Testing the equivalence of translations of widely used response choice labels: results from the IQOLA Project. International Quality of Life Assessment

The similarity in meaning assigned to response choice labels from the SF-36 Health Survey (SF-36) was evaluated across countries. Convenience samples of judges (range, 10 to 117; median = 48) from 13 countries rated translations of response choice labels, using a variation of the Thurstone method of equal appearing intervals. Judges marked a point on a 10-cm line-representing the magnitude of a response choice label (e.g., "good" relative to the anchors of "poor" and "excellent"). Ratings were evaluated to determine the ordinal consistency of response choice labels within a response scale; the degree to which differences between adjacent response choice labels were equal interval; and the amount of variance due to response choice label, country, judge, and interaction between response choice label and country. Results confirmed the hypothesized ordering of response choice labels; the percentage of ordinal pairs ranged from 88.7% to 100% (median = 98.2%) across countries and response scales. Examination of the average magnitudes of response choice labels supported the "quasi-interval" nature of the scales. Analysis of variance (ANOVA) results supported the generalizability of response choice magnitudes across countries; labels explained 64% to 77% of the variance in ratings, and country explained 1% to 3%. These results support the equivalence of SF-36 response choice labels across countries. Departures from the assumption of equal intervals, when observed, were similar across countries and were greatest for the two response scales that are recalibrated under standard SF-36 scoring. Results provide justification for scoring translations of individual items using standard SF-36 scoring; whether these items form the same scales in other countries as they do in the United States is evaluated with tests of scaling assumptions.     

Frequency specificity of vibration dependent discharge of nematocysts in sea anemones

Hair bundles on tentacles of sea anemones are similar to vertebrate hair bundles in terms of structure and function. Anemone hair bundles are involved in regulating discharge of nematocysts, "stinging capsules," used to capture prey. N-acetylated sugars from the prey including N-acetylneuraminic acid (NANA) induce hair bundles to elongate while shifting vibration dependent discharge of nematocysts to lower frequencies matching prey movements. In the present study, we find that vibration dependent discharge of nematocysts exhibits sharp frequency discrimination to within one Hz. Testing at one-Hz intervals over the range of frequencies spanning 1-75 Hz, we find that seven of these are stimulatory in seawater alone. A total of twenty-six frequencies are stimulatory in the presence of NANA. Stimulatory frequencies in NANA are lower than those in seawater alone. We find that antagonists of ryanodine receptors including ryanodine, procaine and tetracaine shift discharge to lower frequencies. Fluorescently tagged ryanodine labels numerous small loci in the apical cytoplasm of supporting cells. We propose that calcium induced calcium release (CICR) via ryanodine receptors may sharpen frequency specificity and/or cause shortening of hair bundles to shift frequency specificity to higher frequencies.     

Do Medicare HMOs cost shift?

We tested the hypothesis that health maintenance organizations (HMOs) increase their commercial premiums when Medicare pays less. Such a linkage would be taken as evidence of "cost shifting." Other studies have tested the cost-shifting hypothesis among health care providers, but this is the first to examine the HMO industry. Our data consisted of annual observations on all HMOs that operated in the United States between 1990 and 1995 and had a Medicare risk contract. A comparison group of HMOs that had no Medicare contract during that period also was analyzed. The main finding from this study is that HMOs have not shifted costs from Medicare to commercial premiums. This results supports the skeptical consensus that is developing toward the cost-shifting hypothesis. Additional findings include the negative effects of competition and for-profit status on HMOs' commercial premiums.     

Voltammetric studies on mechanisms of dopamine efflux in the presence of substrates and cocaine from cells expressing human norepinephrine transporter

The effects of substrates m-tyramine and beta-phenethylamine, as well as cocaine, on the DA efflux from a cell line stably expressing the human norepinephrine transporter (hNET) were investigated by using rotating disk electrode voltammetry. Both the substrates and cocaine induced apparent DA efflux in a concentration-dependent manner. Their EC50 values for inducing DA efflux were similar to their IC50 values for inhibiting DA uptake. The substrate-induced DA efflux was inhibited by various NET blockers, enhanced by raising the internal [Na+] with Na+,K+-ATPase inhibition, but was insensitive to membrane potential-altering agents valinomycin, veratridine, and high [K+]. The initial rate of m-tyramine-induced DA efflux was related to preloaded [DA] in a manner defined by a Michaelis-Menten expression. In contrast, DA efflux in the presence of cocaine displayed a much slower efflux rate, lower efficacy, was not stimulated by elevated internal [Na+], and was nonsaturable with preloaded [DA]. Single exponential kinetic analysis of the entire time course of the DA efflux showed that the apparent first-order rate constant for m-tyramine-induced DA efflux declined with increased preloaded [DA], whereas that for the DA efflux in the presence of cocaine was unchanged with varying preloaded [DA]. These results suggest that the substrates stimulate the NET-dependent DA efflux by increasing the accessibility of the NET to internal DA, whereas cocaine "uncovers" NET-independent DA efflux by reducing the accessibility of diffused/leaked external DA to the NET.     

