Declining testicular function with age. Hormonal and clinical correlates

Testicular endocrine function and androgen-dependent secondary sexual characteristics were assessed in 283 men 18 to 96 years of age. Mean serum total testosterone levels remained unchanged up to age 70 and declined thereafter. In 29 per cent of the men over 70 years of age total testosterone levels were below the lower limit of normal for young adults, In contrast, mean free or unbound testosterone levels declined after age 50 and were below the lower limit of normal for young adults in 40 per cent of the men over 70 years of age. Serum-luteinizing hormone and follicle-stimulating hormone levels showed a slight but steady rise after age 40 which became more abrupt after age 70. Serum gonadotropin levels were elevated in approximately 60 per cent of the men over 70 years of age.Mean testis length and volume were decreased in 78 per cent and 37 per cent, respectively, of the men over 60 years of age. Facial, pubic and axillary hair were also reduced in amount whereas the prostate was enlarged in 73 per cent of the elderly men. There appeared to be an inverse relationship in older men between testicular size and gonadotropin levels, and a direct relationship between testicular and prostatic sizes.It would appear that some degree of Leydig cell hypofunction commonly begins at around 45 to 50 years of age, becoming more pronounced after age 70. The concomitant elevation in serum gonadotropin levels at this time indicates that this is due to a primary decline in testicular function and is not secondary to pituitary hypofunction.     

The role of closed pleural needle biopsy in the diagnosis of malignant mesothelioma of the pleura.

Malignant mesothelioma of the pleura is a disease that requires a biopsy procedure for a definitive diagnosis. In the past, closed pleural needle biopsy (CPNB) has given poor yields due to the small amount of tissue obtained, and the patient has subsequently been subjected to a diagnostic thoracotomy. In recent years, the availability of more accurate histopathologic tests have enabled the pathologist to make a diagnosis more easily on samples obtained at CPNB. In this retrospective study of 20 consecutive cases of malignant mesothelioma of the pleura diagnosed between 1980 and 1990, we found that a blind CPNB was diagnostic in five of seven procedures and CT-guided CPNB was diagnostic in five of six procedures. An open pleural biopsy (OPB) was diagnostic in ten of ten procedures performed. There were no complications associated with any of the CPNB procedures. We conclude that CPNB is a safe and effective manner of diagnosing malignant mesothelioma of the pleura, and should be attempted prior to OPB.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Reliability and validity of the sideways step test and its correlation with motor function after stroke

[Purpose] This study investigated the intra-rater, inter-rater and test-retest reliability of the sideways step test (SST), its correlation with other indicators of stroke-specific impairment, and the cut-off count best discriminating subjects with stroke from their healthy counterparts. [Subjects and Methods] Forty-three subjects with chronic stroke and 41 healthy subjects older than 50 years participated in this study. The SST was administered along with the Fugl-Meyer motor assessment for the lower extremities (FMA-LE), the five-times sit to stand (5TSTS) test, the Berg Balance Scale (BBS), the movement velocity (MVL) by the limits of stability (LOS) test, the ten-metre walk (10mW) test, the timed “Up and Go” (TUG) test and the Activities-specific Balance Confidence (ABC) scale. [Results] The SST showed good to excellent intra-rater, inter-rater and test-retest reliability. The SST counts correlated with 5TSTS times, 10mW times, TUG times, and the FMA-LE and BBS scores. SST counts of 11 for the paretic leg and 14 for the non-paretic leg were found to distinguish the healthy adults from subjects with stroke. [Conclusion] The sideways step test is a reliable clinical test, which correlates with the functional strength, gait speed, and functional balance of people with chronic stroke.Key words: Balance, Stroke, Rehabilitation