Multiple sclerosis and the workplace: report of an industry-based cluster

Eleven cases of MS occurred within a 10-year period in a zinc-related manufacturing plant. The observed disease incidence was greater than expected from population data, using multiple approaches to statistical analysis (p less than or equal to 0.01). A case-control study, performed to examine several zinc parameters in blood, failed to indicate specific abnormalities among the MS patients, but all subjects (both MS and controls) working in the plant demonstrated higher serum zinc levels than all subjects (MS and controls) not working there.     

Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes.

The pharmacological properties of two glutamate receptor subtypes, GluR-A/B and GluR-B/D, were examined in RNA-injected Xenopus oocytes using two-electrode voltage clamp. Concentration-response relations revealed that the potencies of L-glutamate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) varied slightly between the two receptor subtypes, but the rank order of agonist potency did not. The EC50 values for GluR-A/B receptors were 3.31 microM for AMPA, 6.16 microM for glutamate, and 57.5 microM for kainate, whereas the EC50 values for GluR-B/D receptors were 5.01 microM, 32.3 microM, and 64.6 microM for AMPA, L-glutamate, and kainate, respectively. The potencies of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) were quantified by Schild analysis. The potency of NBQX at blocking currents mediated by GluR-A/B receptors changed depending on the agonist used to activate the receptors (pA2 values were as follows: for block of kainate, 7.23 +/- 0.01; L-glutamate, 6.78 +/- 0.02; AMPA, 6.95 +/- 0.02). Differences between agonists were less marked in cells expressing GluR-B/D receptors (pA2 values: kainate, 7.28 +/- 0.01; L-glutamate, 7.30 +/- 0.02; AMPA, 7.35 +/- 0.01). In each case, the slope of the Schild regression was not different from unity, consistent with competitive antagonism of these receptors by NBQX. CNQX also blocked GluR-A/B and GluR-B/D receptors competitively but was less potent than NBQX and did not differentiate between agonists or subunit combination. These data suggest that L-glutamate, kainate, and AMPA bind to different receptor substructures on recombinant AMPA receptors and that NBQX but not CNQX binds to these sites with different affinities. Moreover, because the properties of these binding sites vary between GluR-A/B and GluR-B/D receptors, our findings provide a basis for mutational analysis aimed at identifying receptor domains involved in agonist and antagonist binding.     

Interobserver variability in neonatal cranial ultrasonography

The reliability of cranial ultrasound diagnosis in the premature neonate was examined using data from an ongoing multicentre study of the epidemiology and long-term consequences of neonatal brain haemorrhage. First week ultrasound films (obtained at 4 hours, 24 hours and 7 days) from 60 study subjects were randomly selected for independent review by two groups of experienced interpreters, and results were recorded separately for observations (i.e. presence or absence of an abnormal echodense area on a film) and interpretations (i.e. presence or absence of haemorrhage or ventricular dilatation) in each hemisphere. Because of deaths in the first week of life, the total number of films examined was 138. Concordance on the presence or absence of an abnormal echodensity was examined for each individual film for three areas of interest: the germinal matrix, the ventricles and the parenchyma. Concordance on the presence or absence of haemorrhage or ventricular dilatation was examined only for the seventh-day film, or the final film prior to death. Finally, concordance was analysed with the diagnostic interpretations grouped into categories thought to differ prognostically for long-term outcome. In general, concordance was poorest for germinal matrix lesions and best for parenchymal lesions. Concordance was lower for observations made on each individual film than it was for interpretation of the final film in each case. Fifty-five of 60 cases (92%) were assigned to the same major prognostic category by both readers. Ultrasound review conferences were held periodically and there was evidence that concordance in ultrasound reading and interpretation improved during the course of the study.     

Public–Private Collaboration in Health and Human Service Delivery: Evidence from Community Partnerships

The collaboration among public–private partnerships that applied to the Community Care Network (CCN) demonstration program of the Hospital Research and Educational Trust is examined. These partnerships link broad-based community coalitions with health and human service providers in efforts to improve community health and local service delivery. Although they willingly collaborated in identifying community health needs, coordinating services, and reporting to the community, partnership participants showed less alacrity in joining forces to reduce redundancy and increase efficiency. Such patterns suggest that organizations might best profit from working together on activities that maintain existing power relations and that have the potential to add prestige and attract new clients. Collaboration in these areas may be essential to building a foundation of trust that leads to future cooperation in more sensitive areas.     

