Non-steroidal anti-inflammatory drugs increase MRP4 expression in an endometriotic epithelial cell line in a PPARa dependent manner.

OBJECTIVE: Endometriosis is a debilitating disease characterized by chronic inflammation. The transporter multidrug resistance-associated protein 4 (MRP4/ABCC4) is expressed in human endometrial tissue; it is overexpressed in ectopic endometrial tissue, and is modulated by the anti-inflammatory lipid Lipoxin A4 (LXA4). Recently, it was demonstrated that aspirin induces platelet MRP4 over-expression, through genomic modulation in megakaryocytes. Since patients with endometriosis frequently use aspirin or other non-aspirin Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), the aim of this study was to verify whether aspirin and other NSAIDs enhance MRP4 expression in 12Z human endometriotic epithelial cells and whether this was peroxisome proliferator-activated receptor alpha (PPARa) dependent. MATERIALS AND METHODS: MRP4 and PPARa expression was analyzed by Q-RT-PCR using TaqMan® Master Mix and TaqMan® Assay Reagents (Life Technologies, Monza, Italy) and Western blot. RESULTS: In 12Z cells, aspirin and other NSAIDs enhanced MRP4 mRNA and protein expression; these treatments also induced PPARa expression. Aspirin and diclofenac-induced increases in MRP4 expression were not observed in cells where PPARa was knocked down using siRNA. NSAIDs-induced MRP4 expression was correlated with augmented PGE2 secretion, indicating functional relevance. CONCLUSIONS: MRP4 expression was increased in cells treated with NSAIDs and the nuclear receptor PPARa is involved. Elevated PGE2 levels in cell supernatants correlate with its increased transport by MRP4 after NSAID treatment. More importantly, we provide evidence that in endometriotic epithelial cells aspirin and non-aspirin NSAIDs treatments alter gene expression.

CT Diagnosis of Cerebral Venous Thrombosis: Importance of the First Examination for Fast Treatment.

This study is a retrospective investigation of the role of non contrast-enhanced CT (NCCT) in the diagnosis of cerebral venous thrombosis (CVT) in clinical practice. We retrospectively identified 24 patients discharged with a diagnosis of CVT between January 2002 and December 2008 who had undergone NCCT as the first imaging modality. NCCT had been evaluated by a general radiologist and subsequently by a neuroradiologist in five cases. Final diagnosis was established by CT angiography (CTA), magnetic resonance (MR) and digital subtraction angiography (DSA). NCCT diagnosis was defined as "positive" when the neuroradiologist suggested the diagnosis of CVT on the report, as opposed to the "negative" diagnosis group. All NCCT examinations were reviewed by a neuroradiologist experienced in cerebrovascular pathology. We compared his evaluation and analysed the location and number of direct signs found on NCCT. The neuroradiologist strongly suggested an NCCT diagnosis of CVT in 63% (15/24) of patients: 80% (4/5) with deep venous thrombosis (DVT) and 57% (11/19) with sinus venous thrombosis (SVT). The general radiologist's NCCT evaluation was incorrect in four cases, subsequently diagnosed at NCCT by the neuroradiologist. After reviewing the NCCT examination the experienced neuroradiologist identified the CVT direct sign in two that belonged to the NCCT negative diagnosis group. Thus the direct sign was present in 71% (17/24) of the cases: all the patients with DVT and 63% (12/19) of the patients with SVT. NCCT still plays an important role for fast and accurate diagnosis of CVT in the emergency setting. NCCT displayed the CVT direct sign more frequently than previously thought and it was correctly interpreted in most cases. Neuroradiological consultation adds value to the general radiologist's evaluation.

MR-Cisternography with T2-Weighted Single-Shot Fast Spin Echo Sequence in the Diagnosis of a Spontaneous CSF Fistula of the Sphenoid Sinus Causing Massive Pneumocephalus.

A spontaneous CSF fistula of the sphenoid sinus was preoperatively diagnosed in a young woman presenting with massive pneumocephalus and rhinorrhea. Diagnosis was established by MR cisternography using a heavily T2-weighted 3D single-shot FSE sequence with half-Fourier analysis (3D-EXPRESS(®)), originally developed for imaging the inner ear. While unenhanced CT failed to detect the site of the fistula, MR permitted complete evaluation of the sellar/sphenoid region and tracked the CSF signal down to the nasal cavity.

