Biomedical subjects

Charles E McCulloch

Publications and source records attributed to Charles E McCulloch.

At least 19 recordsLinked to original sources

PubMed2006

MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations.

Brain arteriovenous malformations (BAVM) have high matrix metalloproteinase-9 (MMP-9) expression, the source of which is unclear. We hypothesized MMP-9 production might be due to inflammation in BAVM. Compared to control brain tissues (n = 5), BAVM tissue (n = 139) had a higher expression (by ELISA) of myeloperoxidase (MPO) (193 +/- 189 vs. 6 +/- 3, ng/mg, P < .001), MMP-9 (28 +/- 32 vs. 0.7 +/- 0.6, ng/mg, P < .001), and IL-6 (102 +/- 218 vs. 0.1 +/- 0.1, pg/mg, P < .001), but not eNOS (114 +/- 87 vs. 65 +/- 9, pg/mg, P = .09). MMP-9 expression in BAVM highly correlated with myeloperoxidase (R2 = .76, P < .001), as well as with IL-6 (R2 = .32, P < .001). In contrast, MMP-9 in BAVM poorly correlated with the endothelial marker, eNOS (R2 = .03, P = .05), and CD31 (R2 = .004, P = .57). Compared to non-embolized patients (n = 46), patients with pre-operative embolization (n = 93) had higher levels of myeloperoxidase (236 +/- 205 vs. 106 +/- 108, ng/mg, P < .001) and MMP-9 (33 +/- 35 vs. 16 +/- 20, ng/mg, P < .001), however the correlation between MMP-9 and myeloperoxidase was equally strong for both groups (R2 = .69, n = 93, P < .001, for both). MMP-9 expression correlated with the lipocalin-MMP-9 complex, suggesting neutrophils as the MMP-9 source. MPO co-localized with majority of MMP-9 signal by immunohistochemistry. Our data suggest that inflammation is a prominent feature of BAVM lesional phenotype, and neutrophils appear to be a major source of MMP-9 in these lesions.

Adult↗

PubMed2006

Day 2 transfer improves pregnancy outcome in in vitro fertilization cycles with few available embryos.

OBJECTIVE: Delaying ET to day 3 to optimize embryo selection is well accepted. However, in cases where there are not enough embryos to perform selection, it is not clear whether there is a difference in clinical outcomes with the day of ET. DESIGN: Cohort study. SETTING: Academic medical center. PATIENT(S): Two hundred forty-two fresh IVF/intracytoplasmic sperm injection (ICSI) cycles from 2002-2004, where all generated embryos were transferred irrespective of quality because of an extremely low number of available embryos. INTERVENTION(S): In time period 1, ET was on day 3. In time period 2, ET was on day 2. MAIN OUTCOME MEASURE(S): Patient response to stimulation was analyzed along with pregnancy outcome and implantation rate. RESULT(S): Miscarriage rates were decreased, and ongoing pregnancy rates were increased with a day 2 ET in patients <40 years of age. CONCLUSION(S): In women <40 years of age, the day of transfer is a significant predictor of clinical outcome in cases in which a low number of embryos are available for transfer. The evidence suggests that limiting embryo culture to only 2 days reduces the incidence of miscarriage and increases ongoing pregnancy rates.

Adult↗

PubMed2006

Adrenoceptor polymorphisms and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cardiac abnormalities occur commonly after subarachnoid hemorrhage (SAH) and may be caused by excessive release of catecholamines from the myocardial sympathetic nerves. We hypothesized that adrenoceptor polymorphisms resulting in greater catecholamine sensitivity would be associated with an increased risk of cardiac injury. METHODS: This was a prospective cohort study. The primary outcome variables were the serum level of cardiac troponin I (cTi, abnormal if >1.0 microg/L) and the left ventricular ejection fraction (LVEF, abnormal if <50%). Six adrenoceptor polymorphisms were genotyped: beta1AR Arg389Gly, beta1AR Ser49Gly, beta2AR Gly16Arg, beta2AR Gln27Glu, beta2AR Thr164Ile, and alpha2AR del322-325. The effect of each polymorphism on the risk of developing cardiac abnormalities was quantified using multivariable logistic regression. RESULTS: The study included 182 patients. The CC genotype (Arg/Arg) of beta1AR Arg389Gly (odds ratio [OR] 3.4, P=0.030) and the CC genotype (Gln/Gln) of beta2AR Gln27Glu (OR 3.1, P=0.032) were predictive of cTi release. The presence of the alpha2AR deletion was predictive of reduced LVEF (OR 4.2, P=0.023). The combination of the beta1AR 389 CC and the beta2AR 27 CC genotypes resulted in a marked increase in the odds of cTi release (OR 15.5, P=0.012). The combination of the beta1AR 389 CC and the alpha2AR deletion genotypes resulted in a marked increase in the odds of developing a reduced LVEF (OR 10.3, P=0.033). CONCLUSIONS: Genetic polymorphisms of the adrenoceptors are associated with an increased risk of cardiac abnormalities after SAH. These data support the hypothesis that cardiac dysfunction after SAH is a form of neurocardiogenic injury.

