Factor V Leiden is associated with increased sperm count.

STUDY QUESTION: Is the thrombophilia mutation factor V Leiden (FVL) associated with an increased total sperm count? SUMMARY ANSWER: Carriers of FVL have a higher total sperm count than non-FVL-carriers, which could not be explained by genetic linkage or by observations in a FVL-mouse model. WHAT IS KNOWN ALREADY: FVL has a high prevalence in Caucasians despite detrimental health effects. Carriers have been shown to have higher fecundity, which might partly explain this evolutionary paradox. STUDY DESIGN, SIZE, DURATION: We determined FVL status in two cohorts (Dutch, n = 627; Danish, n = 854) of consecutively included men without known causes for spermatogenic failure, and performed an individual patient data meta-analysis of these two cohorts together with one previously published (Dutch, n = 908) cohort. We explored possible biological underpinnings for the relation between sperm count and FVL, by use of a FVL-mouse model and investigations of genetic linkage. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were male partners of subfertile couples (two Dutch cohorts) and young men from the general population (Danish cohort): FVL carrier rate was 4.0%, 4.6% and 7.3%, respectively. There were differences in smoking, abstinence time and age between the cohorts. We corrected for these in the primary analysis, which consisted of a mixed linear effects model, also incorporating unobjectified population differences. In public haplotype data from subjects of European descent, we explored linkage disequilibrium of FVL with all known single nucleotide polymorphisms in a 1.5 MB region around the F5 gene with an R2 cutoff of 0.8. We sequenced exons of four candidate genes hypothesized to be linked to FVL in a subgroup of FVL carriers with extreme sperm count values. The animal studies consisted of never mated 15-18-week-old C57BL/J6 mice heterozygous and homozygous for FVL and wild-type mice. We compared spermatogenesis parameters (normalized internal genitalia weights, epididymis sperm content and sperm motility) between FVL and wild-type mice. MAIN RESULTS AND THE ROLE OF CHANCE: Human FVL carriers have a higher total sperm count than non-carriers, with an adjusted mean difference of 31 × 106 (95%CI 0.2-61.7; P = 0.048). Mice with the FVL mutation do not have increased spermatogenesis as compared to wildtype mice. None of the studied polymorphisms was in linkage disequilibrium, either in the public databases or in a subgroup of FVL carriers with extremely high sperm counts. LIMITATIONS, REASONS FOR CAUTION: The difference in total sperm count would benefit from confirmation in other cohorts. The finding of higher count in carriers was consistent however, with no heterogeneity between the cohorts. The lack of effect of murine FVL might suggest there is no direct causality. The exploratory efforts on genetic linkage do not rule out that the association is a reflection of FVL co-inheritance with a non-studied causative polymorphism. WIDER IMPLICATIONS OF THE FINDINGS: A high sperm count in FVL-carrying males contributes to understanding the high prevalence of this otherwise disadvantageous mutation. The findings might provide directions for future research on male fertility. STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest. Research was conducted with funding from the Netherlands Organisation for Scientific Research (NWO, VIDI innovative research grant 016.126.364 awarded to S. Middeldorp). The Danish cohort was supported by the Innovation Fund Denmark (InnovationsFonden, grant no. 14-2013-4), The Danish Ministry of Health and the Danish Environmental Protection Agency. TRIAL REGISTRATION NUMBER: Not applicable.

A new approach for the enzymatic estimation of infarct size: serum peak creatine kinase and time to peak creatine kinase activity.

