The prevalence of vitamin D deficiency and its relationship with disease severity in an urban pediatric critical care unit.

OBJECTIVE: To evaluate the prevalence of vitamin D deficiency among patients admitted to a Pediatric Critical Care Unit (PCCU) in an urban children's hospital, and to assess if there is a correlation between vitamin D level and disease severity. PATIENTS AND METHODS: Patients (216) between the ages of 1-21 years admitted to the PCCU in a children's hospital, excluding those readmitted with a previous vitamin D level, were enrolled. Serum 25-OH vitamin D levels were measured in all patients within 24 h of admission to the PCCU. The severity of patient illness was assessed by the Pediatric Logistic Organ Dysfunction (PELOD) score determined on admission. RESULTS: Vitamin D deficiency was found in 28% of patients and vitamin D insufficiency was found in 47% of patients. Adolescent age group, female gender, Black race, winter season, and increasing BMI were determined to be risk factors associated with vitamin D deficiency. No significant correlation was found between vitamin D level and PELOD score (p=0.09). There were six deaths (3%), 5 (83%) of which occurred in patients with low vitamin D levels. Total serum calcium levels correlated with vitamin D (p=0.005) and PELOD score (p=0.001). However, ionized calcium levels did not significantly correlate with vitamin D (p=0.62) or PELOD score (p=0.26). CONCLUSIONS: Vitamin D deficiency is common in children admitted to an urban inner city PCCU, with 75% of patients having abnormal levels. We did not find a significant correlation between disease severity as measured by PELOD score and vitamin D level in a heterogeneous group of critically ill children. Total serum calcium levels significantly correlated with vitamin D and disease severity in this population. There appears to be an association between vitamin D deficiency and mortality.

Respiratory syncytial virus infection following hematopoietic stem cell transplantation.

Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients of autologous or allogeneic transplants. The incidence of RSV following allogeneic or autologous HSCT was 5.7% and 1.5%, respectively. Of the 58 patients with an RSV infection, 16 of 21 patients identified within the first post-transplant month, developed pneumonia. Seventy-two percent of patients received aerosolized ribavirin and/or RSV-IGIV, including 23 of 25 patients diagnosed with RSV pneumonia. In this aggressively treated patient population, three patients died of RSV disease, each following an unrelated HSCT.

Pharmacology of pediatric resuscitation.

The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

Respiratory and cardiac function in children after acute hypoxemic respiratory failure.

OBJECTIVE: To examine the pulmonary and cardiac function of children who survived an episode of acute hypoxemic respiratory failure. DESIGN: Descriptive cohort analysis. SETTING: Pediatric clinical research center of a university hospital. PATIENTS: Utilizing the criteria of PaO2 < 75 torr (< 10 kPa) with an FIO2 of > 0.5 while intubated, bilateral diffuse pulmonary infiltrates on chest radiograph, and exclusion of cardiogenic pulmonary edema, 147 patients were identified during the 6-yr period from July 1, 1986 to August 1, 1993. Fifty patients survived to discharge and 37 were alive at the time of follow-up. Fourteen patients were eventually entered into the study. INTERVENTIONS: The study patients were given a test battery consisting of a questionnaire specific for cardiopulmonary status, a physical examination, a chest radiograph, electrocardiography, echocardiography with detailed examination of the pulmonary circulation, pulse oximetry, complete blood count, and serum chemistries and pulmonary function testing with bronchoprovocation in selected patients. MEASUREMENTS AND MAIN RESULTS: The 14 follow-up patients were evaluated an average of 23 +/- 23 months (range 3 to 66) following intensive care unit discharge. No child reported a significant alteration in lifestyle or limitation of activities. Physical examinations were generally unremarkable. The room air oxyhemoglobin saturation was > or = 0.98 in all patients. Comparison of chest radiographs at the time of follow-up with those chest radiographs during the period of critical illness showed marked but not complete improvement in all. Electrocardiograms and echocardiograms showed new evidence of left ventricular hypertrophy in one child. The right ventricular preejection period to ejection time ratio was normal in all subjects. Eleven patients completed spirometry. Four patients were normal and the other patients had evidence of restrictive or obstructive disease either at baseline or after bronchoprovocation challenge. Ten children had lung volume measurements. Five children were normal, two showed increased volumes consistent with obstruction, and three showed decreased volumes indicative of restriction. Four of seven patients showed evidence of decreased diffusion capacity. Six of seven patients with evidence of abnormal pulmonary function had a positive response to bronchodilator administration. CONCLUSIONS: Although pediatric survivors of acute hypoxemic respiratory failure perceive neither a limitation in lifestyle nor chronic pulmonary morbidity, careful examination of the cardiopulmonary system demonstrates a significant number with abnormal chest radiographs and abnormalities in pulmonary function. These children require careful follow-up and may benefit from use of a bronchodilator.

