HIV testing uptake among the household contacts of multidrug-resistant tuberculosis index cases in eight countries.

SETTING: The household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) index cases are at high risk of tuberculous infection and disease progression, particularly if infected with the human immunodeficiency virus (HIV). HIV testing is important for risk assessment and clinical management. METHODS: This was a cross-sectional, multi-country study of adult MDR-TB index cases and HHCs. All adult and child HHCs were offered HIV testing if never tested or if HIV-negative >1 year previously when last tested. We measured HIV testing uptake and used logistic regression to evaluate predictors. RESULTS: A total of 1007 HHCs of 284 index cases were enrolled in eight countries. HIV status was known at enrolment for 226 (22%) HHCs; 39 (4%) were HIV-positive. HIV testing was offered to 769 (98%) of the 781 remaining HHCs; 544 (71%) agreed to testing. Of 535 who were actually tested, 26 (5%) were HIV-infected. HIV testing uptake varied by site (median 86%, range 0-100%; P < 0.0001), and was lower in children aged <18 years than in adults (59% vs. 78%; adjusted for site P < 0.0001). CONCLUSIONS: HIV testing of HHCs of MDR-TB index cases is feasible and high-yield, with 5% testing positive. Reasons for low test uptake among children and at specific sites-including sites with high HIV prevalence-require further study to ensure all persons at risk for HIV are aware of their status.

Effect of fixation time on breast biomarker expression: a controlled study using cell line-derived xenografted (CDX) tumours.

AIMS: Altering the length of time specimens are placed in fixative without compromising analytical testing accuracy is a continuous challenge in the anatomical pathology lab. The aim of this study was to determine under controlled conditions the effects of variable fixation time on breast biomarker expression in human breast cancer cell line-derived xenografted (CDX) tumours. METHODS: CDX tumours using strong oestrogen receptor (ER)-positive, Her2-negative (MCF7) and weak ER-positive, Her2 equivocal (T47D) breast cancer cell lines were fixed for various times ranging from 1 to 336 hours in 10% neutral buffered formalin. CDX tumours were processed according to routine biomarker testing protocols and stained for ER and Her2 immunohistochemistry (IHC) and processed for HER2 fluorescence in situ hybridisation (FISH). The tumours were evaluated using Allred scoring for ER and current ASCO/CAP guidelines for Her2, and by objective cell counting methodology. RESULTS: No differences were found in expression of ER in either MCF7 or T47D CDX tumours under variable fixation. T47D tumours displayed equivocal Her2 staining when fixed for 24 hours, but fixation for ≤8 hours resulted in consistently negative staining while tumours fixed for >72 hours demonstrated consistent equivocal staining (p<0.01). Cell counting assays revealed only a significant increase in sensitivity in tumours fixed for >72 hours (p<0.01). As expected, FISH results were unaffected by variable fixation. CONCLUSIONS: Neither shortened nor prolonged fixation affects ER expression, consistent with previous findings. In equivocal Her2-expressing tumours, however, increasing fixation increased the sensitivity of Her2 IHC reporting while not affecting FISH.

Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide.

Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.

Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean ± SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 ± 1.29 percent). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 ± 4 ng/mL), luteinizing hormone (control: 1.58 ± 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 ± 2.28 ng/mL), estradiol (control: 14.65 ± 3.22 pg/mL), and total testosterone (control: 138.41 ± 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis.

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean +/- SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 +/- 1.29%). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 +/- 4 ng/mL), luteinizing hormone (control: 1.58 +/- 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 +/- 2.28 ng/mL), estradiol (control: 14.65 +/- 3.22 pg/mL), and total testosterone (control: 138.41 +/- 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery.

