Regulating older drivers: how are the states coping?

The nation's population is growing older and its dependence upon the automobile for mobility has never been higher. Traffic safety data indicate that older operators have more fatal crashes than other age groups. As more people approach their senior years the safety issues surrounding older drivers will become even more important. Findings from a 1995 survey are reported identifying the practices of states and the perceptions of licensing officials concerning the older driver issue. The results indicate a diversity in approaches and a series of institutional and behavioral conflicts in the older driver policy subsystem that contribute to imperfect licensing controls.

Chronic somatostatin analog administration in patients with alpha-subunit-secreting pituitary tumors.

Glycoprotein hormone-producing (GPH) pituitary adenomas represent approximately 25% of all pituitary tumors. Elevated serum levels of intact GPHs or their free alpha- and beta-subunits have been demonstrated in patients with such tumors, and isolated hypersecretion of alpha-subunit has been reported to occur in 7% of patients. Somatostatin has been shown to decrease GPH subunit levels in cultured adenoma cells in vitro, and somatostatin receptors have been identified on the cell membranes of these tumors. We, therefore, investigated the effect of chronic somatostatin analog administration on hormone production and tumor size in six patients with GPH-producing macroadenomas and elevated serum alpha-subunit levels. Patients initially received native somatostatin as an iv 250-micrograms bolus at 0800 h, followed by a constant infusion of 2 mg over 4 h, and serum alpha-subunit concentrations were measured at 30-min intervals after baseline sampling for a total of 9 h. Patients then received a somatostatin analog, octreotide (100 micrograms, twice daily, sc) for 8 weeks. Serum alpha-subunit levels were determined weekly at 30-min intervals before and for 4 h after the 0800 h octreotide dose. Pituitary magnetic resonance imaging scans and visual field testing were assessed before and after the study. During the 4-h somatostatin infusion, four patients had a significant decrease in alpha-subunit levels (P < 0.05). During the 8-week chronic octreotide administration period, two patients had significant decreases in alpha-subunit levels of 34.6% and 26.7% (P = 0.03 and 0.01, respectively). One of these two patients had a small reduction in tumor size. Two patients whose serum alpha-subunit level did not significantly change while receiving octreotide had a reduction in tumor size or definite improvement in visual field abnormalities. Three patients received a maximum octreotide dose of 250 micrograms, three times daily. In one patient, there was a significant decrease in alpha-subunit levels by 45% (P = 0.0001) in association with a marked improvement in visual field abnormalities. In another such patient, continued administration of octreotide to a maximum dose of 250 micrograms, three times daily, was associated with a marked reduction in tumor size. Of the four patients who demonstrated significant decreases in alpha-subunit concentrations during the initial somatostatin infusion, three patients had a significant reduction in alpha-subunit levels while receiving octreotide. One patient who did not have a decrease in alpha-subunit levels during the somatostatin infusion demonstrated a small decrease in tumor size during higher dose octreotide treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Osteopenia in women with hypothalamic amenorrhea: a prospective study.

Hypothalamic amenorrhea, a common disorder associated with abnormalities in gonadotropin pulsatility and subsequent estrogen deficiency, is usually transient, and treatment indications are unclear unless fertility is desired. To determine whether this disorder is associated with progressive bone loss, we studied 24 women with primary or secondary amenorrhea related to stress or simple weight loss, compared with 31 normal women of the same age. Amenorrheic women had significantly lower (P = .01) body fat (26.4 +/- 7.3 versus 30.6 +/- 4.7%) and higher (P = .0001) urine free cortisol levels (250 +/- 100 versus 140 +/- 50 nmol/day) than normals. Trabecular bone density in women with hypothalamic amenorrhea as assessed by spinal computed tomography was significantly (P = .001) lower than in normals (140.2 +/- 27.3 versus 175.1 +/- 24.6 mg K2HPO4/mL, respectively). Twenty of the 24 amenorrheic women had initial spinal bone density below the mean in normals, and in eight it was 2 standard deviations or more below the normal mean. Initial bone density correlated negatively with duration of amenorrhea (r = -0.489, P = .02) and positively with serum free testosterone levels (r = 0.517, P = .02). Prospective evaluation showed a decline in spinal bone density in those who were amenorrheic for fewer than 5 years. The slope of change in bone density correlated with initial weight, percent ideal body weight, and percent body fat (R2 = 0.597, P = .0003; R2 = 0.549, P = .0007; and R2 = 0.618, P = .0002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro synthesis of polypeptides of moderately large size by poly(A)-containing messenger RNA from postmortem human brain and mouse brain.

Studies were undertaken to optimize the conditions for isolation and in vitro translation of poly(A)-containing mRNA from human postmortem brain. The comparison of several methods for preparation of mRNA from frozen mouse brain indicated that although the yield of mRNA was increased using polysomes prepared in the presence of ribonucleoside vanadyl complexes and subsequently extracted with guanidinium thiocyanate, the translation products were indistinguishable from those synthesized by total cellular RNA directly extracted from tissue with guanidinium thiocyanate. The oligo d(T)-cellulose-purified poly(A)-containing mRNA preparations were translated in vitro in a rabbit reticulocyte lysate in the presence of L-[35S]methionine. Messenger RNA from frozen mouse brain stimulated protein synthesis from 9- to 20-fold over endogenous mRNA. Over 450 polypeptides were reproducibly synthesized and separated by two-dimensional polyacrylamide gel electrophoresis (PAGE); size classes up to 130,000 daltons were present. Direct extraction of RNA from frozen human cerebral cortex and cerebellum with guanidinium thiocyanate followed by oligo d(T)-cellulose chromatography yielded 1.8 micrograms/g and 2.0 micrograms/g, respectively, of poly(A)-containing mRNA; this represents a two- to fourfold increase over our earlier results. In the rabbit reticulocyte translation system human brain mRNA stimulated protein synthesis nearly threefold over endogenous mRNA. Compared with earlier studies, the number of newly synthesized polypeptides was increased by 30%. Over 300 species were separated by two-dimensional PAGE, and size classes up to 130,000 daltons were present, as compared to 70,000 in an earlier report. The polypeptides synthesized by human cerebral cortex and cerebellum were indistinguishable. However, several appeared to be uniquely human when compared with the products synthesized by mouse brain mRNA. The method described for the preparation of postmortem human brain mRNA eliminates the need to prepare polysomes, which are recovered in variable and low yield from the postmortem human brain. The procedure appears applicable to studies on the synthesis of moderately large human brain polypeptides and for investigations of brain protein polymorphism when relatively large numbers of products are required for analysis.

Elimination of microdensitometer degradation from scans of photographic images.

In microdensitometry, the tracing of a knife edge does not yield a step function. Therefore, when a photographic image is traced the result is not a spatially true representation of the image. A computational procedure has been developed that corrects for microdensitometer effects. This is achieved by obtaining the inverse Fourier transform of the reciprocal values of the microdensitometer modulation transfer function and convolving the resulting function with the digital output of the microdensitometer scan. The result is the corrected scan data for the photographic image. This technique has been applied successfully to edge gradient analysis for both analytic and experimental edges. The compensation for microdensitometer degradation should have a number of applications.