In vitro activity of MDL 62,879 against gram-positive bacteria andBacteroides species

The new thiazolyl peptide antibiotic MDL 62,879 (GE2270 A) showed excellent in vitro activity in testing against staphylococci and streptococci, with MIC90s ranging from 0.23 to 0.9 mg/l. It was very active againstClostridium difficile andPropionibacterium acnes (MIC90 0.06 mg/l in each case) and had variable activity againstBacteroides spp. MDL 62,879 had exceptionally good activity againstEnterococcus faecalis, including against a collection of high-level aminoglycoside-resistant isolates where it had an MIC90 of 0.047. The antibiotic was bacteriostatic for enterococcal isolates but bactericidal for a methicillin-resistant isolate ofStaphylococcus aureus.     

Hepatic transplantation in a patient with mesoatrial shunt and occlusion of the inferior vena cava

Occlusion of the vena cava has long been considered an insurmountable difficulty in patients needing liver transplantation. We report the case of a patient with a patent mesoatrial shunt and complete vena cava obstruction who underwent liver transplantation.     

Inhalation of ozone produces a decrease in superoxide anion radical production in mouse alveolar macrophages

The potentiation of fatal bacterial pneumonia in mice by prior inhalation of ozone occurs at levels of this oxidant pollutant that are frequently present in ambient air. A likely mechanism for this effect is an ozone-induced inhibition in the ability of pulmonary alveolar macrophages (PAM) to produce superoxide anion radical (O2-) demonstrated in the present study. A 25% decrease in PAM O2- production, as measured by nitroblue tetrazolium reduction, occurred after exposure of Swiss-Webster mice to 0.11 ppm ozone for 3 h (p less than 0.05). After 1 ppm there was almost complete inhibition of O2- release. In contrast, the rat, which is highly resistant to the potentiation of bacterial infections by ozone, was less sensitive to inhibition of PAM O2- production, as measured by cytochrome c reduction (mouse IC50, 0.41 ppm; rat IC50, 3.0 ppm ozone for 3 h). The observed decrement in mouse PAM O2- production was not associated with any change in phagocytic ability, as measured by both latex bead ingestion and 51Cr-labeled sheep red blood cell ingestion. This decrease in O2- production in the presence of normal phagocytic activity is analogous to certain of the findings in the neutrophils of children with chronic granulomatous disease. A decrease in rat PAM membrane cytochrome b558 levels was observed after ozone exposure of 3 ppm for 3 h, preliminarily suggesting that the mechanism by which ozone interferes with PAM O2- production may be through interaction with this heme-containing electron carrier.     

Reliability and predictive value of salivary theophylline levels

The reliability and accuracy of salivary theophylline levels as a predictor of serum theophylline levels was investigated in 28 hospitalized chronic asthmatics, free of other chronic diseases, on continuous aminophylline infusion for greater than 24 hours. Twenty paired blood and saliva theophylline levels from 12 patients (group 1) were used to develop a formula for predicting serum theophylline levels from salivary levels. Twenty-one paired blood and saliva theophylline levels from 16 patients (group 2) were used to test the formula obtained. The formula predicted the serum theophylline concentration within 1.51 microgram/mL in 76% of the samples and within 1.88 microgram/mL in 100% of the samples. There was an excellent correlation between the predicted and actual serum theophylline concentrations, r = .93; thus under controlled conditions of steady-state pharmacokinetics in patients free of other diseases, salivary theophylline levels can be used to accurately predict serum levels.     

Stimulation of in vivo antibody production and concanavalin-A-induced mouse spleen cell mitogenesis by prolactin

Regulation of the immune system by neuroendocrine hormones is receiving increased attention. Prolactin, a hormone normally associated with lactation, has been shown recently to reconstitute immunosuppressed hypophysectomized rats. The present studies demonstrate that prolactin administration to normal mice results in a biphasic stimulation of antibody production to sheep red blood cells. While 100 and 200 micrograms bovine prolactin/animal stimulated antibody production, 400 micrograms had no effect. Potentiation of lectin-induced T-cell mitogenesis by prolactin was also biphasic. As the concentration of prolactin increased the incorporation of [3H]thymidine into the cells first increased and then decreased. Decreasing serum prolactin levels with the dopaminergic agonist bromocriptine resulted in a reduction of antibody titers to sheep erythrocytes and a modulation of thymic weight. These data show that prolactin can stimulate the immune system in a biphasic manner and that a reduction in the basal levels of this hormone results in an attenuated immune response.     

Nursery Neurobiologic Risk Score: important factor in predicting outcome in very low birth weight infants

We developed a nursery Neurobiologic Risk Score (NBRS) based on potential mechanisms of brain cell injury in preterm infants and correlated it with developmental outcome at the corrected ages of 6, 15, and 24 months. The NBRS was determined at 2 weeks of age and at the time of discharge from intensive care in 58 preterm infants with birth weights less than or equal to 1500 gm. The NBRS correlated significantly with the Bayley Scales of Infant Development, Mental Development Index (MDI) (r = -0.61 to -0.40) and Psychomotor Development Index (PDI) (r = -0.59 to -0.46), and with abnormal neurologic examination findings (r = 0.59 to 0.73) at the three testing periods. Although 12 of the 13 items composing the NBRS individually correlated with one or more outcome variables, seven items (infection, blood pH, seizures, intraventricular hemorrhage, assisted ventilation, periventricular leukomalacia, and hypoglycemia) accounted for almost all of the explained variance. Logistic regression of individual items demonstrated intraventricular hemorrhage to be the most important item for predicting the MDI at 24 months; pH was the most influential item for predicting the PDI at every testing period. A shorter, revised NBRS that included only the seven significant items demonstrated as strong a correlation with developmental outcome as the original NBRS. A revised 2-week score of greater than or equal to 5 or a discharge score of greater than or equal to 6 demonstrated 100% specificity and had a 100% positive predictive value for an abnormal outcome at 24 months of age in this group of infants. We conclude that the NBRS identifies during the intensive care nursery stay those infants at highest risk for an abnormal outcome related to nursery events. In addition, analysis of NBRS items provides insight into the relative importance of individual factors for influencing mental, motor, and neurologic outcome.     

Childhood abuse and the use of inhalants: differences by degree of use.

OBJECTIVES: Using two existing ethnographic studies of drug-involved adults, this study evaluates the association between child-abuse victimization and levels of involvement in inhalant use. METHODS: Historical accounts of childhood exposure to physical or sexual abuse were compared among nonusers of inhalants (n = 197), light inhalant users (n = 64), and heavy inhalant users (n = 24). Crude and adjusted odds ratios were used to compare informants with no history of inhalant use with those having a history of light inhalant use and those having a history of heavy inhalant use. RESULTS: Heavy inhalant use was associated with history of any child abuse (adjusted odds ratio [OR] = 4.6) and physical abuse (adjusted OR = 3.8). Light inhalant use showed no association with child-abuse history. CONCLUSIONS: Child abuse may be an important correlate of extensive involvement in inhalant use. The findings invite speculation with respect to a hypothetical causal role for child abuse in the etiology of inhalant use. The lack of support for causality in this study underscores the need for replication and more carefully designed longitudinal research.