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine from healthy volunteers, added protease inhibitors, and stored urine samples at 4, -20, and -80 degrees C for 1 week or 7 months. Samples were thawed with and without extensive vortexing, and three fractions were isolated: urinary sediment, supernatant, and exosome fraction. Protein concentration, electrophoresis patterns, and abundance of seven exosome-associated proteins were measured. Exosome-associated proteins were not detected in sediment or supernatant fractions. Protease inhibitors prevented degradation of exosome-associated proteins. Freezing at -20 degrees C caused a major loss in exosomes compared to fresh urine. In contrast, recovery after freezing at -80 degrees C was almost complete. Extensive vortexing after thawing markedly increased exosome recovery in urine frozen at -20 or -80 degrees C, even if frozen for 7 months. The recovery from first and second morning urine was similar. The abundance of cytosolic exosome-associated proteins did not decrease during long-term storage. We concluded: (1) protease inhibitors are essential for preservation; (2) storage at -80 degrees C with extensive vortexing after thawing maximizes the recovery of urinary exosomes; (3) the difference between first and second morning urine exosome-associated protein was small, suggesting minimal protein degradation in the urinary tract/bladder; (4) urinary exosomes remain intact during long-term storage. These urine collection, storage, and processing conditions may be useful for future biomarker discovery efforts.

Viral induction of central nervous system innate immune responses.

The ability of the central nervous system (CNS) to generate innate immune responses was investigated in an in vitro model of CNS infection. Cultures containing CNS cells were infected with mouse hepatitis virus-JHM, which causes fatal encephalitis in mice. Immunostaining indicated that viral infection had a limited effect on culture characteristics, overall cell survival, or cell morphology at the early postinfection times studied. Results from Affymetrix gene array analysis, assessed on RNA isolated from virally and sham-infected cultures, were compared with parallel protein assays for cytokine, chemokine, and cell surface markers. Of the 126 transcripts found to be differentially expressed between viral and sham infections, the majority were related to immunological responses. Virally induced increases in interleukin-6 and tumor necrosis factor alpha mRNA and protein expression correlated with the genomic induction of acute-phase proteins. Genomic and protein analysis indicated that viral infection resulted in prominent expression of neutrophil and macrophage chemotactic proteins. In addition, mRNA expression of nonclassical class I molecules H2-T10, -T17, -M2, and -Q10, were enhanced three- to fivefold in virus-infected cells compared to sham-infected cells. Thus, upon infection, resident brain cells induced a breadth of innate immune responses that could be vital in directing the outcome of the infection and, in vivo, would provide signals which would summon the peripheral immune system to respond to the infection. Further understanding of how these innate responses participate in immune protection or immunopathology in the CNS will be critical in efforts to intervene in severe encephalitis.

Validity of transabdominal sonography in the detection of a two-vessel umbilical cord.

OBJECTIVE: To determine the validity of transabdominal ultrasound in the detection of a two-vessel and a three-vessel umbilical cord. METHODS: The ultrasound and pathology databases were collated between January 1, 1999, and December 31, 2000. Only those cases with ultrasound and pathology information concerning the number of vessels in the umbilical cord were included for analysis (group 1). In addition, 27 cases with a two-vessel umbilical cord were included from the ultrasound database before January 1, 1999, for which pathologic information was also obtained (group 2). RESULTS: A total of 1295 ultrasound/pathology reports were entered from January 1, 1999, through December 31, 2000; 268 cases did not have complete information, leaving 1027 for analysis (group 1). The visualization rate of the number of vessels in the umbilical cord increased from 15 to 17 weeks' gestation (74.1-97.6%; P <.001). The visualization rate remained stable from 17.0 to 35.9 weeks' gestation, and then declined to 83.3% (P <.01). The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of a two-vessel umbilical cord were 85%, 99.7%, 85%, and 99.7%, respectively. CONCLUSION: The detection rate of either a two-vessel or three-vessel umbilical cord is best achieved between 17 and 36 weeks' gestation. In the majority of two-vessel umbilical cords that were called three-vessel, an appropriate transverse image of the umbilical cord was not obtained.

