Induction of potent Th1-type immune responses from a novel DNA vaccine for West Nile virus New York isolate (WNV-NY1999)

West Nile virus (WNV) is a vectorborne pathogen that induces brain inflammation and death. Recently, confirmed cases of infection and deaths have occurred in the United States Mid-Atlantic region. In this study, a DNA vaccine encoding the WNV capsid protein was constructed, and the in vivo immune responses generated were investigated in DNA vaccine-immunized mice. Antigen-specific humoral and cellular immune responses were observed, including a potent induction of antigen-specific Th1 and cytotoxic T lymphocyte responses. Strong induction of Th1-type immune responses included high levels of antigen-specific elaboration of the Th1-type cytokines interferon-gamma and interleukin-2 and beta-chemokines RANTES (regulated upon activation, normal T cell-expressed and secreted) and macrophage inflammatory protein-1beta. Dramatic infiltration of CD4 and CD8 T cells and macrophages also was observed at the muscle injection site. These results support the potential utility of this method as a tool for developing immunization strategies for WNV and other emerging pathogens.     

Pharmacokinetics of gemcitabine and 2',2'-difluorodeoxyuridine in a patient with ascites

Gemcitabine (dFdC) is a prodrug that undergoes metabolism by cytidine deaminase to form an inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU). The pharmacokinetics of dFdC and dFdU have been studied; however, their disposition has never been evaluated in a patient with ascites. A patient with pancreatic cancer and malignant ascites was treated with dFdC 1,500 mg/m2 over 150 minutes weekly for 3 weeks, repeated every 4 weeks. Serial plasma and ascites samples were obtained on weeks 1 and 2 of cycle 2. High-pressure liquid chromatography was used to quantify dFdC and dFdU in plasma and ascites. The systemic dispositions of dFdC and dFdU were similar to those reported in patients without ascites. The concentration of dFdC in ascites approached 1 mg/ml. Ascitic fluid did not serve as a depot for dFdC, and the agent's concentration in ascites approached that at which its phosphorylation is saturated.     

Tuberculous meningitis

Summary In a five-year-period, 288 cases of tuberculous meningitis were seen in in the R.M. & T.M.C. hospitals, Thanjavur, Tamilnadu. 87 children died. Of 215 cases discharged as relieved, only 117 cases were followed up. The period of follow up varied from 6 months to over 3 years. 41 children were followed up for more than 1 year. 47 children were found to have residual sequelae. The most frequent sequelae were mental retardation, seizures, generalised rigidity and spastic hemiplegia. From the Department of Pediatrics, Thanjavur Medical College, Thanjavur, Tamilnadu     

Early postnatal weight gain as a predictor for the development of retinopathy of prematurity

Objective: The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity).

Study design: Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500?g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool.

Results: A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm.

Conclusions: Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.     

Predictability model of the need for extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome treated with inhaled nitric oxide

Background

As the use of inhaled nitric oxide (iNO) resulted in a decline in the need for extracorporeal membrane oxygenation (ECMO) in neonates with hypoxic respiratory failure, iNO has become an accepted treatment modality even in non-ECMO centers. However, because not all neonates respond to iNO, the timely identification and transfer of nonresponders to an ECMO center are important.

Objectives

The objective of this study was to identify the risk factors predictive of the need of ECMO in neonates with hypoxic respiratory failure after the first 6 hours of iNO treatment in an ECMO center.

Methods and Patient Population

Forty-nine patients with hypoxic respiratory failure transferred for iNO therapy and potential ECMO during a 2-year period were identified in this retrospective study. None of the patients had received iNO before admission. Strict clinical guidelines were used to standardize lung inflation, cardiovascular support, and iNO administration and weaning and to define treatment failure. The relationship between treatment failure (ie, the need for ECMO) and a set of suspected risk factors after 6 hours of iNO administration was examined by logistic regression analysis.

Results

Twenty-two neonates responded to iNO (non-ECMO group) whereas 27 neonates failed and met ECMO criteria (ECMO group). There was no difference between the 2 groups in demographic data, ventilatory support, air leak syndrome at 6 hours of iNO treatment, and survival to discharge. However, the dose and duration of iNO therapy were predictive of the need for ECMO with an adjusted odds ratio of 1.12 (95% CI, 1.01-1.25; P = .04) and 0.45 (95% CI, 0.27-0.65; P = .0002), respectively.

Conclusions

By the end of the first 6 hours of iNO treatment and under the specific conditions established by the use of the clinical guidelines, the dose and the duration of iNO administration were predictive of the probability for the need of ECMO in this patient population. Thus, one can establish a center-specific predictability model for the need of ECMO in neonates with hypoxic respiratory failure treated with iNO if strict clinical guidelines for iNO administration and weaning and respiratory and cardiovascular support are used in the given center.     

Recovery of allograft function after complete withdrawal of immunosuppression

We describe an interesting case of a patient who recovered function of a previously failed kidney allograft after immunosuppressive medications were discontinued for 4 months, requiring maintenance hemodialysis. He had a split-thickness skin graft to his abdomen because of previous surgical complications. His postoperative course was complicated by sepsis and refractory hypotension. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone. At the same time, hemodialysis was stopped for possible catheter-related infection. The patient recovered function of the previously failed allograft and has not required hemodialysis.