Showing papers by "Jewish Hospital published in 2005"

Hypertensive Heart Disease

Abstract: Left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) are the early manifestations of cardiovascular target organ damage in patients with arterial hypertension and signify hypertensive heart disease. Identification of hypertensive heart disease is critical, as these individuals are more prone to congestive heart failure, arrhythmias, myocardial infarction and sudden cardiac death. Regression of left ventricular (LV) mass with antihypertensive therapy decreases the risk of future cardiovascular events. The goal of antihypertensive therapy is to both lower blood pressure (BP) and interrupt BP-independent pathophysiologic processes that promote LVH and CHF-D. The purpose of this review is to summarize current and emerging approaches to the pathophysiology and treatment of hypertensive heart disease.

Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD

Abstract: A heterozygous R1101K mutation of the p150 subunit of dynactin (DCTN1) is reported in a family with amyotrophic lateral sclerosis (ALS) and co-occurrence of frontotemporal dementia (FTD). Two members of our kindred were affected with motor neuron disease and two with dementia in an autosomal dominant pattern of inheritance. We excluded the involvement of the ALS and FTD-linked genes for copper/zinc superoxide dismutase (SOD1) and tau. The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD.

Enoxaparin prevents progression of stages I and II osteonecrosis of the hip.

Abstract: UNLABELLED In a prospective pilot study, we hypothesized that enoxaparin (60 mg/day for 12 weeks) would prevent progression of Stages I and II osteonecrosis of the hip associated with thrombophilia or hypofibrinolysis or both over > or = 108 weeks of followup versus untreated historic controls, with different treatment responses in primary versus corticosteroid-associated secondary osteonecrosis. Patients with one or more thrombophilic-hypofibrinolytic disorder and Ficat Stages I or II osteonecrosis of at least one hip were included. A blinded committee interpreted anteroposterior and frog-leg lateral radiographs at entry in the study and every 36 weeks to > or = 108 weeks. Maintenance of the disease at Stages I and II versus progression of the osteonecrosis to Stages III and IV requiring total hip replacement was the major end point. Sixteen patients had primary osteonecrosis (25 hips; 13 Stage I, 12 Stage II), and 12 had secondary osteonecrosis (15 hips; five Stage I, 10 Stage II). With no Enoxaparin-related complications, 19 of 20 hips (95%) with primary osteonecrosis were unchanged from Stages I and II osteonecrosis at > or = 108 weeks; 12 of 15 hips (80%) with secondary osteonecrosis progressed to Stages III and IV osteonecrosis. In primary osteonecrosis at > or = 108 weeks, survival of 95% hips, or 76% (19/25 hips, based on intent to treat), compared favorably with untreated historical controls (approximately 20% 2-year survival), comparable to 20% survival in secondary hip osteonecrosis. Enoxaparin may prevent progression of primary hip osteonecrosis, decreasing the incidence of total hip replacement. LEVEL OF EVIDENCE Therapeutic study, II-1 (prospective cohort study).

Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS-IV sub study).

Abstract: Randomized clinical trials have shown that paclitaxel-eluting stents significantly reduce restenosis after percutaneous coronary intervention. The impact of lesion calcification on the efficacy of paclitaxel-eluting stents is unknown. In the TAXUS-IV trial, 1,314 patients who underwent percutaneous coronary intervention were randomly assigned to a bare-metal or paclitaxel-eluting stent. By core laboratory analysis, 247 lesions (19%) were moderately or severely calcified. At the 9-month angiographic follow-up examination, the paclitaxel-eluting stent had significantly reduced the amount of late loss compared with the control stent (0.26 ± 0.56 vs 0.51 ± 0.48 mm, p = 0.015) within the analysis segment in the calcific lesions. The analysis segment restenosis rate was similar in patients with calcified and noncalcified lesions after paclitaxel-eluting stent implantation (7.5% vs 8.0%, respectively; p = 1.0). The rate of ischemia-driven target lesion revascularization (TLR) at 1 year was reduced by 56% in patients with calcified lesions (11.9% vs 5.1%, p = 0.09) and by 75% in noncalcified lesions (15.7% vs 4.3%, p <0.0001). By interaction testing, the efficacy of the paclitaxel-eluting stent in reducing TLR at 1 year was similar in the calcified and noncalcified lesions (p = 0.30). Moreover, by multivariate analysis, implantation of the paclitaxel-eluting stent was a powerful independent predictor of freedom from TLR, with similar hazard ratios for efficacy in calcified and noncalcified lesions (0.30 and 0.26, respectively). In conclusion, implantation of paclitaxel-eluting stents in patients with de novo coronary lesions significantly reduced restenosis in patients with and without calcified lesions.

