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Biomedical subjects

T Levy

Publications and source records attributed to T Levy.

At least 37 records · Page 2Linked to original sources

Evaluation of biatrial pacing, right atrial pacing, and no pacing in patients with drug refractory atrial fibrillation.

It has been suggested biatrial pacing may prevent the recurrence of atrial fibrillation (AF). To further evaluate this hypothesis, we performed a randomized, single-blinded study in 19 patients with drug refractory AF. The study compared biatrial pacing with conventional right atrial (RA) pacing and a control period of inhibited pacing. The pacing modes utilized were DDD with a base rate of 70 beats/min for biatrial and RA pace (with and without biatrial resynchronization, respectively) and 40 beats/min for the control period. The duration of each pacing mode was 3 months. The number of AF episodes and their duration were obtained from pacemaker Holter memory (Chorus RM ELA Medical). Comparison of the control period (n = 11) with either pacing strategy showed a significant decrease in the total duration of AF (control 27 +/- 35 days, biatrial 8 +/- 15 days p = 0.02, RA 11 +/- 27 days p = 0.04). However, there was no effect on the number of AF episodes (control 79 +/- 108, biatrial 36 +/- 75 p = 0.32, RA 41 +/- 80 p = 0.11). The total percentage of atrial pacing also significantly increased when the control period (6 +/- 9%) was compared with both RA pace (62 +/- 33%, p = 0.008) and biatrial pace (63 +/- 31, p = 0.003). When biatrial pacing was compared with RA pace (n = 19), there was no significant difference in either the duration of AF (biatrial 16 +/- 26 days vs RA 19 +/- 31 days, p = 0.7) or the number of AF episodes (biatrial 56 +/- 91 vs RA 87 +/- 106, p = 0.34). In conclusion, pacing (either type) at a base rate of 70 beats/min has an antifibrillatory effect when compared with inhibited pacing at 40 beats/min. No additional benefit of biatrial pacing over right atrial pacing was demonstrated in this study.

Aged↗

The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the impact of long-term purified FSH (pFSH) therapy in male partners before intracytoplasmic sperm injection (ICSI). DESIGN: Prospective, randomized, controlled study. SETTING: Large university-based IVF unit. PATIENT(S): Seventy-eight patients made up the study and control groups (39 patients each). All patients had severe male factor infertility. INTERVENTION(S): Induction of ovulation, oocyte retrieval, ICSI, and ET were carried out in both groups. In the study group, male partners received pFSH (75 IU FSH, <1 IU LH) for > or = 50 days before oocyte retrieval. MAIN OUTCOME MEASURE(S): Fertilization rate, embryo quality, implantation and pregnancy rates. RESULT(S): Fertilization and pregnancy rates were higher in the study group (68% and 35.9%, respectively) were higher than in the control group (59% and 17.9%, respectively), although the differences did not reach statistical significance. The implantation rate was significantly higher in the study group (15.5% versus 6.5%). The study group showed a trend toward a higher number of better-quality embryos per transfer (mean +/- SD, 2.2 +/- 1.6 versus 1.6 +/- 1.6). CONCLUSION(S): Purified FSH therapy in male partners before ICSI improves implantation rate. Improved embryo quality may be a contributory factor.

Embryo Implantation↗

The use of a "side-wire" permanent transvenous pacing electrode for left ventricular pacing.

It has been reported that biventricular pacing can improve the symptomatic status of patients with heart failure. However, using currently available transvenous left ventricular pacemaker leads the implantation procedure is difficult and has a high failure rate. We report the successful use of a new type of left ventricular pacing lead, the 'side-wire' pacing lead. This lead is initially introduced through a specifically designed guiding sheath to aid coronary sinus cannulation and then over a pre-positioned guide wire to aid final positioning. The more widespread introduction of this type of left ventricular pacing lead may reduce the difficulty of left ventricular pacing via the coronary sinus and thus improve the overall success rate of this therapeutic approach.

Electrodes↗

Biventricular implantable cardioverter defibrillator use in a patient with heart failure and ventricular tachycardia secondary to Emery-Dreifuss syndrome.

We report a case of fully transvenous single-unit biventricular implantable cardioverter defibrillator (ICD) use in a 43-year-old woman with a manifesting carrier form of muscular dystrophy (Emery-Dreifuss syndrome). The indication for biventricular ICD use was progressive heart failure with ventricular arrhythmia, permanent atrial fibrillation and previous VVIR pacemaker insertion. Single-unit transvenous biventricular ICD implantation was undertaken without complication. No potentially serious device malfunction was noted during subsequent follow-up. We conclude that single-unit biventricular ICD implantation is feasible for pacing and ventricular tachyarrhythmia control in patients with underlying atrial fibrillation.

