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Characterization of the viral population during primary HIV-1 infection.

OBJECTIVE: To study viral heterogeneity at a very early phase of primary HIV-1 infection. DESIGN: Samples were drawn very early during primary HIV-1 infection. A virus population-based approach was used to study the viral heterogeneity in the C2-V3 and p17 regions. METHODS: Plasma samples (n = 33) were obtained before or shortly after onset of acute symptoms in 15 patients. In all subjects, the first sample was drawn within 10 days after onset of symptoms. Peripheral blood mononuclear cells (PBMC) were available in two patients. The number of polymorphic sites in the C2-V3 (15 patients) and p17 regions (eight patients) were determined by direct sequencing. RESULTS: The sequence heterogeneity was restricted in most patients, although only two out of 15 patients had a completely homogeneous C2-V3 sequence. However, pronounced individual differences were seen. Rapid sequence changes occurred during the first month in two patients. In one patient, the major DNA species at day 12 later became the major species in plasma. CONCLUSIONS: The viral population is seldom completely homogeneous during primary HIV-1 infection, although the heterogeneity is restricted in most, but not all, patients. These individual differences do not seem to be due to sex or viral subtype. Rapid changes of the virus population may occur during primary HIV-1 infection. The DNA species detected in PBMC do not only represent earlier viral quasispecies but are also a potential source of future viral RNA species.

Base Sequence↗

Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir.

OBJECTIVE: Although most uninfected infants born to women infected with HIV-1 show no clinical evidence of mitochondrial compromise, mitochondrial dysfunction has been reported in children born to women receiving zidovudine and/or lamivudine during pregnancy. In this pilot study we examined mitochondrial integrity in HIV-1-uninfected infants born to HIV-1-infected women receiving Combivir during pregnancy. DESIGN: : Samples of umbilical cord and cord blood were obtained from HIV-1-uninfected infants born to either HIV-1-infected women receiving Combivir therapy during pregnancy (n = 10) or HIV-1-uninfected women (n = 9). METHODS: Mitochondrial morphological integrity was examined in umbilical cords (n = 16) by electron microscopy and mtDNA quantity was determined in DNA from cord blood (n = 18) and umbilical cord (n = 18) by PCR-chemiluminescence immunoassay detection. RESULTS: In umbilical cords from six of nine infants born to HIV-1-infected mothers taking Combivir moderate to severe mitochondrial morphological damage was observed (P = 0.011), while none of seven unexposed infants showed similar damage. Compared to unexposed infants, statistically significant mtDNA depletion was observed in umbilical cord (P = 0.006) and cord blood (P = 0.003) from drug-exposed infants. CONCLUSIONS: A cohort of HIV-1-uninfected Combivir-exposed infants with no clinical symptoms showed morphological and molecular evidence of mitochondrial damage.

Anti-HIV Agents↗

Pediatric risk of mortality: an assessment of its performance in a sample of 26 Italian intensive care units.

OBJECTIVE: To assess the validity of the Pediatric Risk of Mortality (PRISM) scoring system in accurately predicting the probability of mortality in an Italian intensive care unit (ICU) sample. DESIGN: Prospective, observational, multicenter study. SETTING: Twenty-six Italian ICUs classified into two groups: a) ICUs specifically dedicated to treating pediatric patients; and b) adult ICUs treating children on a regular basis. PATIENTS: Consecutive patients (n = 1,533) <15 yrs of age admitted during 1 yr. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To assess the performance of the PRISM scoring system, the discrimination and calibration measures were adopted both in the whole population and in 12 preselected subgroups. A good discrimination capability of the scoring system was observed for both the whole population and subgroups (areas under the receiver operating characteristic curves were never <0.82). On the other hand, we documented an unsatisfactory calibration capability in the whole population and in most subgroups (p values of the Hosmer-Lemeshow goodness-of-fit test were <.001 in all but two subgroups). CONCLUSIONS: The analyses suggest that the unsatisfactory calibration of PRISM can be attributed to various reasons. Among those reasons, a poor performance of the system, as well as its sensitivity to factors not connected to clinical ICU performance, seem particularly important. A special caution is needed in adopting a severity of illness scoring system to assess quality of care, particularly in contexts different from the one in which the instrument was originally developed.

