Predominant type 1 CMV-specific memory T-helper response in humans: evidence for gender differences in cytokine secretion

Cell-mediated memory immune responses to viral antigens are important for protection against viruses causing persistent or acute infections. This study compared the cytokine profile of memory T-helper cells specific for cytomegalovirus (CMV) in healthy CMV-seropositive men and women. The cytokine response reflected T(H)1 bias, with dominant secretion of interferon (IFN)-gamma along with moderate levels of tumor necrosis factor-alpha, interleukin (IL)-10, and IL-2. Analyzed by gender, women had higher and significant spontaneous release of IFN-gamma and CMV-specific IL-2 secretion. Similar analysis with herpes simplex virus-1 showed a trend toward higher cytokine responsiveness in women, but the differences were not statistically significant. In contrast, men had statistically significant higher influenza virus-specific tumor necrosis factor-alpha secretion. IL-4 and IL-5, both T(H)2 cytokines, were low for all three viruses. The results show a predominant T(H)1 antiviral cytokine T-help memory response with significant differences linked to gender. Such differences may have an impact in the design of immunization strategies against CMV.     

A meta-analysis of the effect of HIV prevention interventions on the sex behaviors of drug users in the United States

We examined the effectiveness of 33 U.S.-based HIV intervention studies in reducing the sexual risk behaviors of drug users by reducing unprotected sex or increasing the use of male condoms. The studies, identified as of June 1998, through the HIV/AIDS Prevention Research Synthesis project, were published in 1988 or later, measured behavioral or biologic outcomes, used experimental designs or certain quasi-experimental designs, and reported sufficient data for calculating an effect size for sexual risk reduction. Of the 33 studies, 94% recruited injection drug users; 21% recruited crack users. The mean age of participants was 36 years. Almost all studies were randomized (94%), provided another HIV intervention to the comparison groups (91%), and evaluated behavioral interventions (91%). On average, interventions were conducted in 5 sessions (total, 10 hours) during 4.5 months. Interventions compared with no interventions were strong and significant (k = 3; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.43-0.85). Interventions compared with other HIV interventions showed a modest additional benefit (k = 30; OR, 0.91; 95% CI, 0.81-1.03). When we extrapolated our result (an OR of 0.60) to a population with a 72% prevalence of risk behavior, the proportion of drug users who reduced their risk behaviors was 12.6% greater in the intervention groups than in the comparison groups. Our meta-analysis shows that interventions can lead to sexual risk reduction among drug users and justifies providing interventions to drug users. Developing interventions with stronger effects to further reduce sexual risk behaviors among drug users must remain a high priority.     

Electrolyte Medium Effects on Measurements of Palmar Skin Potential

Two experiments with 12 subjects each compared skin potential recordings taken simultaneously with four different electrolytes. These were polyethylene glycol, hydrated agar (at a site presoaked with water), fresh agar (i.e., not presoaked), and Unibase. The glycol controlled epidermal hydration at a minimal level, while presoaking produced a high level of hydration at the hydrated agar site. Fresh agar and Unibase represented normal recording conditions for these two electrolytes which have been recommended as “standard” for electrodermal measurements. This design permitted a comparison of two standard electrolytes with each other and with recordings from hydrated and unhydrated sites. These comparisons were made for both monophasic negative SPRs and positive SPRs and the prestimulus levels associated with each. The results replicated previous studies in showing a large effect of epidermal hydration on skin potential measurements. Recordings with agar and Unibase did not differ significantly. The effects of hydration were interpreted in terms of a reduction in the resistance of the stratum corneum and of alterations in the functioning of the dermal and epidermal membranes as a result of blockage of the sweat gland pore. In the light of this interpretation, it was suggested that both agar and Unibase substantially alter the functioning of the sweat glands under some conditions, and neither may be entirely suitable for skin potential measurements.     

Spectral electroencephalographic correlates of iron status: Tired blood revisited

For some time, clinical reports have described impairment of affective and cognitive functions in iron deficient persons. Recent studies suggest that both brain biochemistry and cognitive performance capacity may be disrupted by inadequate intake of dietary iron, but the relationship of the possible neurophysiological effects to psychological ones is unclear. To examine the relationship of iron status to simultaneous measures of cortical activation and cognitive performance, 8 channels of electroencephalographic (EEG) data were recorded during a resting period and during the performance of several cognitive tasks in two groups of men. The EEG data were spectrally analyzed, and measures of total power and frequency of peak power in each of several bands of the power spectrum for each channel were used as predictors in multiple regression analyses with serum iron and serum ferritin as alternative criteria. Measures of power in the delta frequency in the resting period appeared relevant to iron status in both groups, perhaps indicating alertness or arousal level. Consistently in these regressions, the asymmetry of the EEG appeared relevant to iron and ferritin. These findings suggest that the combination of EEG and performance measures may help characterize the neuropsychological effects of trace element nutrition.     