Catecholamines↗

PubMed2006

Oocyte degeneration after intracytoplasmic sperm injection: a multivariate analysis to assess its importance as a laboratory or clinical marker.

OBJECTIVE: Oocyte degeneration has historically been associated with the intracytoplasmic (ICSI) technique. We sought to determine whether oocyte degeneration rates were associated with the technician performing the procedure, the baseline characteristics of the patient, and/or ovarian stimulation variables. We also evaluated whether the degeneration rate could serve as a surrogate marker for implantation potential. DESIGN: Cohort study. SETTING: Academic medical center. PATIENT(S): Couples undergoing ICSI. INTERVENTION(S): Six thousand six hundred fifty-three injected oocytes were analyzed to determine whether the degeneration rate was technician dependent. Two hundred thirty first-entry down-regulated cycles were examined to identify predictors associated with oocyte degeneration. Multivariate analyses were performed using generalized linear model routines. MAIN OUTCOME MEASURE(S): Oocyte degeneration rates and implantation rates. RESULT(S): Neither the ICSI technician nor the stripping technician was associated with the oocyte degeneration rate. However, the day 3 FSH, number of mature oocytes retrieved, and E2 levels on the day of hCG were significant independent predictors of degeneration rate. Physician-adjustable ovarian stimulation variables were not associated with the degeneration rate. The degeneration rate did not appear to be associated with the implantation rate. CONCLUSION(S): These data suggest that oocyte degeneration is not technician or physician dependent. Degeneration is likely a function of the inherent oocyte quality in women who underwent ovarian stimulation. However, the remaining cohort of retrieved oocytes appears to be unaffected by virtue of an uncompromised implantation rate.

Adult↗

PubMed2006

Amphetamine exposure is elevated in Parkinson's disease.

BACKGROUND: Since the 1930's, amphetamine drugs have been used therapeutically and recreationally. High doses are associated with acute injury to axon terminals of dopaminergic neurons. It is unknown whether low dose exposure to amphetamine over a prolonged time period is associated with the development of Parkinson's disease (PD). METHODS: A telephone survey of drug and chemical exposure was administered to patients from three faculty practice clinics at UCSF. Patients were asked to participate if they had been diagnosed with peripheral neuropathy (PN), amyotrophic lateral sclerosis (ALS), or PD between the ages of 40 and 64. Spouses or caregivers were also asked to participate. "Amphetamine exposure" was defined as a prior use of amphetamine, methamphetamine or dextroamphetamine. "Prolonged exposure" was defined as amphetamine use that occurred more than twice a week for > or =3 months or weekly usage for > or =1 year and had to occur before diagnosis of the neurological condition. RESULTS: Prolonged exposure to either prescribed or non-prescribed amphetamine was common, occurring in 15% with PN (11/76), 13% with ALS (9/72), and 11% with PD (17/158). Prolonged amphetamine exposure was more frequent in diseased patients compared to spouses when all diseases were combined (adjusted OR=3.15, 95% CI 1.42-7.00, p=0.005). When tested alone, only the Parkinson's disease group retained statistical significance (adjusted OR=8.04, 95% CI 1.56-41.4, p=0.013). For most individuals, exposure occurred long before diagnosis (averages: PN 25 years, ALS 28 years, and PD 27 years). CONCLUSIONS: The elevated rate of prolonged amphetamine exposure in PD is intriguing and bears further investigation.

Adrenergic Agents↗

PubMed2006

Relationship between accurate auscultation of a clinically useful third heart sound and level of experience.

