Maternal HIV infection, drug use, and growth of uninfected children in their first 3 years

OBJECTIVE: To determine the separate effects of maternal HIV infection and drug use during pregnancy on growth of uninfected children in their first 3 years. DESIGN: Retrospective analysis of measurements from health visitor records made during routine child health surveillance at 6 weeks, 10 months, and 3 years of age. Multilevel analysis allowed for between-infant variation in fitted growth lines, and adjustment for other factors. Growth was described in terms of an intercept (z score at term) and growth slopes (change in z score per year) up to, and from, 4 months. SUBJECTS: 290 case babies delivered in Edinburgh hospitals to women who reported injection drug use by either themselves or their HIV infected partner, and 186 community controls. A total of 131 (45%) of the case babies were born to women who used drugs, predominantly opiates, during pregnancy and 93 (32%) to HIV infected women. The eight infected children were excluded from analysis. MAIN OUTCOME MEASURES: Age and sex standardised z scores for height, weight, and body mass index. RESULTS: 459 (96%) of the 476 records for cases and controls were traced, yielding 1432 weight and 939 height measurements. Maternal HIV infection was not found to affect growth; at 3 years the estimated effect on weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with lighter babies at 40 weeks followed by depressed growth in the first four months, these infants remaining just slightly smaller at 3 years with an estimated effect on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and -0.37 (-0.72 to -0.02) for height. CONCLUSIONS: Maternal HIV infection does not adversely affect growth in uninfected infants, and the effect of drug use during pregnancy is limited to small decrease in size at 3 years.     

Single-tone intensity discrimination based on auditory-nerve rate responses in backgrounds of quiet, noise, and with stimulation of the crossed olivocochlear bundle

We use simple statistical models of the firing patterns of high, medium, and low spontaneous rate auditory-nerve fibers to study mechanisms which determine the overall dynamic range of the auditory periphery. The models relate experimentally measured rate response properties of fibers with best frequency (BF) near 8.0 kHz to their ability to encode changes in BF tone level by changes in discharge rate in backgrounds of quiet and noise, with and without electrical stimulation of the crossed olivocochlear bundle (COCB). Application of the models to the BF tone rate responses of auditory-nerve fibers in backgrounds of quiet shows that optimum processing of the rate responses of fibers with BF near 8.0 kHz yields performance in the intensity discrimination task meeting or exceeding that of human subjects over an 80 dB range of levels. By defining a statistical measure of dynamic range, we confirm the results of Costalupes et al. (1984) demonstrating that masking noise shifts the dynamic range of auditory-nerve fibers to higher stimulus levels, thus preventing rate saturation. However, model analysis shows that masking noise also produces large reductions of dynamic range as well as large increases in the minimum intensity difference that can be encoded by the rate responses of single and ensembles of fibers. Electrical stimulation of the COCB can restore auditory-nerve fiber dynamic range and sensitivity to changes in BF tone level in noise backgrounds, in some cases to roughly that observed in backgrounds of quiet.     

Alternative oxygen therapeutics: products, status of clinical trials, and future prospects

Alternative oxygen therapeutics are oxygen carriers that can potentially replace red blood cell transfusion in clinical instances in which banked blood is unavailable or unsafe. Most of the candidate solutions have been based on hemoglobin, derived from animals, outdated banked human blood, or recombinant systems. Other solutions are based on perfluorocarbons. In contrast to hemoglobin, which chemically binds oxygen, perfluorocarbons carry oxygen as a dissolved gas. Most of the products of either category developed over the past two decades have failed attempts at regulatory approval for clinical use, but their development has led to a large body of research that has defined the way oxygen is normally delivered to tissues. From this research, a new generation of products is emerging, designed specifically to target oxygen to the tissues in most need. It is possible that one or more of the earlier products may be approved by regulatory agencies in 1 or 2 years. However, a universally compatible and safe product most likely will be unavailable for several more years.     

Intracellular ionic concentration by calibration from fluorescence indicator emission spectra,its relationship to the K(d), F(min), F(max) formula,and use with Na-Green for presynaptic sodium

The emission spectra calibration curves for a fluorescence indicator and the F(min), F(max), and K(d) formula were shown to be related. Using the known calibrated fluorescence emitted by Sodium Green (Na-Green) and photo-multiplier-tube quantum efficiency, we calculated the detection signal over a range of sodium concentrations. The calculated calibration curves were compared for optical filters passing a narrow band, medium band or full spectrum. We found that a method based on the full emission spectrum was the most appropriate. Given a known resting concentration of intracellular sodium, calibrated readings can be converted to concentration values. This method is applicable to any fluorescence indicator when curves for emission spectra over a range of concentrations are available. We measured sodium concentration changes during trains of action potentials (APs) at a crayfish motor axon's presynaptic terminals injected with Na-Green. During low frequency AP trains, net sodium increases asymptotically with frequency. Average net Na-flux per AP decreases for increasing terminal size. The terminals of crayfish motor axon have surface area to volume ratio which is 7700 times larger than for squid. Thus, in comparison to squid, crayfish terminals exhibit a larger change in [Na(+)](i) during equivalent AP activity.     

Blood substitutes

Blood substitutes are solutions intended to replace transfusion of banked red blood cells. Several variations of products based on either hemoglobin (animal or human) or perfluorocarbon emulsions are in advanced stages of clinical development. The need for such products is pressing as shortages of banked blood worsen and awareness of the dangers of blood transfusion increases. Animal and human studies with these cell-free oxygen carriers have led to new concepts of how oxygen is delivered to tissue and how the microcirculation is regulated. Although development of products is exciting and timely, understanding how they function to perfuse and oxygenate tissue could be at least as important. Because cell-free oxygen carriers will perfuse every organ of the body, their effects are far-reaching, and the transition from the laboratory to the bedside can be expected to be slow and deliberate. Comparison of oxygen carriers with more traditional starch-based products provides new insight into the interaction of oxygen transport, microvascular perfusion, and blood volume expansion.     

Sarcomatoid renal cell carcinoma: Rapid dissemination detected on FDG PET‐CT

We present the FDG PET‐CT findings in a patient with persistent pain 7 weeks after a nephrectomy and lymph node dissection for a sarcomatoid renal cell carcinoma. Although conventional imaging was unable to detect evidence of metastatic spread outside the para‐aortic nodes, a PET‐CT scan showed unexpected extensive dissemination. Currently, there are no reports in the literature of the PET‐CT findings in sarcomatoid renal cell carcinomas.