A phase I trial in HIV negative healthy volunteers evaluating the effect of potent adjuvants on immunogenicity of a recombinant gp120W61D derived from dual tropic R5X4 HIV-1ACH320

Thirty healthy HIV negative volunteers were randomised to receive 200 micrograms of rgp120W61D in either: 3D-MPL and QS21, with an oil and water emulsion (SBAS-2) (13); or 3D-MPL and QS21 (SBAS-1) (11); or alum (six). Immunizations were given at 0, 4 and 28 weeks and 23 (77%) participants completed the schedule. Adverse events were more frequent (P < 0.001) and more severe (P < 0.001) in the SBAS-2 group. Binding antibodies to the homologous rgp120W61D were detected after the first immunisation only in those receiving SBAS-1 and SBAS-2, were maximal after the third immunization in all three groups, and persisted to week 84 only in the novel adjuvant groups. These differences were significant (p = 0.02). Neutralising antibodies to TCLA-strains of HIV-1 were observed after the second immunization in all three groups, were maximal after the third immunization, but did not neutralise homologous or heterologous PBMC derived primary HIV-1 isolates. Proliferative T-cell responses to rgp120W61D were maximal after the second immunization and reached very high values in the SBAS-2 group. HIV-1 specific CD8+ MHC Class I restricted cytotoxic T-lymphocytes were not seen in a subset of participants tested at a single timepoint. SBAS-2 with rgp120W61D induced antibody titres as high as those seen in HIV infection, but the quality of the antibodies remained different in that there was no evidence of primary isolate neutralisation. Although cell-mediated immunity was enhanced by SBAS-2 in terms of lymphoproliferative responses, HIV-1 specific CD8+ cytotoxicity was not demonstrated.     

Toxic Shock Syndrome Presenting to a Paediatric Service

Summary: A case of toxic shock syndrome occuring in a 13-year-old and presenting to a paediatric service is described. Some implications are discussed including an approach to menstrual protection and the question of future contraceptive needs.     

A predictive index of cure versus no cure in advanced ovarian carcinoma patients—Replacement of second-look laparotomy as a diagnostic test

Three hundred forty-two Stage III and IV epithelial ovarian carcinoma patients received cytoreductive surgery followed by Adriamycin and cisplatin, 50 mg/m2 each, q 4 weeks for 9 courses. One hundred ninety-seven were clinically NED at completion of treatment and 173 of these 197 had a second-look laparotomy. One hundred twenty had persistent disease. Fifty-three were second-look negative and had no further treatment. Thirty of these latter patients relapsed--all (with one exception) within 2 years. Those not relapsing after negative second-look are considered "cured" (median follow-up 42 months, range 24-68 months) and all others "failures." Stage was a significant predictor of treatment failure--there were no Stage IV "cures." In Stage III patients, age and largest residual tumor diameter post initial surgery were significant predictors of failure. Performance status was marginally significant. In our series, any patient with Stage IV disease or Stage III disease with at least two of the following three poor prognostic factors had a chance of cure of 2.2% (2 "cures" out of 90 patients): age greater than 60 years, macroscopic residual initially, or initial performance status of 2 or 3. Under normal circumstances a second-look procedure to identify persistent disease in this group of patients does not appear justified.     

The effects of maternal hyperoxia on fetal breathing movements in third-trimester pregnancies

Fetal breathing movements and gross fetal body movements were observed before, during, and after maternal hyperoxia induced by inhalation of 50% oxygen in 14 women with normal term pregnancies. Studies were performed with real-time B-scan linear-array ultrasound and were standardized for time of day, maternal nutritional status, postprandial interval, and length of observation. Each study included a 30-minute baseline, followed by 15 minutes of hyperoxia, and 45 minutes of continued monitoring. No significant changes occurred in the mean incidences of fetal breathing movements, gross fetal body movements, the mean breathing rate, or breath interval variability, as analyzed in 5-minute epochs. Maternal PO2, as measured by transcutaneous electrodes, increased to the maximum level after 5 minutes of hyperoxia (155% over control levels). The breathing activity of normal third-trimester fetuses appears to be stimulated maximally in the second and third postprandial hours and cannot be further increased by maternal hyperoxia. This protocol represents a possible clinical strategy for investigating fetuses at risk for intrauterine hypoxia, provided that similar experimental conditions are maintained.     

Management of fractures in children with thermal injuries

The purpose of this study is to analyze how fractures are managed in children with associated acute burns. A retrospective review of 20 years of experience at a major U.S. burn center was undertaken. A total of 28 fractures in 18 patients were identified during this time period. Variables studied included mechanism of the burn, fracture location, associated injuries, and type of fracture. The fractures were then analyzed according to management, healing times, and complication rates. Of the 24 available fractures, 22 went on to union in an appropriate amount of time. The average rate to union was 9.9 weeks and average follow-up was 32.5 months. There were five infectious complications, one loss of reduction, one knee instability, and one malunion requiring additional surgery. This study supports early definitive fracture treatment in the burned child. If internal fixation is chosen, it can be safely performed if performed within the first 48 hours after the burn. External fixation is also a viable alternative. High rates of union are possible.     

ADMAdda5]-microcystins in Planktothrix agardhii strain PH-123 (cyanobacteria)--importance for monitoring of microcystins in the environment

Two major and two minor microcystins (MCYST) were isolated from a hepatotoxic Danish strain of Planktothrix agardhii (Gomont) Anagnostidis et Komárek by reversed-phase high-performance liquid chromatography. The microcystins were characterized by UV spectroscopy, amino acid analysis, fast atom bombardment mass spectrometry (FABMS), and high-resolution FABMS. The major microcystins were further analysed by collisionally induced tandem electrospray ionization MS. The microcystins were found to be demethylated variants of MCYST-HtyR (homotyrosine-arginine) and MCYST-LR (leucine-arginine). The two major microcystins contained an acetyl-demethyl variant (ADMAdda) of 3-amino-9-acetoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda). This is the first report of [ADMAdda5]-microcystins in Planktothrix. The two [ADMAdda5]-microcystins inhibited protein phosphatase activity but showed low cross-reactivity with antibodies of an enzyme-linked immunosorbent assay (ELISA), emphasizing the potential underestimation of the toxicity of natural blooms dominated by Planktothrix when microcystin content is quantified using only an ELISA.     

Clinical aspects and management of cytomegalovirus infection

The previous article discussed recent advances in understanding the biology of HCMV infection. Here we discuss current approaches to the clinical management of HCMV disease, and how understanding the biology of the virus may affect these.