Platelet-activating factor in infants at risk for necrotizing enterocolitis.

BACKGROUND: Platelet-activating factor (PAF) is a heterogeneous phospholipid that has been implicated as participating in a number of perinatal disease processes including necrotizing enterocolitis (NEC). METHODS: Baseline blood levels of PAF and related lipids (PAF-LL) were measured for 164 infants at risk for NEC from 3 neonatal intensive care units. Serial levels were obtained from the 11 infants in whom NEC developed. RESULTS: The mean peak PAF-LL in the infants without NEC was 2.03 +/- 1.96 ng/mL. Infants with stage II (n = 6) and III (n = 5) NEC had elevated peak PAF-LL values (mean peak value 13.6 +/- 6.9 ng/mL). No PAF-LL measurements obtained from infants during stage II or III NEC were <2.03 ng/mL. Three infants had PAF-LL elevations before the development of any clinical or radiographic evidence of NEC. PAF-LL level increased as the severity of NEC increased and decreased with its resolution. Setting a PAF-LL level of 10.2 ng/mL as a cutoff for NEC had a positive predictive value of 100%. CONCLUSIONS: PAF-LL determinations can complement clinical and radiographic studies to diagnose and follow the progression of NEC. PAF-LL may have a role in the evolution of NEC.

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Hyperandrogenemia in human immunodeficiency virus-infected women with the lipodystrophy syndrome.

A novel lipodystrophy syndrome characterized by insulin resistance, hypertriglyceridemia, and fat redistribution has recently been described in human immunodeficiency virus (HIV)-infected men and women. Women with the HIV lipodystrophy syndrome exhibit a marked increase in waist-to-hip ratio and truncal adiposity; however, it is unknown whether androgen levels are increased in these patients. In this study, we assessed androgen levels in female patients with clinical lipodystrophy based on evidence of significant fat redistribution in the trunk, extremities, neck and/or face (LIPO: n = 9; age, 35.7+/-1.7 yr; BMI, 24.7+/-0.8 kg/m2) in comparison with age- and BMI-matched nonlipodystrophic HIV-infected females (NONLIPO: n = 14; age, 37.6+/-1.1 yr; BMI, 23.4+/-0.6 kg/m2) and healthy non-HIV-infected control subjects (C: n = 16; age, 35.8+/-0.9 yr; BMI, 23.1+/-0.4 kg/m2). Fasting insulin, lipid levels, virologic parameters, and regional body composition using dual energy x-ray absorptiometry were also assessed. Total testosterone [ LIPO, 33+/-6 ng/dL (1.1+/-0.2 nmol/L); NONLIPO, 17+/-2 ng/dL (0.6+/-0.1 nmol/L); C, 23+/-2 ng/dL (0.8+/-0.1 nmol/L); P < 0.05 LIPO vs. C and LIPO vs. NONLIPO] and free testosterone determined by equilibrium dialysis [LIPO, 4.5+/-0.9 pg/mL (16+/-3 pmol/L); NONLIPO, 1.7+/-0.2 pg/mL (6+/-1 pmol/L); C, 2.4+/-0.2 pg/mL (8+/-1 pmol/L); P < 0.05 LIPO vs. C and LIPO vs. NONLIPO] were increased in the lipodystrophic patients. Sex hormone-binding globulin levels were not significantly different between LIPO and C, but were significantly lower in the LIPO vs. NONLIPO patients (LIPO 84+/-7 vs. NONLIPO 149+/-17 nmol/L, P < 0.05). The LH/FSH ratio was significantly increased in the LIPO group compared with the NONLIPO and C subjects (LIPO, 2.0+/-0.6; NONLIPO, 1.1+/-0.1; C, 0.8+/-0.1; P < 0.05 LIPO vs. NONLIPO and LIPO vs. C). Body fat distribution was significantly different between LIPO and C subjects. Trunk to extremity fat ratio (1.46+/-0.17 vs. 0.75+/-0.05, LIPO vs. C, P < 0.05) was increased and extremity to total fat ratio decreased (0.40+/-0.03 vs. 0.55+/-0.01, LIPO vs. C, P < 0.05). In contrast, fat distribution was not different in the NONLIPO group vs. control subjects. Among the HIV-infected patients, free testosterone correlated with percent truncal fat (trunk fat/trunk mass) (r = 0.43, P = 0.04). These data suggest that hyperandrogenemia is another potentially important feature of the HIV-lipodystrophy syndrome in women. Additional studies are necessary to determine the clinical significance of increased androgen levels and the relationship of hyperandrogenism to fat redistribution and insulin resistance in this population of patients.

