Association of HHV-6 With Outcomes in CMV-seronegative Liver Transplant Recipients With CMV-seropositive Donors Receiving Preemptive Antiviral Therapy.

BACKGROUND: Risk factors, virological parameters, and outcomes associated with HHV-6 viremia in high-risk donor CMV-seropositive and recipient CMV-seronegative (D+R-) liver transplant recipients in the current era are incompletely defined. METHODS: The study population consisted of patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus valganciclovir prophylaxis for CMV prevention in D+R- liver transplant recipients. Weekly blood samples through 100 d in the PET group were tested for HHV-6 viremia using a real-time quantitative polymerase chain reaction. Assessments included virological characteristics and relationship with CMV, risk factors, and impact of HHV-6 viremia with outcomes through 12 mo posttransplant. RESULTS: HHV-6 viremia at any level developed in 42% (40 of 96). Older patient age (P = 0.03), longer hospitalization (P = 0.015), and ICU stay at transplantation (P = 0.029) were significantly associated with high-grade viremia. Concurrent HHV-6 and CMV viremia was associated with earlier onset of HHV-6 viremia (P = 0.004), higher HHV-6 area under the curve (P = 0.043), and higher peak HHV-6 viral load (P = 0.006) versus HHV-6 viremia alone. High-grade viremia was independently associated with biopsy-proven rejection within 12 mo (P = 0.045) posttransplant. CONCLUSIONS: Among D+R- liver transplant recipients receiving valganciclovir as PET, high-grade HHV-6 viremia was associated with increased age and critical illness in ICU at time of transplant and was independently associated with allograft rejection.

Visceral leishmaniasis: a model for infection-induced cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

The combination of ibuprofen and oxycodone/acetaminophen in the management of chronic cancer pain.

Thirty subjects with chronic moderate to severe pain who were receiving oxycodone/acetaminophen (oxy/APAP) for analgesia were initially evaluated for at least 7 days for oxy/APAP requirements for pain control. Each subject then received, in a randomized double-blind fashion, either 600 mg ibuprofen or placebo for an additional 7 days while hospitalized. Oxy/APAP usage was recorded daily along with efficacy and toxicity parameters. Overall global evaluations were also recorded on completion of the study. Comparison of mean differences before and after treatment with ibuprofen or placebo indicated a marked decrease in oxy/APAP use with ibuprofen (p less than 0.01) and a slight increase in use in the placebo group. Reduction in oxy/APAP usage occurred within 24 hours and maximized at 5 days. Overall global scores showed a marked preference for the ibuprofen combination over placebo (p less than 0.01). Daily pain intensity (p less than 0.05) and pain relief scores (p less than 0.05) also improved with the addition of ibuprofen. This study indicates that ibuprofen is efficacious in the management of chronic cancer pain, resulting in both enhanced analgesia and a reduction in concomitant narcotic use.

Outcome in infants of birth weight 500 to 999 g: a continuing regional study of 5-year-old survivors.

During 1979 and 1980, 351 infants of birth weight 500 to 999 g were born in the State of Victoria: 89 (25.4%) survived to the age of 2 years corrected for prematurity, and 83 were fully assessed by a multidisciplinary team; partial data were obtained on the remainder. At the age of 5 years, corrected for prematurity, 85/89 (96%) were evaluated by a multidisciplinary team, although not all children could be fully evaluated by the psychologists. Reports were available for another three children; one child was untraced. Of the survivors able to be classified at 5 years, 59/82 (72%) had no functional handicap. Functional handicaps was severe in 16 (19%), moderate in four (5%), and mild in three (4%). Functional handicaps were present in 50% (8/16) of outborn survivors compared with the 23% (15/66) for the inborn survivors (P = 0.02). Cerebral palsy was diagnosed in eight children at 5 years and in 12 children at 2 years. The diagnosis was stable for the children not ambulant at 2 years; five of seven 2-year-old children with mild cerebral palsy had "outgrown" the diagnosis by 5 years, but ataxic cerebral palsy was not identified in one child until 5 years. Six children were blind; four had severe sensorineural or mixed deafness, one more than at 2 years. Of 82 children assessed according to identical criteria for functional handicap at both 2 and 5 years, 52 (63%) remained in the same category at 5 years, three (4%) were judged to be more severely handicapped, and 27 (33%) were less severely handicapped. The 2-year evaluation of extremely low birth weight children often proved to be unduly pessimistic, for many showed improvement or recovery from functional handicaps and impairments by 5 years of age.