Twenty‐four‐month comparison of immunomodulatory treatments – a retrospective open label study in 308 RRMS patients treated with beta interferons or glatiramer acetate (Copaxone®)

Abstract: A total of 308 patients with relapsing remitting multiple sclerosis (RRMS) documented in a clinical database have been analysed for comparison of treatment effects of first line immunomodulating therapies. During follow up for 24 months the reduction of relapse rates was evaluated in a retrospective and open-label clinical study by comparing the efficacy of interferon (INF)beta-1a i.m. (Avonex), INFbeta-1b s.c. (Betaferon), INFbeta-1a 22 microg s.c. (Rebif 22) and glatiramer acetate (GA; Copaxone) in patients with RRMS (enhanced disability status score (EDSS) < 3.5) who have been treated for at least 6 months. Compared with baseline, relapse rate was reduced to a comparable extend after 6 month treatment with all regimen. For all drugs the effect on the relapse rate was sustained over 24 months.. There was no superiority of one of the INFbeta preparations concerning reduction of relapse rate after 12 and 24 months, however reduction was significantly higher for patients treated with GA compared with all beta interferons (-0.71, P < 0.001). In addition, the discontinuation rate within 24 months was significantly lower for GA. Despite some limitations of the study design, the results provide helpful clinical information regarding the efficacy of immunomodulatory therapies in early stages of RRMS patients in a clinical setting.

Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Abstract: Rationale Phase I/II studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. Patients Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years. The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was documented in 79 of 82 evaluable cases. Results The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (±7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by ≥ 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (±12)% at 3 years being 66 (±23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (±13)%; p = 0.59. The probability of confirmed disease progression was 20 (±11)%. MRI data were available in 78 patients before transplant showing disease activity (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI showed activity at any time in 5/61 (8 %) evaluable cases. Conclusion Autologous HSCT suggest positive early results in the management of progressive MS and is feasible. These multicentre data suggest an association with significant mortality risks especially in some patient groups and are being utilised in the planning of future trials to reduce transplant related mortality.

Familial cognitive deficits in schizophrenia

Abstract: Susceptibility to schizophrenia is considered familial, but the mechanism for transmission has not been found. Since widespread cognitive deficits have been found in patients with schizophrenia, several of these have been proposed as candidate familial endophenotypes that may or may not be predictive of who develops the illness. The current study examines these candidates in individuals from 32 families with at least 2 members having the diagnosis of chronic schizophrenia and normal comparison subjects using an extensive neuropsychological battery. Consistent with previous literature, family members with schizophrenia were significantly impaired on all measures compared with controls. Well relatives demonstrated significantly worse performance on a measure of verbal learning, delayed visual recall, perceptual-motor, and pure motor speed. Expressive and receptive language, but not other functions, were highly correlated within both concordant for schizophrenia and discordant sibling pairs, suggesting that they are familial vulnerability endophenotypes, but not predictive of whom becomes ill. On the other hand, some measures of perceptual-motor, pure motor speed, and frontal/executive functioning were significantly correlated in concordant, but not discordant pairs. These latter correlations suggest that some cognitive measures may be genetically related to the illness.

Associations of thrombophilia, hypofibrinolysis, and retinal vein occlusion.

