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BACKGROUND: Pathologic changes in the motor cortex and corticospinal tracts in ALS may be reflected by abnormal signal intensities on conventional MRI. The sensitivity of these changes in detecting underlying pathology remains unclear. METHOD: The authors used automated image analysis to quantify volumes of cerebral gray and white matter in 16 patients with ALS (eight limb onset, eight bulbar onset) and eight normal controls. Previously they had demonstrated a reduction in N-acetyl aspartate/creatine + phosphocreatine (NAA/[Cr + PCr]) measured by (1)H-MRS in the subcortical white matter in the motor cortex region in the patients with bulbar-onset ALS. To determine whether this resulted from axonal degeneration, they also compared gray and white matter volumes in the patients with limb- and bulbar-onset ALS. RESULTS: There were no differences in the total brain volumes of gray or white matter for the three subject groups (p > 0.23). Comparison of the total ALS group and controls revealed localized deficits in gray matter volume centered on Brodmann areas 8, 9, and 10 bilaterally. Comparison of the patients with limb- and bulbar-onset ALS revealed deficits in the white matter volume in the bulbar-onset group, extending bilaterally from the precentral gyrus into the internal capsule and brainstem, consistent with the course of the corticospinal tract. There was no loss in gray matter volume in the precentral gyri. CONCLUSIONS: The loss of gray matter in the frontal regions (total ALS group) provides further support that ALS is a multisystem disorder. In addition, there is in vivo evidence of axonal degeneration in the subcortical white matter in the motor region in patients with bulbar-onset ALS. This is consistent with a "dying back" process affecting cortical motoneurons in bulbar-onset ALS.  相似文献   
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The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientific reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8% when the man is < 25 years old to 15% when he is > 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a significant decline in fertility (five times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.  相似文献   
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Introduction

The antihypertensive effects of thiazide diuretics such as hydrochlorothiazide are commonly associated with erectile dysfunction. The association of hydrochlorothiazide/amiloride is not associated with erectile dysfunction. The hypothesis is that amiloride has beneficial effect in penile erection and, therefore, counterbalances the hydrochlorothiazide-induced disruptive effect.

Aim

To investigate the effects of amiloride and its analogues hexamethylamiloride and benzamil on rat isolated corpus cavernosa (CC) and intracavernous pressure (ICP) in anaesthetized rats.

Methods

Rat isolated CC were incubated with amiloride, hexamethylamiloride, and benzamil (10 and 100 μmol/L each), followed by phenylephrine, potassium chloride, and electrical field stimulation (EFS). Their effect on the relaxant responses to EFS and sodium nitroprusside were also determined. Oral (30 mg/kg) and intraperitoneal (3 mg/kg) treatments with amiloride were also investigated on nerve-evoked ICP.

Main Outcome Measures

In vitro functional studies and in vivo ICP measurement on rat CC were performed. Additionally, phosphodiesterase type V isoform A1 activity and the mRNA expressions of Na+/H+ pump, epithelial sodium channel exchangers (ENaC) channels (α-, β- and γ subunits) and Na+/Ca2+ exchangers were evaluated in CC tissues.

Results

Amiloride and its analogues significantly reduced the phenylephrine-, potassium chloride–, and EFS-induced CC contractions, which were not changed by nitro-L-arginine methyl ester (100 μmol/L) or indomethacin (6 μmol/L). In phenylephrine-precontracted CC tissues, amiloride itself caused concentration-dependent relaxation and significantly increased the EFS-induced relaxation. Oral and intraperitoneal treatment with amiloride significantly increased the ICP. Phosphodiesterase type V isoform A1 activity was not affected by amiloride. Na+/H+ pump, ENaC, and Na+/Ca2+ exchanger mRNA expressions were all detected in rat CC tissues.

Clinical Implication

Amiloride analogues may have therapeutic potential for erectile dysfunction.

Strength & Limitations

The interesting effect of amiloride in penile erection was observed in both in vitro and in vivo methods. The evidence at the moment is restricted to rat CC.

Conclusion

Amiloride reduces in vitro CC contractility and enhances erectile function after oral and intraperitoneal administration, possibly via inhibition of ENaC.Campos R, Claudino MA, de Oliveira MG, et al. Amiloride Relaxes Rat Corpus Cavernosum Relaxation In Vitro and Increases Intracavernous Pressure In Vivo. J Sex Med 2019;16:500–511.  相似文献   
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The Dundee Ready Educational Environment Measure (DREEM) is a measure of students' perceptions of the educational environment, but its performance in evaluating the educational environment in the residency setting has not yet been described. This study aimed at describing the psychometric performance of DREEM applied to medical residents. DREEM was applied to 97 residents from 12 training programs on four specialties in six institutions in three Brazilian cities. Psychometric measures included factor analysis, Cronbach's alpha coefficients, item-to-total correlations, t-test comparisons of scores between genders, institutions, specialties, and programs, correlations with the global score of the Quality of School Life Scale (concurrent validity), and test-retest reliability. Generalizability theory procedures were applied to a random subset of data. Programs (8) were the objects of measure, while institutions (6), specialties (4), raters-within-programs (40), and items-on-the-scale (50) were facets. Variance components, generalizability (G) and dependability (D) coefficients were calculated. Cronbach's alpha was 0.93. DREEM showed high discriminant and concurrent validities. Test-retest reliability was moderate. Interactions between programs, raters and items accounted for 68% of the total variance. G and D coefficients were 0.95 and 0.67, respectively. The instrument proved to be useful for relative comparisons at both resident and program level.  相似文献   
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