Antibodies elicited against cis-diamminedichloroplatinum(II)-modified DNA are specific for cis-diamminedichloroplatinum(II)-DNA adducts formed in vivo and in vitro.

Rabbit antiserum elicited against calf thymus DNA modified to 4.4% (Pt drug/nucleotide ratio = 0.044) with the antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) contains antibodies specific for the Pt-modified DNA immunogen as well as for Pt-DNA adducts formed in both cultured mouse leukemia L1210 cells and in L1210 cells from the ascites fluid of tumor-bearing mice exposed to cis-DDP. Pt-modified DNA was electrostatically complexed to methylated bovine serum albumin and injected into rabbits. Early bleedings of the derived antiserum were used to establish a competitive enzyme-linked immunosorbent assay (ELISA), which demonstrated specificity for the Pt-modified DNA but not for DNA or the Pt drug alone. In the ELISA, 50% inhibition occurred at a concentration of 0.5 nM Pt (on DNA) as determined by atomic absorption spectroscopy. This value corresponds to a lower limit of detectability of one adduct in 10(7) nucleotides, with 50 micrograms of sample DNA added per microtiter well. DNA isolated from cultured mouse L1210 cells exposed to increasing doses of the Pt drug was found by ELISA to contain from 0.2 to 10.0 fmol of Pt adduct per microgram of DNA. These levels remained stable for up to 4 hr after a 1-hr drug treatment, during which time DNA interstrand crosslinks developed. Thus, the antiserum appears not to be specific for DNA interstrand crosslinks. DNAs from L1210 cells exposed to trans-diamminedichloroplatinum(II) and L-phenylalanine mustard were not recognized in the ELISA. DNA prepared from the ascites cells of mice bearing the L1210 tumor 5 hr after injection of cis-DDP was found to contain about 2 fmol of Pt per microgram of DNA. This work establishes that cis-DDP-DNA adducts prepared in vitro are relevant to the in vivo binding of the Pt drug to its biological target, DNA, and opens new avenues for studying the mechanism of action of the Pt anticancer drugs.

Binding of [(dien)PtCl] Cl to poly(dG-dC)-poly(dG-dC) facilitates the B goes to Z conformational transition.

Chlorodiethylenetriamineplatinum(II) chloride, [(dien)PtCl]Cl, bound to less than or equal to 10% of the nucleotide bases of poly(dG-dC) . poly(dG-dC) reduces the amount of ethanol necessary to bring about the B goes to Z conformational transition in proportion to the amount of platinum complex bound as monitored by CD spectroscopy. The transition may be effected by 25% ethanol with 9.3% of the bases modified polymer an ethanol with 5.4% of the bases modified. With an unmodified polymer an ethanol concentration of 55-60% is necessary to bring about the transition. The assignment of the Z conformation was supported by 31P NMR spectroscopy. This covalent modification of the DNA is reversed by treatment with cyanide ion after which the normal amount of ethanol is necessary to achieve the transition. The platinum complex shows no enhanced binding to DNA in the Z versus the B conformation. Between 20 and 33% (saturation binding) modification, [(dien)PtCl]Cl binds cooperatively to the heterocopolymer as judged by CD spectroscopy. At this high level of modification it is no longer possible to induce the Z DNA structure with ethanol. When [(dien)PtCl]Cl is bound to preformed (with ethanol) Z DNA at saturating levels the CD spectrum is altered but reverts to the spectrum of highly modified DNA upon removal of ethanol. The antitumor drug cis-diaminedichloroplatinum(II), cis-DDP, binds to poly(dG-dC) . poly(dG-dC) and alters the CD spectrum. It does not facilitate the B goes to Z conformational change, however, and actually prevents it from happening even at very high ethanol concentrations.