Exposure to isocyanates and organic solvents, and pulmonary-function changes in workers in a polyurethane molding process

The extent of adverse health effects of isocyanates when combined with other chemicals is not well documented. This study was conducted as a 2.5-year follow-up as well as to determine daily and weekly effects of exposure to isocyanates and organic solvents on pulmonary function. The concentrations of chemicals sampled were below the recommended exposure criteria. No daily or weekly reduction in the subjects' pulmonary function was observed. The isocyanate/solvent-exposed subjects showed significant long-term reduction in their forced vital capacity (P < 0.05) and expiratory volume in 1 second (P < 0.001). No such changes were observed in non-exposed subjects or in those exposed only to organic solvents. The proportion of subjects who developed respiratory symptoms in the isocyanate-exposed group was not significantly greater than that of the non-exposed group. The results of this study indicate that long-term exposure to isocyanates, even in very low concentrations, may contribute to impaired pulmonary function.     

Deep brain stimulation for essential tremor

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.     

Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function

Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele.     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a randomized, controlled trial

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.     

Projection status of calbindin- and parvalbumin-immunoreactive neurons in the superficial layers of the rat's superior colliculus

Immunocytochemistry and retrograde labeling were used to define the thalamic projections of calbindin- and parvalbumin-containing cells in superficial layers of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8 +/- 2.2% (mean +/- standard deviation) of the calbindin-immunoreactive neurons in the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate nucleus (LGNd) and that 91.3 +/- 4.3% of calbindin-immunoreactive neurons in the stratum opticum (SO) projected to the lateral posterior nucleus (LP). In contrast, only 17.3 +/- 2.5% of parvalbumin-immunoreactive neurons in the SGS were found to project to the LGNd and 16.5 +/- 3.1% of the parvalbumin-immunoreactive SO cells were retrogradely labeled after LP injections. Few of the parvalbumin-immunoreactive neurons in either the SGS (7.2 +/- 2.5%) or the SO (9.2 +/- 2.5%) were GABA positive. The retrograde-labeling results suggest that parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be primarily interneurons or have descending projections, while calbindin-containing cells are primarily thalamic projection neurons. These results are consistent with data from other rodents, but almost exactly the opposite of data that have been reported for the cat for these same populations of SC projection neurons. Such interspecies differences raise questions regarding the functional importance of expressing one calcium-binding protein versus another in a specific neuronal population.