Tissue reaction after injection of polyvinylpyrrolidone (PVP) preparation into knee joint. Experiment

Internally netted miscogelatinated preparation on the basis of polyvinylpyrrolidone PVP desioned for viscosuplementation of joint fluid was worked out. Netted structure of microgel grains presents larger resistance to the degrading action of free radicals than analogical linear polymer chains. Application of zoogeous preparations of hyaluronic acid results in short-term effects of their usage in evoking reaction foreign protein. Replenishment of joint fluid with preparation with higher biostability from biocompatible synthetic polymer-polyvinylpyrrolidone could improve the function of synovial through restoration of its proper viscosity and protection of the joint for a longer period of time. The aim of the experiment was determination of bioresistance and reaction of microgel PVP on the tissues of synovial joint. The tests were carried out on 10 white New Zealand rabbits after injection PVP into the knee joint for 3, 7, 14 and 30 days and submitted to macroscopic and histological evaluation. The results of tests were compared with the data obtained after injection of normal saline. Macroscopically, there were no changes in the limits of articular capsule and cartilage; there was only slight and enlargement of synovial membrane in the first 7 days after PVP injection. In histological tests it was observed that reaction in the knee joint after PVP injection was characterised it single inflammatory chains without essential participation of neutrophils observed only in synovial membrane and limited to places were tested preparation was seen. Microgel PVP was present in diverticula of synovial membrane to 30th day after injection.     

Cytochrome P450 3A and their regulation

CYP3A isozymes collectively comprise the largest portion of the liver and small intestinal CYP protein and they are involved in the metabolism of 45–60% of all currently used drugs. In addition to drugs, CYP3A isozymes metabolise a variety of other compounds including steroid hormones, toxins and carcinogens. It is also well known that the hepatic expression and activity of CYP3A isozymes varies from individual to individual. The involvement of this variability in harmful interactions frequently encountered in development and application of drugs that are CYP3A substrates is well documented. It has also been postulated that variable CYP3A expression could affect an individuals predisposition to cancers caused by environmental carcinogens that are metabolised by CYP3A. The elucidation of factors controlling an individuals CYP3A activity could permit personalised dose adjustments in therapies with its substrates and may also possibly lead to the identification of sub-populations at increased risk for several common cancers. However, until recently, the development of markers predictive for the individual CYP3A expression has been slower than for other drug metabolising enzymes. Here we summarise the current status of our understanding of the genetics and regulation of the expression of CYP3A, including the recently described markers of the CYP3A5 and CYP3A7 polymorphisms. These latter markers are expected to speed up the development of activity probes for the individual CYP3A isozymes and to aid in our understanding of their individual functions.     

Hysteroscopic evaluation of the uterine cavity in postmenopausal women with uterine bleeding

Postmenopausal uterine bleeding is the most characteristic and frequent endometrial adenocarcinoma symptom. Patient with uterine bleeding appeared at least 12 months after the last menstruation needs diagnostic management before initiation of any treatment. OBJECTIVES: Evaluation of hysteroscopy for the recognition of pathologies causing postmenopausal uterine bleeding. MATERIALS AND METHODS: Seventy-nine women aged 48-80 without hormonal replacement therapy hospitalized in the 1st Department of Gynecology and Gynecological Oncology of the Medical University of ?ód? between 1998-2002 because of postmenopausal uterine bleeding were included in the study. In each case diagnostic hysteroscopy with visualisation of the uterine cavity was performed and then histopathologic biopsy by a curretage was taken. Hysteroscopic images were analyzed and compared with the histopathological results. RESULTS: 2 women had the oncologically suspected hysteroscopic images. In both cases endometrial adenocarcinoma was histopathologically confirmed. Among 5 patients with hysteroscopic images suggesting non-malignant endometrial proliferation 4 cases of endometrial hyperplasia were found. 11 times hysteroscopic visualisation of endometrial polyps enabled their complete deletion. In 8 cases intrauterine adhesions were found and dissected: 11 patients presented submucous myomas during hysteroscopy. In 3 cases visualisation of the uterine cavity was not possible because of technical failure. Any patient with absence of hysteroscopically found uterine abnormalities had a poor histopathological result. CONCLUSIONS: Hysteroscopic investigation in postmenopausal women with uterine bleeding reduce the risk of false negative histopathological result. Hysteroscopy is useful method of the uterine cavity visualisation. Thanks to localization and elimination of the pathologies like endometrial polyps and intrauterine adhesions the repeated bleeding and the second time admission of the patient for the same reason can be avoided.     

Comparison of assessing the patency of the Fallopian tubes during laparoscopy and during hysterosalpingography on television in infertile women with endometriosis

