Risk of dengue virus infection according to serostatus in individuals from dengue endemic areas of Mexico.

The variability in the host immune response directed against dengue virus (DENV) has demonstrated the need to understand the immune response associated with protection in incident infection. The objective was to estimate the association between serostatus and the risk of incident DENV infection. We used a prospective study from 2014 to 2016 in the localities of Axochiapan and Tepalcingo, Morelos, Mexico. We recruited 966 participants, of which, according to their infection history registered were categorized in four groups. To accomplish the objectives of this study, we selected to 400 participants older than 5 years of age were followed for 2.5 years. Blood samples were taken every 6 months to measure serological status and infection by ELISA. In individuals with at least two previous infections the risk of new infection was lower compared to a seronegative group (hazard ratio adjusted 0.49, 95% CI 0.24-0.98), adjusted for age and locality. Therefore, individuals who have been exposed two times or more to a DENV infection have a lower risk of re-infection, thus showing the role of cross-immunity and its association with protection.

Spatiotemporal dynamics of human leptospirosis and its relationship with rainfall anomalies in Colombia.

Background: In Colombia, human leptospirosis (HL) is a disease that has had a mandatory notification rule since 2007. Humans usually acquire the infection through water contaminated with animal urine that comes into direct contact with cutaneous lesions, eyes or mucous membranes. Objectives: To analyze the spatiotemporal variability in the occurrence of HL cases in Colombia between 2007 and 2016, and its relation with the El Niño Southern Oscillation (ENSO) cycle and the consequent anomalies in rainfall in spatiotemporal clusters. Methods: An ecological study of the HL cases, aggregated by municipality, and reported between 2007 and 2016, is presented. Findings: During the period of study, 9928 cases of HL were reported, and 58.9% of the municipalities reported at least one case of leptospirosis. Six spatiotemporal clusters were identified-five were in the Andean region and one was in the Caribbean region. The assessment of the ENSO cycle and rainfall anomalies suggests the importance of La Niña episodes, and excess rainfall periods in the occurrence of cases of HL. Conclusions: Our results demonstrate the importance of the ENSO cycle, rainfall periods and periods with excess rainfall in the occurrence of cases and outbreaks of HL in Colombia, and suggest the importance of the topography of valleys and flood zones as zones in which the risk of infection is elevated.

Early predictors of haemorrhage in acute febrile syndrome patients from Bucaramanga, Colombia: a dengue endemic area.

INTRODUCTION: Spontaneous haemorrhage is an important cause of hospitalisation in dengue patients. Early predictors of these complications could help to make opportune decisions. METHODS: We prospectively evaluated 51 febrile patients (without previous spontaneous haemorrhage), including 32 cases of dengue fever. Initial evaluation was performed during the first 96 hours after the onset of fever and included complete blood cell count and coagulation tests. Participants were followed-up daily until the seventh day of the disease. RESULTS: Overall, 15 patients developed spontaneous haemorrhage during the follow-up. Tourniquet test and dengue infection were not associated with haemorrhage (p-value is greater than 0.2). In a logistic regression analysis, platelet count (odds-ratio [OR] 0.78; 95 percent confidence interval [CI] 0.65-0.94) and partial thromboplastin time (OR 1.78; 95 percent CI 1.06-2.99) were independently associated with spontaneous haemorrhage. CONCLUSION: Early alterations in platelet count and coagulation test could predict spontaneous bleeding in the acute febrile syndrome.

[Early indicators of dengue infection in children]. / Indicadores tempranos de infección por dengue en niños.