Endovascular procedures in critical leg ischemia of elderly patients.

PURPOSE: Purpose of this study was to evaluate angiographic and clinical results of popliteal, infrapopliteal, and multi-level disease percutaneous transluminal angioplasty (PTA) in over-80 years old patients with chronical clitical leg ischemia. In fact such patients with extensive peripheral vascular disease and critical limb ischemia (CLI) are generally poor surgical candidates. METHODS: Between 1998 and 2003, 37 elderly patients aged 80-89 years old (mean age 83.3) with critical leg ischemia were treated with PTA. All patients were at high surgical risk. 31/37 (81.5%) patients had chronic non-healing wounds, and 14/37 (37%) had multi-level disease of superficial femoral, popliteal and crural arteries. One hundred and two lesions were treated by angioplasty. Immediate angiographic and 1 year clinical results were retrospectively analyzed. RESULTS: The overall procedural success rate was 32/37 (84.2%). There were three major complications (7.9%), but no deaths, and three technical failures, all were of infrapopliteal lesions. After 1 year, 27 patients could be followed, five patients died during the first year of unrelated causes. Twenty-three patients (85.2%), were clinically re-occluded within 1 year, but complete and partial wound healing was achieved in 80% (16/20) and rest pain improvement in 57% (4/7), so that overall limb salvage was 74% (20/27). CONCLUSIONS: Elderly patients with multi-level CCLI have a short patency term following angioplasty of 14.8% after 1 year. Nevertheless, this temporary vascular patency enables wound healing or improvement in 74% of these patients, thus such endovascular interventions are recommended in this age group.

Carotid endarterectomy under local anesthesia in elderly: is it worthwhile?

Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded elder patients. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. A total of 262 carotid operations were performed under local anaesthesia between 1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of age. Twenty patients (26%) presented with asymptomatic critical stenosis. Transient ischemic symptoms were the reason for presentation in 35 patients (46%). Progressive stroke was documented in two patients (3%) and a stroke with persisting neurological deficit was demonstrated in 19 cases (25%). Coronary artery disease was present in 47 patients (38%) and arterial hypertension in 55 (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one thromboendarterectomies of the carotid bifurcation with direct closure were performed. Five patients had other types of reconstruction. Postoperative complications occurred in three patients. One had a transient neurological deficit and another a lethal stroke; the third patient died from myocardial infarction. The in-hospital mortality was 2.9%, which was not significantly higher than the results of the reconstructions in younger patients (1.5%). Surgery for carotid artery occlusive disease under local anaesthesia can be safely performed in selected patients of more than 75 yr of age.

[Heparin-like factors in pregnancy. Report of a clinical case]. / Fattori heparin-like e gravidanza. Descrizione di un caso clinico.

Some authors have described the presence of circulating heparin-like anticoagulants; these substances are frequently associated with neoplastic pathology. Personal experience proves that this pathology of coagulation may be present also in pregnancy. The clinical case of a primipara, nullipara pregnant woman twenty-eight years aged is described; the case history showed that the patient presented circulating heparin-like substances. During this study, routine biochemical examinations were within normal limits as well as the coagulation tests. In the course of this experience, coagulation anomalies and hemorrhagic episodes in the intraoperative and postoperative period were not observed.

[Evaluation of bone loss in patient treated with Gn-Rh analogs]. / Valutazione della perdita di massa ossea in pazienti in trattamento con analoghi del Gn-RH.

BACKGROUND: The increasing use of analogs of Gn-RH during treatment of some benign gynaecological diseases, has induced the authors to investigate the principal collateral effects, fixing one's attention on the loss of bony mass. METHODS: This perspective research has considered 38 patients selected for two diseases "endometriosis" and "uterine fibromyomatosis". The therapy has been effected with triptorelin intramuscularly in a dose of 3.75 mg every 28 days for six months, in all six phials. RESULTS: After a half-yearly cycle of therapy, the loss of bony mass was valued about 3% medium. CONCLUSIONS: In the light of other studies too, it was decided to confirm the necessity of associating other medicines able to prevent the side effects caused by their analogs of Gn-RH.

[Retrospective study of cervical papillomavirus lesions: early Herpes simplex virus proteins as markers of risk for progression]. / Studio retrospettivo delle lesioni cervicali da papillomavirus: le proteine ad espressione precoce dell'Herpes simplex virus come marker del rischio di progressione.

