Azoospermia is the complete absence of spermatozoa in the ejaculate in two or more semen analyses after centrifugation. Nonobstructive azoospermia (NOA) represents the most severe form of male factor infertility accounting for 10%-15% of cases and stems from an impairment to spermatogenesis. Understanding of the hypothalamic-pituitary-testicular axis has allowed NOA to be subcategorized by anatomic and/or pathophysiologic level. The etiologies of NOA, and therefore, the differential diagnoses when considering NOA as a cause of male factor infertility, can be subcategorized and condensed into several distinct classifications. Etiologies of NOA include primary hypogonadism, secondary hypogonadism, defects in androgen synthesis and/or response, defective spermatogenesis and sperm maturation, or a mixed picture thereof. This review includes up-to-date clinical, diagnostic, cellular, and histologic features pertaining to the multitude of NOA etiologies. This in turn will provide a framework by which physicians practicing infertility can augment their clinical decision-making, patient counseling, thereby improving upon the management of men with NOA.
Humans ; Azoospermia/diagnosis* ; Male ; Spermatogenesis/physiology* ; Hypogonadism/complications* ; Infertility, Male/etiology* ; Testis/pathology*

The Simulium gombakense species-group, one of the 15 species-groups of the subgenus Gomphostilbia Enderlein, is small, being represented by only 12 species, all of which are distributed in the Oriental Region. It is characterized by the pupal gill composed of an inflated structure and eight or ten slender filaments. Among the 12 species, S. sachini Takaoka & Henry, and S. williei Takaoka & Thapa were originally described from two pupae, and one pupa and two larvae, respectively, from Darjeeling, India. In the present paper, the adult females and males of these species are described for the first time from specimens reared from pupae collected at the type locality. Simulium sachini is distinctive in the female by the claw with a medium-sized basal tooth, and in the male by the somewhat enlarged, spindleshaped hind basitarsus and ventral plate with its ventral margin much depressed medially, while S. williei is characterized by the small number of male upper-eye (large) facets in 12 vertical columns and 13 or 14 horizontal rows and ventral plate much produced posteroventrally. Taxonomic notes are given to separate these two species in the adult stage from their related species.

BACKGROUND: Programmed intermittent epidural bolus (PIEB) techniques are a new area of interest for maintaining labor analgesia due to the potential to decrease motor block and improve labor analgesia. This study compares continuous epidural infusion (CEI) to 2 PIEB regimens for labor analgesia. METHODS: One hundred fifty patients undergoing scheduled induction of labor at term gestation having epidural labor analgesia were randomized to receive an epidural analgesia regimen of bupivacaine 0.125% with fentanyl 2 μg/ml at either PIEB 5 ml every 30 min (Group 5q30), PIEB 10 ml every 60 min (Group 10q60), or 10 ml/h continuous infusion (Group continuous epidural infusion [CEI]). The primary outcome is the pain scores throughout labor. Secondary outcomes include degree of motor block, dermatomal sensory levels, the number of physician-administered boluses, and patient satisfaction. RESULTS: While the average pain scores throughout labor did not differ significantly between groups, fewer patients in group 10q60 received physician-administered boluses for breakthrough pain (34.9% in 10q60 vs. 61.0% in 5q30 and 61.9% in CEI, P = 0.022). Dermatomal sensory levels, degree of motor block, and patient satisfaction did not differ significantly between groups. CONCLUSIONS Our study suggests that high volume PIEB regimens for labor analgesia decrease breakthrough pain and physician-administered boluses.

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.

