Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites

AIM: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial. METHODS: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator ( approximately 5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. RESULTS: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. CONCLUSION: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.     

Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with tissue eosinophilia and the activation of T lymphocytes. The novel eosinophil chemoattractants, eotaxin and monocyte chemotactic protein (MCP)-4, are up-regulated at sites of allergic inflammation, yet their contribution to the pathophysiologic mechanisms of AD remains to be determined. OBJECTIVE: We sought to investigate the expression of eotaxin and MCP-4 in acute and chronic lesions from patients with AD and to determine their relationship to the numbers of resident inflammatory cells. METHODS: With use of in situ hybridization, the expression of eotaxin and MCP-4 messenger RNA (mRNA) in skin biopsy specimens from patients with acute and chronic AD skin lesions was compared with that of uninvolved skin from these patients and skin from healthy volunteers. RESULTS: There was a constitutive expression of eotaxin and MCP-4 mRNA in skin biopsy specimens from healthy subjects. Positive signal for chemokine mRNA was observed both within the epidermis and inflammatory cells (macrophages, eosinophils, and T cells) of the subepidermis in AD skin lesions. Within the subepithelium acute and chronic skin lesions exhibited a significant increase in the numbers of eotaxin and MCP-4 mRNA-positive cells compared with uninvolved skin (P <.01), whereas the numbers of eotaxin and MCP-4 mRNA-positive cells were significantly higher in chronic AD compared with acute AD skin lesions (P <.005, P <.001, respectively). Correlations were observed between the expression of eotaxin and MCP-4 mRNA and the presence of eosinophils and macrophages, respectively, in AD lesions (r(2) = 0.84, r(2) = 0.94). CONCLUSION: There is an increased expression of eotaxin and MCP-4 in acute and chronic lesions, suggesting that these chemotactic factors play a major role in the pathophysiologic mechanisms of AD.     

Télomères monofonctionnels du chlorure de vinyle, 3. Cinétique par catalyse rédox

A kinetic study of the redox telomerization of vinyl chloride with carbon tetrachloride was carried out. Transfer constants of PVC to the metallic ion (C_Feⁿ), initiation rate (k_i), and functionnality of the resulting telomers were measured. Instantaneous and cumulated polymerization degrees, (DP_n )_i and (DP_n )_cum were determined with the help of a theoretical study. These constants provide a rigorous control of the telomerization of vinyl chloride with RCCl₃, (R containing an alcohol or ester group).     

Synthèse de macromères à base de chlorures de vinyle et de vinylidène au moyen de télomères

New macromers 4, 8, and 10, containing ester, alcohol, or acid functions, were prepared starting with vinyl chloride (CV) or vinylidene dichloride (CV₂). The telomer 1, resulting from CV₂ and CCI₄ was telomerized with allyl acetate and the product was transformed into the acrylate 4 by hydrolysis of the reaction product and subsequent esterification. Macromers 8 and 10 were prepared from CV by radical telomerization with thioglycolic acid (7) and 2-mercaptoethanol (9), respectively. Reactive double bonds were introduced into these macromers by reaction with acrylic acid, Vinyl chloroformate, methacryloyl chloride, or 2,3 -epoxypropyle methacrylate, leading to new macromers 12, 13, 14, and 15, respectively.     

Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

Background:This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe^®) and the conventional fixed-size ice probe.Materials and methods:We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe^® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage.Results:A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65–74 years), 7 (IQR: 6–7) and 5.9 ng/mL (IQR: 4.6–8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2–48.6 months). V-Probes^® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe^® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003).Conclusions:The use of the V-Probe^® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.     

Prediction of post-cardiopulmonary bypass cardiac output by venous oximetry

The present study evaluates two equations for predicting the post-cardiopulmonary bypass cardiac output (CO) in 10 patients undergoing coronary artery bypass grafting. One equation is based on the relationship of CO with mixed venous oxygen saturation (SVO 2), while the second equation is based on the relationship with oxygen extraction (1 - SVO 2). Each patient served as his own control. During bypass, when the patients were normothermic and perfused with a pump flow of 2.4 L/min/m 2, the SVO 2 was monitored by an in-line Bentley oxystat Meter. Just before termination of bypass, the pump flow was decreased to 0.4 L/min/m 2 and the left atrial pressure was increased to 10-15 mmHg; the resulting SVO 2 was recorded. The post-bypass CO was predicted in every patient by the two equations. Immediately after weaning from bypass, the cardiac output was measured by thermodilution. The thermodilutional CO measurement was correlated with the CO predicted by the two equations. Correlation analysis suggests that CO prediction is more accurate and approaches the 1:1 ratio when the calculation of predicted CO is based on the relationship between cardiac output and oxygen extraction.     

Plasma melphalan and prednisolone concentrations during oral therapy for multiple myeloma

Summary Nine patients with myeloma were studied over 13 oral administrations of 10 mg melphalan and 5–10 mg prednisolone. Plasma melphalan concentrations were estimated by high-pressure liquid chromatography, prednisolone concentrations by quantitative thin-layer chromatography. The mean plasma half-life of unchanged melphalan was 0.9±0.5 (SD) h. The lag-time before melphalan was detected in the plasma varied from 1 to 4 h, the mean peak concentration was 96±21 ng/ml, and the mean area under the plasma concentration by time curve was 160±78 ng h/ml. This variability was consistent with observations made elsewhere following much higher oral doses of melphalan and illustrates the relatively wide interindividual variability of absorption. Observations made in the same subjects on two separate occasions showed lower variability. The melphalan elimination rate was not significantly affected by moderate impairment of creatinine clearance (to 31 ml/min). Absorption of prednisolone in five of these patients was apparently normal and unaffected by concurrent administration of melphalan.     

Is regional tonometry a reliable index of tissue oxygenation? A comparative study with conventional global monitoring

This study was carried out on 30 critically ill patients admitted to the ICU of Farwania Hospital (Kuwait). All patients had clinical evidence of organ dysfunction or impending multiple organ failure. The severity of their pathology on admission was assessed according to the APACHE II score. The study of each patient began after inserting the pulmonary artery catheter. The prospectively defined end-point of the study was the removal of the pulmonary artery catheter (72 hours) or death of the patient with the catheter in situ. The aim of the study was to determine the sensitivity and specificity of the intra-gastric mucosal pH (pHi) and other derived data in assessing the adequacy of tissue oxygenation, guiding therapy and prediction outcome. The results showed that pHi, pHa-Hi and PaCO2-PO2regional (reg) gradients were the most sensitive indices of tissue oxygenation and predictors of outcome. The mortality rate increased when pHi, PaCO2-PCO2reg and pHa-pHi gradients were < 7.3, > 10 mm Hg and < 0.2 respectively. The derived variables obtained by invasive monitoring like base deficit (BD), lactate concentration in mixed venous blood (Lmv) and oxygn uptake index (O2 UI) were valuable adjunct indices of tissue oxygenation. The risk ofmortality increased whten the BD was > -5.5 +/- 1.2 meq.L-1, Lmv was > 4.5 +/- 1.2 mmol.L-1, and O2UI was < 100 +/- 6 ml.min-1.m-2. We recommend the use of gastric tonometry in routine ICU clinical practice.