Specific types of human papillomavirus (HPV) are currently implicated as etiologic agent of benign and malignant lesions of the genital tract. Previous studies highlighted the presence of early proteins (ICSP 11/12) of Herpes simplex virus type 2 (HSV-2) mainly in HPV infected lesions of the cervix. This paper reports a retrospective study on the clinical course of benign cervical alterations in a 70 women population followed-up for 24 months. HPV and HSV-2 (late and early) antigens were detected by immunoperoxidase; HPV 6/11 and 16/18 were identified by in situ hybridization. All CIN III, vs only one CIN I progressed. The majority of regressions (55%) was CIN I, and 61% was characterized by the negativization of viral markers. There was a cyclic and/or chronic expression of viral antigens in progressed and persistent cases (67% and 53%, respectively). Furthermore, a significant correlation between progression and the presence of ICSP 11/12 protein has been found (89% of cases). The simultaneous detection of ICSP 11/12 and HPV 16/18 in 78% of progressed, and in 13% of persistent lesions was noteworthy. This association (ICSP 11/12 and HPV DNA 16/18) may be considered as a risk factor for progression of the lesions, and supports the hypothesis of a synergism of both viruses in the natural history of cervical cancer: the continuous expression of ICSP 11/12 during herpetic recurrences might act as a mutagenic factor in HPV infected tissues.

[Acute pelvic inflammatory disease: comparison of therapeutic protocols]. / Malattia infiammatoria pelvica acuta: protocolli terapeutici a confronto.

Acute pelvic inflammatory disease is a serious medical and economic consequence of sexually transmitted diseases among young women. The aim of the study is to compare the efficacy and safety of gentamycin plus clindamycin with that of ceftazidime plus doxycycline in the treatment of hospitalized patients with acute pelvic inflammatory disease. A total of 78 patients with acute PID, hospitalized in II Obstretic and Gynecologic Clinic of II University of Naples (Italy), entered and randomized into two treatment groups: gentamycin plus clindamycin (N = 40) and ceftazidime plus doxycycline (N = 36). Patients were excluded if they were pregnant or were not over the age of 16 years of had a history of allergy to one of the drugs used in the Study of had hepatic disease or kidney trouble or had IUD. Acute PID was diagnosed by the following criteria: 1) lower abdominal pain; 2) cervical motion tenderness; 3) adnexal tenderness (all three should be present); plus at least one of the following additional criteria: a) temperature over 38 degrees C; b) leukocytosis (greater than 10.500 mm3); c) purulent material from the peritoneal cavity bt culdocentesis; d) inflammatory mass present on binomial pelvic examination and/or sonography; e) erythrocyte sedimentation rate > 15 mm/hr. Patients were enrolled into the study after obtaining informed consent, pretreatment and posttreatment cultures were obtained from the endocervix from Neisseria gonorrhoeae and Chlamydia trachomatis and aerobic-anaerobic bacteria. The study has shown that the acute PID has a polymicrobal origins. Both antibiotic regimens were very effective in the treatment of the PID: a complete recovery was obtained in over 90% of patients.

Effects of white cell reduction on the resistance of blood components to bacterial multiplication.

BACKGROUND: While prestorage white cell (WBC) reduction by filtration may improve platelet and red cell quality, it also may remove an important anti-bacterial defense mechanism, especially if blood is WBC-reduced shortly after collection. STUDY DESIGN AND METHODS: The question of whether WBC reduction of platelet concentrates and red cells altered bacterial proliferation kinetics in components prepared from deliberately contaminated, freshly collected blood was investigated. Two-unit pools of whole blood were inoculated, at a concentration of approximately one colony-forming unit per mL, with one of 17 bacterial species reported to have caused septicemia in transfusion recipients. Each pool was divided after inoculation, and components were prepared from the 2 units after a 7-hour room-temperature holding period. One unit of each AS-1 red cell or platelet pair was WBC-reduced, and the pairs were then stored for 42 days at 4 degrees C (red cells) or for 10 days at 22 degrees C (platelets). Quantitative bacterial cultures were performed at periodic intervals. RESULTS: In red cells, clinically significant bacterial proliferation occurred in only one instance (Serratia marcescens), and growth was less rapid in the WBC-reduced unit than in the control. Three patterns of growth were seen in platelet concentrates. In four cases, there was rapid proliferation in both test and control units, while on 13 occasions there was minimal replication in either pair. On six occasions, substantial growth was noted in control units, while few or no bacteria could be found in the WBC-reduced units. There was no evidence in either red cells or platelets that bacteria proliferated more rapidly in units that had been WBC-reduced before storage than they did in units in which WBCs were retained. CONCLUSION: Rather than increasing the risk of bacterial proliferation through removal of active phagocytic cells, WBC reduction by filtration before blood storage may act to reduce the likelihood of significant bacterial proliferation, possibly by removal of microorganisms along with WBCs.