BACKGROUND: Poor performance by physicians-in-training and interobserver variability between physicians have diminished clinicians' confidence in the value of the third heart sound (S3). METHODS: To determine whether auscultation of a clinically useful S3 improves with advancing levels of experience, we performed a prospective, blinded, observational study of 100 patients undergoing left-sided heart catheterization. Patients underwent blinded auscultation by 4 physicians (each from 1 of 4 different levels of experience), phonocardiography, measurement of blood B-type natriuretic peptide levels, echocardiography for measurement of left ventricular ejection fraction, and cardiac catheterization for measurement of left ventricular end-diastolic pressure. RESULTS: Whereas residents' and interns' auscultatory findings demonstrated no significant agreement with phonocardiographic findings, an S3 auscultated by cardiology fellows (kappa = 0.37; P<.001) and cardiology attendings (kappa = 0.29; P = .003) agreed with phonocardiographic findings. Although the sensitivities of the S3 were low (13%-52%) for identifying patients with abnormal measures of left ventricular function, the specificities were high (85%-95%), with the best test characteristics exhibited by phonocardiography and more experienced physicians. The S3 detected by attendings and fellows was superior in distinguishing an elevated B-type natriuretic peptide level, a depressed left ventricular ejection fraction, or an elevated left ventricular end-diastolic pressure (P = .002-.02 for attendings and .02-.03 for fellows) compared with residents (P = .02-.47) or interns (P = .09-.64). CONCLUSIONS: The S3 auscultated by more experienced physicians demonstrated fair agreement with phonocardiographic findings. Although correlations were superior for phonocardiography, the associations between the S3 and abnormal markers of left ventricular function improved with each level of auscultator experience.

Adult↗

PubMed2006

Body mass index and risk for end-stage renal disease.

BACKGROUND: Although interest in the relationship between obesity and kidney disease is increasing, few epidemiologic studies have examined whether excess weight is an independent risk factor for end-stage renal disease (ESRD). OBJECTIVE: To determine the association between increased body mass index (BMI) and risk for ESRD. DESIGN: Historical (nonconcurrent) cohort study. SETTING: A large integrated health care delivery system in northern California. PARTICIPANTS: 320,252 adult members of Kaiser Permanente who volunteered for screening health checkups between 1964 and 1985 and who had height and weight measured. MEASUREMENTS: The authors ascertained ESRD cases by matching data with the U.S. Renal Data System registry through 2000. RESULTS: A total of 1471 cases of ESRD occurred during 8,347,955 person-years of follow-up. Higher BMI was a risk factor for ESRD in multivariable models that adjusted for age, sex, race, education level, smoking status, history of myocardial infarction, serum cholesterol level, urinalysis proteinuria, urinalysis hematuria, and serum creatinine level. Compared with persons who had normal weight (BMI, 18.5 to 24.9 kg/m2), the adjusted relative risk for ESRD was 1.87 (95% CI, 1.64 to 2.14) for those who were overweight (BMI, 25.0 to 29.9 kg/m2), 3.57 (CI, 3.05 to 4.18) for those with class I obesity (BMI, 30.0 to 34.9 kg/m2), 6.12 (CI, 4.97 to 7.54) for those with class II obesity (BMI, 35.0 to 39.9 kg/m2), and 7.07 (CI, 5.37 to 9.31) for those with extreme obesity (BMI > or = 40 kg/m2). Higher baseline BMI remained an independent predictor for ESRD after additional adjustments for baseline blood pressure level and presence or absence of diabetes mellitus. LIMITATIONS: Primary analyses were based on single measurements of exposures. CONCLUSIONS: High BMI is a common, strong, and potentially modifiable risk factor for ESRD.

Adult↗

PubMed2006

Triploidy formation after intracytoplasmic sperm injection may be a surrogate marker for implantation.

OBJECTIVE: Triploidy after intracytoplasmic sperm injection (ICSI) is due mostly to retention of the second polar body. Our interest was to determine the predictors of triploidy and to determine whether the presence of triploidy can serve as a surrogate marker of implantation for the remaining cohort of zygotes. DESIGN: Cohort study. SETTING: Academic research center. PATIENT(S): Infertile couples undergoing IVF/ICSI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Triploid zygote (3PN) rate, implantation rate. RESULT(S): The 3PN rate is a significant predictor of implantation rate for the remaining cohort of zygotes. The starting and total dose of gonadotropins administered and the total days of stimulation are independent predictors of the 3PN rate. CONCLUSION(S): In couples with a normal semen analysis undergoing IVF/ICSI, the 3PN rate may serve as a surrogate marker of oocyte quality and may be altered by adjusting the stimulation protocol.