Abstract: We prospectively assessed whether thrombophilia and hypofibrinolysis, amplified by thrombophilic hormone replacement therapy (HRT), were associated with retinal vein occlusion (RVO). We studied 44 cases (18 men, 26 women), ≥ 3 months after RVO, 42 with central RVO, 2 with branch RVO, in the consecutive order of their referral by 2 community-based ophthalmologists. PCR and serologic coagulation assays were compared to 83 and 40 healthy adult normal controls, respectively. The 4G allele frequency of the plasminogen activator inhibitor-1 (PAI-1) gene, associated with hypofibrinolysis, was 56 of 88 (64%) in cases vs 79 of 166 (48%) in controls, X2 = 5.95, p = .015. The PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx), was higher in cases than controls (age-race-sex-adjusted mean 12.2 U/mL vs 6.3, p = .013). By stepwise logistic regression, the PAI-1 gene 4G allele was associated with RVO, odds ratio 1.94, 95% CI 1.12-3.34, p = .018. Thrombophilic resistance to activated protein C (RAPC) w...

The effects of microgravity on the development of surface righting in rats

Abstract: The active interaction of neonatal animals with their environment has been shown to be a decisive factor in the postnatal development of sensory systems, which demonstrates a critical period in their maturation. The direct demonstration of such a dependence on the rearing environment has not been demonstrated for motor system function. Nor has the role of gravity in mammalian motor system development been investigated. Here we report the results of two space flight missions examining the effect of removing gravity on the development of surface righting. Since the essential stimulus that drives this synergy, gravitation, was missing, righting did not occur while the animals were in the microgravity environment. We hypothesize that this absence of contextual motor experience arrested the maturation of the motor tactics for surface righting. Such effects were permanent in rats spending 16 days (from postnatal day (P), P14 to P30), but were transient in animals spending nine days (from P15 to P24) in microgravity. Thus, active, contextual interaction with the environment during a critical period of development is necessary for the postnatal maturation of motor tactics as exemplified by surface righting, and such events must occur within a particular time period. Further, Earth's gravitational field is not assumed by the developing motor system. Rather, postnatal motor system development is appropriate to the gravitational field in which the animal is reared.

Na/K-ATPase, endogenous digitalis like compounds and cancer development -- a hypothesis.

Abstract: The primary transport system of sodium and potassium across the plasma cell membrane, the Na/K-ATPase, is a vital enzyme involved in numerous cellular events. This enzyme is the receptor for plant and amphibian steroids such as ouabain, digoxin and bufalin. In the past decade several endogenous steroids, identical or similar to the plant and amphibian steroids, termed here collectively digitalis-like compounds (DLC), have been identified in human tissues. This paper raises the hypothesis that alterations in the metabolism of endogenous DLC and in their interactions with the Na/K-ATPase may be associated with the development of malignancies. This hypothesis is based on the review of the literature pointing to: 1. An abnormal activity of the Na/K-ATPase and its sensitivity to DLC in malignant cells; 2. Abnormal plasma DLC concentrations in cancer patients; 3. Abnormal synthesis and release of DLC in immune compromised mice; and 4. Beneficial effects of DLC in the treatment of cancer.

First-bite syndrome after resection of the styloid process.

Abstract: Background: First-bite syndrome (FBS) may occur after operations on parapharyngeal space. The main symptom is excruciating pain only after the first one or two bites of meals. Objective: The objective of this article is to report a case of FBS after resection of the styloid process (SP). Case Report: This 51-year-old woman had a 4-month history of pain on her left neck. Computed tomography scan showed a left hypertrophic SP. A diagnosis of Eagle syndrome (ES) was then established. She underwent excision of the left SP through a lateral cervicotomy. Postoperative recovery was uneventful with pain relief. However, 2 months postoperatively, intense pain appeared related to the first bite in every meal. She received 800 mg carbamazepine per day with good pain control. Medication was discontinued after 2 years with no further relapse. Conclusions: This is the first report on FBS after surgical treatment of ES. It is important to remember the possibility of the diagnosis and to maintain the patient under heavy specific medication, sometimes for longer periods.