Adult↗

Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet.

Our study was conducted to assess the pharmacokinetics of natural progesterone administered in the novel formula of an effervescent vaginal tablet. Fifty post-menopausal women, with a median age of 43.5 years (range 28-55), volunteered to participate in the research. All women discontinued their hormonal replacement therapy 1 month prior to the study. The pharmacokinetics of 50 and 100 mg of progesterone administered as a vaginal tablet were evaluated. After the initial administration of 50 mg or 100 mg, a mean serum Cmax of 20.43 +/- 8.01 nmol/l and 31.61 +/- 12.62 nmol/l (P < 0.0004) was reached at a Tmax of 6.1 +/- 2.63 and 6.4 +/- 3.35 h respectively. The terminal half-life was 13.18 +/- 1.3 and 13.7 +/- 1.05 h respectively. Continuous use of the 100-mg tablet resulted in a mean serum progesterone concentration of 26.08 +/- 13.96 nmol/l and 21.42 +/- 16.32 nmol/l after 14 and 30 days respectively. Women >40 years were found to have a significantly lower Tmax compared to younger women (P = 0.02). The continuous use of vaginal progesterone did not influence the hormonal, liver or lipid profiles evaluated. Only three (6%) women suffered from mild vaginal irritation. Natural progesterone given as a vaginal tablet is well tolerated, safe and an easily administered treatment. Even in a non-oestrogenized vagina the absorption was efficient and the 100 mg dosage resulted in adequate serum progesterone concentrations.

Absorption↗

Initial experience in the extraction of chronically implanted pacemaker leads using the Excimer laser sheath.

OBJECTIVE: To assess the safety and efficiency of the Excimer laser sheath in extracting chronically implanted pacemaker leads. PATIENTS: Eight patients were studied (one female, mean age 62 years, range 34 to 77) with 17 pacemaker leads (five atrial, 10 ventricular, two implantable defibrillator). The mean implantation time was 65 months (range 23 to 188). The indications for lead extraction were chronic infection (7), superior vena cava obstruction (4), lead malfunction (4), and pain (2). METHODS: A prospective analysis of the use of the Excimer laser sheath in extracting chronically implanted pacemaker leads. Laser sheath extraction was undertaken if conventional extraction techniques with simple traction or traction with a locking stylet had failed. If laser sheath extraction was unsuccessful, basket retrieval of the lead from the groin was performed. RESULTS: Complete lead removal was achieved in 16 leads (94%). In one case the electrode tip was left behind without complication. Extraction was achieved with the laser sheath alone in 16 leads. Basket retrieval was required in one case after laser failure. There were no complications. CONCLUSIONS: The Excimer laser sheath appears to be an effective and safe technique for extracting chronically implanted pacemaker leads. It can be used in combination with the currently available techniques for successful lead extraction.

Adult↗

[Simultaneous utilization of an implantable automatic defibrillator in a patient with previously implanted bi-ventricular pacemaker for end-stage heart failure].

We report a case of implantable cardioverter defibrillator (ICD) use after previous biventricular pacemaker insertion for end-stage heart failure. A 75-year-old man with inoperable three-vessel coronary artery disease, permanent atrial fibrillation and end-stage heart failure underwent bi-ventricular pacemaker insertion and His bundle ablation for symptomatic control. NYHA class decreased from class III to II after this procedure. Four months after implant the patient developed paroxysmal sustained, symptomatic ventricular tachycardia. ICD implantation was undertaken. No potentially serious ICD-pacemaker interaction was noted during subsequent follow-up. We conclude that ICD implantation is feasible after previous bi-ventricular pacemaker insertion, without the need to explant the bi-ventricular pacing device.

Aged↗

The effects of digitalis-like compounds on rat lenses.

PURPOSE: Fundamental to the maintenance of ionic concentration gradients and transparency of the lens is the activity of Na+,K+-adenosine triphosphatase (ATPase) in the epithelial layer. Recent studies have identified endogenous digitalis-like compounds (DLCs) and 19-norbufalin and its peptide derivatives in human cataractous lenses. These compounds inhibit the activity of Na+,K+-ATPase and have been suggested to be involved in cataract formation. The present experiments were designed to test this hypothesis by determining the ability of digitalis and DLCs to induce changes in protein composition and leakage from rat lenses in organ culture. METHODS: DLCs were determined in rat lenses using three independent assays: interaction with ouabain antibodies, interaction with bufalin antibodies, and inhibition of [3H]-ouabain binding to red blood cells. Rat lenses were incubated in modified TC-199 medium in 5% CO2 atmosphere at 37 degrees C for the time of the experiment. The onset of cataractogenesis was assessed by measuring protein leakage from lenses and by crystallin composition in the lens and media. RESULTS: DLCs were present in rat lens with concentrations 7 to 30 times higher in the capsular-epithelial layer than in the lens fibers regions. Ouabain, bufalin, digoxin, and DLC induced dose- and time-dependent leakage of protein from rat lenses. Lenses incubated with these compounds showed alterations in crystallin content consistent with changes that initiate opacity. All the compounds caused a multilayering of epithelial cells in the region surrounding the mitotic area and, at the same time, cell death in the central anterior region. CONCLUSIONS: Digitalis and endogenous DLCs are cataractogenic factors. These results, together with the demonstration of DLCs in the normal lens and their increased levels in human cataractous lenses, strongly suggest their involvement in the molecular mechanisms responsible for cataract formation.