Adult↗

PubMed2006

Antibiotic treatment of acute respiratory infections in acute care settings.

OBJECTIVES: To examine the patterns of antibiotic use for acute respiratory tract infections (ARIs) in acute care settings. METHODS: Chart reviews were performed retrospectively on a random sample of adult ARI visits to seven Veterans Affairs (VA) and seven non-VA emergency departments (EDs) for the period of November 2003 to February 2004. Visits were limited to those discharged to home and those with primary diagnoses of antibiotic-responsive (pneumonia, acute exacerbation of chronic bronchitis, pharyngitis, sinusitis) and antibiotic-nonresponsive conditions (acute bronchitis, nonspecific upper respiratory tract infection [URI]). Results are expressed as adjusted odds ratios with 95% confidence intervals. RESULTS: Of 2,270 ARI visits, 62% were for antibiotic-nonresponsive diagnoses. Seventy-two percent of acute bronchitis and 38% of URI visits were treated with antibiotics (p < 0.001). Stratified analyses show that antibiotic prescription rates were similar among attending-only and housestaff-associated visits for antibiotic-responsive diagnoses (p = 0.11), and acute bronchitis (76% vs. 59%; p = 0.31). However, the antibiotic prescription rate for URIs was greater for attending-only visits compared with housestaff-associated visits (48% vs. 15%; p = 0.01). Antibiotic prescription rates for total ARIs varied between sites, ranging from 42% to 89%. Patient age, gender, race and ethnicity, smoking status, comorbidities, and clinical setting (VA vs. non-VA) were not independently associated with antibiotic prescribing. CONCLUSIONS: Acute care settings are important targets for reducing inappropriate antibiotic prescribing. The mechanisms accounting for lower antibiotic prescription rates observed with housestaff-associated visits merit further study.

Acute Disease↗

PubMed2006

Apolipoprotein E epsilon 2 is associated with new hemorrhage risk in brain arteriovenous malformations.

OBJECTIVE: Patients with brain arteriovenous malformation (AVM) are at life-threatening risk of intracranial hemorrhage (ICH). Identification of genetic variants associated with increased new ICH risk would facilitate risk stratification and guide therapeutic intervention. METHODS: Brain AVM patients evaluated at University of California, San Francisco or Kaiser Permanente Northern California were followed longitudinally. Primary outcome was new ICH after diagnosis; censoring events were any AVM treatment or last follow-up examination. The association of ApoE epsilon2 and epsilon4 genotype with new ICH was evaluated by Kaplan-Meier survival analysis and further characterized via a Cox proportional hazards model. RESULTS: We genotyped 284 brain AVM patients (50% women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a history of new ICH). ApoE epsilon2, but not ApoE epsilon4 genotype, was associated with new ICH (P = 0.0052). ApoE epsilon2 carriers had fivefold increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46-17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and clinical presentation). Subset analysis in the largest homogenous ethnic subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE epsilon2 carriers (hazard ratio, 8.71; 95% confidence interval, 1.4-53.9; P = 0.020; multivariate model adjusting for clinical presentation). CONCLUSION: ApoE genotype may influence the risk of ICH in the natural course of brain AVM. The identification of genetic predictors of ICH risk may facilitate estimation of AVM natural history risk and individualize clinical decision-making and therapeutic recommendations.

Adult↗

PubMed2006

Impact of a piperacillin-tazobactam shortage on antimicrobial prescribing and the rate of vancomycin-resistant enterococci and Clostridium difficile infections.

UNLABELLED: States in 2002 on antimicrobial prescribing and associated rates of vancomycin-resistant enterococci (VRE) and Clostridium difficile infections.Design. Retrospective chart review.Setting. University-affiliated medical center. Measurements and Main Results. Microbiologic reports, patient demographics, and antimicrobial utilization were evaluated for patients admitted 6 months before the shortage (March 1-August 31, 2001) and for 6 months during the shortage (March 1-August 31, 2002). Significant increases in usage of alternative mu-lactamase inhibitor combinations, cefepime, levofloxacin, vancomycin, clindamycin, and metronidazole were observed during the shortage; in contrast, a significant decrease in the use of ceftriaxone took place. No change in the rate of VRE infection was observed from before to during the piperacillin-tazobactam shortage. However, a paradoxical 47% decrease in the rate of C. difficile colitis was documented during the shortage. Subsequent multivariate analyses suggested the reduced use of ceftriaxone and increased use of levofloxacin, but not the reduced use of piperacillin-tazobactam, correlated with the decreased rate of C. difficile infections. CONCLUSION: The piperacillin-tazobactam shortage was associated with significant changes in antimicrobial prescribing, which resulted in a significant reduction in the rate of C. difficile but not VRE infections.

