from the mitochondrial large subunit of P. carinii. All patients suffered from acute episodes of respiratory disease. The resulting data were correlated with clinical evidence of PCP. A high degree of association of positive P. carinii PCR results and clinical evidence of PCP in HIV-infected patients with AIDS was found. When calculated for bronchoalveolar lavage and lung biopsy samples, the positive and the negative predictive values of P. carinii PCR for PCP diagnosis in HIV-infected patients with AIDS were 1 and the specificity and the sensitivity were 100%. In contrast, in the group of patients with leukemia or lymphoma, the positive predictive value of the nested PCR for these materials was found to be as low as 0.09, the negative predictive value was 0.73, the specificity was 44.4%, and the sensitivity was 25.0%. No P. carinii DNA could be detected in specimens from immunocompetent patients. In summary, in contrast to patients with leukemia and lymphoma, nested PCR seems to be a sensitive and specific tool for PCP diagnosis in HIV-infected patients with AIDS.     

Streptococcus pneumoniae blood culture isolates from patients with and without human immunodeficiency virus infection: alterations in penicillin susceptibilities and in serogroups or serotypes

We performed a 3-year retrospective study of Streptococcus pneumoniae blood culture isolates recovered at Baragwanath Hospital, Soweto, South Africa, from 1993 to 1995. The study group comprised 457 patients, including 98 children, of known human immunodeficiency virus (HIV) serostatus. Of these patients, 70 (30 [8.4%] of 359 adults and 40 [40.8%] of the 98 children) were infected with penicillin-resistant S. pneumoniae strains (minimal inhibitory concentration, > or = 0.12 microg/mL); 56 of these strains were intermediately resistant to penicillin. HIV-positive patients had significantly more penicillin-resistant isolates than did HIV-negative patients (43 [29.7%] of 145 HIV-positive patients vs. 27 [8.6%] of 312 HIV-negative patients; P < .001); this difference was found for both adults (19% vs. 4.3%; P < .001) and children (53.3% vs. 30.2%; P < .0343). Multiple resistance occurred more frequently in HIV-positive children (P = .02). HIV-positive adults had a statistically significant increase in the percentage of serogroups and serotype usually found in children and commonly associated with antimicrobial resistance, i.e., serotype 14 and serogroups 6, 19, and 23 (48% vs. 28.6%; P < .001). The increased prevalence of serogroups or serotypes usually found in children was also found among penicillin-susceptible strains. These data suggest that HIV-infected adults may again become susceptible to the serogroups or serotypes found in children.     

Impact of pregnancy on maternal AIDS

OBJECTIVE: To assess the impact of pregnancy on maternal acquired immunodeficiency syndrome (AIDS) among tribal women in India. STUDY DESIGN: From February 1992 to February 1996, 71 tribal women from Manipur, India, with AIDS (Centers for Disease Control stage iii/iv), matched for age, parity, CD4 lymphocyte count and demographic characteristics, were recruited into a prospective study. Thirty-two (49%) of these women were pregnant (8-10 weeks) (group A) and 38 (51%) nonpregnant (group B). RESULTS: Pneumocystis carinii pneumonia followed by miliary tuberculosis and wasting disease were the most common AIDS-defining illness and cause of maternal death in both groups. A total of 28 (39%) women died as a direct result of their AIDS-defining illness; 10 (27%) of them were among the nonpregnant women as compared to 18 (56%) deaths among the pregnant women (P = .17, odds ratio 3.7285, 95% confidence interval 1.23, 11.58). Three (16%) of these 18 deaths occurred within 14 weeks of an uneventful first-trimester medical termination of pregnancy. Thirteen women (41%) died undelivered at 30-34 weeks' gestation, and two died within 3 weeks of delivery. Fourteen (44%) women vaginally delivered 14 preterm infants, between 28 and 35 weeks' gestation. Eleven of these infants died within six weeks; nine deaths were a direct result of prematurity and clinical diagnosis of an AIDS-defining illness. The mean survival time was 9.72 months for the pregnant women and 22.6 months for the nonpregnant women (P = .066). CONCLUSION: Pregnancy increased maternal and fetal mortality in these AIDS-infected women.     