Determinación de anticuerpos IgM contra el virus dengue a partir de sangre absorbida en papel filtro: un método alternativo y sencillo / Determination of IgM antobodies for dengue virus from blood absorbed in filter paper: an alternative and simple method

Objetivo: Se propone como alternativa la obtención de muestras de sangre total en papel filtro, para la determinación de anticuerpos IgM contr dengue, por ser un método de recolección sencillo y no requerir de muchos cuidados en el envío al laboratorio. Materiales y métodos: De 100 pacientes con diagnóstico clínico de dengue clásico, se obtuvieron en forma simultánea, muestras de suero en tubos al vacío y de sangre total en papel filtro. Ambas muestras fueron evaluadas con el método serológioco ELISA Captura de IgM a los 30 días de obtenida la muestra. Resultados: De las 100 muestras 25 fueron positivas y 75 negativas en suero, 24 positivas y 74 negativas en papel filtro. Se obtuvo una concordancia por índice Kappa de 0,97, sensibilidad y especificidad de 96,0 y 98,0 respectivamente, el valor predictivo positivo fue 96,0, y valor predictivo negativo fue 98,0. Conclusión: Se evidencia muy buena sensibilidad, específicidad y concordancia en la determinación de IgM contra el dengue, al utilizar papel filtro en la obtención de muestra de sangre

Implementing a syphilis elimination and importation control strategy in a low-incidence urban area: San Diego County, California, 1997-1998.

OBJECTIVES: This study assessed a strategy designed to contain imported cases of syphilis and prevent reestablishment of ongoing transmission. METHODS: Reported syphilis cases during an endemic period (1990-1992) and an elimination period (1997-1998) were compared in San Diego, Calif. The elimination strategy, which focuses on rapid reporting of infectious syphilis cases by clinicians, prompt partner and sexual network management, outreach to marginalized populations, and implementation of an outbreak containment plan, was evaluated. RESULTS: Infectious syphilis incidence rates declined from 18.3 per 100,000 in 1998 to 1.0 per 100,000 in 1998. Of the 46 cases involving probable infection during 1997-1998, 19 (41%) were imported, mostly (79%) from Mexico. Outbreak containment procedures were implemented successfully for 2 small clusters. Outreach workers provided sexually transmitted disease information to a large number of individuals; however, no cases of infectious syphilis were identified, suggesting that syphilis transmission was not occurring among marginalized groups. CONCLUSIONS: This syphilis elimination and importation control strategy will require monitoring and adjustments. Controlling syphilis along the US-Mexico border is a necessary component of syphilis elimination in the United States.

Determinación de Anticuerpos IgM contra Virus dengue partir de sangre absorbida en papel filtro: Un método alternativo y sencillo

Objetivo: Se propone como alternativa la obtención de muestras de sangre total en papel filtro, para la determinación de anticuerpos IgM contra dengue, por ser un método de recolección sencillo y no requerir de muchos cuidados en el envío al laboratorio. Materiales y métodos: De 100 pacientes con diagnóstico clínico de dengue clásico, se obtuvieron en forma simultánea, muestras de suero en tubos al vacío y de sangre total en papel filtro. Ambas muestras fueron evaluadas con el método serológico ELISA Captura de IgM a los 30 días de obtenida la muestra. Resultados: De las 100 muestras 25 fueron positivas y 75 negativas en suero, y 24 positivas y 74 negativas en papel filtro. Se obtuvo una concordancia por índice Kappa de 0,97, sensibilidad y especificidad de 96,0% y 98,0% respectivamente; el valor predictivo positivo fue 96,0%, y valor predictivo negativo fue 98,0%. Conclusión: Se evidencia muy buena sensibilidad, especificidad y concordancia en la determinación de IgM contra dengue, al utilizar papel filtro en la obtención de muestra de sangre.

Objective: This study proposes the use of filter paper, in whole blood samples to test for Dengue, as an alternate method, due to the fact that it is very simple and does not require of much detail for shipping samples to the laboratory. Materials and Methods: Using vacutainers and filter papers, whole blood sample obtained simultaneously from 100 patients diagnosed as classic dengue. All samples were tested using IgM capture ELISA. Findings: Out of 100 samples, 25 were positive and 75 were negative in sera, in filter paper 24 positive and 74 negative, with a Kappa concordance index of 0,97 and a sensitivity and specificity of 96,0% and 98,0% respectively: the positive predictive value was 96.0% and the negative predictive value was 98,0%. Conclusions: A very good sensitivity, specificity and concordance in the determination of IgM antibodies against Dengue is evidenced using filter paper when obtaining blood samples.

