Abnormalities of somatosensory evoked potentials in the quinolinic acid model of Huntington's disease: evidence that basal ganglia modulate sensory cortical input.

Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD). One of the very early neurophysiological signs in HD is a diminution of amplitude of early somatosensory evoked potentials (SEPs) recorded over the parietal cortex. The present study investigated whether the QA model exhibits similar neurophysiological abnormalities. Two weeks after unilateral intrastriatal injection of QA (240 nmol) or of the solvent, early SEPs were recorded with chronically implanted electrodes from the somatosensory cortex or from the ventrobasal nucleus of the thalamus of lightly pentobarbital-anesthetized rats, in response to single-shock electrical stimulation of the contralateral forepaw. Whereas intrastriatal injection of solvent did not influence SEPs, the striatal QA lesion significantly reduced the amplitude of early cortical SEPs by about 40% without affecting the latency. SEPs recorded from the ventrobasal nucleus were unchanged after QA lesion. Histological examination and glial fibrillary acid protein staining after intrastriatal injection of QA revealed no evidence for damage in the somatosensory system. It is concluded that (1) the QA animal model of HD mimics some of the SEP abnormalities of patients, and (2) a striatal lesion modulates somatosensory transmission to the cortex in rats.     

Deuterium nuclear spin relaxation in biological tissues

The deuterium nuclear spin relaxation times have been measured in tissues taken from rats given 20% deuterium oxide in their drinking water. The spin-lattice and spin-spin relaxation times were measured at 13.7 MHz by the inversion-recovery and Carr-Purcell-Meiboom-Gill FT methods, respectively. The reciprocals of the spin-lattice (T1) relaxation times were found to correlate well with those of protons in similar nondeuteriated tissues at a similar frequency (13.6 MHz) measured in a separate study. A least-squares analysis of the data yields (1/T1)H = (0.991)(1/T1)D - 3.48 for five tissues (standard deviations of 0.097 for the slope and 0.383 for the intercept with a correlation coefficient of 0.986). Implications with respect to relaxation mechanisms are discussed.     

Can people hear the pitch change on a variable-pitch pulse oximeter?

The introduction of the variable-pitch feature on pulse oximeters in 1983 by the Nellcor Corporation (Hayward, CA) allowed users to rapidly detect changes in oxygen saturation by listening for changes in the pitch of the tones emitted by the pulse oximeter. A few individuals have reported that they have been unable to detect a change in pitch when oxygen saturation changes. To these individuals, the variable-pitch feature of these pulse oximeters has not been beneficial. Using the pitches from one manufacturer of oximeters, we created a computer program to simulate the pitches that accompanied various oxygen saturations. The pitches were recorded onto a tape player and played for 75 volunteer subjects unfamiliar with the pitches of a variable-pitch pulse oximeter. Of our sample, 67% were able to detect a single change in pitch corresponding to a 1% fall in oxygen saturation, and 11% of the population could not detect a change in pitch until there was a change in pitch with every beat. We suggested four alternative designs that may prove beneficial to this group of individuals.     

Juvenile Rheumatoid Arthritis: Benefits from Massage Theraphy

Studied children with mild to moderate juvenile rheumatoid arthritiswho were massaged by their parents 15 minutes a day for 30 days(and a control group engaged in relaxation therapy). The children'sanxiety and stress hormone (cortisol) levels were immediatelydecreased by the massage, and over the 30-day period their paindecreased on self-reports, parent reports, and their physician'sassessment of pain (both the incidence and severity) and pain-limitingactivities     

Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A

OBJECTIVE   Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto-oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations.
DESIGN  Total DNA was extracted from leucocytes. Linkage analysis was performed using five RFLP systems from three loci that flank the MEN2A locus (FNRB, RBP3, D10S15). RET proto-oncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Screening for medullary thyroid carcinoma or C-cell hyperplasia was performed by the pentagastrin provocation test. Adrenal medullary function was assessed by measurements of 24-hour urinary excretion of catecholamines and their metabolites. Serum calcium and phosphate measurements were the initial screen for hyperparathyroidism. Serum PTH was determined only if hyperparathyroidism was suggested by the former determinations.
PATIENT   Genetic study was performed in 59 individuals (39 at risk) from seven kindreds of Mediterranean origin with MEN 2A.
RESULTS   Diagnosis by linkage analysis was not possible in 30% of individuals at risk, but RET proto-oncogene analysis identified all these individuals. Mutations of the RET proto-oncogene were detected in exon 10 (codon 618) in one MEN 2A kindred and in exon 11 (codon 634) in the others. The results of direct analysis were concordant with linkage studies in each case. Three individuals from different MEN 2A kindreds, who were subsequently shown not to be gene carriers, had false positive pentagastrin stimulation tests.
CONCLUSION   Biochemical tests can be replaced by direct DNA mutation analysis as the first line screening test in order to identify gene carriers of MEN 2A.     

Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.

BACKGROUND: Calcific aortic stenosis (AS), the most frequent heart valve disorder in developed countries, leads to the calcification and fibrous thickening of the valve. While several studies have addressed the process of valvular calcification, the molecular pathomechanisms of the extensive matrix remodeling remain unclear. Because inflammation is present in stenotic valves, we hypothesized that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) might influence cell proliferation and regulate the expression and activation of matrix metalloproteinases (MMPs)--enzymes that are thought to be involved in calcific AS. METHODS: Immunohistochemistry for leukocytes, TNFalpha, MMP-1, and the endogenous MMP inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 was performed on human stenotic (n = 19) and control (n = 8) valves. Primary cultures of human aortic valve myofibroblasts were incubated with and without TNFalpha, and cell proliferation was assessed. The expression and activation of MMP-1 were detected by Western blotting and a specific MMP-1 activity assay. RESULTS: Control valves showed scattered macrophages and low expression of TNFalpha, MMP-1, and TIMP-1. In stenotic valves, leukocyte infiltration and a strong, colocalized expression of TNFalpha and MMP-1 were present, while TIMP-1 remained unchanged. Double-label immunofluorescence localized TNFalpha mainly to macrophages. In cultured human aortic valve myofibroblasts, TNFalpha stimulated proliferation and induced a time-dependent increase in MMP-1 expression and activation, while TIMP-1 remained unchanged. CONCLUSION: The results indicate that matrix remodeling in calcific AS involves the expression and activation of MMPs. Activated leukocytes, by the secretion of TNFalpha, may stimulate valvular myofibroblasts to proliferate and express MMPs, thus regulating actively the matrix remodeling in calcific AS.