Epidemiology of immediate and early trauma deaths at an urban Level I trauma center

The objective of this study is to identify and differentiate the injury patterns and causes of death among patients who died within the 1st hour and those in the period between 1 and 48 hours after hospital admission. Information was collected from the 1994 to 1996 trauma data base at an urban Level I trauma center. The records of 155 trauma patients who died within the 1st hour (immediate trauma death, ITD) and between 1 and 48 hours (early trauma death, ETD) were examined retrospectively. Total and constituent Injury Severity Score (ISS), Trauma Score (TS), and Glasgow Coma Score were analyzed. ITDs constituted 49 per cent of all deaths within 48 hours. Blunt mechanisms accounted for 37 per cent of ITDs and 40 per cent of ETDs (not significant), whereas penetrating trauma accounted for 59 per cent of ITDs and 56 per cent of ETDs (not significant). Exsanguination most commonly caused death among ITDs (54%) and head injury (51%) among ETDs (P < 0.01). Patients who died within the 1st hour had higher ISS (42.6 +/- 23.2, P < 0.03), lower TS (1.7 +/- 1.9, P < 0.0001), and lower Glasgow Coma Score (3.1 +/- 1.1, P < 0.0001) than those who died after the 1st hour. Patients with ITD had a significantly worse chest ISS than those with ETD (47.4 +/- 28.6 vs 19.0 +/- 19.1, P < 0.0001). We conclude that 1) ITD is caused primarily by exsanguination, whereas ETD is largely due to the sequelae of severe neurologic injury; 2) ITD has a significantly lower TS and higher ISS than ETD; and 3) thoracic injuries are more severe among patients with ITDs than among those with ETDs. The severity of thoracic injury among ITDs suggests that rapid surgical intervention is critical during the resuscitation of these severely injured patients.     

Pediatric AIDS prognosis using somatic growth velocity

OBJECTIVE: To describe the natural history of somatic growth in HIV infection by constructing age-specific growth velocity norms and to assess specific prognostic information available using these norms. DESIGN: Observations on 1338 HIV-infected children aged 3 months to 15 years who participated in one of four US clinical trials of pediatric anti-HIV therapies were pooled; baseline growth velocity data were obtained using the first 6 months of observation for each child. METHODS: Distributions of physical growth velocities in HIV-infected children in the Pediatric AIDS Clinical Trials Group were computed. Statistical smoothing of growth histories was employed to derive velocity estimates, and quantile regression analysis of growth velocities was performed to allow comparisons of growth rates in age- and gender-heterogeneous cohorts in the context of HIV infection. The quantile regressions provide corrected z-scores for growth velocity that appropriately compare HIV-infected children with one another for the purpose of distinguishing more from less favorable prognoses. RESULTS: Consistent deficits in growth velocity amongst HIV-infected children were revealed when compared with the Fels Institute velocity standards. Approximately 33% of height (and 20% of weight) age- and sex-corrected velocity measurements obtained in the first 6 months of clinical trial participation lay beneath the corresponding third percentiles of the Fels reference distributions, which are commonly regarded as critical indicators of growth failure. Proportional hazards regression tests indicated that both weight and height velocity contributed significant information on the risk of death among children with AIDS after adjusting for antiretroviral therapy received, CD4 cell counts, and age at trial enrollment. Comparing subjects who differ in initial weight velocity by one age- and sex-corrected SD, the relative hazard of death was 0.63 (95% confidence interval, 0.55-0.72; P < or = 0.0001) in favor of the child with greater weight velocity, controlling for antiretroviral therapy received, age and CD4 cell count at baseline. The analogous hazard ratio for height velocity was 0.68 (95% confidence interval, 0.57-0.79; P < or = 0.0001). CONCLUSIONS: Suitably normalized growth velocities are informative and inexpensive criteria for pediatric AIDS prognosis; the growth velocity distributions presented will be useful for comparing growth effects of new therapeutic strategies to those of single and combination antiretrovirals employed for maintenance of pediatric HIV infection in the mid-1990s.     

Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial

We conducted a randomized, double-blind, placebo-controlled multicenter trial of azithromycin (1,200 mg once weekly) for the prevention of Mycobacterium avium complex (MAC) infection in patients with AIDS and a CD4 cell count of < 100/mm3. In an intent-to-treat analysis through the end of therapy plus 30 days, nine (10.6%) of 85 azithromycin recipients and 22 (24.7%) of 89 placebo recipients developed MAC infection (hazard ratio, 0.34; P = .004). There was no difference in the ranges of minimal inhibitory concentrations of either clarithromycin or azithromycin for the five breakthrough (first) MAC isolates from the azithromycin group and the 18 breakthrough MAC isolates from the placebo group. Of the 76 patients who died during the study, four (10.5%) of 38 azithromycin recipients and 12 (31.6%) of 38 placebo recipients had a MAC infection followed by death (P = .025). For deaths due to all causes, there was no difference in time to death or number of deaths between the two groups. Episodes of non-MAC bacterial infection per 100 patient years occurred in 43 azithromycin recipients and 88 placebo recipients (relative risk, 0.49; 95% confidence interval, 0.33-0.73). The most common toxic effect noted during the study was gastrointestinal, reported by 78.9% of azithromycin recipients and 27.5% of placebo recipients. Azithromycin given once weekly is safe and effective in preventing disseminated MAC infection, death due to MAC infection, and respiratory tract infections in patients with AIDS and CD4 cell counts of < 100/mm3.     

Effect of prednisone on response to influenza virus vaccine in asthmatic children

OBJECTIVE: To evaluate the immunogenicity of the influenza virus vaccine in children receiving short-course (a burst) prednisone therapy for acute asthmatic exacerbations. DESIGN: Prospective cohort study. SETTING: Outpatient pediatric clinic of a military medical center. PATIENTS: Children aged 6 months to 18 years requiring the 1996 influenza virus vaccine were eligible for the study. A total of 58 children were enrolled initially. The control group included 37 asthmatic children requiring less than 900 microg/d of inhaled prednisone and their siblings. The prednisone group included 21 children vaccinated at the beginning of a course of prednisone prescribed to treat an asthma exacerbation. Thirty-one control subjects (84%) and 19 patients in the prednisone group (90%) completed the study. Dropout was due to failure to come in for the postvaccination serum sampling. INTERVENTIONS: All study patients underwent immunization with the 1996-1997 trivalent subvirion influenza virus vaccine (FluShield; Wyeth Laboratories Inc, Marietta, Pa) containing 15-microg hemagglutinin antigens each of A/Texas/36/91 (H1N1) (A/H1), A/Wuhan/359/95 (H3N2)(A/H3), and B/Beijing/184/93 (B). The prednisone cohort received a burst of oral prednisone therapy (2 mg/kg per day for 5 days). MAIN OUTCOME MEASURES: To assess the immunogenicity of the vaccine between both groups, at least a 4-fold rise in titer and end titers of at least 1:40 to each of the 3 antigens were compared. Mean changes in geometric titers to the 3 antigens were also compared. RESULTS: Proportion of patients in each group with at least a 4-fold rise in titer to each of the influenza antigens was as follows: for A/H3N3 antigen, 15 patients (79%) in the prednisone group vs 22 controls (71%) (P = .74); for A/ H1N1 antigen, 16 patients in the prednisone group (84%) vs 20 controls (64%) (P = .20); and for B antigen, 7 patients in the prednisone group (37%) vs 8 controls (26%) (P = .53). Proportion of patients in each group with an end titer of at least 1:40 to each of the antigens was as follows: for A/ H3N2 antigen, 18 patients in the prednisone group (95%) vs 28 controls (90%) (P = .69); for A/H1N1 antigen, 17 patients in the prednisone group (89%) vs 26 controls (84%) (P = .99); and for B antigen, 7 patients in the prednisone group (37%) vs 13 controls (42%) (P = .99). There were also no significant differences between groups in the mean changes in geometric titers to any of the 3 antigens. CONCLUSIONS: Prednisone bursts did not diminish the response of asthmatic children to the 1996 influenza virus vaccine, compared with controls. Children can be effectively vaccinated against influenza virus while they are receiving prednisone therapy bursts for asthmatic exacerbations.     