OBJECTIVE: To identify clinical manifestations and laboratory findings useful for the early diagnosis of dengue in children. MATERIALS AND METHODS: We prospectively evaluated 125 children (aged 5 to 12 years old) with acute febrile syndrome with no apparent etiology. Paired serologic tests and/or viral culture were performed and dengue infection was confirmed in 40 patients and ruled out in 68 (17 indefinite cases). Early clinical manifestations (within the first 4 days of the disease) in the groups with dengue and other causes of febrile syndrome were compared. Independent indicators of dengue were determined in a multivariate logistic regression analysis. RESULTS: When clinical manifestations and complete blood count were considered, the independent indicators of dengue were: absence of nasal discharge, facial flushing, and leukocyte count < or = 4,500/.l. With at least two of these findings, a sensitivity of 67 % and a specificity of 72 % for the diagnosis of dengue were obtained. When coagulation tests were considered, a model for diagnosis was composed of: absence of nasal discharge, leukocyte count < or = 4500/.l, prothrombin time > 14 seconds, and partial thromboplastin time > 29 seconds. Two of these findings suggested a diagnosis of dengue with a sensitivity of 90 % and a specificity of 52.9 %. With at least 3 findings, specificity increased to 89.7 % and sensitivity decreased to 50 %. The presence of the four components of this latter model shows a specificity of 100 %. CONCLUSIONS: Some clinical manifestations and simple laboratory tests could aid the early detection of dengue infection in children.

Predictors of adverse events after percutaneous transluminal coronary angioplasty in a group of Hispanic patients.

OBJECTIVE: To identify predictors of adverse events after PTCA during hospitalization and after hospital discharge in a private hospital in Puerto Rico. BACKGROUND: A review of the literature shows limited information about predictors of adverse events associated to percutaneous transluminal coronary angioplasty (PTCA) in Hispanic patients. METHODS: This is a non-concurrent prospective study. Baseline variables were analyzed using multivariate logistic regression to identify predictors of adverse events. Data were collected from medical charts and telephone reports from referring physicians. RESULTS: Data from 197 subjects undergoing PTCA were analyzed for this study. Median age of patients was 65 years, and 62.9% of patients were male. Angiographic success rate was 81.6%. A total of 8.1% of patients had at least one in-hospital adverse event, and 39.8% had at least one adverse event after hospital discharge. After multivariate analysis, a statistically significant association was found between the presence of at least one lesion with residual stenosis of 50% or greater and the risk of developing adverse events in-hospital (RO 11.75; 95% CI 4.32-31.97). A marginally significant association was found between family history of heart disease (RO 2.75; 95% CI 0.93-8.11) and the risk of adverse events during hospitalization. Family history of heart disease (RO 1.41; 95% CI 0.98-2.04) and the presence of at least one lesion with residual stenosis of 50% or greater (RO 2.87; 95% CI 0.82-10.01) showed marginally significant associations with increased risk for adverse events after discharge. CONCLUSIONS: These findings suggest that the presence of at least one lesion with residual stenosis of 50% or greater and family history of heart disease may be risk factors for adverse events after PTCA during hospitalization and after discharge.

Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine.

The experiments were conducted to determine the effects of the administration of growth hormone-releasing peptide-2 (GHRP-2, also named KP102), both orally by gavage and in feed, on the release of growth hormone (GH) in swine and to investigate whether attenuation of the GH response occurs after short-term treatment with the peptide in feed. In the first experiment, saline or GHRP-2 at doses of 1, 4.5 and 9 mg/kg body weight (BW) was dissolved in 15 ml saline and administered orally as a bolus by gavage to cross-bred castrated male swine (n = 6). Orally administered GHRP-2 stimulated dose-related increases in peak concentrations of GH, with a return to basal by 120 min. After administering GHRP-2 orally, peak concentrations of GH and areas under the GH response curves (GH AUCs) for 180 min were higher (P < 0.05) than those in saline controls. In Experiment 2, GHRP-2 at doses of 0 (served as control), 1, 4.5 and 9 mg/kg BW was mixed in 150 g of feed and offered to cross-bred castrated male swine (n = 6) at 0900 hr and 1700 hr daily for a 3-d period. Administration of 1 mg/kg BW GHRP-2 to swine in feed failed to stimulate the release of GH, but GHRP-2 at doses of 4.5 and 9 mg/kg BW significantly (P < 0.05) increased plasma concentrations of GH after initial and final treatments at 0900 hr on Days 1 and 3 of treatment, respectively. Peak concentrations of GH and GH AUCs for 180 min after the initial and final treatments in the 4.5 and 9 mg/kg BW GHRP-2-treated swine were higher (P < 0.05) than those in controls. After 3 d of treatment with GHRP-2 in feed at doses of 4.5 and 9 mg/kg BW, GH responses to the peptide were maintained. The results of the present study indicate that the administration of GHRP-2 orally by gavage and in feed stimulates the release of GH in swine, and that the GH-releasing effect of the peptide does not become desensitized after short-term administration in feed.

