Genital anomalies in human and animal models reveal the mechanisms and hormones governing testicular descent

A systematic examination of the conditions characterized by the presence of genital anomalies in humans, noting in each condition the position of the gonad, the nature of the gubernaculum and cranial suspensory ligament can provide valuable information regarding the mechanisms controlling the final position of the gonads. In conditions where MIS is absent, the gubernaculum is "feminized', resulting in a testis in the position normally occupied by an ovary or an abnormally mobile testis that can prolapse to the inguinal region. In conditions of androgen insensitivity the testis is located in the inguinal region, indicating that the first phase of descent is normal but that inguinoscrotal descent has failed to occur. Ovarian descent fails to occur in congenital adrenal hyperplasia, despite exposure of the developing fetus to high levels of androgens, indicating that androgen alone does not control gonadal descent. Moreover, ovarian descent fails to occur despite androgen-dependent regression of the cranial suspensory ligament. The correlation between the degree of Müllerian duct retention and scrotal position in mixed gonadal dysgenesis further strengthens the hypothesis that the first stage of testicular descent is controlled by MIS. The study of genital anomalies suggests that MIS controls the swelling reaction in the male gubernaculum, which is responsible for the first phase of testicular descent to the inguinal region. The second or inguinoscrotal phase of descent is androgen-dependent. Regression of the cranial suspensory ligament is also androgen-dependent: however, it is the gubernaculum and not the presence or absence of the cranial suspensory ligament which controls testicular descent. A combined knowledge of the hormonal basis controlling sexual differentiation and the biphasic model of testicular descent enables the clinician to accurately predict the internal anatomy of these complex sexual anomalies.     

New therapeutic prospects for the glycosphingolipid lysosomal storage diseases

The Differential Straight Arch technique, more commonly known as "Tip-Edge" (TP Orthodontics Inc.), uses a modified edgewise type bracket to allow differential tooth movement. As bracketed teeth incline toward their finishing positions, the geometry of the arch wire slot causes the vertical slot dimension available to the arch wire to increase. Advantage has been taken of this facility, to evolve an entirely new torquing system for final finishing, during the root correction phase. Instead of increasing rectangular arch wire size to fit the arch wire slot, as with conventional edgewise brackets, the Tip-Edge method reduces the vertical arch wire slot dimension to achieve a precise, three-dimensional relationship to a full-sized rectangular arch wire. The active component is provided by auxiliary springs. The method, which awaits mathematical analysis, is described and illustrated with two case reports.     

Comparison of three different methods for measuring classical pathway complement activity

A 30-year-old man was referred as an acute case for keratitis. Two days earlier he had had photorefractive keratectomy for myopia at another clinic; a bandage contact lens was placed over the eye, but prophylactic antibiotics were not prescribed. The keratitis was treated with gentamicin sulfate (Garamycin) and chloramphenicol eyedrops. Scrapings from the cornea showed nonhemolytic streptococci. Two and a half months later, visual acuity was finger counting because of gross distortion of the corneal contour. The combination of a bandage contact lens and the lack of prophylactic antibiotics may have been the source of bacterial keratitis.     

Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD

Several previous families with differing clinical and pathologic characteristics have demonstrated linkage to the 17q21-22 region. We have performed a linkage analysis with chromosome 17 markers on three families showing autosomal dominant inheritance of non-Alzheimer dementia and 60 kindreds with late-onset familial Alzheimer's disease (FAD). Family A shows unequivocal evidence of linkage with a maximum lod score of 5.0 for marker D17S934 (theta = 0.001). This family has an unusual syndrome of a schizophrenia-like psychosis beginning in the fifth or sixth decade followed by severe dementia with an average disease duration of 13.8 years. Neuropathology from five autopsies in this family has shown marked neurofibrillary tangle formation (NFT), degeneration of the amygdala, and no amyloid plaques. This confirms the presence of a gene associated with dementia on 17q and extends the related phenotype to include schizophrenia-like symptoms and classic NFT pathology. A second family with early aphasia progressing to dementia and cortical-basal ganglion-like degeneration also has suggestive evidence for linkage to 17q. A third family with very early-onset dementia (mean, 31 years) and nonspecific pathology can be excluded from the 17q region and emphasizes additional genetic heterogeneity in non-Alzheimer hereditary dementia. Finally, we also present evidence against linkage to D17S579 in the set of 60 families with late-onset FAD, providing further evidence that the chromosome 17 gene is unlikely to be involved in the pathogenesis of typical AD.     

Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs

The present study was conducted to determine the effects of dietary fatty acids on hepatic LDL receptor (LDLr) protein abundance and mRNA levels. Sixty pigs were randomized into 10 groups and fed corn-soybean meal diets containing three cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no added fat, or fats rich (30% of calories) in palmitic acid or linoleic acid. A control group was fed the base diet with no added fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels increased as the dietary cholesterol increased (P < 0.05); however, there was no significant effect of either fatty acid. Dietary fatty acids, however, had distinctly different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA (analyzed by Northern blot) abundance. When pigs consumed diets containing 0.25% cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas palmitic acid reduced it 40% (P < 0.05). These changes in LDLr protein abundance were accompanied by parallel changes in hepatic LDLr mRNA; linoleic acid increased LDLr mRNA 2-fold (P < 0.01), whereas palmitic acid decreased it 60% (P < 0.01). The differential effects of fatty acids on LDLr expression were only observed at 0.25% cholesterol, suggesting that higher intakes of cholesterol have a dominant and repressive effect on regulation of LDLr expression. Cholesterol intake increased hepatic total cholesterol levels (P < 0.01) while dietary fatty acids had no effect on hepatic sterols. In summary, our results indicate that dietary linoleic acid and palmitic acid have markedly different effects on hepatic LDLr protein abundance that are mediated by differential effects on LDLr mRNA and protein levels. Further studies are needed to fully elucidate the molecular mechanisms by which fatty acids regulate LDLr mRNA and protein levels.     

Absence of vitamin D deficiency in young Nigerian children

OBJECTIVE: To determine the prevalence of vitamin D deficiency in young Nigerian children residing in an area where nutritional rickets is common. Study design: A randomized cluster sample of children aged 6 to 35 months in Jos, Nigeria. RESULTS: Of 218 children evaluated, no child in the study had a 25-hydroxyvitamin D (25-OHD) concentration <10 ng/mL (the generally held definition of vitamin D deficiency). Children spent an average of 8.3 hours per day outside of the home. Twenty children (9.2%) had clinical findings of rickets. Children with clinical signs of rickets were more likely to be not currently breast fed and have significantly lower serum calcium concentrations than those without signs of rickets (9.1 vs 9.4 mg/dL, respectively, P =.01). Yet, 25-OHD levels were not significantly different between those children with clinical signs of rickets and those without such clinical signs. CONCLUSION: Vitamin D deficiency was not found in this population of young children in whom clinical rickets is common. This is consistent with the hypothesis that dietary calcium insufficiency, without preexisting vitamin D deficiency, accounts for the development of clinical rickets in Nigerian children.     

What you should know about dental practice management companies

The unfavourable tuberculosis situation in the corrective labour facilities affects the main rates of tuberculosis in the region. Presently, the total registered cases of tuberculosis among prisoners are 36.7 times as high as those in the age-matched general population of the Sverdlovsk Region. The rates of relapses, incidence, death due to tuberculosis show 72.0-, 36.1-, and 10.4-fold increases, respectively. Almost every 10 persons from the labour corrective facilities suffer from active tuberculosis. In the past decade, the growth rates of main tuberculosis parameters in the corrective labour facilities were much higher (total tuberculosis morbidity by 2.1 times, relapses by 2.1 times, general morbidity by 1.7 times, and total tuberculosis mortality by 2.8 times) than those in the region's general population. Extrapulmonary tuberculosis was not virtually detected in the labour corrective facilities) due to the lack of special diagnostic methods.     

Measurement of kinetic perfusion parameters of gadoteridol in intact myocardium: effects of ischemia/reperfusion and coronary vasodilation

Quantitation of myocardial perfusion is feasible using contrast enhanced magnetic resonance imaging. A method to quantitate myocardial blood flow is provided by the Kety model modified to account for a diffusable tracer such as gadoteridol. In the present study, perfusion parameters of the modified Kety model (partition coefficient and extraction efficiency) were determined for gadoteridol in intact myocardium using a constant flow, isolated, perfused heart model. Perfusion conditions included hearts with normal perfusion, hearts made globally ischemic for 20 min then perfused normally, and hearts whose coronary flow was more than doubled with 9 microM adenosine. T1 relaxation times were rapidly measured at 0.5 T following step increases in perfusate gadoteridol concentration and at steady state. Both the partition coefficient and extraction efficiency were found to be significantly increased in ischemic/reperfused hearts compared to normal. While flow rates in adenosine hearts were too high for accurate extraction efficiency determination using this technique, the partition coefficient was no different between adenosine and normally perfused hearts. The method described in this article allowed the kinetic parameters of the modified Kety model to be determined in intact heart using NMR relaxation time measurements as the basis of the calculation.