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Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3-12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

BACKGROUND The safety and efficacy of tenofovir disoproxil fumarate (TDF) in HIV-1-infected children have not been evaluated in a randomized controlled trial. METHODS Subjects (2 to

Background: Enfuvirtide is the only entry inhibitor approved for the treatment of human immunodeficiency virus (HIV)-1 infection. It is approved for use in adults and dosage recommendations exist for children aged 6 years or older. Methods: T20-310 was a multicenter, open-label, nonrandomized, noncomparative study of the safety and efficacy of 2.0 mg/kg (maximum 90 mg) twice-daily subcutaneous enfuvirtide for 48 weeks in 52 treatment-experienced, HIV-1-infected pediatric patients (3-16 years) receiving optimized background therapy. Results: Enfuvirtide was generally well tolerated, and no new patterns of adverse events compared with adults were observed. Mild-to-moderate injection-site reactions were the most common adverse event. Of those participants on treatment for 48 weeks, the median change from baseline in HIV-1 RNA was -1.17 log 10 copies/mL (n = 32), and there was a median CD4 change of +106 (n = 25) cells/mm 3 and +4.7 CD4%. Seventeen (32.7%) patients achieved a viral load decrease of >! log 10 copies/mL and 11 (21.2%) achieved HIV-1 RNA

Background. Entry inhibitors, a new class of antiretroviral agents, interfere with the attachment, coreceptor interaction or fusion of HIV-1 with host target cells. The fusion inhibitor T-20 is the first in this new class, and the present study is the first to examine chronic sc administration of T-20 to HIV-1-infected children. Methods. Fourteen children, 4 to 12 years of age, with incompletely suppressed HIV-1 were studied. The median plasma viral load at baseline was 26 866 copies/ml (4.4 log 10 ), and the median CD4 count was 523 cells/mm 3 . T-20 was administered twice daily by sc injection at 30 or 60 mg per m 2 of body surface area per dose. For 7 days T-20 was added to the patients' background antiretroviral regimens; at Day 7 each subject's background therapy was changed to a regimen that was predicted to be virologically active, while T-20 was continued. Results are presented for the first 24 weeks of chronic T-20 dosing. Results. T-20 was generally well-tolerated. One child discontinued the drug because of aversion to injections, but no child discontinued because of adverse events. Eleven (79%) of 14 children had local injection site reactions at some time during the chronic T-20 dosing. Eleven of 14 subjects achieved the protocol-specified milestone of at least a 0.7-log 10 reduction in plasma HIV-1 RNA by Day 7. In 10 subjects (71%) virologic suppression of 1.0 log 10 or greater was achieved at 24 weeks; 6 subjects (43%) had viral loads

Live varicella virus vaccine was administered to 10 stable human immunodeficiency virus type 1 (HIV-1)-infected children. Subjects were monitored for adverse reactions, HIV-1 plasma levels, CD4 T cell counts and immune responses. The vaccine was well-tolerated. Varicella-zoster virus-specific lymphocyte proliferative responses were detected in all subjects by 4 weeks and in 9 of 10 subjects 1 year after vaccination.

We describe a patient with chronic granulomatous disease and receiving immunosuppressive therapy for refractory granulomatous colitis who developed fatal fulminant pneumonia, with Trichosporon pullulans isolated from multiple sites. This case highlights potential difficulties in treating chronic granulomatous disease colitis with high dose immunosuppressants and suggests that T. pullulans may represent an opportunistic organism with high morbidity and mortality in such patients.

Objectives. To determine the prevalence of an acquired deficiency of protein S, a coagulation inhibitor, in children infected with the human immunodeficiency virus (HIV) and to identify clinical and laboratory features associated with this coagulation abnormality. Methods. A convenience sample of HIV-infected children, ages 2 to 18 years, was evaluated for total, free and functional protein S ; total and functional protein C ; prothrombin and activated partial thromboplastin times ; fibrinogen ; antithrombin III activity ; dilute Russell viper venom time ; IgG anticardiolipin antibodies ; von Willebrand factor antigen ; C4b-binding protein ; CD4+ T lymphocyte counts ; HIV p24 antigen concentration ; and serum β 2 -microglobulin concentrations. Results. Thirty-four subjects were evaluated. Twenty-four subjects were infected perinatally and 10 by transfusion. Nine of the subjects were CDC Class N (asymptomatic), 13 were Class A/B (symptomatic without AIDS-defining condition) and 12 were Class C (AIDS). None had previously documented thrombosis, nephrosis or significant hepatic dysfunction. Twenty-six subjects (76.5%) had decreased free protein S, and 19 (55.9%) had functional protein S

We report three HIV-infected children with bilateral progressive outer retinal necrosis caused by varicella-zoster virus. All three lost vision in both eyes. Aggressive treatment strategies with combination intravenous antiviral therapy in addition to intravitreal antiviral therapy and appropriate surgical management may prevent blindness. Rapid recognition of this distinct clinical syndrome is essential to improve visual outcome.

For identification of the features of disseminated Mycobacterium avium complex (DMAC) in human immunodeficiency virus (HIV)-infected children, a retrospective medical record review of 31 long-term survivors with transfusion-acquired HIV was conducted. Nine patients developed DMAC defined as positive isolation of M. avium complex from peripheral blood. DMAC was diagnosed in patients 51 to 132 months of age (mean, 101). The time from HIV-infecting transfusion to DMAC diagnosis ranged from 37 to 132 months (mean, 92) and survival from the time of DMAC diagnosis ranged from 4 to 21 months (mean, 10). Selected laboratory and clinical measures in DMAC-positive and DMAC-negative subjects were compared. DMAC-positive patients had significantly lower CD4+ T cell counts and higher HIV p24 antigen concentrations than DMAC-negative patients at comparable times. Increased percentages of circulating leukocyte band forms and increased aspartate aminotransferase values were seen more often in DMAC-positive patients. Fever and abdominal pain were the only clinical features seen more often in DMAC-positive than in DMAC-negative patients. At the end of the study period overall survival of DMAC-positive patients was less than that of DMAC-negative children, at 33% vs. 73%. DMAC occurs in profoundly immunocompromised children with advanced HIV disease and significantly affects survival. The clinical and laboratory features of DMAC are relatively nonspecific and a high index of suspicion in patients with markedly reduced CD4+ T cells is essential.

A case of a 10-year-old asthmatic patient who had cardiac arrest during induction for elective ear surgery is presented. The patient's serum theophylline level was 21.6 micrograms/mL one hour after surgery. It is likely that, since other factors that can contribute to cardiac arrest during the perioperative period were not present, the combined use of aminophylline and halothane was responsible.