Reciprocal relationships between undernutrition and the parasitic disease visceral leishmaniasis.

Little is known about the interrelationship between undernutrition and parasitic infections in areas of the world where both are prevalent. The associations between undernutrition and visceral leishmaniasis, an important protozoal disease, were assessed in a study of residents of an area in Brazil with endemic leishmaniasis. Mid-arm anthropometry was used to assess fat and muscle area. Children with visceral leishmaniasis came from large families (9.6 +/- 1.1 members vs. 6.8 +/- 0.7 members in neighborhood control families), and patient housemates had fat areas that were 78% (P less than .05) those of age- and sex-matched neighborhood controls. The children with visceral leishmaniasis who were studied four months or less after diagnosis had fat areas that were 66% (P less than .05) those of age- and sex-matched household controls or 41% (P less than .01) those of neighborhood controls and muscle areas that were 81% (P less than .025) those of household controls or 75% (P less than .05) those of of neighborhood controls. It is hypothesized, on the basis of these data and other findings, that undernutrition is associated with the development of clinically apparent visceral leishmaniasis and that the disease itself has a profound effect on nutritional status, resulting in loss of both muscle and fat, effects that possibly are mediated by interleukin-1 and/or other factors produced by Leishmania donovani-infected macrophages.

Outcome in infants with birth weight 500 to 999 gm: a regional study of 1979 and 1980 births.

During 1979 and 1980, 351 infants weighing 500 to 999 gm were born in the State of Victoria, Australia; 89 (25.4%) survived to 2 years of age. Survival was better for tertiary center births (29%) than for those born elsewhere (17%). Multidisciplinary teams reviewed 83 of the survivors at 2 years of age postterm; some data were available for the other six children. Overall, 22.5% of infants had severe functional handicap, 29.2% had either moderate or mild handicap, and 48.3% had no handicap. Severe functional handicap was present in 50% of outborn infants; this was significantly more common than in those born in tertiary centers (15.5%), and the Bayley Mental Developmental Index was also significantly lower in outborn infants. The prevalence of cerebral palsy (13.5%), bilateral blindness (3.4%), and severe sensorineural deafness (3.4%) did not differ significantly in the inborn and outborn infants. Singleton inborn infants of appropriate weight for gestational age had significantly less severe functional handicap (9.1%), compared with 37.5% for the group of infants who were either small for gestational age or one of multiple births. Six of the 18 outborn infants could have been transferred in utero, and improvements in immediate neonatal care were possible in seven other infants.

The effect of maternally administered drugs on bilirubin concentrations in the newborn infant.

The effects of drugs administered to pregnant women on bilirubin concentrations in 1,107 consecutively born infants are presented. Administration of narcotic agents, barbiturates, aspirin, chloral hydrate, reserpine, and phenytoin sodium all resulted in lowering of infant serum bilirubin concentrations. Diazepam and, to a lesser extent, oxytocin caused an elevation of infant serum bilirubin concentrations. Although many drugs were shown to alter serum bilirubin levels significantly, the clinical importance of such alterations was not dramatic except possibly in special circumstances. The phenothiazine derivatives, general or local anesthesia, sulfadimidine, ampicillin, and penicillin had no such effect on the newborn infant when given to the mother before delivery.

Jaundice in infants of Greek parentage: the unknown factor may be environmental.

Studies of infants born in Melbourne, Australia, to parents who migrated from Greece failed to demonstrate an increased incidence or severity of neonatal jaundice. No effect of birthplace of parents within Greece on serum bilirubin levels could be discerned. These findings indicate that the high frequency of severe neonatal jaundice which has been demonstrated throughout Greece, and especially in certain regions of that country, is not carried with those who immigrate. Further studies of this problem in Greece should concentrate on regional environment rather than upon genetic influences.