Formaldehyde in cryoprotectant propanediol and effect on mouse zygotes

Cryopreservation of human zygotes and embryos has been routinely performed by in-vitro fertilization clinics for many years. Karran and Legge (1996) first reported that formaldehyde (FA) present in the cryoprotective solutions can have a deleterious effect on mouse oocytes. FA is a cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse zygotes was investigated. In addition, the concentrations of FA in propanediol (PROH) obtained from various sources were determined. Pooled 1-cell embryos were dispensed into droplets of modified Ham's F10 or human tubal fluid containing various concentrations of FA. Since bovine serum albumin (BSA) may minimize toxicity additional trials were done as above in the absence of BSA. FA concentration in the standard 1.5 M PROH, from different sources in water, was measured in the same assay using a standard curve of 0-100 microM FA. FA in a complex medium had a significant deleterious effect on embryo development and hatching but only at 1 mM concentration (P < 0.000001; see Tables I-III). There was no significant effect of FA at 100 microM. However, in a simple medium even 50 microM FA decreased embryo hatching. FA was present in 1.5 M PROH from different sources (range 1.0-35.3 microM concentration). It appears that FA concentrations do not increase with storage because FA concentrations were low even after opening and storage for 3 years on the shelf. This suggests that FA is a contaminant during the manufacturing process and may vary from manufacturer to manufacturer and batch to batch. Until further studies are done to confirm the lack of toxicity to embryos during cryopreservation (with or without FA scavengers) it may be prudent to screen all batches of cryoprotectants for FA as part of quality control.      

Two large French pedigrees with non syndromic sensorineural deafness and the mitochondrial DNA T7511C mutation: evidence for a modulatory factor

Hearing impairment is the most frequent sensory defect in children, with a genetic basis in about 50% of cases. Several point mutations and deletions in mitochondrial DNA (mtDNA) have been identified in non-syndromic sensorineural hearing loss (NSSNHL). Beside the frequent A1555G mutation, a number of mutations in tRNAs have been reported recently, but their incidence remains unknown. We identified the T7511C mutation in the tRNASer(UCN) gene in two French families with isolated deafness. Maternal transmission was obvious in both. The 15 patients with hearing impairment exhibited a variable disease phenotype in terms of onset, severity, and progression. T7511C was present in all the patients screened. Homoplasmic and heteroplasmic levels were observed and did not correlate with the severity of the disease. T7511C was also present in 12 hearing offspring of the oldest deaf mothers, confirming the existence of modulatory factors. Our data suggest that this mtDNA mutation should be screened for in all cases of familial NSSNHL compatible with maternal transmission.     

Outbreak of JK diphtheroid infections associated with environmental contamination.

The group JK diphtheroid organism is a multiply resistant opportunistic pathogen which infects immunocompromised patients sporadically. We describe the first reported outbreak of JK diphtheroid infections, in which four cases of bacteremia and one Hickman catheter site infection occurred during 4 weeks on a hematology ward. On this ward, JK diphtheroid was recovered from 17 of 39 patients, 10 of 17 30-ft3 (0.840-m3) air samples, surfaces in 9 of 13 patient rooms, and hands of 4 of 22 personnel. Previously identified risk factors for JK diphtheroid sepsis (male gender, broad-spectrum antibiotic therapy, granulocytopenia, and prolonged hospital stay) were present in infected patients but did not distinguish them from patients who were only colonized. Emphasis on aseptic practices was associated with termination of the outbreak and negative hand cultures from personnel, despite continued patient colonization and environmental contamination.     

The kidney in streptozotocin diabetic rats. Morphologic, ultrastructural, and function studies.