Anti-Bacterial Agents↗

PubMed2005

Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study.

Adult↗

PubMed2005

Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Mutations in endoglin (ENG) and activin-like kinase (ALK1) cause hereditary hemorrhagic telangiectasias, disorders characterized by pulmonary and brain arteriovenous malformations (BAVMs). We investigated whether polymorphisms in these genes are also associated with sporadic BAVM. METHODS: A total of 177 sporadic BAVM patients and 129 controls (all subjects white) were genotyped for 2 variants in ALK1 and 7 variants in ENG. RESULTS: The ALK1 IVS3-35A>G polymorphism was associated with BAVM: (AnyA [AA+AG] genotype: odds ratio, 2.47; 95% CI, 1.38 to 4.44; P=0.002). Two ENG polymorphisms, ENG -1742A>G and ENG 207G>A, showed a trend toward association with BAVM that did not reach statistical significance. CONCLUSIONS: A common polymorphism in ALK1 is associated with sporadic BAVM, suggesting that genetic variation in genes mutated in familial BAVM syndromes may play a role in sporadic BAVMs.

Activin Receptors, Type I↗

PubMed2005

Long-term hemorrhage risk in children versus adults with brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Children with brain arteriovenous malformations (BAVMs) are said to be at higher risk for intracranial hemorrhage (ICH) than adults. Although this notion affects treatment decisions, the evidence to support this claim is limited. METHODS: To compare the risk of ICH in children versus adults with BAVM, we studied all cases of BAVM evaluated at the University of California, San Francisco (January 2000 to December 2004; n=400) and Kaiser Permanente Northern California (January 1993 to December 2004; n=819). In Kaplan-Meier survival analyses, the index date was the date of initial BAVM detection; cases were censored at time of subsequent ICH (the primary outcome, defined as ICH after initial presentation), first BAVM treatment, or loss to follow-up. Cox proportional hazards models included childhood presentation (<20 years old), hemorrhagic presentation, and other potential confounders. RESULTS: Our study included 996 person-years of follow-up in the childhood presentation group and 3260 in the adult presentation group. In the unadjusted survival analysis, the subsequent ICH rates were similar for the 2 age groups (average annual rate 2.0% for children; 2.2% for adults; P=0.82 by log-rank test). BAVMs in childhood were more likely to present initially with ICH (P<0.001). After adjustment for presentation in the multivariate model, subsequent ICH rates were lower in children (hazard ratio, 0.10; 95% CI, 0.01 to 0.86; P=0.036). CONCLUSIONS: Children with BAVMs do not appear to be at increased risk for a subsequent ICH compared with adults, and may even be relatively protected. Confounding by hemorrhagic presentation should be considered in any study comparing BAVM hemorrhage rates in children versus adults.

Adolescent↗

PubMed2005

Association between phonocardiographic third and fourth heart sounds and objective measures of left ventricular function.

CONTEXT: The third (S3) and fourth (S4) heart sounds detected by phonocardiography are considered to represent the criterion standards of the gallop sounds, but their test characteristics have not been explored. OBJECTIVE: To determine the diagnostic test characteristics of the S3 and S4 for prediction of left ventricular dysfunction using a computerized heart sound detection algorithm. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 90 adult patients undergoing elective left-sided heart catheterization at a single US teaching hospital between August 2003 and June 2004. The mean age was 62 (SD, 13) years (range, 24-90 years) and 61 (68%) were male. Within a 4-hour period, participants underwent computerized heart sound phonocardiographic analysis, cardiac catheterization, transthoracic echocardiography, and blood sampling for assessment of an S3/S4, left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP), respectively. MAIN OUTCOME MEASURES: Diagnostic test characteristics of the computerized phonocardiographic S3 and S4 using markers of left ventricular function as criterion standards. RESULTS: Mean (SD) LVEDP was significantly elevated (18.4 [6.9] mm Hg vs 12.1 [7.3] mm Hg; P<.001), mean (SD) LVEF was reduced (49.4% [20.2%] vs 63.6% [14.8%]; P<.001), and median (interquartile range) BNP was elevated (330 [98-1155] pg/mL vs 86 [41-192] pg/mL; P<.001) in those with an S3, S4, or both compared with patients without a diastolic heart sound. The sensitivities of these heart sounds to detect an elevated LVEDP, reduced LVEF, or elevated BNP were 41%, 52%, and 32% for an S3, and 46%, 43%, and 40% for an S4, respectively. For abnormal levels of the same markers of ventricular function, the specificities of the S3 were 92%, 87%, and 92%, while the specificities of the S4 were 80%, 72%, and 78%, respectively. CONCLUSIONS: Neither the phonocardiographic S3 nor the S4 is a sensitive marker of left ventricular dysfunction. The phonocardiographic S3 is specific for left ventricular dysfunction and appears to be superior to the moderate specificity of the phonocardiographic S4.