Ethical Considerations in the Early Composite Tissue Allograft Experience: A Review of the Louisville Ethics Program

Abstract: This paper reviews the formulation and evolution of the ethical component in one of the earliest clinical composite tissue allograft (CTA) programs, the hand transplantation program in Louisville, Kentucky, USA. The purpose was to derive lessons and define principles to give guidance for future programs and introduction of new CTA. We reviewed the initial ethical considerations, including input from respected ethical scholars, guidelines for innovative procedures transparency in public and professional scrutiny, and compliance with human studies regulations (IRB approval). We found the initial focus on ethics, scholarly input, guidelines for innovative procedures, and human studies protection regulations to be valid. Moreover, we noted the effect of autonomy in subjective, quality-of-life benefits on equipoise and effective risk-benefit analysis in effective informed consent. We found that psychiatric screening and support to be exceptionally valuable in protecting autonomy, suitability for participation, assessing personality organization, and determining compliance ability. We conclude that the program ethical principles were validated. For future CTA programs and procedures, we recommend an ethical emphasis with adherence to high standards and transpire to independence to scrutiny and oversight. We recommend protection of autonomy judgments in equipoise judgment and informed consent. We recommend skilled psychiatric screening and support. We endorse scholarship, scientific accuracy, and data sharing.

Intravenous immunoglobulins in the treatment of relapsing remitting multiple sclerosis - results of a retrospective multicenter observational study over five years

Abstract: Use of intravenous immunoglobulins (IVIG) has been recommended for treatment of RRMS if first line therapy with beta-interferon or glatiramer acetate is not tolerated, or if contraindications exist. This consensus recommendation is based on the demonstration of efficacy and tolerability of IVIG in four randomized controlled trials (RCTs). The impact of non-randomized observational trials on evidence-based recommendations for treatment is still under discussion. In order to evaluate the transferability of study results derived from RCTs into a routine practice setting, we carried out a retrospective data analysis on patients with RRMS who had been treated with IVIG during the last five years. Data sets from 308 out of 1122 screened patients were available for analysis. Treatment with IVIG resulted in a 69% reduction of the mean annual relapse rate (ARR) (calculated over two years) from 1.74+/-1.15 before IVIG treatment to 0.53+/-0.61 after start of IVIG treatment. Mean expanded disability status scale (EDSS) values remained stable throughout the observation period. The results of this observational study were similar to the results of previous RCTs with IVIG.

Accuracy of implanted port placement with the use of the electromagnetic CathTrack catheter locator system.

Abstract: Purpose To test whether an electromagnetic guidance system such as CathTrack would allow long-term central venous access devices to be reliably placed at a decreased cost and without radiation exposure to patients and staff. The following study was undertaken to verify accuracy of the CathTrack system for catheter placement and to develop guidelines for its use. Methods Twenty-nine consecutive patients were prospectively enrolled in the study and taken to the operating room for implantation of a permanent central venous access port. By protocol, the CathTrack system was used to guide initial catheter positioning using the center of the third intercostal space along the right sternal border as the desired external target. Fluoroscopy was then used to visualize tip position and relocate the catheter tip to the exact position desired by the surgeon. Results Catheter placement using the CathTrack system was successfully accomplished in 27 out of 29 patients. In two instances CathTrack was abandoned and fluoroscopy utilized because of difficulty in threading the initial guidewire into the superior vena cava. Conclusion The CathTrack electromagnetic locator system can be used to reliably position catheters for the establishment of long-term central venous access. Decreased cost and elimination of radiation exposure are distinct advantages of this system over fluoroscopy.

