Neuropsychological functioning and sleep patterns in the elderly.

OBJECTIVE: To discover whether reported sleep-wake disturbances in the elderly (more frequent nocturnal awakenings, earlier waking and more day time naps) are associated with neuropsychological dysfunction. DESIGN AND SETTING: A sample of 124 residents of a retirement village complex were interviewed about their sleep patterns and given neuropsychological assessments. Reported sleep-wake difficulties were combined to form two variables, "night sleep" and "day sleep". Additional sleep variables analysed were reported sleep duration and time of wakening. Principal components analysis of the neuropsychological test scores yielded four factors: "general ability", "memory", "motor", and "cerebral efficiency". MAIN OUTCOME MEASURES: A correlation analysis was performed for sleep variables, neuropsychological factors and age, mood scale and scores on indices of participation in physical and passive activities. RESULTS: There was no correlation between "night sleep" and the factor scores derived from the neuropsychological tests. "Day sleep" was correlated with "cerebral efficiency" only. Age was correlated with the "memory" and "motor" factors, the latter also being associated with participation in physical activities. CONCLUSION: Night sleep problems are not associated with neuropsychological deficits in a non-clinic population.     

Intracellular calcium modulates gallbladder ion transport

Although experimentally induced cholesterol gallstone formation has been associated with altered gallbladder (GB) absorption and increased biliary Ca2+, the relationship between these events remains unclear. Recent studies suggest that extracellular Ca2+ ([Ca2+]ec) influences GB ion transport. Whether the effects of [Ca2+]ec are mediated by changes in intracellular Ca2+ ([Ca2+]ic) has not been determined. This study was designed to define the effects of altered [Ca2+]ic on GB ion transport. Prairie dog GBs were mounted in a Ussing chamber and short-circuit current (Isc), potential difference (Vms), and resistance (Rt) were recorded. Mucosal surfaces were exposed to either Dantrolene (Dt) or nickel (Ni2+). Dt "traps" [Ca2+]ic within intracellular organelles, thereby lowering cytosolic Ca2+; and Ni2+ prevents influx of [Ca2+]ec, presumably by binding Ca2+ channels. Although Dt reduced both Isc and Vms (P less than 0.01), these effects were transient. Transport recovery was probably due to increased [Ca2+]ec influx with restoration of [Ca2+]ic. Ni2+ resulted in sustained decreases in Isc and Vms (P less than 0.05) despite subsequent addition of 10 mM Ca2+. These findings are consistent with the prevention of [Ca2+]ec influx by Ni2+. We conclude that: (1) [Ca2+]ic may be a modulator of GB ion transport and (2) previously reported [Ca2+]ec effects on ion transport may be mediated through [Ca2+]ic concentration changes.     

Simple pressure bandage technique for free skin grafts.

We applied sterile packed cellulose sponges in the dehydrated state as a pressure dressing from skin grafts by using the classic "tie-over" technique. At the end of the procedure, the sponges were hydrated, and provided flat, even pressure to a localized area. By using this simple technique, we obtained 26 of 27 successful free skin grafts with flat apposition.     

Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomized trial of continuous hyperfractionated accelerated radiotherapy.

PURPOSE: Identification of factors that assist prediction of tumor response to radiotherapy may aid in refining treatment strategies and improving outcome. Possible association of molecular marker expression profiles with locoregional control of head and neck squamous cell carcinoma was investigated in a randomized trial of conventional versus continuous hyperfractionated accelerated radiotherapy (CHART). EXPERIMENTAL DESIGN: Tumor material was obtained from 402 patients. Immunohistochemistry was used to assess Ki-67, CD31, p53, Bcl-2, and cyclin D1 expression. A hierarchical clustering algorithm with a Bayesian information criterion was used to group tumors with similar marker expression; resulting expression profiles were then compared in terms of their difference in outcome after CHART and conventionally fractionated radiotherapy. RESULTS: Molecular marker profile was an independent prognostic factor for locoregional control. This was confirmed in multivariate analysis, including clinical variables such as tumor and nodal status, primary site, histological grade, age, and gender (P < 0.001 and P = 0.006 for local and nodal relapse, respectively). In particular, Bcl-2-positive tumors responded significantly better than average in both arms of the trial. Tumors negative for p53- and Bcl-2, with high and randomly patterned Ki-67 expression, responded worse than average with no benefit from CHART. Tumors with similarly negative p53 and Bcl-2, but low Ki-67 staining, with an organized pattern, benefit significantly from CHART schedule. CONCLUSIONS: This study demonstrates the potential of molecular profiles to predict radiotherapy response of head and neck squamous cell carcinoma and for treatment stratification. Distinct expression profiles correlate with three distinct clinical phenotypes, including good locoregional control, poor locoregional control, and an outcome strongly dependent upon fractionation schedule.     

The immunohistochemical assessment of hypoxia, vascularity and proliferation in bladder carcinoma.