Adolescent↗

Identification of neonatal hearing impairment: hearing status at 8 to 12 months corrected age using a visual reinforcement audiometry protocol.

OBJECTIVES: 1) To describe the hearing status of the at-risk infants in the National Institutes of Health-Identification of Neonatal Hearing Impairment study sample at 8 to 12 mo corrected age (chronologic age adjusted for prematurity). 2) To describe the visual reinforcement audiometry (VRA) protocol that was used to obtain monaural behavioral data for the sample. DESIGN: All neonatal intensive care unit infants and well babies with risk factors (including well babies who failed neonatal tests) were targeted for follow-up behavioral evaluation once they had reached 8 mo corrected age. Three thousand one hundred and thirty-four (64.4%) of the 4868 surviving infants returned for at least one behavioral hearing evaluation, which employed a well-defined VRA protocol. VRA thresholds or minimum response levels (MRLs) were determined for speech and pure tones of 1.0, 2.0, and 4.0 kHz for each ear using insert earphones. RESULTS: More than 95% of the infants were reliably tested with the VRA protocol; 90% provided complete tests (four MRLs for both ears). Ninety-four percent of the at-risk infants were found to have normal hearing sensitivity (MRLs of 20 dB HL) at 1.0, 2.0, and 4.0 kHz in both ears. Of the infants, 2.2% had bilateral hearing impairment, and 3.4% had impairment in one ear only. More than 80% of the impaired ears had losses of mild-to-moderate degree. CONCLUSIONS: This may be the largest study to attempt to follow all at-risk infants with behavioral audiometric testing, regardless of screening outcome, in an effort to validate the results of auditory brain stem response, distortion product otoacoustic emission, and transient evoked otoacoustic emission testing in the newborn period. It is one of only a few studies to report hearing status of infants at 1 yr of age, using VRA on a clinical population. Successful testing of more than 95% of the infants who returned for the VRA follow-up documents the feasibility of obtaining monaural behavioral data in this population.

Age Factors↗

Neuropeptide Y-like immunoreactivity and hypertension.

OBJECTIVE: Neuropeptide Y is a co-transmitter with noradrenaline in sympathetic neurons supplying arteries and veins with potent contractile effects. To investigate the role of neuropeptide Y in hypertension, we measured the circulating levels of neuropeptide Y and noradrenaline in patients with severe hypertension. DESIGN: Samples were collected from patients with untreated, severe hypertension (diastolic blood pressure > 120 mmHg) and in age- and sex-matched controls. After treatment with beta-adrenoceptor blockers, diuretics, angiotensin converting enzyme inhibitors of calcium antagonists, samples were taken from the patients during 12 months. METHODS: The circulating levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured with a radioimmunoassay using a rabbit antiserum. Catecholamines were measured using high-performance liquid chromatography and electrochemical detection. RESULTS: There was a significantly higher level of NPY-LI in the patients when they were compared with the controls. However, there was no correlation either in the controls or in the hypertensives between systolic blood pressure, diastolic blood pressure and NPY-LI or noradrenaline. The increased level of NPY-LI in plasma remained elevated for up to 12 months despite reduction in blood pressure to acceptable levels. The noradrenaline level was not increased before treatment, after 2-4 weeks or after 2-12 months treatment. CONCLUSION: The high level of NPY-LI may represent a marker for higher activity of the sympathetic nervous system which is not controlled by the treatment of blood pressure to normotension.

Acute Disease↗

A polymorphism in the gene for the angiotensin II type 1 receptor is not associated with hypertension.