Fasting hyperinsulinemia in human immunodeficiency virus-infected men: relationship to body composition, gonadal function, and protease inhibitor use.

Fat redistribution in the setting of protease inhibitor use is increasingly common and is associated with insulin resistance in human immunodeficiency virus (HIV)-infected patients. However, little is known regarding the factors that may contribute to abnormal insulin regulation in this population. We assessed fasting insulin levels in HIV-infected men and determined the relationship among insulin, body composition, endogenous gonadal steroid concentrations, and antiviral therapy in this population. We also determined the effects of exogenous testosterone administration using the homeostatic model for insulin resistance (HOMA IR) in hypogonadal HIV-infected men with the acquired immunodeficiency syndrome wasting syndrome. Fifty HIV-infected men with acquired immunodeficiency syndrome wasting were compared with 20 age- and body mass index (BMI)-matched healthy control subjects. Insulin concentrations were significantly increased in HIV-infected patients compared to those in control patients (16.6+/-1.8 vs. 10.4+/-0.8 microU/mL; P<0.05) and were increased in nucleoside reverse transcriptase (NRTI)-treated patients who did not receive a protease inhibitor (PI; 21.7+/-4.3 vs. 10.4+/-0.8 microU/mL; P<0.05). Insulin concentrations and HOMA IR were inversely correlated with the serum free testosterone concentration (r = -0.36; P = 0.01 for insulin level; r = -0.30; P = 0.03 for HOMA), but not to body composition parameters, age, or BMI. In a multivariate regression analysis, free testosterone (P = 0.05), BMI (P<0.01), and lean body mass (P = 0.04) were significant. Lower lean body mass and higher BMI predicted increased insulin resistance. The HIV-infected patients demonstrated an increased trunk fat to total fat ratio (0.49+/-0.02 vs. 0.45+/-0.02; P<0.05) and an increased trunk fat to extremity fat ratio (1.27+/-0.09 vs. 0.95+/-0.06, P = 0.01), but a reduced extremity fat to total fat ratio (0.44+/-0.01 vs. 0.49 + 0.01; P = 0.02) and reduced overall total body fat (13.8+/-0.7 vs. 17.2+/-0.9 kg; P<0.01) compared to the control subjects. Increased truncal fat and reduced extremity fat were seen among NRTI-treated patients, but this pattern was most severe among patients receiving combined NRTI and PI therapy [trunk fat to extremity ratio, 1.47+/-0.15 vs. 0.95+/-0.06 (P<0.01); extremity fat to total fat ratio, 0.40+/-0.02 vs. 0.49+/-0.01 (P<0.05)]. Insulin responses to testosterone administration were investigated among 52 HIV-infected men with hypogonadism and wasting (weight <90% ideal body weight and/or weight loss >10%) randomized to either testosterone (300 mg, im, every 3 weeks) or placebo for 6 months. Testosterone administration reduced HOMA IR in the HIV-infected men (-0.6+/-0.7 vs. +1.41+/-0.8, testosterone vs. placebo, P = 0.05) in association with increased lean body mass (P = 0.02). These data demonstrate significant hyperinsulinemia in HIV-infected patients, which can occur in the absence of PI use. In NRTI-treated patients not receiving PI, a precursor phenotype is apparent, with increased truncal fat, reduced extremity fat, and increased insulin concentrations. This phenotype is exaggerated in patients receiving PI therapy, with further increased truncal fat and reduced extremity fat, although hyperinsulinemia per se is not worse. Endogenous gonadal steroid levels are inversely related to hyperinsulinemia in HIV-infected men, but reduced lean body mass and increased weight are the primary independent predictors of hyperinsulinemia. Indexes of insulin sensitivity improve in response to physiological androgen administration among hypogonadal HIV-infected patients, and this change is again related primarily to increased lean body mass in response to testosterone administration.

Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus.

Our report describes the outcome of a twin pregnancy in a woman who was maintained on tacrolimus after a living related renal transplant. Both babies born at 32 weeks of gestation developed severe respiratory distress requiring ventilator assistance and went on to develop congestive heart failure. Echocardiograms on both babies showed dilated heart chambers. Twin A succumbed to complications, but twin B, who was treated more aggressively with vasopressors, recovered. Autopsy findings on twin A revealed a thrombotic cardiomyopathy with degeneration of cardiac muscle. We believe that the unusual outcome in this set of twins may have been a result of cardiomyopathy secondary to tacrolimus used by the mother during her pregnancy.