Biochemical markers of compliance in the Physicians' Health Study

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer. To evaluate self-reported compliance with assigned treatment, we measured serum thromboxane B2, which is decreased after aspirin use, and plasma beta-carotene in samples of study participants drawn from three geographic locations in three different time periods. Thromboxane B2 levels were markedly lower in those assigned to aspirin (median = 63.5 pg/mL) than in those given aspirin placebo (median = 3,600 pg/mL, P less than .0001). Similarly, those assigned to beta-carotene had significantly higher levels (median = 1,176 ng/mL) than those given placebo (median = 306 ng/mL, P less than .0001). In addition, there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance (r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene, P less than .0001). These findings support the validity of the self-reported compliance in the Physicians' Health Study.     

Flow cytometric DNA ploidy pattern in dysplastic mucosa, and in primary and metastatic carcinomas in patients with longstanding ulcerative colitis

Eighty-nine fresh tissue samples from flat colonic mucosa, polypoid lesions, macroscopically evident carcinomas, and metastatic carcinomas from ten patients with longstanding ulcerative colitis (greater than or equal to 8 years duration) were analysed by DNA flow cytometry and light microscopy. Of a total of ten carcinomas found in six patients, six showed DNA aneuploidy. Three patients developed metastatic carcinomas, all with aneuploid cell populations with similar DNA indices as in the primary carcinoma. Furthermore, aneuploid cell populations with similar DNA indices often occurred, both in separate mucosa samples, as well as in mucosa and carcinoma samples, from the same patient. DNA aneuploidy was found in flat mucosa in five of the six patients with carcinoma, and in one of the four patients without carcinoma (P greater than 0.1). High grade dysplasia was found in only four of the six cases with carcinoma, indicating that high grade dysplasia is insufficient as marker for malignant development. DNA aneuploidy was found in 24% of the dysplastic mucosa samples, and in 18% of the non-dysplastic mucosa samples (n.s., both with regard to high and low grade dysplasia). Since abnormal DNA ploidy pattern was not confined to dysplastic epithelium only, DNA aneuploidy in flat mucosa may constitute an additional marker in the identification of patients at increased cancer risk who could benefit from a closer surveillance.     

The organization of trigeminotectal and trigeminothalamic neurons in rodents: a double-labeling study with fluorescent dyes

Retrogradely transported fluorescent dyes (fast blue and diamidino-dihydrochloride yellow) were used to compare the distributions of trigeminofugal neurons that project to the superior colliculus and/or the thalamus in three rodent species. The objective was to determine what the projection and collateralization patterns of these trigeminofugal pathways are and whether they are similar among different species. In each anesthetized animal, one dye was injected into the superior colliculus and the other into the topographically congruent area of the thalamus. Counts of the numbers of yellow, blue, and double-labeled neurons were made throughout the trigeminal complex: principalis, pars oralis, pars interpolaris, and pars caudalis. Trigeminothalamic projections were similar in each of the rodent species studied. The densest concentration of retrogradely labeled neurons was in principalis, with substantially fewer neurons in pars interpolaris, and fewer still in pars oralis and pars caudalis. These neurons were generally small and tended to have round or fusiform somata. A common pattern was also noted among the three species for trigeminotectal neurons. Most trigeminotectal projections originated from neurons in pars interpolaris, somewhat fewer from pars oralis, and the fewest from principalis and pars caudalis. These neurons tended to be the largest in each subdivision and were often multipolar. Following paired injections of the tracers, double-labeled neurons were scattered throughout the sensory trigeminal complex and had morphologies characteristic of single-labeled trigeminotectal neurons. Although comparatively few double-labeled neurons were observed in any species, most of those seen were restricted to the ventrolateral portion of pars interpolaris, a position that corresponds to the representation of the vibrissae. These data indicate that, regardless of the rodent species, the vast majority of labeled trigeminal neurons project either to the superior colliculus or the thalamus, but not to both targets. This might be expected on the basis of the very different behavioral roles these structures play. On the other hand, a subpopulation of trigeminal neurons exists (mainly in pars interpolaris) that does project to both the superior colliculus and the thalamus, perhaps because both structures require some of the same somatosensory information to perform their behavioral functions.