Animals↗

Endometrial carcinoma in a post-menopausal woman with atrophic endometrium and intra-cavitary fluid: a case report.

Measurement of endometrial thickness by vaginal ultrasonography is used to detect post-menopausal women at risk for endometrial pathology. The efficacy of this procedure is doubtful in cases of intrauterine fluid accumulation, which is a common finding in this population. We present a case of endometrial carcinoma in an asymptomatic, post-menopausal woman with ultrasonographic imaging of an atrophic endometrium and intra-cavitary fluid. It may be suggested that, in a case of intrauterine fluid accumulation (IFA), endometrial biopsy should be performed regardless of the sonographic endometrial thickness, since the fluid may increase the intracavity pressure and can mask endometrial pathology.

Aged↗

Pre-operative ultrasonographic evaluation of nongravid, enlarged uteri--correlation with bimanual examination.

OBJECTIVE: To correlate the size of the nongravid uterus measured by ultrasound and bimanual examination before hysterectomy, with the actual size of the specimens. PATIENTS AND METHODS: Uterine size of 49 consecutive patients, who underwent elective hysterectomy, was assessed by bimanual pelvic examination, preoperative ultrasonographic evaluation and actual postoperative size. RESULTS: All preoperative ultrasonographic uterine dimensions significantly correlated with the corresponding actual dimensions of the uterine specimens. Furthermore, ultrasonographic uterine length had the best correlation with uterine size estimation by bimanual examination. A formula was established in an attempt to calculate clinical uterine size by gestational week, using preoperative ultrasonographic dimensions. CONCLUSIONS: By using the aforementioned formula, ultrasonographic uterine dimensions can be extrapolated to uterine size in terms of gestational week, and therefore, be applicable to traditional clinical practice.

Female↗

Probing of the spliceosome with site-specifically derivatized 5' splice site RNA oligonucleotides.

We have developed a site-specific chemical modification technique to incorporate a photoreactive azidophenacyl (APA) group at designated internal positions along the RNA phosphodiester backbone. Using this technique, we have analyzed interactions of the 5' splice site (5'SS) RNA within the spliceosome. Several crosslinked products can be detected within complex B using the derivatized 5'SS RNAs, including U6 snRNA, hPrp8p, and 114-, 90-, 70-, 54-, and 27-kDa proteins. The 5'SS RNAs derivatized at intron positions +4 to +8 crosslink to U6 snRNA, confirming the previously reported pairing interaction between these sequences. hPrp8p and p70 are crosslinked to the 5'SS RNA when the APA is placed within the 5' exon. Finally, a set of unidentified proteins, including p114, p54, and p27, is detected with the 5'SS RNA derivatized at intron positions +4 to +8. Introduction of the bulky APA group near the 5'SS junction (positions -2 to +3) strongly interferes with complex B formation and thus no APA crosslinks are observed at these positions. Together with our earlier observation that hPrp8p crosslinks to the GU dinucleotide at the 5' end of the intron, these results suggest that the inhibitory effect of APA results from steric hindrance of the hPrp8p:5'SS interaction. Unexpectedly, thio-modifications within the region of the 5'SS RNA that is involved in base pairing to U6 snRNA strongly stimulate complex B formation.

Allosteric Site↗

Simplifying ovulation induction for surrogacy in women with Mayer-Rokitansky-Kuster-Hauser syndrome.

A simple approach for ovulation induction in women with Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH-S) during in-vitro fertilization (IVF)/freezing/surrogacy cycles was evaluated. Weekly progesterone plasma concentrations were measured in order to accurately establish the luteal phase in MRKH-S women. When a rising titre was detected, a gonadotrophin-releasing hormone analogue (GnRHa) was administered as part of a long protocol. Two weeks later human menopausal gonadotrophin (HMG) therapy was started. Ten treatment cycles in four women with MRKH-S were carried out. In all cases, three or less progesterone estimations were needed. Three of the four women are now, through surrogacy, genetic mothers; one of them has two children. We concluded that weekly determination of progesterone plasma concentration is a convenient, efficient and inexpensive simple approach to identify the luteal phase, and therefore suitable to the start of a GnRHa/HMG protocol in MRKH-S women enrolled in an assisted reproduction technology programme.