Functional organization of owl monkey lateral geniculate nucleus and visual cortex

The nocturnal, New World owl monkey (Aotus trivirgatus) has a rod-dominated retina containing only a single cone type, supporting only the most rudimentary color vision. However, it does have well-developed magnocellular (M) and parvocellular (P) retinostriate pathways and striate cortical architecture [as defined by the pattern of staining for the activity-dependent marker cytochrome oxidase (CO)] similar to that seen in diurnal primates. We recorded from single neurons in anesthetized, paralyzed owl monkeys using drifting, luminance-modulated sinusoidal gratings, comparing receptive field properties of M and P neurons in the lateral geniculate nucleus and in V1 neurons assigned to CO "blob," "edge," and "interblob" regions and across layers. Tested with achromatic stimuli, the receptive field properties of M and P neurons resembled those reported for other primates. The contrast sensitivity of P cells in the owl monkey was similar to that of P cells in the macaque, but the contrast sensitivities of M cells in the owl monkey were markedly lower than those in the macaque. We found no differences in eye dominance, orientation, or spatial frequency tuning, temporal frequency tuning, or contrast response for V1 neurons assigned to different CO compartments; we did find fewer direction-selective cells in blobs than in other compartments. We noticed laminar differences in some receptive field properties. Cells in the supragranular layers preferred higher spatial and lower temporal frequencies and had lower contrast sensitivity than did cells in the granular and infragranular layers. Our data suggest that the receptive field properties across functional compartments in V1 are quite homogeneous, inconsistent with the notion that CO blobs anatomically segregate signals from different functional "streams."     

New p-terphenyl and polyketide metabolites from the sclerotia of Penicillium raistrickii

Three new p-terphenyls (1-3), a new xanthone derivative (4), and two known fungal metabolites (5 and 6) have been isolated from the sclerotia of Penicillium raistrickii (NRRL 2039). The structures for 3,3"-dihydroxy-6'-desmethylterphenyllin (1); 3'-demethoxy-6'-desmethyl-5'-methoxycandidusin B (2); 6'-desmethylcandidusin B (3); and 1,3,5, 6-tetrahydroxy-8-methylxanthone (4) were determined on the basis of HRMS and NMR data. Although compounds 1 and 4 exhibited mild antiinsectan and antibacterial activity, griseofulvin (5) was responsible for most of the activity of the sclerotial extract in dietary assays against the corn earworm Helicoverpa zea.     

Nuclear matrix proteins distinguish normal diploid osteoblasts from osteosarcoma cells

We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of the disease, several patients developed myoclonus and generalized epileptic seizures and eventually died with profound dementia. The "Torino family" shows several genealogic and clinical similarities with other large multigenerational familial Alzheimer's disease pedigrees originating from the Calabria region.     

Echocardiogram in common (single) ventricle: angiographic-anatomic correlation

Common ventricle is a rare congenital anomaly in which the ventricular chamber receives blood from two separate atrioventricular (A-V) valves or a common A-V valve. Diagnosis of common ventricle was established in 55 patients aged 3 months to 33 years (mean 10 years) at cardiac catheterization in all 55 and at operation or autopsy in 24. In common ventricle with two angiographically demonstrable A-V valves (47 patients), the echocardiographic features included: (1) simultaneous recording (in the same sonic beam with the transducer held stationary) of the echoes of an anterior and a posterior A-V valve without an intervening septal echo (45 of 47 patients); (2) absence, on a base to apex scan, of the ventricular septal echo in the usual position separating the A-V valves (47 of 47 patients); (3) recording, in patients with common ventricle and outflow chamber, of this small outflow chamber anterior to the A-V valves (20 of 23 patients); and (4) recording of echographic continuity of the posterior A-V valve and great artery (27 of 31 patients). In common ventricle with a common A-V valve (8 patients), the echocardiographic features included: (1) a single demonstrable A-V valve, located posteriorly in the ventricle, which showed a large amplitude of excursion during diastole; and (2) absence of a second A-V valve echo or ventricular septal echo. Eight patients were studied postoperatively after surgical correction by ventricular septation. Echographic features included visualization of a prosthetic septum that produced a dense echo and divided the common ventricle into "right" and "left" ventricular chambers. This septum had a large excursion anteriorly during systole. Because common ventricle is now amenable to surgical correction, echocardiography should play an important role in assessment of ventricular anatomy in this complex congenital cardiac defect.     

Suggested guidelines for rating cardiac disability in workers' compensation. Medical and Chiropractic Advisory Committee to the Administrative Director of the California Division of Industrial Accidents

Cardiac disability ratings in workers' compensation cases currently lack any consistent scientific basis, with varying medical evidence used by different examiners in the same case. Opinions about the extent of disability may differ with the same patient, delaying resolution and the delivery of benefits. We describe guidelines for determining cardiac impairment and suggest a schedule for rating disability based on evidence. Our experience is in California, but arriving at equitable ratings for disability purposes is a nationwide challenge. Exercise stress testing provides the best reproducible data to test the heart's ability to do work. When exercise stress testing is not possible or adequate, alternative or supplemental testing is necessary. Certain conditions, such as hypertension, arrhythmias, coronary artery spasm, and a history of coronary artery operations or myocardial infarction, may affect "cardiac disability" but may not necessarily be reflected in exercise testing.     

Combined silver Perls's stain for differential staining of ringed sideroblasts and marrow iron

During a study of nucleolar organiser regions, a modified silver stain was found to be a sensitive marker for the iron in ringed sideroblasts, more so than Perls's stain when the marrow iron stores were low. To enhance the usefulness of the silver stain, a combined silver Perls method was developed. This stains the ringed sideroblast iron black and haemosiderin blue, thus rendering the detection of ringed sideroblasts easier even when marrow iron stores are excessive. AT the same time, it allows marrow iron content to be evaluated. The silver reagent in this combined method probably shows phosphate rather than the iron present in the abnormal mitochondria in ringed sideroblasts. This facilitates the differential staining of ringed sideroblast "iron" and haemosiderin.