MRI of female genital and pelvic organs during sexual arousal

We utilized contrast enhanced magnetic resonance imaging (MRI) to delineate the anatomy of the female genital and pelvic organs during sexual arousal. Eleven healthy pre-menopausal women and eight healthy post-menopausal women underwent MRI of the pelvis while watching an erotic video. A 1.5 Tesla MR system was used to produce T1-weighted images following administration of MS-325, a gadolinium-based blood pool contrast agent. Selected structural dimensions and enhancement were measured prior to and during sexual arousal. In both pre- and post-menopausal subjects, vestibular bulb and labia minora width increased with arousal. Enhancement measurements increased in the bulb, labia minora and clitoris in both pre- and post-menopausal subjects, and in the vagina in pre-menopausal subjects. There were no marked changes in size or enhancement of the labia majora, urethra, cervix, or rectum during sexual arousal in pre- or post-menopausal subjects. Using MRI, we observed specific changes in the female genitalia and pelvic organs with sexual arousal, in both pre- and post-menopausal women. MRI can potentially provide detailed anatomical information in the assessment of female sexual function, particularly with regard to changes in blood flow.     

Retrievable Gunther Tulip inferior vena cava filter: Experience in 317 patients

The aim of our study was to assess our experience with the retrievable Gunther Tulip (GT) inferior vena cava (IVC) filter, with regard to its insertion, efficacy, ease of placement and retrieval, and associated complications. Between November 2001 and October 2005, 322 GT filters were placed in 317 patients. Insertion indications included the following: pulmonary embolus (PE) prophylaxis in trauma patients (n = 232), PE prophylaxis in perioperative patients (n = 27), PE prophylaxis in moribund intensive care unit patients (n = 22), recent PE (n = 48), extensive deep venous thrombosis (n = 66), contraindication to anticoagulation (n = 63), anticoagulation complication (n = 8) and deep venous thrombosis with failed anticoagulation (n = 8). Some patients had more than one indication for caval filter placement. Two hundred and five attempted retrievals have been carried out, with 15 failures. Our successful retrieval rate is 92%. Nineteen filters were originally inserted permanently. There have been three minor complications associated with insertion and five with retrieval. The mean time from filter insertion to attempted retrieval was 76.95 days. The ideal filter implantation time gives the patient the benefit of PE protection, while avoiding the long‐term risks associated with caval filters. Although GT retrieval times have lengthened considerably, our data suggest that this is at the expense of successful retrieval rates.     

用(+)-FLEC手性试剂自动柱前衍生高效液相色谱法拆分麻黄碱类药物对映体

报道了以(+)-FLEC作为手性衍生化试剂,用反相高效液相色谱技术分离麻黄碱类药物对映异构体的方法。dl-麻黄碱、dl-伪麻黄碱、dl-去甲麻黄碱、dl-去甲伪麻黄碱先与(+)-FLEC形成衍生物后,经过一ODSHypersil柱分离,以水和乙腈为流动相梯度洗脱.二极管阵列检测器在266nm检测。该法从样品衍生化到最终报告全部自动完成。上述各对对映体均达到基线分离,分离度R均大于1.5,方法灵敏度高,最低检出限达10pmo1,保留时间和峰面积的上现性较好,RSD分别为1.1/和3.0%。     

Epidemiology of dry eye disease in Africa: The sparse information,gaps and opportunities

Dry eye disease (DED) is an increasingly significant clinical problem in developing countries and/or emerging economies. Existing studies on DED conducted in these areas have largely reported on associations between DED and infectious disease (trachoma) and malnutrition (hypovitaminosis A), but current trends of industrialization, urbanization, and modernization in these areas could result in a shift to other forms of DED. Herein, we review the epidemiology of DED in these geographic areas, highlighting potential causes and risk factors of DED while presenting information on diagnostic tools and algorithms and insight into some treatment modalities of DED that could prove useful to clinicians and investigators in these regions.     

Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects

Spontaneous mutation rates at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were measured in human cancer cell lines defective in the mismatch repair (MMR) genes hMLH1, hPMS2, or GTBP, as well as in a cell line carrying mutations in both hMLH1 and hPMS2. The mutation rate was determined by quantitating mutant frequency increases within a single culture as a function of cell division. These MMR- deficient cell lines exhibited a 50- to 750-fold increase in mutation rate relative to a MMR-proficient cancer cell line. From lowest to highest, the spontaneous mutation rates relative to the MMR-gene defects studied here are as follows: hMLH1- < GTBP- < hPMS2- < hMLH1- / hPMS2-. In addition, a cell line in which MMR was restored by chromosome transfer exhibited a mutation rate 12-fold below the MMR- deficient parental cell line. These data support the notion that MMR plays an important role in controlling the rate of spontaneous mutation and suggest that different MMR-gene defects may vary in their ability to repair different types of DNA mismatches, thus leading to measurable quantitative differences in spontaneous mutagenesis. Furthermore, a difference in mutation rates was observed between a hPMS2-defective cell line (3.1 x 10(-5) mutations/cell/generation) and two hMLH1- defective cell lines (4.0 x 10(-6) and 7.3 x 10(-6) mutations/cell/generation). Assuming the hPMS2- and hMLH1-gene products only function in the proposed hMutL alpha heterodimer, then defects in either gene should yield comparable mutation rates. These data suggest that hPMS2 plays a critical role in MMR, while additional hMLH1 homologues or hPMS2 alone may function to partially complement defects in hMLH1.      

Toxicology and toxicokinetics of acute and subchronic administration of histamine dihydrochloride in rats

Histamine dihydrochloride is currently being evaluated as an adjuvant to immunotherapy regimens in neoplastic and infectious diseases. The no-observed-effect-level (NOEL), no-observable-adverse-effect-level (NOAEL), and pharmacokinetics of subcutaneously administered histamine dihydrochloride were determined via 5 and 28 day repeated dose studies in Sprague-Dawley rats. In the five day study, male rats received 0 (vehicle), 5, 30, 500, or 1000 mg/kg BID. Acute tissue damage was observed at one or more injection sites in the two highest dose groups after 24 h. At five days, animals in these groups displayed indications of pathological inflammation at the injection sites. In the 28 day study, male and female rats received 0 (vehicle), 0.5, 5, or 100 mg/kg BID. The most significant treatment-related pathological findings were signs of inflammation at the injection sites for animals in the 100 mg/kg BID group. Hematology and clinical chemistry changes in the highest dose groups in both studies were consistent with inflammation and anemia but were found to be reversible following a 14-day recovery. Plasma histamine levels were quantified from male and female animals receiving 0.5, 5, and 100 mg/kg injections on Day 1 and 28 of the twenty-eight day study. Cmax was achieved within 0.25 h and was dose-proportional. The elimination half-life and tmax were longer at the 100 mg/kg dose than the lower doses. No marked differences between genders or between Day 1 and 28 were found. Based on these findings, the NOEL and NOAEL were established at 0.5 mg/kg BID and 5 mg/kg BID, respectively. When converted to human equivalent dose, the NOAEL is 0.81 mg/kg which is 54 times the intended human dose. These studies support a wide safety margin for histamine dihydrochloride.