BACKGROUND: Programmed intermittent epidural bolus (PIEB) techniques are a new area of interest for maintaining labor analgesia due to the potential to decrease motor block and improve labor analgesia. This study compares continuous epidural infusion (CEI) to 2 PIEB regimens for labor analgesia. METHODS: One hundred fifty patients undergoing scheduled induction of labor at term gestation having epidural labor analgesia were randomized to receive an epidural analgesia regimen of bupivacaine 0.125% with fentanyl 2 μg/ml at either PIEB 5 ml every 30 min (Group 5q30), PIEB 10 ml every 60 min (Group 10q60), or 10 ml/h continuous infusion (Group continuous epidural infusion [CEI]). The primary outcome is the pain scores throughout labor. Secondary outcomes include degree of motor block, dermatomal sensory levels, the number of physician-administered boluses, and patient satisfaction. RESULTS: While the average pain scores throughout labor did not differ significantly between groups, fewer patients in group 10q60 received physician-administered boluses for breakthrough pain (34.9% in 10q60 vs. 61.0% in 5q30 and 61.9% in CEI, P = 0.022). Dermatomal sensory levels, degree of motor block, and patient satisfaction did not differ significantly between groups. CONCLUSIONS: Our study suggests that high volume PIEB regimens for labor analgesia decrease breakthrough pain and physician-administered boluses.
Analgesia ; Analgesia, Epidural ; Breakthrough Pain ; Bupivacaine ; Fentanyl ; Humans ; Patient Satisfaction ; Pregnancy ; Prospective Studies

OBJECTIVE: Disturbances in potassium (K) levels are relatively common and may be associated with significant morbidity and mortality; however, treatments vary. Our purpose was to determine the incidence, treatments, and outcomes associated with hyperkalemia and hypokalemia in emergency department (ED) patients. METHODS: We performed a structured, retrospective review of electronic medical records of consecutive adult ED patients with K measured while in the ED. Demographic, clinical, and laboratory data as well as treatments, disposition, and in-hospital complications were collected. Univariate and multivariate analyses, presented as adjusted odds ratios, were used to compare outcomes by K levels. RESULTS: Of 100,260 visits in 2014, an ED K level was ordered in 48,827 (49%). A total of 1,738 patients (3.6%) were excluded because of sample hemolysis. The K was low (<3.5 mEq/L) in 5.5%, normal (3.5 to 5.0 mEq/L) in 90.9%, and elevated (>5.0 mEq/L) in 3.6% of patients. Patients with hyperkalemia were older (64 vs. 49 years, P<0.001) and more likely male (58% vs. 40%, P<0.001). Treatment for hyperkalemia varied greatly. After adjusting for confounders, both hyperkalemia and hypokalemia were associated with inpatient hospitalization and death. At least one medication was used to manage hyperkalemia in 11.5% of patients with a K of 5.1 to 5.4 mEq/L, 36.4% of those with a K 5.5 to 6 mEq/L and 77.0% of the cohort with K >6 mEq/L. CONCLUSION: Hyperkalemia or hypokalemia occur in 1 of 11 ED patients and are associated with inpatient admission and mortality. Treatment of hyperkalemia varies greatly suggesting the need for evidence-based treatment guidelines.
Adult ; Cohort Studies ; Electronic Health Records ; Emergencies* ; Emergency Service, Hospital* ; Hemolysis ; Hospitalization ; Humans ; Hyperkalemia ; Hypokalemia ; Incidence ; Inpatients ; Male ; Mortality ; Multivariate Analysis ; Odds Ratio ; Potassium* ; Retrospective Studies*