Secular trends in recombinant erythropoietin therapy among the U.S. hemodialysis population: 1990-1996

BACKGROUND: Chronic anemia is a major cause of morbidity among the end-stage renal disease (ESRD) population. Recombinant erythropoietin (rHuEPO) has been recognized as a major advance in the treatment of anemia among the ESRD population. This study examines the secular trends in the use of and response to rHuEPO therapy among severely, moderately and mildly anemic hemodialysis patients. METHODS: We designed a cohort analytic study using seven years of claims data. The study population comprised all facility-based adult hemodialysis patients receiving rHuEPO therapy, who were initially reimbursed by Medicare in each of the first quarter of the calendar years 1990 through 1996 (N = 64,957). RESULTS: Between 1990 and 1996, the mean rHuEPO dose increased by 139% for the patient cohorts with a first observed hematocrit < 0.25, 122% for the 0.25 to 0.29 cohorts, and 107% for the > or = 0.30 cohorts, and produced a 0.02 to 0.03 increase in achieved hematocrit (A-Hct) over this time. Dosing of rHuEPO did not appear to be influenced by patient or provider characteristics, although African-Americans, the elderly, non-diabetics and persons receiving dialysis in a non-profit facility had a larger percent change in hematocrit compared to their counterparts (P < 0.001). CONCLUSIONS: The results of the clinical use of rHuEPO seven years after FDA approval found in the general ESRD hemodialysis population have not equaled the results obtained in the initial clinical trials. Overall, our findings suggest that substantial increases in rHuEPO dose provided to anemic patients have resulted in only modest increases in hematocrit in the seven years since rHuEPO's introduction. Resistance to rHuEPO, prior rHuEPO treatment, inadequate use of supplemental iron, and policy and financial incentives may explain this finding.     

Pneumocystis carinii alters surfactant protein A concentrations in bronchoalveolar lavage fluid

To understand better the interaction between surfactant protein A (SP-A), human immunodeficiency virus (HIV) and Pneumocystis carinii pneumonia (PCP), we measured SP-A from bronchoalveolar lavage (BAL) fluid in immunosuppressed patients (HIV-positive [HIV+] and HIV noninfected [HIV-]) who were examined for possible pneumonia. Forty-five HIV+ patients, 16 with PCP and no other pathogen (HIV+/Pc) and 29 with no evidence of pulmonary pathogen (HIV+ controls), were compared with 6 HIV- patients with PCP (HIV-/Pc) and 11 control patients with no underlying disease (controls). Despite a similar inflammatory response in the HIV-infected patients whether they had PCP or not, we found increased BAL SP-A concentrations in HIV+/Pc patients as compared with HIV+ control patients (HIV+/Pc: median, 10.3 micrograms/ml; range, 2.8 to 24.3 micrograms/ml; HIV+ control: median, 1.9; range, 0.06 to 3.83 micrograms/ml; p < 0.05). The amount of SP-A in the HIV+ control group was significantly lower than healthy, uninfected volunteers, suggesting that HIV itself may lower SP-A levels. Six HIV+/Pc patients underwent BAL after 21 days of therapy and showed complete resolution of the P. carinii organism. There was a significant drop in the amount of SP-A at follow-up lavage (initial mean, 14.1 micrograms/ml; follow-up mean, 7.4 micrograms/ml; p < 0.02). We also found a significant correlation between the amount of P. carinii and the amount of SP-A in the BAL fluid (Spearman rank, 0.74; p < 0.01). We conclude that SP-A content is increased in HIV+ patients with PCP. The relationship between SP-A concentration and the abundance of P. carinii present in the BAL fluid may be related to SP-A binding to P. carinii or to alterations in surfactant protein homeostasis.     