In order to study the nephropathy associated with experimental streptozotocin diabetes, serila morphologic, ultrastructural, immunohistologic, and functional studies were done in diabetic Lewis rats to study the course of the nephropathy. Early in the course of diabetes, these animals developed an increase in mesangial matrix, with electron-dense material, IgG, and C3 in the mesangium. These alterations were progressive. Mesangial bars, proximal tubular vacuolization, and myeloid bodies were also present. Progressive increase in protein excretion and increase in creatinine clearance were observed. Hyperglycemia was accompanied by weight loss, persistent glycosuris, hyperphosphaturia, and hypercalcuria. Urinary glomerular basement membrane-like protein and major urinary protein were decreased. Normal age-matched controls showed no abnormalities. Some of the changes observed in diabetic rats are present in human diabetes.     

The AMDP scales in a phase II evaluation of psychotropic drugs

Four multicentre double blind trials (two studies comparing placebo to a marketed activating drug and two comparing placebo to a new drug with central adrenergic modulating properties) were pooled, totalling 77 placebo Ss, 30 reference drug Ss and 73 study drug Ss. The AMDP-4 and -5 scales were filled out at day 0 and 7 by trained raters. Four statistical analyses were performed on the pre- vs. postdrug differences: an analysis of variance, a principal components factor analysis, a discriminant analysis and a cluster analysis. The results indicate that 9 out of the 14 AMDP factor scores significantly decrease within 1 week while the factor Mania-Agitation increases, without differences between both active compounds; on the item level, the "inhibition of drive" is specifically improved by the study drug; the discriminant analysis confirms that the two most improved items are "Inhibition of drive" and "Hopelessness". Three factor scores significantly improve on placebo (Depression, Retardation, Psycho-organic Symptoms), which points to the necessity of placebo-controlled studies in clinical trials of new drugs.     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

The introduction of treatment and the cultural adaptability of western psychotherapies for eating disorders in China

In the past 40 years, the prevalence of eating disorders (ED) in China has shown an increasing trend, leading to an urgent need to develop efficient treatment modes and methods. Since the beginning of the new century, the diagnosis, treatment, and research of ED in China have been under development. This article gives an introduction and commentary on the treatment modes, treatment methods and their applications in ED in China. There are two main treatment forms for ED until now, that is, inpatient treatment and outpatient treatment. Inpatient treatment is recommended as the first choice. Since 2008, clinical psychotherapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and family-based treatment (FBT), which are effective for pathological symptoms of ED, have been introduced into China and developed clinically. Group CBT and group DBT for patients with ED and group FBT for caregivers might be the most efficient psychotherapy in China nowadays. A multi-family FBT support group could be developed as the basic treatment of ED patients. Although these new types of psychotherapy have observed effectiveness in clinical application, the Randomized Controlled Trials (RCT) are rare and need to be developed.     

Intraoperative measurement of javid shunt flow with transit-time ultrasound

Transit-time ultrasound methods were used to measure blood flow in 37 patients undergoing carotid endarterectomy. Internal carotid flow before (ICF^bef) and after (ICF^aft) endarterectomy was measured with a 6 mm perivascular probe, and Javid shunt flow (SF) was measured with a clamp-on probe. For the entire group ICF^bef averaged 117±67 ml/min and ICF^aft was 173±67 ml/min. Shunt flow averaged 123±51 ml/min. The differences between ICF^bet and ICF^aft and between SF and ICF^aft were significant (ANOVA,p<0.01) but the difference between ICF^bef and SF was not. The relationship between ICF^bef and SF appeared to define two groups of patients. Those in whom SF was greater than ICF^bef (SF > ICF^bef) had more stenosis evident on preoperative arteriograms (64.7%±14.55% maximum single diameter stenosis) and a greater average increase in ICF (151%±159%) than those with SF ICF^bef (43.3%±20.9% stenosis and 34%±54% increase in ICF), suggesting that the relationship between SF and ICF^bef defines groups with different hemodynamic responses. The similarity between SF and ICF^bef indicates that Javid shunt flow offers adequate protection from cerebral ischemia. A practical benefit of the shunt clamp-on flow probe is the ability afforded to recognize shunt occlusions.Presented at the Twelfth Annual Meeting of the Southern California Vascular Surgical Society, Coronado, Calif., September 17–19, 1993.