BACKGROUND: A mutation in the gene for the angiotensin II type 1 (AT1) receptor (A1166C) has been reported to be associated with primary hypertension. OBJECTIVE: To determine whether this observation could be confirmed with a different population sample. DESIGN: We examined 414 individuals with primary hypertension and 172 normotensive controls. METHODS: The mutation in the gene for the AT1 receptor was detected using restriction polymerase chain reaction. CONCLUSIONS: We detected no association of the AT1 receptor polymorphism with hypertension, but a trend towards a decreased prevalence of the 1166C allele among hypertensive patients with a late age at diagnosis (> or = 50 years) was observed.

Adult↗

Effects of time in the United States and Indian ethnicity on DSM-III-R psychiatric disorders among Mexican Americans in California.

The study examines the effects of time in the United States and Indian ethnicity on prevalence of 12 DSM-III-R psychiatric disorders among Mexican Americans in California. In Fresno County, primarily an agricultural area, 3012 participants of Mexican origin (18 to 59 years) were selected under a cluster sampling design and interviewed using a version of the World Health Organization's Composite International Diagnostic Instrument (WHO-CIDI). Lifetime prevalence of any psychiatric disorder was 46.4% for Indians and 32.9% for non-Indians. Alcohol dependence was the most prevalent disorder (Indians = 17.4%, non-Indians = 10.7%). Indians had significantly higher risk of affective disorders (adjusted OR = 2.9) and drug abuse/dependence (adjusted OR = 2.6) compared with non-Indians. Time in the United States was associated with higher risk of lifetime affective disorders and drug abuse/dependence. This effect was more pronounced among Indians. Mexican immigrants are ethnically heterogenous and Indians appear to be more vulnerable to negative effects of exposure to U.S. society.

Acculturation↗

A review of weight loss programs delivered via the Internet.

The escalating obesity epidemic has prompted healthcare professionals to seek interventions that can reach large numbers of individuals in a timely and cost-effective manner. The Internet, with its growing audience, seems an obvious solution. Commercial weight loss programs already abound on the Internet. The purpose of this review is to describe the efficacy of weight loss programs delivered via the Internet in the United States. A search for clinical trials evaluating weight loss via Internet programs was conducted using PubMed, CINAHL, Cochrane Library, Academic Search Premier, the National Institutes of Health Clinical Trials Database, and the Internet as well as a cross-check of reference lists. Eight published studies that met the inclusion criteria were reviewed. Data were extracted on study design, sample characteristics, attrition, weight loss, duration of treatment, and maintenance of weight loss. Of the 8 studies, 3 evaluated the Internet as a means to maintain long-term weight loss. All studies examining weight loss via Internet programs reported positive results, except for one investigating a commercial program. Results from the 3 weight loss maintenance programs conducted on the Internet were equivocal. Because the subjects of all these studies were predominately white, educated women, generalization of findings is limited. Data from the reviewed studies suggest that the Internet may be an alternative to traditional face-to-face weight loss programs. Questions still remain as to the efficacy of using the Internet for long-term weight loss maintenance. Findings from these studies provide beginning guidelines for healthcare providers who may choose to use Internet-based weight loss interventions. Future research is still needed to determine the applicability of such interventions in diverse age, ethnic, and socioeconomic groups.

Adult↗

A comparison of response error by adolescents and adults: findings from a health care study.

OBJECTIVES: Most assessments of response error have focused only on reports by adult respondents; we know little about the propensity to misreport or the magnitude or direction of response error for self-reports by adolescents. To the extent that adults and adolescents differ in the magnitude or direction of response error, comparisons between adults and adolescents will be confounded. This study compares the quality of self-response among adolescents and adults in their reporting of health conditions and health care utilization. METHODS: Approximately 2,000 members of an HMO were interviewed, and by use of medical record information, the accuracy of their responses was assessed for several measures: number of outpatient visits, date of the most recent outpatient visit, site of care, type of professional seen during the last visit, and an indicator as to whether the respondent had asthma. RESULTS: The findings indicate that both the magnitude and the direction of response error vary by the age of the respondent. In multivariate models predicting erroneous response, adolescents were more likely to misreport than were adult respondents. In addition, among erroneous respondents, adolescents tended to err in the direction of overreporting, whereas adult respondents tended to err in the direction of underreporting. CONCLUSIONS: Although the results should be viewed cautiously because of limitations in both the sample design and the survey topic, the findings suggest that substantive comparisons of health care utilization between adolescents and adults may be confounded by differential measurement error.