Allelic exclusion of {alpha} chains in TCRs

Although the ß chains of ß⁺ T cells exhibitallelic exclusion it has recently been shown that 20–30%of such cells express both chain alleles on their surface.Potentially these cells have dual specificity, and it has beensuggested that they may play a role in autoimmunity and alloreactlvtty.The analysis presented in this paper examines critically thepossibility that the observed violation of allelic exclusionof chain expression arises as a natural consequence of a chainrearrangement and intrathymlc positive selection. It is concludedthat, subject to certain identified conditions being satisfied,the observed frequency of T cells expressing two chains iscompatible with such a mechanism. However, It is an essentialassumption of the theory that, of the two ß chaincomplexes on these cells, only one mediates positive selection.It follows that to what extent both receptors are actually functionaldepends on whether an ß chain complex that has failedto satisfy the criterion of positive selection can mediate antigenrecognition in the periphery. In principle the answer to thisquestion may be different if one is considering autoreactlvltyor alloreactlvlty. Finally, attention is drawn to the apparentdiscrepancy between the frequency of peripheral T cells expressingtwo chains and the failure to find T cell clones of this phenotype.Possible explanations are discussed.     

Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease)

Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30–20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG light-rise potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of non-invasive diagnosis.     

Mechanisms of central conduction time prolongation in brain-stem auditory evoked potentials

The wave I-wave V delay in the auditory brain-stem response is commonly used as a diagnostic tool in otoneurology. Normative values have been established for different populations and different types of stimuli. This I-V delay has been known for some time as "central conduction time" or "central transmission time." This implies that the measure reflects in normal and in pathologic cases delays due to nerve conduction, synaptic transmission, and neural integration and is not caused by cochlear processes. By virtue of the traveling wave delay in the cochlea, amounting to some 4 ms from the base to the "500-Hz place," it is conceivable that this delay contributes to the I-V delay. From a series of 69 pontine angle tumors in which the auditory brain-stem response was recorded, we selected cases with an apparent peripheral origin of a prolonged I-V delay by comparing the whole-click response to responses derived from high-pass noise masking. It seems that cases with an increased I-V delay in the whole-click response but (almost) normal I-V delays in the narrow-band response are indicative of small intracanalicular acoustic neuroma.     

Pharmacokinetics of vindesine bolus and infusion

Summary The pharmacokinetics of vindesine were investigated during treatment of 15 patients with progressive malignancies refractory to conventional treatment. Patients were administered one of three IV dose schedules: 3.0 mg/m² bolus injection, 1.2 mg/m²/day infusion for 5 days, or 2.0 mg/m²/day infusion for 2 days. Concentrations of the drug in the serum and urine were determined by radioimmunoassay. Serum concentrations were highest (5×10^-7 M) in patients receiving a bolus injection, but fell to nondetectable levels by 48 h in four of five patients (terminal t_1/2 15.0±9.4 h). Compared with bolus injection, 1.2-to 1.4-fold greater areas under the blood concentration curve were observed during infusions of 2.0 mg/m² and 1.2 mg/m². Whereas steady-state concentrations (1×10^-8 M) were maintained throughout the infusion of 1.2 mg/m²/day progressively increasing serum levels were observed during the infusion of 2.0 mg/m²/day. Serum concentrations fell rapidly following discontinuation of the 2.0-mg/m² infusion, but were somewhat more sustained in the 1.2-mg/m² infusion group. The average urinary excretion was similar for each dose-schedule (8%–11% of the total dose). The pharmacokinetics of vindesine are influenced by variations in dose schedule.     

Jan Hendrik Louw and intestinal atresia – a personal quest in pediatric surgery

Jan Hendrik Louw (1915–1992), considered the father of pediatric surgery in South Africa, gained prominence for his work on congenital intestinal atresia, a condition that had a mortality as high as 75 percent. His hypothesis, that jejunoileal atresia arose from mesenteric circulatory accidents in utero, was the dominant view until recent research uncovered the involvement of genetic and embryological mechanisms. In the mid-1950s he was one of a number of surgeons to resect the enlarged bulbous segment proximal to the site of the atresia, a crucial step in the surgical approach to intestinal atresia that brought mortality below 10 percent. A world leader in surgery as chair of surgery at the Groote Schur Hospital in Cape Town for more than a quarter century, his work in surgical research took root from his private tragedy early in his career of the death of his own infant son of intestinal atresia, a condition to which he would contribute so much.     

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.