Niflumic acid and MSI-2216 reduce TNF-α–induced mucin expression in human airway mucosa

Abstract: Background Human chloride channel, calcium-activated 1 (hCLCA1) has been shown to induce mucin (MUC) gene expression and mucus production in bronchial epithelial cells. Objective To investigate whether blocking hCLCA1 decreases mucus production. Methods Expression of hCLCA1 and mucus was stimulated with TNF-α in human upper airway mucosal explant tissue. MUC5AC mRNA and mucus protein expression was blocked by inhibiting hCLCA1 by using channel blockers (niflumic acid [NFA] and MSI-2216) without and with TNF-α stimulation. Expression of MUC5AC, hCLCA1, and COX-2 mRNA was quantified by using real-time PCR. Mucus protein was assessed by periodic acid Schiff staining. Laser capture microdissection was performed to quantify hCLCA1 and MUC5AC mRNA expression in epithelial cells derived from mucosal explant tissue. Results TNF-α significantly increased MUC5AC and hCLCA1 mRNA as well as mucus and hCLCA1 protein expression in the mucosal explant tissue ( P P Conclusions Unstimulated and TNF-α–induced mucin expression could be decreased by NFA and MSI-2216. Inhibiting hCLCA1 may be a potential new approach to reduce mucus overproduction.

The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: Etiologies for sporadic miscarriage

Abstract: We hypothesized that the thrombophilic G1691A factor V Leiden gene mutation was a common significant cause of sporadic first trimester miscarriage. We compared thrombophilia and hypofibrinolysis in 92 women (85 white, 5 black, 2 other) with 1 or more pregnancies and 1 miscarriage (143 live births, 92 miscarriages) (cases) and in 380 female controls (355 white, 21 black, 4 other) with 1 or more pregnancies and 0 miscarriages (964 live births). We used polymerase chain reaction techniques to characterize thrombophilic gene mutations (G1691A V Leiden [FV], G20210A prothrombin, C677T/A1298C MTHFR) and hypofibrinolytic gene mutations (plasminogen activator inhibitor [PAI-1] activity 4G4G). We carried out serologic measures of thrombophilia (homocysteine, anticardiolipin antibodies [ACLA] immunoglobulin G and immunoglobulin M, lupus anticoagulant, factor VIII, factor XI, protein C, total and free protein S, antithrombin III) and hypofibrinolysis (plasminogen activator inhibitor activity [PAI-Fx], lipoprotein[a]). Of the 380 controls, 6 (1.6%) had FV heterozygosity vs 12 heterozygous and 2 homozygous FV cases (15.2% [14/92]; P 150%) in 15 (31%) of 48 cases vs 19 (18%) of 103 controls (P = .079). By logistic regression, with age and factor VIII (categorical [≤150%, >150%]) as explanatory variables and group (cases, controls) as the dependent variable, after adjusting for age, high factor VIII was a significant predictor for miscarriage (odds ratio, 3.28; 95% confidence interval, 1.34-8.04; P = .01). There were no other group differences (P > .05) in measures of thrombophilia and hypofibrinolysis. After unexplained sporadic first trimester miscarriage, we suggest that measurements be done of the FV mutation, PAI-Fx, and factor VIII, etiologies for sporadic miscarriage.

Immunoadsorption patients with multiple sclerosis: an open-label pilot study.

Abstract: Background Immunoadsorption (IA) is occasionally applied in patients with acute relapses of multiple sclerosis (MS). This pilot study was undertaken to determine whether IA might help in secondary progressive and relapsing-remitting multiple sclerosis. Design IA was performed at 1-week intervals in 12 patients with secondary progressive or relapsing-remitting MS. These patients had an extended disability status scale (EDSS) score of 4·5–7 and an EDSS increase of 0·5 within 6 months before inclusion in the study despite conventional drug therapy. The change in the EDSS and that in the MS functional composite (MSFC) score, which consisted of quantitative tests of arm function, ambulation, visual acuity and cognition, served as the primary outcome variables, which were measured at baseline and at 3, 6 and 12 months. Changes in quality of life and cerebral lesions by magnetic resonance imaging (MRI) were also assessed at baseline and after the last immunoadsorption (month 3). Results A significant reduction of the median EDSS change was observed after the treatment period, which reversed 3 months after the immunoadsorptions had been stopped. Ten of 12 patients remained stable during the first year of follow-up with no significant changes of the MSFC scores. No significant changes in magnetic resonance imaging T2-hyperintense brain lesions or in the number of gadolinium-positive lesions and in the patients’ quality of life were observed. Western blot analyses demonstrated a reduction of serum myelin-specific antibodies, which were collected in the adsorber eluates. Conclusions Removal of immunoglobulins, including myelin-specific antibodies by immunoadsorption, seems to delay disease progression as defined by EDSS, MSFC and MRI, while the patients’ quality of life did not deteriorate.