OBJECTIVE: Introduction of target specific anticoagulants and recent guidelines encourage outpatient management of low risk patients with venous thromboembolism. We describe hospital admission rates over time for patients presenting to US emergency departments (EDs) with deep vein thrombosis (DVT) and pulmonary embolism (PE) and estimate the proportion of low-risk PE patients who could potentially be managed as outpatients. METHODS: We performed a structured analysis of the National Hospital Ambulatory Medical Care Survey (a nationally representative weighted sampling of US ED visits) database for the years 2006–2010 including all adult patients with a primary diagnosis of DVT or PE. Simplified pulmonary embolus scoring index (sPESI) scores were determined in patients with PE to identify low risk patients. RESULTS: There were an estimated 652,000 and 394,000 ED visits for DVT and PE over the 5-year period (0.17%). Mean (SE) age was 59 (1.3), 50% were female, and 40% were > 65 years. Admission rates for DVT and PE were 52% and 90% respectively with no significant changes over time. In patients with DVT, predictors for admission were age (odds ratio, 1.03 per year of age [95% confidence interval, 1.01 to 1.05]) and race (odds ratio, 4.1 [95% confidence interval, 0.9 to 19.8] for Hispanics and 2.9 [1.2 to 7.4] for Blacks). Of all ED patients with PE, 51% were low risk based on sPESI scores. CONCLUSION: Admission rates for DVT and PE have remained high and unchanged, especially with PE, minorities, and in older patients. Based on sPESI scores, up to half of PE patients might be eligible for early discharge or outpatient therapy.
Adult ; Anticoagulants ; Continental Population Groups ; Diagnosis ; Embolism ; Emergencies* ; Emergency Service, Hospital* ; Female ; Hispanic Americans ; Humans ; Outpatients ; Pulmonary Embolism* ; Venous Thromboembolism* ; Venous Thrombosis

We describe New World cutaneous leishmaniasis (Leishmania amazonensis), a disease not endemic in the Philippines, in a 45-year-old man with ulcerating lesions on his hand and leg ater returning from South America. The patient responded to treatment with liposomal amphotericin B. This imported case of leishmaniasis highlights the importance of obtaining a detailed travel history in patients with chronic, non-healing skin lesions which should lead to earlier recognition and treatment.

Human ; Male ; Middle Aged ; Liposomal Amphotericin B ; Philippines ; Amphotericin B ; Leishmaniasis, Cutaneous ; Leishmania Mexicana ; South America

INTRODUCTIONInfection-related complications after transrectal ultrasound guided prostatic biopsy (TRPB) could be life threatening. Our centre observed sepsis after TRPB despite prophylactic oral ciprofloxacin. We reviewed all cases of post-TRPB sepsis with their bacteriology and evaluated if the addition of intramuscular (I/M) gentamicin to standard prophylaxis before TRPB could reduce its incidence.

MATERIALS AND METHODSIn a single urological centre, we performed an interventional study that compared a prospective group with retrospective control. The latter is known as the "cipro-only" group included consecutive patients who underwent TRPB between 1 September 2003 and 31 August 2004. The addition of I/M gentamicin 80 mg half an hour before TRPB started on 1 September 2004. All subsequent patients who underwent TRPB until 31 August 2005 were included in the "cipro+genta" group. Patients who did not receive the studied antibiotics were excluded.

RESULTSThere were 374 patients in the "cipro+genta" group and 367 patients in the "cipro-only" group with comparable profiles. There were 12 cases of post-TRPB sepsis in the "cipro-only" group and 5 cases in the "cipro+genta" group. Ciprofloxacin-resistant Escherichia coli (E. coli) was the only pathogen isolated in both groups. In the "cipro-only" group, 9 patients had positive blood cultures and 8 were sensitive to gentamicin. In the "cipro+genta" group, the only positive E. coli was gentamicin-resistant. One patient in the "cipro+genta" group was admitted to the intensive care unit with septicaemia.

CONCLUSIONThe addition of I/M gentamicin to oral ciprofloxacin is a safe and effective prophylactic antibiotic regime in reducing the incidence of post-TRPB sepsis.

Administration, Oral ; Adult ; Aged ; Antibiotic Prophylaxis ; methods ; Biopsy ; Ciprofloxacin ; administration & dosage ; therapeutic use ; Drug Resistance, Bacterial ; Escherichia coli ; drug effects ; isolation & purification ; Gentamicins ; administration & dosage ; Humans ; Injections, Intramuscular ; Male ; Middle Aged ; Prospective Studies ; Prostate ; diagnostic imaging ; pathology ; Rectum ; Ultrasonography