Removal of Yersinia enterocolitica from AS-1 red cells.

The growth of Yersinia enterocolitica in AS-1 red cells was investigated so as to study the organism's proliferation kinetics and to evaluate the effect of prestorage white cell (WBC) reduction on bacterial multiplication. Twenty-four 2-unit pools of ABO-compatible whole blood were prepared and inoculated with Y. enterocolitica to final concentrations ranging from 0.3 to 132 organisms per mL. After inoculation, pools were split equally, AS-1 red cells were prepared, and 1 unit of each pair (test unit) was WBC-reduced with a WBC-reduction filter. Quantitative bacterial cultures of both WBC-reduced and control units were performed at several points throughout preparation and storage. Less than 10 percent of the inoculated organisms was recovered from blood samples taken after a 7-hour room-temperature holding period. By the end of 42 days of storage, Y. enterocolitica was recovered from unfiltered red cells in 2 of the 6 units inoculated at the lowest levels (0.3 and 0.7 organism/mL), from 8 of the 12 units inoculated at the intermediate levels (2.8, 5.2, 30.7, and 43 organisms/mL) and from 6 of the 6 units inoculated at the highest levels (98.8 and 132 organisms/mL). Positive cultures were seen as early as Day 7. In contrast, filtered units inoculated at all levels less than or equal to 98.8 organisms per mL (21/21 units) were sterile at the end of the 42-day storage period, while 2 units (2/3) inoculated at 132 organisms per mL showed growth despite filtration.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocarditis caused by relatively penicillin-resistant Stomatococcus mucilaginosus.

We report a case of Stomatococcus mucilaginosus endocarditis in which the isolate was relatively resistant to penicillins and cephalothin. The patient was treated successfully with vancomycin and valve replacement.

Phenotypic characteristics of coliform and noncoliform bacteria from a public water supply compared with regional and national clinical species.

During the summer and fall of 1984, elevated total coliform counts were observed in the distribution system of a public water supply serving 350,000 people in south central Connecticut. As part of an investigation of possible health risks associated with the presence of bacteria in the water supply, bacterial isolates from the distribution system were compared with bacterial isolates of the same species obtained from a large regional teaching hospital and from a national compendium of clinical isolates. Characteristics analyzed included phenotypic metabolic activity, antimicrobial susceptibilities to clinically utilized antibiotics, temperature tolerance at 44.5 degrees C, and beta-glucuronidase activity in single-test form and on a selective medium. Environmental isolates lacked known plasmid-mediated characteristics, with the exception of one Escherichia coli isolate which showed some antibiotic resistance. Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter agglomerans from all sources were temperature tolerant and yielded positive fecal coliform tests. Only E. coli showed beta-glucuronidase activity (both in a single biochemical test and on a selective medium). No single characteristic analyzed was sufficient to establish an organism as either environmental or clinical in origin.

Differential diagnosis between Streptococcus agalactiae and Listeria Monocytogenes in the clinical laboratory.

Streptococci of the group B (S. agalactiae) and Listeria monocytogenes resemble each other in many morphological and biochemical characteristics. Ten beta-hemolytic strains of each species were subjected to 26 tests commonly and easily performed in the clinical laboratory. Macroscopic and microscopic morphology on solid media showed differences only in the size of the colonies and in the length of the individual organisms. Among many other tests, hippurate hydrolysis and the CAMP reaction were positive in both species. In the presence of these two reaction, a negative catalase test and chaining in broth would make a presumptive diagnosis of S. agalactiae, while motility at 25 C, the presence of the Henry effect, and resistance to furadantin would be indicative of L. monocytogenes.