Successful treatment of late-onset infection due to resistant Klebsiella pneumoniae in an extremely low birth weight infant using ciprofloxacin.

OBJECTIVE: This paper presents a case in which an extremely low birth weight infant with multidrug-resistant Klebsiella pneumoniae infection was successfully treated with ciprofloxacin and gentamicin. STUDY DESIGN: A clinical case report of a neonate who received broad spectrum antibiotics for possible infection despite negative cultures. The infant developed sepsis and meningitis resulting from multidrug-resistant K. pneumoniae, which was treated with ciprofloxacin and gentamicin. The literature for the use of ciprofloxacin in pediatric patients was reviewed. RESULTS: The infant responded to the antibiotic regimen with sterilization of blood and cerebrospinal fluid; no adverse effects were attributable to the ciprofloxacin. Although ciprofloxacin has been found to cause irreversible injury to cartilage in juvenile laboratory animals, a review of the literature found that this complication occurs rarely if at all in pediatric patients. Ciprofloxacin has been found to be effective in the treatment of multidrug-resistant Gram-negative infections in pediatric patients, including premature infants. CONCLUSION: Ciprofloxacin should be considered in the treatment of neonatal infection caused by multidrug-resistant Gram-negative organisms. Although the published experience with this drug suggests that it is effective and that significant toxicity is not common, its use should be restricted to the treatment of serious infections for which an alternative antibiotics is not available.

Fatal early onset infection in an extremely low birth weight infant due to Morganella morganii.

OBJECTIVE: This paper reports a case of chorioamnionitis due to Morganella morganii in a mother who presented with ruptured membranes at 24 weeks' gestation and was treated with dexamethasone and prophylactic ampicillin. Her premature infant developed severe early onset infection due to the same organism and expired. STUDY DESIGN: A clinical case report of M. morganii infection complicating preterm rupture of membranes is presented. Possible risk factors for maternal and neonatal infection with this organism as well as the therapy of neonatal M. morganii infection are discussed. RESULTS: Risk factors in the mother included having a cervical cerclage in place and treatment with dexamethasone and prophylactic ampicillin. The major risk factors in the infant were maternal chorioamnionitis and extreme prematurity. The mother responded to treatment with ampicillin, metronidazole, and gentamicin following delivery and had an uncomplicated recovery. Her infant developed severe early onset M. morganii infection complicated by neutropenia, thrombocytopenia, and severe acidosis and expired. Postmortem cultures of pleural fluid, peritoneal fluid, and blood were positive despite treatment with gentamicin, an antibiotic to which the organism was sensitive. CONCLUSION: M. morganii may cause serious infection in pregnancy and in the neonatal period. The use of dexamethasone and prophylactic ampicillin may have increased the risk of infection with this ampicillin-resistant organism. The failure of gentamicin to sterilize the infant's blood and body fluids emphasizes the necessity of treating such infections with a combination of an aminoglycoside and a third-generation cephalosporin, such as cefotaxime.

Changes in atrioventricular conduction properties with refractory-period modulation.

Dofetilide, clofilium, and risotilide, three drugs known to prolong cardiac action potentials and refractory periods, were studied by using a perfused isolated rabbit heart preparation with intermittent premature pacing and bipolar surface electrograms. The rate-related effects of these drugs on atrioventricular (AV) conduction were tested by pacing at a long (400 ms) and a short (250 ms) basic cycle length (BCL). All three drugs increased refractory periods in a concentration-dependent manner in most segments of the AV axis. The maximal atrio-His (AH) conduction interval (AHmax) and delta AH (AHmax - AHmin) produced by premature pacing was decreased by the highest concentration of each drug at the 400-ms BCL, whereas only clofilium reduced AHmax and delta AH at the 250-ms BCL. Changes in delta AH correlated best with changes in the atrial functional refractory period. The His-Purkinje system conduction interval (HV), represented by delta HV, was unaffected by any drug at either BCL. These results show that if atrial or nodal refractory periods are increased sufficiently, AHmax but not AHmin was decreased at the 400-ms BCL. Because dofetilide and risotilide did not affect AHmax at the 250-ms BCL, these drugs may be less effective at preventing AV nodal reentrant tachycardias than a drug such as clofilium that displays less rate dependency.