Adolescent↗

Social and professional support for pregnant and parenting women.

PURPOSE: A literature review to contrast the role of social and professional support in improving maternal and infant outcomes in pregnant and parenting women. In addition, recommendations are made for future research and policy and program development concerning support needed by pregnant and parenting women. DATA SOURCES: Data were limited to published studies. Searches of computerized databases, hand searches of journals, and backward searches from reference lists of studies were conducted. Nursing, medicine, psychology, public health, sociology, and social work literatures were searched (CINAHL, Medline, PsychLit, Social Sciences Abstracts, Social Sciences Citation, and Social Work Abstracts). STUDY SELECTION: The studies focused on outcomes of social support and professional support to pregnant and parenting women. The samples of the studies included pregnant women and parenting women up to 2 years postpartum. Studies reviewed were conducted in the United States or Canada and included maternal and/or infant outcomes. All ages and races of pregnant and parenting women were considered. DATA EXTRACTION: Data were extracted from each study concerning the theoretical framework, variables, sample, design, measuring instruments, interventions, and outcomes. DATA SYNTHESIS: Social support outcomes were summarized in paragraphs while a table was used to summarize professional support intervention outcomes. CONCLUSIONS: Outcomes associated with specific support interventions should be clearly identified, informed by theory, and include assisting the pregnant and parenting woman to improve her social support.

Clinical Competence↗

A statistical analysis of Modified Clinical Technique vision screening of preschoolers by optometry students.

Fourth year optometry students screened 745 preschoolers using a slightly altered Modified Clinical Technique (MCT) under the supervision of a faculty doctor. Children who failed the MCT were randomly selected and then matched by age, sex, and ethnic origin to children who had passed the screening battery. The 61 screening failures and 45 matched controls were later given full eye examinations with cycloplegia by University of Alabama at Birmingham faculty doctors who were unaware of the screening results. The positive predictive value (PPV) (0.52) and negative predictive value (NPV) (0.78) of the MCT were calculated directly from the 2 x 2 contingency table crossing screening results and a standard diagnosis. Sensitivity [0.50, k(1,0) = 0.29], specificity [0.79, k(0,0) = 0.30], efficiency [0.70, k(0.5,0) = 0.29] of the MCT, and the prevalence (0.30) of children failing the standard diagnosis were estimated using statistics appropriate to the prospective sampling design. The reproducibility of the diagnosis, estimated by analyzing multiple, independent diagnosis of each study child by seven doctors was moderate (kappa D 0.58). Statistics summarizing the agreement between the MCT and the diagnosis by the individual study doctor are similar to those obtained with comparison to the standard diagnosis. The characteristics of the MCT may be generalized only to similar populations that are screened by clinicians with similar experience, using the same tests.

Child↗

Pain and hip fracture outcomes for older adults.

PURPOSE: To determine if postoperative pain is a predictor of functional outcomes for elderly hip fracture patients who were previously independent ambulators (with or without assistive device). DESIGN: Prospective comparative survey design. SAMPLE: Convenience sample. 85 hip fracture patients age 65 years or older from two Midwestern urban hospital orthopaedic units. METHODS: Subjects were interviewed between day 2 and 5 (M = 2.6) postoperatively and again 2 months postoperatively. Independent variables of cognitive status and pain status were measured using the Folstein Mini Mental State Exam (MMSE) and two pain measures, the Verbal Descriptor Scale (VDS) and Ferrell's Pain Experience Interview (FPEI). The dependent variable, functional outcome, was measured using the degree of assistance required for basic ADLs from Jette's Functional Status Index (FSI). FINDINGS: Pain with movement was significantly higher than pain at rest (p < .0001). Mental status, pain report with movement (during hospital interview), illness severity, and age accounted for 51% of the variance in functional outcomes 2 months postoperatively. CONCLUSIONS: Undertreated postoperative pain contributes to poor functional outcomes. IMPLICATIONS FOR NURSING PRACTICE: Pain assessment of postoperative older patients should be conducted during movement. Efforts to reduce postoperative pain severity in the immediate postoperative period may yield better functional outcomes months later.

