Effectiveness and Safety of Posterior Vaginal Repair with Single-Incision, Ultralightweight, Monofilament Propylene Mesh: First Evidence from a Case Series with Short-Term Results.

OBJECTIVE: The use of transvaginal mesh is controversial, and over time, multiple surgical methods for the treatment of posterior vaginal prolapse (PVP) have been proposed including different surgical approaches and techniques. To date, no clear conclusion has been reached about the use of mesh for reinforcing transvaginal posterior repair. The aim of this study was to evaluate the feasibility, safety, and effectiveness of a novel, ultralightweight mesh for the treatment of PVP. METHODS: We performed a single-center, prospective observational study on consecutive patients referred for primary or recurrent, symptomatic stage II PVP (according to the international Pelvic Organ Prolapse Quantification System) from April 2017 to September 2018. In all patients, transvaginal posterior repair was augmented with a single-incision, isoelastic polypropylene mesh. Data about the postoperative outcomes were collected until December 2019. RESULTS: A total number of 15 patients were included. The median follow-up after surgery was 18 months (IQR = 14). Surgery was completed in all cases without complications. Regarding the anatomical outcomes (as measured according to POP-q classification), a significant improvement was observed in terms of Bp, D, and C (p < 0.05). The functional outcomes were significantly ameliorated after surgery, with a reduction of bulge symptom, stypsis, incomplete evacuation, and excessive staining (p < 0.05). The quality of life was significantly improved in the majority of patients (p < 0.05). Median patients' satisfaction rate was 100% (IQR = 22.5%). Neither early nor late postoperative complications occurred. CONCLUSIONS: Single-incision, ultralightweight polypropylene meshes were safe and highly effective in the treatment of PVP. As our study has some limitations, further large, controlled studies are needed.

The efficacy and safety of salvianolic acids on acute cerebral infarction treatment: A protocol for systematic review and meta analysis.

BACKGROUND: Salvianolic acids (SA) has been widely used for the treatment of acute cerebral infarction (ACI) combined with basic western medicine therapy in China. This study was aimed to evaluate the efficacy and safety of SA on ACI treatment and its influence on neurological functions, activity of daily living, and cognitive functions. METHODS: We retrieved related articles from PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Medline, Ovid, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database without date and language restrictions. Finally, 58 randomized controlled trials were included from 239 retrieved records. Two researchers extracted the basic information and data from included articles and assessed the quality and analysis of data by using Review Manager 5.3. RESULTS: The administration of SA significantly increased the total clinical effective rate of ACI treatment (P < .001) and improved the National Institute of Health Stroke Scale scores, modified Rankin Scale scores, and Barthel Index scores after treatment and 3 months after ACI (P < .05). The activities of daily living scores in the SA group were significantly increased after treatment (P < .001), whereas they were remarkably decreased 3 months after ACI (P < .001) compared with that in the control group. Besides, SA profoundly promoted the recovery of Montreal Cognitive Assessment scores (P < .001). However, the use of SA increased the risk of adverse events occurrence (P = .007). CONCLUSION: SA combined with basic western medicine treatment could promote neurological functions, daily living activities, and cognitive functions recovery of ACI patients. Although SA increased the risk of adverse events occurrence, these adverse events were easily controlled or disappeared spontaneously.

Simultaneous identification of three pseudoallergic components in Danshen injection by using high-expression Mas-related G protein coupled receptor X2 cell membrane chromatography coupled online to HPLC-ESI-MS/MS.

Adverse drug reactions of Danshen injection mainly manifested as pseudoallergic reactions. In the present study, salvianolic acid A and a pair of geometric isomers (isosalvianolic acid C and salvianolic acid C) were identified as pseudoallergic components in Danshen injection by a high-expression Mas-related G protein coupled receptor X2 cell membrane chromatography coupled online with high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. Their pseudoallergic activities were evaluated by in vitro assay, which were consistent with the retention times on the cell membrane chromatography column. Salvianolic acid C, the most outstanding compound, was further found to induce pseudoallergic reaction through Mas-related G protein coupled receptor X2. All the results above indicated that the system developed in this study is an effective method for simultaneously analyzing pseudoallergic components, even those with similar structures and the microcomponents in complex samples (salvianolic acid C in Danshen injection).