Isradipine blocks cocaine's ability to facilitate pressing for intracranial stimulation.

Using rats pressing for rewarding electrical intracranial stimulation of the medial forebrain bundle, it was found that a single administration of isradipine blocked the rate-enhancing effects of cocaine (5.0 mg/kg) at doses of 3.0 and 10.0 mg/kg. Also, when isradipine (3.0 mg/kg) was administered alone (without cocaine) for 5 consecutive days, pressing for intracranial stimulation was not reduced relative to placebo levels. In another experiment, isradipine (3.0 mg/kg) persistently blocked the rate-enhancing effects of cocaine (5.0 mg/kg) across 5 consecutive days. These results support the continued investigation of isradipine as a useful adjunct to other treatments for cocaine addiction.

[Electroencephalographic changes in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency]. / Alterações eletrencefalográficas em pacientes com hiperplasia supra-renal congênita secundária à deficiência da 21-hidroxilase.

Electroencephalographic changes have been detected in children with premature pubarche. These findings might be the result from past or current central nervous system dysfunction, or from increased sex steroids. In order to test the last assertion we have performed electroencephalographic studies in 10 patients (7F, 3M) with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, of whom 4 classic and 6 nonclassic forms of the syndrome. Traditional neurologic examination was performed in 7 patients, the result being considered normal in everyone, while evolutional neurologic examination detected hyperactive disturbance and attention deficit in two patients. In another patient, the clinical findings were compatible with delay of neuropsychomotor development. Quantitative electroencephalography with brain mapping in patients over three years-old (n = 9), and conventional EEG in the remaining patient, were considered abnormal for age in 8 patients (80%), the record being characterized as slow in 7 patients. The high rate of electroencephalographic changes in this sample, as well as in premature pubarche, suggests that these findings might result from high inappropriate for age androgenic levels, and warns about the importance of neurologic examination and follow-up in children with CAH.

Conocimientos y comportamientos acerca del SIDA alumnos de quinto y sexto bachillerato Medellín 1990 y 1991 / Knowledge and behavior about AIDS. Fifth and sixth grade high school students. Medellín, 1990 and 1991

La infección por el virus VIH es uno de los grandes problemas de salud de nuestro tiempo que cada día afecta a más personas sin que haya solución para ofrecer. La principal arma con la que se cuenta es la educación, por lo que debemos conocer los conceptos previos de la población y así orientar la enseñanza. Puesto que quienes componen los grupos de riesgo en su mayoría son adolescentes, este estudio se propuso averiguar la información y el comportamiento de ellos acerca de la enfermedad...

Reassessment of the clinical significance of periodic lateralized epileptiform discharges in pediatric patients.

A review of clinical data from 18 pediatric patients with periodic lateralized epileptiform discharges and bilateral independent periodic lateralized epileptiform discharges (PLEDs and BIPLEDs) showed 2 with chronic neurologic illness, 6 with a history of prior seizures, 14 with depressed sensorium at the time of EEG, 5 deaths, and 8 of 13 survivors with neurologic deficits. These findings are similar to the combined data from reports involving adult patients only. Separating pediatric patients with PLEDs from those with BIPLEDs shows some influence from patients with BIPLEDs. Overall, our data do not suggest significant clinical differences for PLEDs between children and adults.

Defining the role of structural lesions and metabolic abnormalities in periodic lateralized epileptiform discharges.

We reviewed the EEG, clinical manifestations, computed tomography (CT) and magnetic resonance imaging (MRI) scans of 39 patients with periodic lateralized epileptiform discharges (PLEDs) or bilateral periodic lateralized epileptiform discharges (BIPLEDs) to determine the role of structural lesions (SL) and metabolic abnormalities (MA) in their pathogenesis. Thirty-eight patients had CT and 7 had MRI scans. Thirty-eight had lesions on CT or MRI. All those with PLEDs consistently had lesions on the side of the discharges, and 5 of 6 with BIPLEDs had lesions on both hemispheres. A subgroup of 23 patients with metabolic determination within 24 h of EEG all showed mild to moderate MA. They all also had SL. These findings support a primary role for SL but cannot exclude an additional role for MA.