The relations of several creatine kinase (CK) variables to angiographic left ventricular ejection fraction and abnormally contracting segments in the chronic phase were examined in 2 groups of patients with a first anterior acute myocardial infarction. In group A (n = 22), emergency coronary angiography was performed and nonsurgical early reperfusion was attempted. Such an early revascularization, which was considered partially present in group B (n = 16), which received conventional therapy, shifted the CK time-activity curve to the left and altered its relation to angiographic cardiac function. At similar levels of peak CK, myocardial damage was significantly smaller in patients with successful thrombolysis than in those with unsuccessful reperfusion and conventional therapy (p less than 0.01). In patients whose infarct was considered to be moderate according to peak CK (1,000 to 3,000 U/liter), there was significant correlation between time to peak CK and left ventricular ejection fraction or percent abnormally contracting segments irrespective of their group. The results suggest that one should take into account rapid washout and shorter time to peak CK when estimating enzymatic infarct size in humans. The multivariate analysis of cardiac function with peak CK and time to peak CK resulted in a closer correlation in all patients. Such a correction in the time to peak CK may be a clinically useful approach for better interpretation of infarct size.

Comparison of coronary arteriographic findings during angina pectoris associated with S-T elevation or depression.

Coronary arteriographic findings during an attack of angina pectoris associated with S-T segment elevation and angina associated with S-T depression were compared in 54 patients. Thirty-eight attacks with S-T segment elevation included 2 that were spontaneous, 6 induced by methacholine, 4 by epinephrine with or without propranolol, 9 by arm exercise, 5 by hyperventilation with or without Tris-buffer infusion and 12 by ergonovine maleate. Twenty-nine of the 38 attacks were associated with total occlusion, 8 with subtotal occlusion and 1 with diffuse narrowing of a major coronary artery caused by spasm. Twenty-six attacks with S-T segment depression included 3 induced by methacholine, 13 by arm exercise, 3 by hyperventilation with or without Tris-buffer infusion and 7 by ergonovine maleate. Eight of the 26 attacks were associated with subtotal occlusion and 9 with diffuse narrowing of a major coronary artery caused by spasm; 3 attacks were associated with total occlusion of a major coronary artery well supplied with collateral vessels and 2 with total occlusion of a small coronary branch caused by spasm. Four attacks were associated not with spasm but with fixed subtotal occlusion of a major coronary artery (3 attacks) or total occlusion of a major coronary artery receiving collateral vessels (1 attack). Only 2 of the 31 patients with S-T segment elevation had collateral vessels compared with 8 of the 16 patients with S-T segment depression (p less than 0.001). It is concluded that angina pectoris associated with S-T segment elevation usually indicates more severe myocardial ischemia than angina associated with S-T segment depression.

Exertional angina pectoris caused by coronary arterial spasm: effects of various drugs.

In four patients with exertional angina induced by arm exercise, coronary arteriograms taken before, during and after the attack demonstrated that spasm appeared in the large coronary artery supplying the area of myocardium shown to be ischemic in the electrocardiogram during the attack. The spasm disappeared with subsidence of the attack after administration of nitroglycerin. Anginal attacks induced by treadmill exercise were not suppressed by propranolol, 60 mg orally, in two of the four patients. However, such attacks were suppressed in all patients by oral administration of diltiazem (90 mg, four patients) or nifedipine (20 mg, three patients) or intramuscular injection of phentolamine (0.2 mg/kg body weight, three patients). It is concluded that coronary arterial spasm can be induced by exercise and can cause exertional angina in some patients. Diltiazem and nifedipine, calcium antagonistic drugs, prevent spasm.

Cataract survey in the local area using photographic documentation.

An epidemiological survey of cataract was performed in a limited local population. 1,020 individuals over 40 years of age were examined. The crystalline lens findings were documented by both Scheimpflug and retroillumination photography. Cataractous changes were classified into three groups according to early senile changes, incipient cataractous changes and only prominent cataractous changes. Forms of opacification were classified as cortical, subcapsular, nuclear, mixed type and others. The percent prevalence of cataracts including early senile changes was 33.9% in the 40-year-old population, 62.8% in the 50, 76.2% in the 60, 84.0% in the 70 and 100% for those in their 80s. Prominent cataractous opacification was 1.6% in the 40-year-old population, 3.1% for those in their 50s, 19.0% in their 60s, 28.6% in their 70s and 57.1% in their 80s, respectively. Until age 60, the type of opacification was mainly cortical alone; however, after age 70, cortical opacity accompanied by nuclear and/or capsular opacities increased. The pure nuclear type increased in individuals over 70.