Potential roles of myeloperoxidase and hypochlorous acid in metabolism and toxicity of alkene hydrocarbons and drug molecules containing olefinic moieties.

INTRODUCTION: Adverse drug reactions (ADRs) pose a significant health problem and are generally attributed to reactive metabolites. Olefinic moieties in drugs can undergo cytochrome P450-mediated bioactivation to produce reactive metabolites but myeloperoxidase (MPO)-mediated bioactivation of these moieties has not been reported. Thus, small molecules of alkene hydrocarbons are used as model compounds to characterize the MPO-mediated metabolism. Areas covered: The authors focus on MPO-mediated metabolism of alkene hydrocarbons to form chlorohydrins and the potential role of chlorohydrins in alkene toxicity and carcinogenicity. A case study is presented, in which a carcinogenic alkene, 1,3-butadiene, is demonstrated to form 1-chloro-2-hydroxy-3-butene (CHB) through the MPO-mediated pathway. Further bioactivation of CHB yields a cross-linking metabolite, 1-chloro-3-buten-2-one (CBO), which is highly reactive toward glutathione, proteins, nucleosides, and DNA. Toxicity and mutagenicity of CHB and CBO are also presented. Expert opinion: Alkene hydrocarbons readily undergo MPO-mediated bioactivation to form chlorohydrins, which can further be biotransformed into proteins/DNA-modifying reactive metabolites. Therefore, chlorohydrin formation may play an important role in alkene toxicity and carcinogenicity. Olefinic moieties in drugs are expected to undergo similar bioactivation, which may contribute to ADRs. Studies to investigate the roles of MPO and chlorohydrin formation in ADRs are thus warranted.

The effect of two sock fabrics on physiological parameters associated with blister incidence: a laboratory study.

The goal of the present study was to investigate physiological effects, mainly at the level of the foot, of two sock fabrics with distinct moisture properties. Twelve participants wore two different socks, one on each foot. The following two sock types were used: PP: 99.6% polypropylene and 0.4% elastane and BLEND: 50% Merino wool, 33% polypropylene, and 17% polyamide. The participants walked three times on a treadmill at 5 km h(-1), with no gradient for the first and third phase and a 10% upward inclination for the second walking phase. The microclimate temperature between the boot and foot was measured during walking. Preceding and following the walking phases, additional measurements were carried out at the level of the foot, i.e. skin temperature and skin hydration on three locations and skin friction between the posterior surface of the calcaneus and a glass plate. In addition, the moisture absorption of boots and socks was determined. Differences between the sock fabrics were found for weight gain and microclimate temperature: (i) PP tended to hold less water compared to BLEND, (ii) the boot's microclimate temperature resulted in larger values for BLEND measured at the dorsal surface at the level of the third metatarsal, and (iii) warmer microclimates of the boot were measured for PP compared to BLEND at the distal anterior end of the tibia. The established differences in moisture behavior of both socks did not result in detectable differences in parameters measured on the skin of the foot.

Abscess formation at the ischiorectal fossa 7 months after the application of a synthetic transobturator sling for stress urinary incontinence in a type II diabetic woman.

A 50-year-old diabetic woman was referred to our unit because of high fever, foul-smelling vaginal discharge and pain in the leg, 7 months after undergoing surgery for application of a transobturator suburethral sling. Patient evaluation revealed erosion of the tape through the vaginal wall; the infection had spread to the region of the internal obturator muscle and then up to the anterior recess of the ischiorectal fossa. The patient underwent surgery for sling removal, antibiotic therapy and, finally, surgical incisions to facilitate drainage of the abscess. All these passages were necessary to obtain complete resolution of the symptoms. Infectious complications are possible after transobturator sling procedures. Patients should then be informed about the risks of erosion and infection and be warned that the appearance of pain and foul-smelling vaginal discharge may indeed be the first symptom of subsequent and much more severe infectious complications.