Metformin-diet benefits in women with polycystic ovary syndrome in the bottom and top quintiles for insulin resistance☆

Abstract: We prospectively assessed whether metabolic and menstrual benefits of metformin-diet were equally realized in women with polycystic ovary syndrome (PCOS), categorized by pretreatment top (n = 32) and bottom (n = 35) quintile homeostasis model assessment insulin resistance (IR). Effects of metformin (2.55 g/d) and diet (6300-8400 J/d [1500-2000 cal/d], 26% protein, 44% carbohydrate) were prospectively assessed for 12 months. Pretreatment, the bottom and top insulin-resistant quintile groups differed by median weight (84 vs 121 kg), insulin (7.8 vs 40.5μU/mL), IR (1.62 vs 9.28), homeostasis model assessment insulin secretion (131 vs 416), glucose (82 vs 98 mg/dL), sex hormone–binding globulin (40 vs 15 nmol/L), (all P .05 for both), and 22% (P .01) in the top insulin-resistant group. The pretreatment percentage of expected menses in the top insulin-resistant quintile (26 ± 39%) was 1.6 times less than in the bottom insulin-resistant quintile (41 ± 38%) (P = .026). Over the 12-month treatment period, the percentage of spontaneous regular normal menses increased to 72 ± 27% in the top insulin-resistant quintile group (P

Large gastric mesenteric cyst: case report and literature review.

Abstract: The case is a 33-year-old white female presenting with a 3-day history of abdominal pain. On initial examination, she was found to have significant right lower quadrant tenderness. Workup included computed tomography, which demonstrated a large cystic mass appearing to be of ovarian origin. The patient required an exploratory laparotomy, at which time she was found to have a large cyst involving the lesser curvature of her stomach. The cyst was successfully resected, and the patient had a rapid postoperative recovery with complete resolution of symptoms. Histopathologic evaluation of the specimen identified a mesenteric cyst. Mesenteric cysts are uncommon; gastric involvement is exceedingly rare. A review of the literature is presented.

Differential fly-throughs (DFT): a general framework for computing flight paths

Abstract: In this paper, we propose a new variational framework based on distance transform and gradient vector flow, to compute flight paths through tubular and non-tubular structures, for virtual endoscopy. The proposed framework propagates two wave fronts of different speeds from a point source voxel, which belongs to the medial curves of the anatomical structure. The first wave traverses the 3D structure with a moderate speed that is a function of the distance field to extract its topology, while the second wave propagates with a higher speed that is a function of the magnitude of the gradient vector flow to extract the flight paths. The motion of the fronts are governed by a nonlinear partial equation, whose solution is computed efficiently using the higher accuracy fast marching level set method (HAFMM). The framework is robust, fully automatic, and computes flight paths that are centered, connected, thin, and less sensitive to boundary noise. We have validated the robustness of the proposed method both quantitatively and qualitatively against synthetic and clinical datasets.

Idiopathic intracranial hypertension: associations with thrombophilia and hypofibrinolysis in men.