Acute myocardial infarction induced by ergotamine tartrate: possible role of coronary arterial spasm.

A 45-year-old woman with almost normal coronary arteries suffered from acute inferior myocardial infarction after taking 2 tablets (2.0 mg) of ergotamine tartrate for headache. She had had attacks of variant angina and spasm of the right coronary artery had been demonstrated during the attack. After the recovery from myocardial infarction the intravenous injection of ergonovine maleate 0.05 mg induced spasm of the right coronary artery again. We conclude that acute myocardial infarction in this patient was probably caused by coronary arterial spasm induced by ergotamine tartrate.

Coronary arteriographic findings during early hours of acute myocardial infarction: response to intracoronary injection of nitrates.

We performed coronary arteriography and gave intracoronary injection of nitrates within 8 hours after the onset of symptoms of acute myocardial infarction in eighteen patients. Improved distal filling or patency of the total occluded coronary artery after intracoronary injection of nitrates occurred in 4 of 18 patients. In one of four patients the first intracoronary nitrates injection failed to release the initial total occlusion, but after intracoronary Urokinase administration, the second nitrates injection succeeded to dilate the completely occluded coronary artery. Coronary arteriography was again performed in sixteen patients in the chronic stage (4-15 weeks after the onset of acute myocardial infarction) and ergonovine maleate was injected intravenously in seven patients. Focal spasm was induced by ergonovine injection in three patients in one of whom intracoronary nitrates failed to release the complete obstruction in the acute stage. We conclude that coronary spasm as well as intracoronary thrombosis plays an important role in the production of acute myocardial infarction.

[Papillary renal cell carcinoma complicated with emphysematous pyelonephritis: a case report].

A case of papillary renal cell carcinoma complicated with emphysematous pyelonephritis is reported. A 75-year-old woman with diabetes mellitus was admitted to our hospital with macroscopic hematuria and a child's head-sized firm mass in the left hypochondrium. Computed tomographic (CT) scanning revealed a huge left renal tumor with hydronephrosis. The patient had acute pyelonephritis and antibacterial therapy was initiated. Ten days later, conservative therapy was not effective and CT scan revealed emphysematous necrotic tissue in the tumor. We performed percutaneous drainage. Then dark red liquid and gas were discharged. Her general condition was improving. Left radical nephrectomy was performed. The mass was solid and pathological diagnosis was papillary renal cell carcinoma with necrotic tissue and coated by a thick pseudocapsule. She has remained free of disease for 27 months after operation.

[Percutaneous resection of renal pelvic fibroepithelial polyp with medullary sponge kidney: a case report].

Benign polyp of the renal pelvis is extremely rare. We report a case of fibroepithelial polyp in the renal pelvis complicated with medullary sponge kidney successfully treated by percutaneous resection. The patient had recurrent bilateral renal stones because of medullary sponge kidney. Percutaneous resection of renal pelvic polyps was carried out through a 26 Fr Amplatz sheath using a 24 Fr resectoscope. Pathological diagnosis was a fibroepithelial polyp. The etiology of this polyp was suggested to be chronic irritation of renal stone.

[A clinical study of secondary osteoporosis induced by endocrine therapy for prostate cancer].

PURPOSE: There is one of the big problems that endocrine therapy for prostate cancer causes to induce secondary osteoporosis. The risk factors and future treatments for osteoporosis were investigated. MATERIALS AND METHODS: 31 patients treated with luteinizing hormone releasing hormone agonists (LHRH-a) or combination of chlormadinone acetate (CMA) and LHRH-a, and 19 patients with no treatments for prostate cancer were included in the analysis. Lumber spine bone mineral density (BMD) was measured by quantitative computed tomography. RESULTS: Aging had much influence on decreases of BMD than the other risk factors (p < 0.01). There were statistically decreases of BMD in the patients with CMA + LHRH-a compared with no treatments (p < 0.05). Adrenal androgen which had an important role of maintenance in BMD was statistically decreased by the administration of CMA (p < 0.01). CONCLUSIONS: Measurement of BMD before endocrine therapy is necessary for the patients with prostate cancer. It is important for the patients with decreases of BMD that CMA is not combined or the therapy for osteoporosis is preventively employed.