Activities of Daily Living↗

Postoperative pain management in frail older adults.

PURPOSE: To evaluate the Frail Elder Pain Management Program (FEPMP) implemented for patients who had hip fracture repairs at a community hospital in 1995. Based on standards of geriatric and pain management practice, the FEPMP included education sessions, preprinted analgesic orders, pain flow sheets, written resources, and clinical support. A Logic Model reflected the program's conceptualization. DESIGN: Preexperimental pretest and posttest design. SAMPLE: A random sample of 50 charts of patients aged 75 and older who had hip fracture repairs were audited from each of two periods: the preimplementation period (1994-95) and the postimplementation period (1997-98). METHODS: A chart audit tool was developed, tested, and used. Data were analyzed using descriptive, parametric and nonparametric statistics. FINDINGS: Surgeons' prescriptions and nurses' pain management practices improved significantly (p = .0001). Pain assessment modestly improved. Patient outcomes also improved. IMPLICATIONS FOR PRACTICE AND EDUCATION: A programmatic approach to pain management is effective for improving practice and outcomes for frail elders.

Aged↗

A population-based survey of Haemophilus influenzae type b nasopharyngeal carriage prevalence in Lombok Island, Indonesia.

BACKGROUND: The Haemophilus influenzae type b (Hib) nasopharyngeal carriage prevalence and invasive disease incidence rates are unknown in Indonesia; consequently Hib vaccine is not included in the routine vaccine schedule. METHODS: To determine carriage prevalence we conducted a population-based, island-wide prospective study of a systematic sample of 484 children 0 to 2 years of age in Lombok, Indonesia. We conducted a risk factor questionnaire and determined serotypes and antibiotic sensitivity patterns. RESULTS: We identified 155 H. influenzae isolates, of which 22 were type b and 12 were encapsulated but not type b. The age- and population-weighted Hib carriage prevalence, adjusted for the sampling design, was 4.6% (95% confidence interval, 3.7 to 5.5%). Children younger than 6 months of age had a carriage prevalence less than one-half that of older children, and carriage varied within the four administrative regions of the island; otherwise no risk factors for Hib carriage were identified. All Hib specimens were sensitive to ampicillin and 20 (91%) were sensitive to chloramphenicol. CONCLUSIONS: The Hib carriage prevalence in Lombok is similar to that found in developed countries before vaccine introduction. This suggests that further studies should proceed to determine whether Lombok has invasive disease rates as high as those that justified vaccine introduction in developed countries.

Carrier State↗

Comparison of two rapid Streptococcus pyogenes diagnostic tests with a rigorous culture standard.

BACKGROUND: Comparisons of rapid antigen tests for the diagnosis of pharyngitis are often made between published studies but may not be reliable given differences in study design, sampling and reference standard definitions. Tests are rarely compared against each other in a single study. METHODS: The sensitivity and specificity of two rapid diagnostic tests were compared against a multiplate culture standard defined as the identification of on any of four culture plates. Paired swabs were tested for antigen using Genzyme's OSOM Ultra Strep A Test and compared with Biostar's Strep A OIA Max Test. RESULTS: Ninety-four (31.1%) of 302 matched samples were identified with The sensitivity of Genzyme's OSOM Ultra Strep A Test against the multiplate culture standard was 92.6%, significantly higher ( P= 0.001) than that (75.5%) of Biostar's Strep A OIA Max Test. Specificities were 92.8 and 97.1%, respectively. Data analysis of culture results and statistical modeling showed that cultures of two or more samples are necessary for a sensitivity of 95% or greater for a comparison standard compared with true disease status. CONCLUSIONS: When comparing the performance of rapid antigen tests for pharyngitis, a rigorous culture standard should be used consisting of at least two separate samples (swabs and/or pledgets), ultimately plated on selective agar. Genzyme's OSOM Ultra Strep A Test was significantly more sensitive than Biostar's Strep A OIA Max Test in comparison with a multiplate culture standard and a same swab, single plate culture standard.