BACKGROUND AND PURPOSE: Hypoxia and proliferation are important determinants of radiation responsiveness; prospective measures of these before radiotherapy may enable individualisation of treatment schedules. Immunohistochemical techniques offer a potential means of achieving this in routine biopsy material. MATERIAL AND METHODS: Cellular hypoxia as measured by pimonidazole fixation and immunohistochemistry has been evaluated in a series of human bladder cancers with dual staining of sections for pimonidazole and either the vascular markers, CD31/34, or proliferation markers, Ki-67 or cyclin A. Twenty one tumour specimens were examined suitable for the double staining technique. RESULTS: The median hypoxic fraction was 9% (range 0-38). Seven tumours did not stain for pimonidazole and 11 exhibited necrosis. The mean vascular density ranged from 16.7 to 160.6 vessels per mm2. The median hot spot count was 30 (range 16-43). There was a statistically significant increase in vessel density in hypoxic compared to oxic regions measured by both vessel density (P = 0.02) and hot spot count (P = 0.004). Proliferation indices decreased from oxic to hypoxic areas close to blood vessels. CONCLUSIONS: We have demonstrated that bladder cancer exhibits a range of hypoxia, proliferation and vascular density which may be used to form the basis for patient selection for hypoxia modification, accelerated radiotherapy and vascular targeting agents.     

Membranes for endotoxin removal from dialysate: considerations on feasibility of commercial ceramic membranes

As the quality of water in dialysis fluid varies considerably, dialysate is often contaminated by large amounts of bacteria and endotoxins. Membrane properties and operating pressures are acknowledged to give high-flux dialysis with bicarbonate the bacteriological potential to favor passage of endotoxin fragments from the dialysate into the blood stream. Therefore, a sterile dialysate will have to become a standard. Ultrafiltration across hydrophobic synthetic membranes was shown to remove endotoxins (and their fragments) from dialysis water by the combined effect of filtration and adsorption. However, each module can be used for a limited time only. Ceramic membranes may represent an alternative to polymeric membranes for endotoxin removal. In this article, we tested the capacity of different commercial ceramic membranes with nominal molecular weight cut-off down to 1,000 to retain endotoxins from Ps. aeruginosa. The tested membranes did not generally produce dialysate meeting the Association for the Advancement of Medical Instrumentation standard. When using aluminum-containing membranes, we detected aluminum leaking into the dialysate that could possibly be transported into the blood stream.     

Assault,PTSD, Family Substance Use,and Depression as Risk Factors for Cigarette Use in Youth: Findings from the National Survey of Adolescents

A national household probability sample of 4,023 adolescents aged 12 to 17 years was surveyed by telephone via structured clinical interview to determine the impact of familial substance use, sexual and physical assault, witnessed violence, depression and posttraumatic stress disorder (PTSD) on risk of smoking. Results indicated that familial substance use increased risk of smoking only for boys and sexual assault or depression increased risk of smoking only for girls. Age, Caucasian ethnicity, and experiencing physical assault or witnessing violence elevated risk of current cigarette use for both genders. By contrast, PTSD per se was not associated with increased risk of smoking, after the effects of other variables were controlled.     

Thermal stress and radiation protection principles.

Exposure to radiofrequency (RF) fields can occur in residential, occupational and medical settings. Since many technologies use RF fields, it is important to fully investigate their effects on the human body. Since the demonstrated effect of RF exposure is heating, it is important to critically evaluate studies of elevated temperature effects on the human body, from the cellular and tissue level to the whole body level, including potential effects on the susceptible groups such as the very young and the very old. WHO convened a Workshop in the Spring of 2002 on the subject of Adverse Temperature Levels in the Human. The goal of the workshop was to evaluate most recent data useful for the development of science-based RF exposure limits. This paper outlines radiation protection principles that underline such an evaluation. It discusses the quality of literature needed for sound scientific reviews, provides the hierarchy of scientific evidence used to establish effects, distinguish between biological effects and adverse health consequences and indicates how evidence is evaluated. In addition, criteria for determining the most sensitive effects, the value of an effect that has a dose-response and methods of extrapolation are also described. Finally, the need to account for scientific uncertainty in the formulation of guidance on exposure is discussed.     

Effects of heat on embryos and foetuses.

OBJECTIVES: This paper reviews the effects of elevated maternal temperature on embryo and foetal development in experimental animals and in humans. CONCLUSIONS: Hyperthermia during pregnancy can cause embryonic death, abortion, growth retardation and developmental defects. Processes critical to embryonic development, such as cell proliferation, migration, differentiation and programmed cell death (apoptosis) are adversely affected by elevated maternal temperatures, showing some similarity to the effects of ionizing radiation. The development of the central nervous system is especially susceptible: a 2.5 degrees C elevation for 1 h during early neural tube closure in rats resulted in an increased incidence of cranio-facial defects, and a 'spike' temperature elevation of 2-2.5 degrees C in an exposure of 1 h during early neurogenesis in guinea pigs caused an increase in the incidence of microencephaly. However, in general, thresholds and dose-response relationships vary between species and even between different strains of the same species, depending on genotype. This precludes rigorous quantitative extrapolation to humans, although some general principles can be inferred. In humans, epidemiological studies suggest that an elevation of maternal body temperature by 2 degrees C for at least 24 h during fever can cause a range of developmental defects, but there is little information on thresholds for shorter exposures. Further experimental and epidemiological studies are recommended, focusing on stage-specific developmental effects in the central nervous system using a variety of sensitive assays.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.