[Bone fracture receiving LH-RH agonists for prostatic cancer].

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers. RESULTS: The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

[Double cancer observed from bladder cancer].

BACKGROUND: In recent years, despite of the improvement of treatment results for cancer and long life, the occurrence of second primary cancer was increased. In this paper, we analyzed present condition of double cancer observed with bladder cancer in our hospital. METHOD: Last 21 years, we have treated 969 cases (828 male and 141 female) of primary bladder cancer. For those cases, we analyzed in term of frequency, involved organ, age, interval between two cancer occurrence, risk factor and prognosis of double cancer patients. RESULT: Of 969 cases with bladder cancer, 81 cases (8.36%) had double cancer involving 6 cases (0.61%) of triple cancer. In sex, 70 males (9.78%) and 11 females (7.80%) had double cancer. As involved organs, 25 cases (3.02%) had in prostate, 23 cases (2.37%) in stomach, 3 case (2.13%) in breast, 14 cases (1.44%) in colon and rectum. In diagnosis timing of complicated cancer from bladder cancer, 28 cases (34.6%) were diagnosed previously to bladder, 28 cases (34.6%) were simultaneously and 31 cases (38.3%) were secondary. An average interval of diagnosis of two cancer were 49 +/- 42.5 months. An average age of occurrence of second cancer was 70.3 +/- 8.8 years. Actual survival rate from diagnosis of bladder cancer were 90.8%, 68.6%, 53.3% and 30.3%, after 1, 3, 5 and 10 years, respectively. Ten cases were dead by bladder cancer, 21 cases by complicated cancer and 16 cases by another cause. CONCLUSION: The incidence of double cancer with bladder cancer were increased. Prostate cancer, colorectal cancer and breast cancer were gradually increased as complicated organs in Japan. The prognosis of double cancer patients with bladder cancer was poor than single bladder cancer patients.

[Effects of calcium channel blockers on nocturnal polyuria in the elderly].

Factors reducing the quality of life (QOL) related to micturition and their treatment were studied based on frequency volume chart for 52 consecutive patients with hypertension (the administration of calcium channel blockers) and 28 controls without hypertension, aged 50 years and over (mean age 68.6, range 50-85) without lower urinary tract dysfunction. The micturition records for two days and the QOL index related to urinary symptoms were reviewed. The factors reducing the QOL were increase of the voided volume and frequency during the night and the ratio of night-time voided volume to 24-hour urine output, which significantly increased in the controls (p < 0.05, respectively). Especially, the voiding frequency during the night and the ratio of night-time voided volume increased significantly in the controls aged 70 years and over (p < 0.01, p < 0.05, respectively). Overall, it was suggested that the administration of calcium channel blockers for control of blood pressure might be effective to reduce the nocturnal polyuria in the elderly.

[A case of dual origin of the left anterior descending coronary artery from the left and right coronary arteries with variant angina].

We present a case of a 68-year-old male inflicted with a rare anomaly of the coronary artery. He had been suspected to have worsening effort angina and underwent urgent cardiac catheterization. The coronary angiography revealed 75% stenosis in the first diagonal branch. The left anterior descending artery was terminated in the mid portion and did not reach the apex. Instead, an anomalous coronary artery from the portion just proximal to the right coronary artery reached the apex. After cardiac catheterization, nocturnal chest pain at rest started to occur frequently. We suspected that vasospasm may have occurred because ST segment elevations in leads II, III, aVF were recorded on the electrocardiogram. Administration of diltiazem (120 mg per day) suppressed angina. Exercise stress electrocardiogram and thallium-201 myocardial scintigram did not show apparent ischemia. This case suggests that we must consider the presence of coronary vasospasm even in patients with clinically-supposed effort angina, to be possibly due to vasospasm occurring in anomalous coronary arteries.