Primary repair is superior to initial palliation in children with atrioventricular septal defect and tetralogy of Fallot

OBJECTIVE:The objective was to explore the best management algorithm for atrioventricular septal defect in conjunction with tetralogy of Fallot. METHODS: We reviewed the cases of 38 children referred to our division (March 1981-August 1997) who had atrioventricular septal defect associated with tetralogy of Fallot; 32 (84%) had Down syndrome. Twenty-one received initial palliation with a systemic-to-pulmonary artery shunt; of these, 2 (9.5%) died before complete repair. Thirty-one children underwent complete repair; 14 of these (45%) had undergone initial palliation (mean age at shunt 20 +/- 24 months). Right ventricular outflow obstruction was relieved by a transannular patch in 22 (71%); 14 (64% of 22) had a monocuspid valve inserted. Four required an infundibular patch. RESULTS: Two children (6.4%) died early after repair; 1 had undergone previous palliation. Patients with palliation underwent repair at an older age (78 vs 36 months), required longer ventilatory support (8 vs 4 days) and inotropic support (8 vs 4 days), and had longer intensive care stays (11 vs 6 days) and hospital stays (24 vs 15 days). Eleven children (35%) underwent reoperation, 7 (58%) for right ventricular outflow reconstruction and pulmonary arterioplasty. Reoperation was more frequent in the palliation group than in the primary operation group (64% vs 12%). The single late death was related to a reoperation in the palliation group. CONCLUSIONS: Atrioventricular septal defect with tetralogy of Fallot can be repaired with a low mortality rate. Initial palliation with a shunt resulted in a more complex postoperative course and a higher reoperative rate. Primary repair is superior to initial palliation with later repair.     

Detection of Pneumocystis carinii DNA in blood specimens from human immunodeficiency virus-infected patients by nested PCR

The detection of Pneumocystis carinii DNA in blood by PCR could be useful for studying the natural history of pneumocystosis and could also be a noninvasive diagnostic method. The results of previous studies are nevertheless conflicting. In our study, we compared three commercially available DNA extraction kits (GeneReleaser, QIAamp Tissue Kit, and ReadyAmp Genomic DNA Purification System) and proteinase K and proteinase K-phenol-chloroform treatments for the extraction of P. carinii DNA from dilutions of a P. carinii f. sp. hominis cyst suspension mixed with human whole blood. A rapid and simple nested PCR protocol which amplifies a portion of the mitochondrial large-subunit rRNA gene was applied to all the extraction products. The QIAmp Tissue Kit was the most effective kit for the isolation of amplification-ready P. carinii DNA and was used with nested PCR for the testing of whole-blood specimens from 35 immunocompetent control patients and 84 human immunodeficiency virus (HIV)-infected patients investigated for pulmonary disease and/or fever. In HIV-infected patients, P. carinii DNA was detected by nested PCR in blood samples from 3 of 14 patients with microscopically proven P. carinii pneumonia, 7 of 22 patients who were considered to be colonized with P. carinii, and 9 of 48 patients who were neither infected nor colonized with P. carinii. P. carinii DNA was not detected in blood specimens from the 35 immunocompetent patients. P. carinii DNA in blood might represent viable P. carinii organisms or DNA complexes released from pulmonary phagocytes. In conclusion, P. carinii DNA may be detected in whole blood from HIV-infected patients, but the nature and the meaning of the circulating form of P. carinii remain to be established.