Development and descent of the testis in relation to cryptorchidism

The testis descends in two phases. Animal studies suggest, that the transabdominal descent of the testis depends on the insulin-like hormone 3 (INSL3). Androgens are important in the inguinoscrotal testicular descent in animals and humans. In general, the cause of cryptorchidism is unknown and the aetiology is possibly multifactorial. Histological changes in cryptorchid testes demonstrate disturbed development. Conclusion: Since testicular descent is regulated by testis-derived hormones, cryptorchidism may reflect a functional defect of the testis.     

Glycerophosphocholine in seminal plasma of fertile and infertile men

Glycerophosphocholine (GPC) was measured in seminal plasma from 65 fertile men, 276 infertile men and 10 men before and after vasectomy, using a new enzymatic method. Extra-epididymal excretion of GPC accounted for 30% of the total seminal levels of GPC. From a diagnostic point of view, GPC determination did not appear to be a specific tool which could discriminate between secretory and excretory azoospermia. Although the seminal content of GPC was related positively to the total sperm count in both fertile and infertile men, there was an inverse relationship between the level of GPC and sperm motility when considering classes displaying the same total sperm count. This was observed in all classes from infertile men as well as in fertile men with a total sperm count lower than 200 x 10(6) sperm/ejaculate. These results suggest a possible role of GPC in the regulation of human sperm motility, which warrants further investigation.     

Clinical and biological significance of carcinoma in situ of the testis

Carcinoma in situ (CIS) of the testis is a preinvasive lesion that with time progresses into invasive germ cell tumour. CIS precedes all types of germ cell tumours except spermatocytic seminoma. An increased risk of harbouring CIS has been reported in men with a history of cryptorchidism, in contralateral testes of men previously treated for unilateral germ cell tumour, in intersex patients, in men with assumed extragonadal germ cell tumour and possibly in infertile men. CIS develops into invasive germ cell cancer in 50% of untreated patients within five years of diagnosis, and it is believed that with time CIS will progress into germ cell cancer in almost all patients. A testicular biopsy is necessary to diagnose CIS. Cells with the characteristics of CIS cells have been detected in seminal fluid, and it may be possible to develop methods for diagnosing the condition by analysis of the semen. We recommend orchidectomy as the treatment of choice in cases of unilateral CIS, if the other testis has a potential for fertility. In other cases, such as patients with testicular tumour and CIS of the contralateral testis, we recommend localized irradiation of the testis with CIS. Leydig cell function seems to be slightly impaired, but sufficient for sexual function, after irradiation. CIS cells show morphological and immunohistochemical similarities with primordial germ cells (gonocytes), whereas they share only few features with spermatogonia. Therefore, we suggest that CIS cells are malignant cells derived from gonocytes during embryonic development.     

Symptoms of classic migraine attacks: Modifications brought about by metoprolol

There is little information available concerning whether, and to what extent, migraine-prophylactic agents interfere with the symptoms of migraine attacks. The present study is a placebo-controlled, double-blind study concerning metoprolol in classic migraine. The data refer to the symptoms of single migraine attacks. During metoprolol treatment more attacks were characterized as mild (p = 0.002), and mean global rating (an integrated estimate of headache intensity and of other discomfort) was lower (4.2 versus 5.2, p = 0.003). The mean headache intensity per attack (1.97 versus 2.15) and the mean duration (5.5 versus 6.8 h) were not significantly different. Consumption of analgesics per attack was lower during metoprolol treatment (0.6 versus 1.1; p = 0.02). Attacks with associated symptoms accompanying the headache were fewer during metoprolol treatment (p = 0.014). Total visual and non-visual aura symptoms occurred with similar frequency, but scintillations and paraesthesia were more frequent during metoprolol treatment, whereas speech disturbances were less frequent. In spite of lower consumption of analgesics, the symptoms appeared milder during metoprolol than during placebo. The pattern of changes indicates that metoprolol exerts its action via the sympathetic nervous system; peripheral vasoconstriction is hardly the underlying mechanism of action.     

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.