Mode of regulation of natural killer cell activity by interferon

Whereas xenogeneic tumors such as baby hamster kidney or HeLa cells grow in nude mice, the same cells persistently infected with a variety of viruses are rejected. Spleen cells from normal nude mice were found to be induced to produce interferon and to exert natural killer (NK) activity on virus persistently infected (PI) tumor cells, and not on uninfected parental cells in vitro. The phenotype of the interferon-producing cells and the NK effector cells was found to be the same namely, Qa 5(+), Ly 5(+), ganglio-N- tetraosylceramide, with 35 percent of the NK cells also expressing Thy 1.2. NK activity against virus PI tumor cell lines could be nonspecifically augmented both in vivo and in vitro by prior contact with virus PI tumor cells. It was unambiguously demonstrated with chemically homogeneous mouse interferon that interferon, and not a contaminant, was responsible for the augmentation of NK activity in vitro. Studies on the mode of interferon action in augmenting NK activity revealed that the target cell for interferon action was serologically distinct from the NK effector cell. Anti-Ly 5 + complement (C)-treated spleen cells were depleted of NK activity and the ability to produce interferon, but, upon incubation with interferon for 1-3 h, regained both NK activity and susceptibility to anti-Ly 5 + C. Treatment with anti-Qa 5 + C eliminated NK activity, which could not be restored by the addition of interferon. We conclude that interferon produced by Ly 5(+) cells in response to virus PI tumor cells acts on Ly 5(-) precursor cells and induces their differentiation into functional Ly 5(+) NK effector cells.     

Can point‐of‐care ultrasound predict spinal hypotension during caesarean section? A prospective observational study

Spinal anaesthesia for elective caesarean section is associated with maternal hypotension, secondary to alteration of sympathetic tone and hypovolemia, in up to 70% of cases. Measurement of the subaortic variation in the velocity time integral (VTI) after passive leg raising allows prediction of fluid responsiveness. Our objective, in this prospective single‐centre observational study, was to assess the ability of change in VTI after 45° passive leg raising to predict hypotension after spinal anaesthesia. Ultrasound measurements were performed just before elective caesarean section. Anaesthesia, intravenous coloading and prophylactic vasopressor treatment were standardised according to current guidelines. We studied 40 women. Hypotension occurred in 17 (45%) women. The area (95%CI) under the receiver operating characteristics (ROC) curve for the prediction of spinal hypotension was 0.8 (0.6–0.9; p = 0.0001). Seventeen women had a change in VTI with leg elevation ≤ 8%, which was predictive for not developing hypotension, and 11 had a change ≥ 21%, predictive for hypotension. The grey zone between 8% and 21%, with inconclusive values, included 12 women. We suggest that cardiac ultrasound provides characterisation of the risk of hypotension following spinal anaesthesia at elective caesarean section, and therefore may allow individualised strategies for prevention and management.     

Indocyanine green fluorescence-guided parathyroidectomy for primary hyperparathyroidism

Background

Our aim was to evaluate the ease and utility of using indocyanine green fluorescence angiography for intraoperative localization of the parathyroid glands.

Indinavir trough concentration as a determinant of early nephrolithiasis in HIV-1-infected adults

Indinavir plasma levels are associated with antiretroviral efficacy; however, little data are available regarding toxicity. We assessed the relationship between indinavir pharmacokinetic (PK) characteristics and severe nephrolithiasis as well as other severe or serious adverse reactions. Patients included in the ANRS CO8 APROCO-COPILOTE cohort and receiving 800 mg indinavir three times daily as a first-line protease inhibitor were eligible for this study. To be included in the analysis, their plasma sample at month 1 (M1) had to be available (n = 282) to estimate using population PK modeling, indinavir PK characteristics, ie, maximum (Cmax) and trough plasma (Cres) concentrations, area under the curve (AUC), and observed/predicted concentration ratio (CR). A Cox model was used to estimate the independent effect of Cmax, Cres, AUC, and CR on the hazard of severe nephrolithiasis and serious adverse reactions. At M1, median Cmax was 6205 ng/mL, Cres 631 ng/mL, AUC 24,242 ng . h/mL, and CR 0.6. After a median follow up of 12 months, 11% of patients (30 of 282) had experienced at least one serious adverse reaction among which 12 were nephrolithiasis. In the multivariate analyses, early high indinavir Cres (ie, >/=1000 ng/mL at M1) was associated with a higher rate of severe nephrolithiasis (hazard ratio = 6.7; 95% confidence interval = 1.8-25.2; P < 0.01) and was also associated with a higher rate of all serious adverse reactions but only when nephrolithiasis were included among those cases. Prospective and early indinavir Cres determination should be recommended in the patient's care management and dosage adjustments.     

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.     

Personal sports training in the management of obese boys aged 12 to 16 years]

OBJECTIVE: Estimation of both physical and psychological effects of an adapted physical training on children undergoing an obesity treatment. MATERIAL AND METHODS: The survey was carried out on 36 obese boys (ages = 12-16 years) who stayed in the medical center for at least four months. Eighteen of them were trained with the SELF method (the SELF-training is global, progressive, adapted to each boy, controlled and takes place within a ten-week period with five sessions a fortnight, each session lasting 30 to 40 minutes). The parameters that were studied concerned auxology, breathing function exploration, aerobic and anaerobic capacities, muscle strength and psychomotor qualities; the subjective effects of the training were estimated with a questionnaire about life quality, and the hand test. At inclusion the results were reported to a standard kind of population. At the end of the training the results of the 18 boys that were trained were compared to those of the 18 controls. RESULTS: Compared to a standard population, the obese children' aerobic capacity is diminished for the maximum power but is identical in absolute value for the VO2 max; their anaerobic capacities, muscle strength and psychomotor capacities are lower and their psyche is affected by the disease. After a three-month training period and after comparison with the 'control' group, there can be noticed a significant improvement in the psychomotor capacities, a major tendency for the improvement of the aerobic capacities and very positive effects on the psyche. CONCLUSION: SELF-training in association with dietetics appears to be very useful in the therapeutic care of obese children. For the follow-up at home it would need to be registered within the domain of physiotherapy.