Adult↗

PubMed2005

Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease.

BACKGROUND: Many cases of end-stage renal disease (ESRD) are ascribed to hypertension. However, because renal disease itself can raise blood pressure, some investigators argue that ESRD seen in patients with hypertension is due to underlying primary renal disease. Previous cohort studies of the relationship between blood pressure and ESRD did not uniformly screen out baseline kidney disease. METHODS: We conducted a historical cohort study among members of Kaiser Permanente of Northern California, a large integrated health care delivery system. The ESRD cases were ascertained by matching with the US Renal Data System registry. RESULTS: A total of 316 675 adult Kaiser members participated in the Multiphasic Health Checkups from 1964 to 1985. All subjects had estimated glomerular filtration rates of 60 mL /min per 1.73 m(2) or higher and negative dipstick urinalysis results for proteinuria or hematuria. During 8 210 431 person-years of follow-up, 1149 cases of ESRD occurred. Compared with subjects with a blood pressure less than 120/80 mm Hg, the adjusted relative risks for developing ESRD were 1.62 (95% confidence interval [CI], 1.27-2.07) for blood pressures of 120 to 129/80 to 84 mm Hg, 1.98 (95% CI, 1.55-2.52) for blood pressures of 130 to 139/85 to 89 mm Hg, 2.59 (95% CI, 2.07-3.25) for blood pressures of 140 to 159/90 to 99 mm Hg, 3.86 (95% CI, 3.00-4.96) for blood pressures of 160 to 179/100 to 109 mm Hg, 3.88 (95% CI, 2.82-5.34) for blood pressures of 180 to 209/110 to 119 mm Hg, and 4.25 (95% CI, 2.63-6.86) for blood pressures of 210/120 mm Hg or higher. Similar associations between blood pressure level and ESRD risk were seen in all subgroup analyses. CONCLUSIONS: Even relatively modest elevation in blood pressure is an independent risk factor for ESRD. The observed relationship does not appear to be due to confounding by clinically evident baseline kidney disease.

Adult↗

PubMed2005

Human T lymphotropic virus type II infection and humoral responses to pneumococcal polysaccharide and tetanus toxoid vaccines.

Infection with human T lymphotropic virus type II (HTLV-II) has been linked to an increased incidence of bacterial pneumonia. To determine whether HTLV-II infection is associated with impaired humoral immune responses, we immunized a cohort of HTLV-II-infected subjects and matched uninfected control subjects with 23-valent pneumococcal polysaccharide and tetanus toxoid vaccines. The pneumococcal polysaccharide vaccine elicited comparable and significant increases in concentrations of IgG against all 5 serotypes tested at 1 and 6 months after immunization in both groups. The avidity and opsonophagocytic functions of the anticapsular IgG were similar. The concentrations of tetanus toxoid-specific IgG also increased comparably and significantly over time in both groups. Thus, HTLV-II-infected persons develop robust humoral responses to potentially protective polysaccharide and protein vaccines.

Adult↗

PubMed2005

Ethics and sample size.

The belief is widespread that studies are unethical if their sample size is not large enough to ensure adequate power. The authors examine how sample size influences the balance that determines the ethical acceptability of a study: the balance between the burdens that participants accept and the clinical or scientific value that a study can be expected to produce. The average projected burden per participant remains constant as the sample size increases, but the projected study value does not increase as rapidly as the sample size if it is assumed to be proportional to power or inversely proportional to confidence interval width. This implies that the value per participant declines as the sample size increases and that smaller studies therefore have more favorable ratios of projected value to participant burden. The ethical treatment of study participants therefore does not require consideration of whether study power is less than the conventional goal of 80% or 90%. Lower power does not make a study unethical. The analysis addresses only ethical acceptability, not optimality; large studies may be desirable for other than ethical reasons.

Bias↗