OBJECTIVES: Sterility become nowadays not only medical, but as well socio-economic problem. One of its major causes is endometriosis. Recurrent adnexitis--one of the most common symptoms of endometriosis might be the cause of fallopian tubes occlusion. The hysterosalpingography (HSG) can be helpful to diagnose this tubal pathology. DESIGN: To compare the assessment of fallopian tubes patency during HSG with the results of laparoscopy in infertile women with endometriosis. MATERIAL AND METHODS: 331 women with endometriosis who were diagnosed during laparoscopy examination between 1998-2002 due to sterility. The presence of endometriosis was confirmed during laparoscopy. In each patient the control of the patency of both fallopian tubes was performed. These data were confirmed with those from HSG performed during follicular phase on the television path. The absence of the contrast passage through fallopian tubes as well as the only trace contrast passage into abdominal cavity were classified as tubal obstruction. RESULTS: In patients during the HSG physiological uterine shape and size in 91.3%, the bicornis uterus in 6.6%, and the unicornis uterus in 2.1% were observed. During laparoscopy we diagnosed the physiological uterine shape and size in 88.8%, the bicornis uterus in 8.2%, and the unicornis uterus in 3.0%. The diagnostic compatibility of these both examinations was 90.6%. In HSG the correct anatomical course of both fallopian tubes without occlusions in 51.7%, the only unilateral patency in 36.7%, and bilateral occlusions in 11.6% were found. During laparoscopy we diagnosed the anatomical course of both fallopian tubes without occlusions in 36.7%, the only unilateral patency in 33.3%, and bilateral occlusions in 30.0%. The diagnostic compatibility of these both examinations was 49.6% for both fallopian tubes, and 34.2% for the only one fallopian tube. In 16.2% both results were incompatible. CONCLUSIONS: The incorrect contrast passage through the fallopian tubes and its increased pressure during HSG in women with the characteristic history and clinical symptoms can suggest endometriosis. In these cases laparoscopy is necessary as the additional examination in the diagnostics of fallopian tubes patency, but the only objective method in diagnosis of endometriosis.     

Success of laparoscopic ovarian wedge resection is related to obesity,lipid profile,and insulin levels

OBJECTIVE: To evaluate the effects of laparoscopic ovarian wedge resection on hormonal and metabolic parameters of polycystic ovary syndrome (PCOS) and to compare profiles of women who achieved pregnancy with those who did not. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Thirty-three women with PCOS. INTERVENTION(S): Laparoscopic ovarian wedge resection using harmonic scalpel. MAIN OUTCOME MEASURE(S): Pregnancy; levels of testosterone, DHEAS, gonadotropins, sex hormone-binding globulin (SHBG), and glucose and insulin during 2-hour glucose tolerance test; lipid profile; body mass index; and waist-to-hip ratio. RESULT(S): Twenty-two women (67%) achieved clinical pregnancy within the mean of 4.9 months after surgery. Baseline parameters of women who became pregnant differed from those who did not: those who became pregnant were less obese, had lower levels of total cholesterol, low-density lipoprotein, and triglycerides; higher levels of SHBG; lower levels of fasting insulin; lower insulin area under the curve; and higher insulin sensitivity index. Subjects not pregnant by 12 weeks after surgery underwent repeat endocrine and metabolic evaluations. In these women, wedge resection was followed by declines in testosterone, LH, and insulin sensitivity index. Wedge resection had no significant effect on SHBG, DHEAS, or lipid profile. CONCLUSION(S): Laparoscopic wedge resections are associated with the highest pregnancy rates among less obese subjects with favorable lipid profiles and lower insulin. In this study, the postoperative decline of serum testosterone and LH is not attributable to improvement of insulin sensitivity.     

Kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions

The kinetics of hydrolysis of diltiazem hydrochloride in aqueous solutions at 313, 323, 333 and 353 K over the pH-range 0.4-9.7 has been investigated. The decomposition was followed by the HPLC method. The pH-rate profile was accounted for by the specific acid- and base-catalysed reactions and also by assuming spontaneous or water-catalysed decomposition of both dissociated and undissociated molecules of diltiazem. Various buffer substances were found to exhibit general acid and base catalysis of the degradation. Thermodynamic parameters of the reaction: energy and enthalpy of activation and the frequency factor for the specific rate constants were determined.     

Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune Maintenance Regimen Study

INTRODUCTION: The purpose of this study was to evaluate early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen. METHODS: Within 48 hr after transplantation, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of SRL (troughs >5 ng/mL; immunoassay), CsA, and ST. Those eligible (430) were randomly assigned (1:1) at 3 months +/- 2 weeks to remain on triple-drug therapy (SRL-CsA-ST group) or to have CsA withdrawn and SRL trough concentrations targeted to 20 to 30 ng/mL (SRL-ST group) until month 12, and 15 to 25 ng/mL thereafter. RESULTS: At 24 months, there were no statistically significant differences in patient survival (94.0% vs. 95.3%), graft survival (91.2% vs. 93.5%), acute rejection after randomization (5.1% vs. 9.8%) or discontinuations (34% vs. 33%) for SRL-CsA-ST versus SRL-ST, respectively. Serum creatinine level was significantly better in patients who had CsA withdrawn (167 vs. 128 micromol/L, P<0.001), as was the slope of 1/creatinine. Similarly, systolic blood pressure was lower in patients who had CsA withdrawn (141 vs. 134 mm Hg, P<0.001). High-density lipoprotein cholesterol was significantly higher in the SRL-ST group, whereas total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were not significantly different. Hypertension, creatinine increase, abnormal kidney function, toxic nephropathy, edema, hyperuricemia, cataracts, Herpes zoster, and malignancy were reported significantly more often in patients continuing CsA. Thrombocytopenia, hypokalemia, abnormal liver function tests, abnormal wound healing, ileus, and pneumonia were reported significantly more frequently with SRL-ST. CONCLUSION: Data at 2 years confirm that early CsA withdrawal followed by an SRL-ST maintenance regimen results in long-term improvement in both renal function and blood pressure, without increased risk of graft loss or late acute rejection.