Hemolytic anemia and induction of phase II detoxification enzymes by diprop-1-enyl sulfide in rats: dose-response study.

Epidemiological evidence indicates that a high dietary intake of plants of the Allium family, such as garlic and onions, is associated with a decreased risk of cancer in humans. It has been suggested that this chemopreventative effect involves the ability of the aliphatic sulfides derived from these vegetables to increase tissue activities of phase II detoxification enzymes. Several highly effective inducers from garlic have been identified, but most of the previously studied compounds from onion have proved to be only weakly active. In the present study, the inductive activity of another onion-derived sulfide, diprop-1-enyl sulfide, has been investigated. This substance was a potent inducer of phase II enzymes in rats, showing significant effects in the lungs and in the lower part of the gastrointestinal tract, suggesting that diprop-1-enyl sulfide could be a useful chemopreventative agent at these sites. At high dose levels, diprop-1-enyl sulfide caused hemolytic anemia, which may be due to in vivo conversion of the sulfide to active metabolites.

Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.

Fostriecin (CI-920) is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosphatase 4(PP4) found to have anticancer activity in preclinical testing. A phase I study was conducted to evaluate the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of this drug. Forty-six patients were treated with escalating doses of fostriecin (2-47 mg/m2) administered as a daily bolus infusion for five consecutive days. PK studies were performed at different time points following administration of fostriecin. Dose-limiting toxicities included: elevation of creatinine, bilirubin, and hepatic transaminases; nausea, anorexia, lethargy, and hypotension. PK studies were compatible with a two-compartment model. Regression analysis revealed a significant relationship between dose and clearance; however, the r2 value was only 0.168 indicating a low predictive value for the model. No significant difference was seen in PK parameters with repeated dosing during the same cycle. Although no tumor responses were seen, 16 patients had stable disease with a median duration response of 2.6 months. The study was closed before reaching MTD due to problems with the supply of fostriecin from the National Cancer Institute of the United States (NCI US). New methods for synthesizing fostriecin have recently been described and therefore further development of this unique anticancer agent may be warranted.

[Determination of DNA adducts in persons with occupational exposure to alkenes]. / Stanovení DNA adduktu u osob exponovaných alkenum v pracovním prostredí.

DNA adducts induced by alkenes were studied in in vitro systems (cell cultures) and in experimental animals. Properties of DNA adducts, their relationship with other parameters of genotoxic effect and DNA repair were followed. Based on these results, human biomonitoring studies were conducted in order to elucidate the effect of exposure on enhanced levels of DNA and haemoglobin adducts, single-strand breaks in DNA and HPRT mutant frequencies. Surprisingly, no correlation was found between primary DNA lesions and HPRT mutant frequencies, suggesting that no simple quantitative relationship could be drawn between primary DNA damage and mutagenesis. In order to understand mechanisms of genotoxic effects of xenobiotics, further studies aimed at individual susceptibility, individual repair capacity and the role of specific DNA adducts in mutagenesis, are required.

Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin.

We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60 min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1) to 20 mg m(-2) day(-1) in 20 patients. Drug pharmacokinetics was analysed with high performance liquid chromatography with UV-detection. Plasma collected during drug administration was tested in vitro for growth inhibition of a teniposide-resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities were elevated liver transaminases (maximum common toxicity criteria (CTC) grade 4) and serum creatinine (maximum CTC grade 2). These showed only a limited increase with increasing doses, often recovered during drug administration and were fully reversible. Duration of elevated alanine-amino transferase (ALT) was dose-limiting in one patient at 20 mg m(-2). Other frequent toxicities were grade 1-2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was 0.36 h (initial; 95% CI, 0-0.76 h) and 1.51 h (terminal; 95% CI, 0.41-2.61 h). A metabolite, most probably dephosphorylated fostriecin, was detected in plasma and urine. No tumour responses were observed, but the plasma concentrations reached in the patients were insufficient to induce significant growth inhibition in vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply was stopped at the 20 mg m(-2) dose level. However, further escalation seems possible and is warranted to achieve potentially effective drug levels. Fostriecin has a short plasma half-life and longer duration of infusion should be considered.