Antigens, Bacterial↗

Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic pancreatitis.

In an attempt to study the mechanisms leading to fibrosis in chronic pancreatitis, an in situ immunohistochemical investigation of lymphocytes and of class II major histocompatibility complex expression (HLA-DR) by epithelial cells has been designed. Samples of normal pancreas (n = 8), chronic calcifying pancreatitis (n = 4), chronic obstructive pancreatitis (n = 6), and diffuse fibrosing pancreatitis (n = 6) have been studied. In normal pancreas, T-lymphocytes were rare and were located in the epithelial layer of pancreatic ducts and in the periductal connective tissue. Duct cells were constantly HLA-DR negative. In chronic calcifying pancreatitis and chronic obstructive pancreatitis, T cells were numerous and were located around ducts and in the spreading areas of fibrous septa. In chronic obstructive pancreatitis, the duct cells strongly expressed the HLA-DR antigen. In diffuse fibrosing pancreatitis, fibrous tissue was devoid of lymphocytes and duct cells never expressed the HLA class II antigen. These results suggest that lymphocytes are involved in the fibrosing process occurring in chronic calcifying pancreatitis and chronic obstructive pancreatitis but not in diffuse fibrosing pancreatitis. The significance of de novo expression of HLA-DR antigen by duct cells is discussed.

Adult↗

Diagnosis of male Chlamydia trachomatis urethritis by polymerase chain reaction.

BACKGROUND AND OBJECTIVES: A quick and highly sensitive diagnostic test would be valuable in the diagnosis of Chlamydia trachomatis. GOAL OF THIS STUDY: We compared a new polymerase chain reaction (PCR) technique to Chlamydiazyme (Abbott, North Chicago, IL) in the detection of male chlamydial urethritis, and evaluated the performance of PCR on urine samples. STUDY DESIGN: Urethral samples for analysis by PCR and Chlamydiazyme were obtained from 474 unselected patients attending a sexually transmitted diseases (STD) clinic. Urine samples were analyzed by PCR from 362 of these patients. RESULTS: Twenty seven (5.7%) urethral samples were positive by Chlamydiazyme, while 64 (13.5%) were positive by PCR. After resolution of discrepant results, the sensitivity of PCR on urethral swabs was 98.4% and the specificity was 99.0%, with positive and negative predictive values of 93.8% and 99.8%, respectively. These same measures for Chlamydiazyme were 43.5%, 100%, 100%, and 92.2%, respectively. The sensitivity of PCR on urine samples was 87.1%, the specificity was 98.0%, and the positive and negative predictive values were 90.0% and 97.4%, respectively. CONCLUSIONS: This PCR test is more sensitive than Chlamydiazyme in detecting male urethral chlamydial infections in an STD clinic population, and appears to be equally efficacious on urethral swabs and urine samples.

Chlamydia Infections↗

Curable sexually transmitted infections among the clientele of a family planning clinic in Istanbul, Turkey.

BACKGROUND: Integrating screening and treatment of sexually transmitted infections into existing family planning programs can be a good way to fight this problem. Also, the number of studies on the prevalence of certain sexually transmitted infections in this population in Turkey is limited. GOAL: To find out the prevalence of the most common sexually transmitted infections among the clients of an urban family planning clinic and to evaluate demographic characteristics and clinical signs related to sexually transmitted infections. STUDY DESIGN: Samples for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis were collected from 569 women who attended the clinic from December 15, 1997 to March 31, 1998. RESULTS: No case of N gonorrhoeae was found among the samples. The prevalence of C trachomatis infection was 1.9%, whereas the prevalence of of T vaginalis was 2.6%. None of the demographic characteristics or clinical signs was related to these infections. CONCLUSION: Larger studies using more sensitive laboratory tests are needed to determine the prevalence of chlamydial infections in family planning clinics in Turkey.

Adult↗