Visual abnormalities in albino wallabies: a brief note

Abnormally reduced uncrossed retinofugal pathways and abnormally low retinal cell densities have been described in albinos of a number of species of eutherian mammal, but have not been studied in marsupials. The optic chiasm of marsupials differs from that of the eutherian brains that have been studied, with uncrossed fibres segregating from crossed fibres prechiasmatically in the marsupials, but not in the eutherians. We have examined the optic chiasm and the retina in albino and normally pigmented wallabies (Macropus rufogriseus) to determine whether the abnormalities found in eutherian albinos are also present in this marsupial. The uncrossed pathway of the albino wallaby is smaller than that of the pigmented animals and the cell density in the retinal ganglion cell layer is reduced at the area centralis. We conclude that the characteristic albino abnormalities are present in both groups of mammals in spite of the other known differences in the visual pathways. The albino mutation acts at the chiasm in a similar manner in both groups even though the determinants of the chiasmatic pathway differ.     

Risk factors for rape, physical assault, and posttraumatic stress disorder in women: examination of differential multivariate relationships

The National Women's Study, a 2-year, three-wave longitudinal investigation, employed a national probability sample of 3,006 adult women to: (a) identify separate risk factors for rape and physical assault, and (b) identify separate risk factors associated with post-rape posttraumatic stress disorder (PTSD) and post-physical assault PTSD. This investigation differed from previous studies in that it prospectively examined risk factors at the multivariate, as opposed to univariate level. Overall, past victimization, young age, and a diagnosis of active PTSD increased women's risk of being raped. By contrast, past victimization, minority ethnic status, active depression, and drug use were associated with increased risk of being physically assaulted. Risk factors for PTSD following rape included a history of depression, alcohol abuse, or experienced injury during the rape. However, risk factors for PTSD following physical assault included only a history of depression and lower education.     

Plasminogen activator inhibitor type 2 in human corneal epithelium

PURPOSE: To examine normal human corneal epithelium in vivo and in vitro for expression and status of plasniinogcn activ:ltor inhibitor type 2 (PAI-2). METHODS: Normal hiuman corneas were prepared for frozen sections and for culture of corneal keratinocytes. PAI-2 was analyzed by immunohistochemistry and western blot analysis uising antibodies that recognize all forms of PAI-2. RESULTS: In vivo and in vitro, PAI-2 was immunohistochemically localized to the superficial corneal keratinocytes. Immunostaining also revealed the presence of PAI-2 in its relaxed (i.e., cleaved) conformation. In vivo, the staining pattern of the relaxed form was identical with that of total PAI-2, but in vitro the relaxed form was detected in a smaller subpopulation of superficial cells. In vitro, the staining pattern indicated a cytoplasmic localization for PAI-2. Western blot analysis revealed that most of the PAI-2 was cell associated and functionally active. CONCLUSIONS: The present results are the first to show that PAI-2 is found in normal human corneal epithelium in vivo and in vitro, where it can be considered as a differentiation product. At least in vitro, all detectable PAI-2 is cell associated, with a cytoplasmic distribution. A subpopulation of keratinocytes also contains PAI-2 in its relaxed (i.e., cleaved) conformation. Cleavage by an as yet unidentified cytoplasmic proteinase may constitute a crucial aspect of the function of corneal epithelial PAI-2, which may be relevant to terminal differentiation and death of the corneal keratinocyte.     

Studies on the stability of trimelamol, a carbinolamine-containing antitumor drug

The stability of trimelamol (N2,N4,N6-trimethylol-N2,N4,N6-trimethylmelamine) a synthetic carbinolamine-containing antitumor drug, has been studied. Two major degradation pathways have been characterized and a unified mechanism proposed to rationalize the chemistry involved. One degradation pathway involves the consecutive loss of hydroxymethylene units by elimination of formaldehyde until the parent trimethylmelamine (4) results. An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products. This pathway was shown to follow first-order kinetics at all pH values studied at both 18 and 37 degrees C. The second pathway involves the coupling of two trimelamol molecules via a methylene bridge to form bis(trimelamol) (6) which had been previously referred to in the literature as a "polymer". This reaction is acid catalyzed and temperature dependent. Bis(trimelamol) is virtually water insoluble and adheres strongly to glass surfaces. Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature. The data reported here are relevant to both the formulation and clinical administration of trimelamol, and may contribute to an understanding of mechanism of action and future analogue development studies.     

The no-reflow phenomenon is a post-mortem artifact

Summary Post-ischemic reperfusion impairment, (no-reflow phenomenon), was studied in rats subjected to 8–30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and³¹P-high energy phosphates (ATP/PCr) was observed.Brain intravascular perfusion defects were examined by injecting carbon blackintravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy andintraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats givenintraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in pale tissue areas suggestive of impaired perfusion (no-reflow). All rats given carbon blackintravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of pale tissue areas. In addition, post-ischemic cerebral reperfusion following 8–30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised.These findings indicate that the no-reflow phenomenon is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.     

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.