Renal toxicity of the anticancer drug fostriecin.

PURPOSE: Fostriecin is an inhibitor of topoisomerase II catalytic activity. In a phase I trial we observed renal toxicity, documented as a rise in serum creatinine, which was reversible and non-dose-limiting. The purpose of this study was a detailed analysis of this toxicity. METHODS: A total of 20 patients received fostriecin as a 1-h i.v. infusion daily x 5 at doses ranging from 2 to 20 mg/m2 per day. Serum creatinine determination and urinalysis were performed daily during drug administration. Renal hemodynamics were measured by means of clearance studies using 125I-iothalamate and (131)I-hippuran in eight patients at doses of > or =4 mg/m2 per day at baseline, on day 3 or 4 during the first course, and 3 weeks after the second course. RESULTS: The rise in serum creatinine was maximal after one to two doses despite continued administration. This increase showed no correlation with the dose level at fostriecin doses of > or =4 mg/m2 per day. Urinary beta2-microglobulin concentrations increased 150-fold (median), which is compatible with impaired tubular reabsorption. The median change in the glomerular filtration rate (GFR) was -36% (range -28% to -44%), that in effective renal plasma flow (ERPF) was -23% (range -11% to -36%), and the filtration fraction (FF) decreased in all patients during the first course of treatment. The values measured 3 weeks after the second course, however, did not differ from baseline. CONCLUSIONS: Fostriecin induces reversible renal hemodynamic changes compatible with renal tubular damage.

On cancer risk estimation of urban air pollution.

The usefulness of data from various sources for a cancer risk estimation of urban air pollution is discussed. Considering the irreversibility of initiations, a multiplicative model is preferred for solid tumors. As has been concluded for exposure to ionizing radiation, the multiplicative model, in comparison with the additive model, predicts a relatively larger number of cases at high ages, with enhanced underestimation of risks by short follow-up times in disease-epidemiological studies. For related reasons, the extrapolation of risk from animal tests on the basis of daily absorbed dose per kilogram body weight or per square meter surface area without considering differences in life span may lead to an underestimation, and agreements with epidemiologically determined values may be fortuitous. Considering these possibilities, the most likely lifetime risks of cancer death at the average exposure levels in Sweden were estimated for certain pollution fractions or indicator compounds in urban air. The risks amount to approximately 50 deaths per 100,000 for inhaled particulate organic material (POM), with a contribution from ingested POM about three times larger, and alkenes, and butadiene cause 20 deaths, respectively, per 100,000 individuals. Also, benzene and formaldehyde are expected to be associated with considerable risk increments. Comparative potency methods were applied for POM and alkenes. Due to incompleteness of the list of compounds considered and the uncertainties of the above estimates, the total risk calculation from urban air has not been attempted here.

Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels.

PIP: Tamoxifen (ICI 46474) is the trans-isomer of 1(p-beta-dimethylaminoethoxy-phenyl)-1, 2-diphenylbut-1-ene. In several but not all mammal species it is a potent anti-estrogen. It is thought to act by blocking estrogen receptors. Patients were 68 women with advanced primary carcinoma of the breast, recurrences in the chest wall or soft tissue metastases. The oral dose of tamoxifen was either 10 mg or 20 mg twice daily. Patients were seen and laboratory tests done monthly for 6 months. Side effects were usually trivial and their incidence was the same at both dose levels. Of 26 patients who showed a reduction in tumor size to half or less, 5 had been in remission for over a year and another 10 for over 6 months. Some tumor responses were spectacular. The drug was less effective for bone deposits. In this study 12 of 33 patients (36%) receiving 10 mg of tamoxifen twice daily showed a definite response while a futher 8 (24%) showed a partial response. A definite response was seen in 14 out of 35 (40%) receiving 20 mg twice daily and a partial response in a further 13 (37%). The total response for low dosage was 60% and for high dosage 77%.^ieng