Clinical applications of fundus reflection densitometry

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.     

Cross-cultural generalizability of personality dimensions: relating indigenous and imported dimensions in two cultures

The cross-cultural generalizability of personality dimensions was investigated by (a) identifying indigenous Philippine dimensions, (b) testing the cross-cultural replicability of the NEO 5-factor model (P. T. Costa & R.R. McCrae, 1992), and (c) relating Philippine and Western dimensions in Philippine and U.S. samples of college students. Filipino self-ratings (N = 536) on indigenous items were factor analyzed, and 6 Philippine dimensions were obtained. Conclusions about the replicability of the 5-factor model in the Philippines (N = 432) depended on whether exploratory, Procrustes, or confirmatory factor methods were used. In regression and joint factor analyses, moderate to strong associations were found between the Philippine dimensions and (a) dimensions from the 5-factor model in both Philippine (N = 387) and U.S. (N = 610) samples, and (b) the Tellegen model (A. Tellegen, 1985; A. Tellegen & N.G. Waller, in press) in a U.S. sample (N = 603).     

The influence of hypoxia on the cytotoxicity of concomitant KW-2149 and ionizing irradiation in Chinese hamster fibroblasts

7-N-((2-((2-(gamma-L-glutamylamino)ethyl)dithio)ethyl))-mitomycin C (KW-2149) is a newly synthesized water-soluble mitomycin C (MMC) analog. Preclinical testing showed an interesting activity profile and a superior hematological tolerance in murine models. The aim of this study was to investigate the interaction of this compound with ionizing radiation, both under normoxic and hypoxic conditions, in Chinese hamster fibroblasts (V79). V79 cells were irradiated both under normoxic conditions and after a 1 h period of hypoxia. Paired irradiation dose-response curves confirmed the significance of radioresistance under hypoxia with an oxygen enhancement ratio of approximately 3. In contrast to MMC, KW-2149 showed no increased cytotoxic effect on hypoxic V79 cells. The cytotoxic effect of KW-2149 increased with increasing concentration, irrespective of the ambient oxygen pressure. When KW-2149 was combined with irradiation under hypoxic conditions, cytotoxicity was significantly enhanced under these conditions. The difference in survival between normoxic and hypoxic conditions was statistically significant (p < 0.004). These data suggest a radiosensitizing effect of KW-2149, more pronounced under hypoxic conditions. This effect increases with radiation dose. It also corroborates earlier suggestions of a different mode of action of KW-2149 as compared to MMC.     

PLA2 promotes fusion between PMN-specific granules and complex liposomes

Neutrophil stimulation results in the activation of a variety of phospholipases, including phospholipase A2 (PLA2), which releases arachidonic acid from the 2 position of membrane phospholipids, leaving a lysophospholipid. Because arachidonic acid is known to be a potent fusogen in vitro, we examined the effect of metabolism by PLA2 on the fusion of complex liposomes (liposomes prepared with a phospholipid composition similar to that found in neutrophil plasma membrane). We observed that PLA2 augmented the fusion of complex liposomes with each other as well as with specific granules isolated from human neutrophils, lowering the Ca2+ requirement for fusion by three orders of magnitude. Furthermore, although lysophospholipids inhibited fusion, the incorporation of arachidonic acid into liposome membranes overcame the inhibitory effects of the lysophospholipids. Thus with PLA2 and annexins we were able to obtain fusion of complex liposomes at concentrations of Ca2+ that are close to physiological. Our data suggest that the activation of PLA2 and the generation of arachidonic acid may be the major fusion-promoting event mediating neutrophil degranulation.     

Status of cerebral circulation in patients with hemiplegia of vascular and traumatic origin treated with decimeter therapy and an alternating magnetic field

Results of treating 181 patients for hemiparesis after a cerebral stroke or a craniocerebral injury by local exposure of the pathological focus to decimeter electromagnetic waves (DW) and alternating magnetic field (AMF) are presented. It is shown that these treatment methods improve the cerebral circulation and contribute to earlier restoration of the motor functions, especially, if used in combination with sulfide baths, therapeutic physical exercises and massage. The therapeutic effectiveness of the DW- and AMF-therapy is confirmed objectively by so informative examination methods, as rheoencephalography, ultrasonic dopplerography, and thermography.     