Amenorrhea↗

Activation of enhancer elements by the homeobox gene Cdx2 is cell line specific.

Cdx2 is a caudal-related homeodomain transcription factor that is expressed in complex patterns during mouse development and at high levels in the intestinal epithelium of adult mice. Cdx2 activates transcription of intestinal gene promoters containing specific binding sites. Moreover, Cdx2 has been shown to induce intestinal differentiation in cell lines. In this study, we show that Cdx2 is able to bind to two well defined enhancer elements in the HoxC8 gene. We then demonstrate that Cdx2 is able to activate transcription of heterologous promoters when its DNA binding element is placed in an enhancer context. Furthermore, the ability to activate enhancer elements is cell-line dependent. When the Cdx2 activation domain was linked to the Gal4 DNA binding domain, the chimeric protein was able to activate Gal4 enhancer constructs in an intestinal cell line, but was unable to activate transcription in NIH3T3 cells. These data suggest that there are cell-specific factors that allow the Cdx2 activation domain to function in the activation of enhancer elements. We hypothesize that either a co-activator protein or differential phosphorylation of the activation domain may be the mechanism for intestinal cell line-specific function of Cdx2 and possibly in other tissues in early development.

3T3 Cells↗

Comparison of intestinal phospholipase A/lysophospholipase and sucrase-isomaltase genes suggest a common structure for enterocyte-specific promoters.

Intestinal phospholipase A/lysophospholipase (IPAL) is an intestine-specific brush-border enzyme expressed during development and along the intestinal crypt-villus axis in a pattern similar to another well characterized brush-border enzyme, sucrase-isomaltase (SI). A tissue-specific DNase I hypersensitive site was identified in chromatin from intestinal nuclei immediately upstream from the transcriptional start site of the IPAL gene. Footprinting analysis showed that two DNA elements within the IPAL promoter were protected by intestinal nuclear proteins. The IPAL-FP1 element was shown to be a monomer binding site for Cdx1 and Cdx2, intestine-specific homeobox proteins. Moreover, this site was important for transcriptional activation of the promoter in intestinal cell lines via interaction with Cdx proteins. Nuclear proteins from both liver and intestine interacted with the IPAL-FP2 element, forming a complex consistent with binding to HNF1. Cdx and HNF1 binding sites have also been shown to be the two major regulatory elements responsible for transcriptional activation of the SI gene promoter, which directs intestine-specific transcription in transgenic mice. These findings suggest that enterocyte genes that are expressed in similar developmental patterns may be regulated by the interaction of common DNA elements and their associated transcription factors.

Animals↗

Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix.

PURPOSE: A phase II study was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11), a water-soluble derivative of camptothecin, in patients with prior chemotherapy-treated squamous cell cancer of the cervix. PATIENTS AND METHODS: Forty-two patients were included in the study. The median age was 44 years (range, 24 to 59 years). The median Zubrod performance status was 1. All patients were refractory to first-line chemotherapy and 88% had received prior radiotherapy. The initial dose of CPT-11 was 125 mg/m2 given as a weekly 90-minute intravenous infusion for 4 weeks, every 6 weeks. Subsequent doses were unchanged, reduced, or omitted according to toxicity grade. RESULTS: Forty-two patients were assessable for response. The overall response rate was 21%. The median time to response was 6 weeks and the median duration of response was 12 weeks. The overall median duration of survival was 6.4 months. A statistically significant survival advantage (median of 12.6 v 5.1 months) was found in patients whose disease responded to the treatment (P < .015). The major dose-limiting toxic effects (grade > or = 3) were nausea and vomiting (45%), diarrhea (24%), and granulocytopenia (36%). Grade > or = 3 anemia was encountered in 62% of patients and the incidence of thrombocytopenia was negligible. Less severe side effects were alopecia (48%), drug fever (43%), anorexia (33%), fatigue (33%), skin rash (21%), stomatitis (14%), and allergic reaction (9%). The gastrointestinal intolerance was dose-related. The incidence of bone marrow depression did not decrease with dose reduction, possibly because of a cumulative effect or hematologic intolerance by a subset of patients. CONCLUSIONS: CPT-11 has significant activity in refractory cervical carcinoma. Gastrointestinal intolerance and hematologic toxicity must be monitored carefully. Further studies of alternative schedules may improve the tolerance and response rate.

Adult↗