The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine.

The effects of GHRP-2 (also named KP102), a new growth hormone-releasing peptide, on the release of growth hormone (GH) and growth performance were examined in swine. The single intravenous (i. v.) injection of GHRP-2 at doses of 2, 10, 30 and 100 microg/kg body weight (BW) to cross-bred castrated male swine stimulated GH release in a dose-dependent manner, with a return to the baseline by 120 min. The peak GH concentrations and GH areas under the response curves (GH AUCs) for 180 min after the injections of GHRP-2 were higher (P < 0.05) than those after the injection of saline. The GH responses to repeated i.v. injections of GHRP-2 (30 microg/kg BW) at 2-h intervals for 6 h were decreased after each injection. The chronic subcutaneous (s.c.) administration of GHRP-2 (30 microg/kg BW) once daily for 30 days consistently stimulated GH release. The GH AUCs for 300 min after the injections on d 1, 10 and 30 of treatment in GHRP-2-treated swine were higher than those in saline-treated swine. However, chronic administration of GHRP-2 caused a partial attenuation of GH response between d 1 and 10 of treatment. The chronic s.c. administration of GHRP-2 also increased average daily gain for the entire treatment period by 22.35% (P < 0.05) and feed efficiency (feed/gain) by 20.64% (P < 0.01) over the saline control values, but did not significantly affect daily feed intake. These results indicate that GHRP-2 stimulates GH release and enhancing growth performance in swine.

The effect of growth hormone-releasing peptide-2 (KP102) administration on plasma insulin-like growth factor (IGF)-1 and IGF-binding proteins in Holstein steers on different planes of nutrition.

This study was conducted to investigate the nutrition-dependent changes in insulin-like growth factor (IGF)-1 and IGF-binding proteins (IGFBPs) with growth hormone releasing peptide-2 (D-Ala-D-betaNal-Ala-Trp-D-Phe-Lys-NH(2); GHRP-2 or KP102) treatment in growing Holstein steers. Eight 13 month-old Holstein steers were grouped on two levels of feed intake (high intake (HI); 2.43% body weight or low intake (LI); 1.22%) and each group was daily injected with KP102 (12.5 microg/kg body weight/day) or saline solution into the jugular vein during 6-day period. The concentration of plasma GH showed an increase after an i.v. bolus injection of KP102 on Day 1 and Day 6 in both the LI and HI groups. Plasma IGF-1 began to increase 10 hr following an i.v. bolus injection of KP102, but this was only observed in the HI group (P < 0.05). Also, the plasma IGF-1 in the HI group with daily injections was significantly greater than the LI group from Day 1 of KP102 administration (P < 0.05). It reached maximum values of 125.1 +/- 7.6 ng/ml after Day 2, and returned to pre-injection levels after Day 4, however, no change in plasma IGF-1 was observed in LI with administration of KP102. During 6 days of treatment, plasma 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 were significantly higher in KP102 treated steers but only in the HI group (P < 0.05). Plasma 34 kDa IGFBP-2 decreased in the HI group and did not show any change following an injection of KP102. In conclusion, the effect of stimulated endogenous GH with KP102 administration increased plasma IGF-1, 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 levels in the HI group of growing Holstein steers, but not in the LI one. Thus, we strongly believe that the plasma IGF-1 and IGFBPs response to KP102 treatment is modulated by the nutritional status of growing Holstein steers and the increased plasma IGF-1 concentration with KP102 treatment may be regulated by plasma 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 in Holstein steers.

Prevalence of tuberculin reactivity and prevalence of risk factors for the development of active tuberculosis in a nursing home in Puerto Rico.

A total of 91 nursing home patients were evaluated to determine the prevalence of tuberculous infection and the prevalence of risk factors for active TB in those with positive tuberculin reactions. Overall prevalence rate for positive PPD was 42.9%. No association was found between prevalence of positive PPD and time since admission to the nursing home. The most prevalent risk factors for active TB among PPD positive patients were diabetes mellitus (38.5%), being 10% below ideal body weight (25.6%), chest X ray with fibrotic changes (13.2%), and carcinoma of oropharynx (5.1%). Twenty-one patients (53.8% of patients with positive test) met criteria for prophylactic treatment with isoniazid. This study detected a high prevalence of positive PPD reactions in this nursing home population and a high prevalence of risk factors for the development of active TB in the group with positive reaction to PPD. Due to the high risk for the development of active tuberculosis in this population, aggressive screening and preventive therapy are mandatory.

Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. A Pediatric Oncology Group Phase II study.

BACKGROUND: The prognosis for children with recurrent or resistant malignant solid tumors remains dismal. More effective rescue therapy is needed for these children. METHODS: Between August 1987 and November 1990, 311 children with recurrent or resistant malignant solid tumors were treated by investigators in the Pediatric Oncology Group with intravenous infusions of 2.0 g/m2 of ifosfamide and 100 mg/m2 of etoposide (VP-16) plus mesna as uroprotection three times daily, with courses being repeated every 14-21 days for as long as the patients responded to therapy. RESULTS: Seventy-four percent of the 294 assessable patients entered in the study had metastatic disease and previously had been treated heavily. The complete response/partial response rate was 30%, and the overall response rate was 39.5%. Toxic effects included nephrotoxicity, mild liver dysfunction, neurotoxicity, and myelosuppression. Sixty-eight percent had an absolute neutrophil count (ANC) of less than 500/microliters. In 1606 courses of therapy administered, only 3.6% of patients developed a bacterial infection. Only two patients died of gram-negative sepsis. Four percent of the patients had gross hematuria (> 50 erythrocytes/high-power field), and 18.5% had microscopic hematuria (< 20 erythrocytes/high-power field). Fanconi syndrome developed in eight children. CONCLUSIONS: Ifosfamide/VP-16 is an active combination in children with recurrent malignant solid tumors. Although it was myelosuppressive, the incidence of infection was quite low (3.6%). Mesna was very effective in preventing the development of hematuria.

Characterization and molecular analysis of nondisjunction in 18 cases of trisomy 21 and leukemia.

We recently began a cytogenetic and molecular study of nondisjunction in leukemic Down syndrome individuals to determine whether the mechanism by which the extra chromosome 21 originates predisposes the individual to leukemia. In the present report, we summarize our observations on 18 patients with trisomy 21 and acute or transient leukemia, including 11 patients with acute lymphocytic leukemia, three with acute myeloid leukemia, one with B-cell lymphoma, one with acute megakaryoblastic leukemia, and two with transient leukemia. Results of DNA marker studies of the parental origin of the extra chromosome 21 indicated that 16 of the 18 cases (89%) were maternally derived, a percentage similar to that seen among nonleukemic Down syndrome patients. We noted that most leukemic Down syndrome patients had one locus or more in which parental heterozygosity was maintained in the trisomic individual, indicating a meiotic rather than a mitotic origin for the trisomy.

Bone marrow transplantation in the treatment of children with cancer. Current status.

Bone marrow transplantation (BMT) is a promising method of treatment for children with resistant malignancies. The discrepancies in the results of BMT from institution to institution are based on patient selection, timing of transplantation, and preparatory regimens that differ from place to place. Studies that address specific questions are needed: questions like Under what conditions is BMT superior to conventional chemotherapy? Which preparatory regimen is superior? What are the results based on the status of the patients' malignancies and quality of life? Multi-institutional studies are needed to answer these questions.

The effect of naproxen on fever in children with malignancies.

Naproxen was used as an antipyretic agent in febrile pediatric cancer patients with evidence of active malignant disease. Sixteen children with leukemia and lymphoma who had fever for more than 72 hours were given naproxen to control fever. Their ages ranged from 16 months to 17 years. There were ten female and six male patients. Their temperature was greater than 38.3 degrees C and the leukocyte count ranged from 400/microliters to 33.3 X 10(3)/microliters, with an absolute neutrophil count (ANC) from 0 to 4514/microliters. The children had no evidence of infection by clinical or laboratory evaluations. All patients were receiving triple antibiotics when naproxen was started. Fourteen patients responded to naproxen with complete lysis of fever within 6 hours of initiation of treatment. Two patients did not respond to naproxen, but proved to have culture-positive infections. There were no side effects from the drug. Naproxen is an effective antipyretic in patients with cancer. It may be useful as a means of differentiating fever secondary to active malignant disease from that due to infection.