Metabolism and biochemical effects of 3,3',4,4'-tetrachlorobiphenyl in pregnant and fetal rats

The metabolism and distribution of a single oral dose of 25 mumol 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (14C-TCB) were investigated in pregnant female Wistar rats and their fetuses. TCB was administered on day 13 of gestation and the elimination was followed for 7 days. Non-pregnant rats were treated similarly for comparison. Fecal elimination of 14C-TCB derived radioactivity was significantly lower in pregnant rats than in non-pregnant rats. The major metabolite found in adult liver and plasma, placental tissue, whole fetuses and fetal plasma was 3,3',4',5-tetrachloro-4-biphenylol (4-OH-TCB). Tissue levels (liver, abdominal fat, skin, skeletal muscle, kidney and plasma) of 14C-TCB-derived radioactivity declined by 65-85% over a 7-day period following administration in the adult animals. However, 14C-TCB-derived radioactivity accumulated more than 100-fold in the fetuses over the same time period, and GC/MS analysis revealed that the fetal accumulation in radioactivity was due primarily to 4-OH-TCB, and not the parent compound. On day 20 of gestation, concentrations of 4-OH-TCB were 14 times greater in fetal plasma than maternal plasma. Treatment with 14C-TCB significantly reduced plasma thyroxine levels by at least 28% up to 7 days after administration in non-pregnant animals and up to 4 days after administration in pregnant rats (31% decrease). By 7 days after administration plasma thyroxine levels had returned to control levels in the TCB-treated pregnant rats. However, fetal plasma thyroxine levels were significantly decreased by 35% in fetuses from 14C-TCB-treated dams 7 days after TCB administration. Hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity was significantly induced in TCB-treated dams relative to controls at 4 and 7 days after administration, while no EROD activity was detected in hepatic microsomes from control or TCB treated fetal rats at day 20 of gestation. These data suggest that hydroxylated metabolites of polychlorinated biphenyls may play a role in the development toxicity of these compounds.     

Prevalence of asymptomatic carotid stenosis in patients undergoing infrainguinal bypass surgery

BACKGROUND: The prevalence of asymptomatic carotid stenosis in patients with lower-extremity ischemia is unknown. This report represents the largest carotid screening program to date of patients undergoing leg bypass. DESIGN: Patients undergoing infrainguinal bypass from 1987 through 1993 on the vascular surgery service at Oregon Health Sciences University, Portland, underwent routine carotid duplex examinations to detect the presence of asymptomatic carotid stenosis. PATIENTS: During the study period, 352 patients underwent infrainguinal revascularization for ischemia, of whom 225 (64%) had no prior carotid surgery, carotid arteriography, or cerebrovascular symptoms. There were 117 men and 108 women, with a mean age of 67 years. The indication for surgery was limb salvage in 67% and claudication in 33% of patients. RESULTS: Sixty-four patients (28.4%) who required lower-extremity revascularization had hemodynamically significant asymptomatic carotid artery stenosis or occlusion; 12.4% had stenosis of 60% or greater, the qualifying level for randomization in the Asymptomatic Carotid Atherosclerosis Study. Based on these findings, eight patients with carotid stenosis of 80% or greater underwent elective carotid endarterectomy. There were no postoperative neurologic events in the 225 leg bypass patients. By multivariate logistic regression analysis, the presence of carotid bruit (P < .001) and the presence of rest pain (P = .006) were associated with carotid stenosis of 50% or greater. Limiting screening to patients with carotid bruit, limb salvage indications for surgery, and/or advanced age excluded significant numbers of patients with stenosis; thus, these were not effective screening strategies. CONCLUSION: Screening carotid duplex scanning is indicated in patients who require lower-extremity revascularization.     

Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen

This paper examines why the law concerns itself with euthanasia. The nature of the right to life and its protection in law is explored. Such a right demands legal intervention to prohibit, or at least control, involuntary and non-voluntary euthanasia. Voluntary euthanasia is not a violation of the individual's right to life as such, so on what grounds can law limit autonomy by prohibiting such conduct? It is suggested that, while concepts of sanctity of life still play a part in the legal debate, fears of abuse in any scheme for voluntary euthanasia largely explain the reluctance of many jurisdictions to follow the example of The Netherlands. Finally, the paper asks whether reform and regulation of voluntary euthanasia are as attractive options as they are sometimes portrayed.