Abstract: The existence of an association between idiopathic intracranial hypertension (IIH) and coagulation disorders in men was assessed prospectively. Microthrombi, associated with thrombophilia-hypofibrinolysis, occlude arachnoid sinus villi, thus reducing resorption of cerebrospinal fluid, leading to IIH. Ten consecutively referred men with IIH, nine whites, one African American, median age 36 years, were 2 to 1 matched by age and race by healthy male controls. Polymerase chain reaction assays were done for four thrombophilic and one hypofibrinolytic gene mutations: G1691A factor V Leiden, G20210A prothrombin, C677T MTHFR, platelet glycoprotein IIb/IIIa (PL A1/A2), and 4G/5G polymorphism of the plasminogen activator inhibitor (PAI-1) gene promoter. Coagulation measures in plasma included dilute Russel's viper venom time (dRVVT), activated partial thromboplastin time (aPTT), the lupus anticoagulant, factor VIII, factor XI, plasminogen activator inhibitor activity (PAI-Fx), protein C antigenic, protein S total (antigenic), protein S free (antigenic), antithrombin III (functional), and resistance to activated protein C (RAPC). Tests performed on serum included anticardiolipin antibodies, homocysteine, and Lp(a). The body mass index was 40 kg/m(2) or greater (extremely obese) in two men, 30 to 40 kg/m(2) (obese) in three, and was 25 to 30 kg/m(2) in five (overweight). Cases differed from controls for inherited 4G4G homozygosity of the PAI-1 gene, four of 10 (40%) vs. one of 20 (5%), Fisher's p [p(f)]= .031, and for high levels (>21.1 U/mL) of the hypofibrinolytic PAI-1 gene product, PAI-Fx, 5 of 10 (50%) vs. one of 18 (6%), p(f) = .013. Thrombophilic factor VIII was high (> or = 150%) in three of 10 (30%) cases vs. zero of 16 (0%) controls, p(f)=. 046. The thrombophilic lupus anticoagulant was present in two of 10 (20%) cases vs. zero of 32 (0%) controls, p(f) = .052. Heritable hypofibrinolysis and heritable and acquired thrombophilia appear, speculatively, to be treatable etiologies of IIH in men. Understanding contributions of hypofibrinolysis and thrombophilia to the development of IIH should facilitate development of novel new approaches to treat this often-disabling neurologic disorder.

Left ventricular volume reduction surgery: The 4th International Registry Report 2004.

Abstract: Background and methods An international registry of left ventricular volume reduction (LVVR) procedures, including partial left ventriculectomy, has been expanded, updated, and refined to include 568 cases voluntarily reported from 52 hospitals in 12 countries. Results Gender, age, ventricular dimension, ethnology, myocardial mass, presence or absence of mitral regurgitation, as well as transplant indication, had little effect on event-free survival, which was defined as either absence of death or ventricular failure requiring mechanical assist or transplantation. Poor preoperative patient condition such as New York Heart Association classification IV, depressed contractility and decompensation requiring an emergency procedure were associated with reduced event-free survival. Other risk factors included an early surgery date, lack of experience, dilated cardiomyopathy as the underlying pathology and extended myocardial resection. Performance of LVVR reached a peak by 1998, but was largely abandoned by 2001, except in Asia, where experienced institutes continue to perform it in patients in better condition with preserved myocardial contractility. Conclusion Avoidance of risk factors appears to have contributed to the recent survival improvement and may help stratify patients for LVVR. While performance has been decreasing, the concept has been extended to other LVVR and less invasive procedures, which are now under clinical trials.

Diltiazem prophylaxis reduces incidence of atrial fibrillation after coronary artery bypass grafting.

Abstract: Aim. To evaluate the prophylactic effect of diltiazem on the incidence of atrial arrhythmia (fibrillation and/or flutter) following coronary artery bypass grafting (CABG). Data were retrospectively gathered. Methods. Patients undergoing elective CABG by one surgeon at one institution over a three-year period were considered for inclusion. Those selected were divided into 3 groups: A (patients placed on intravenous diltiazem intraoperatively, then converted to oral diltiazem upon initiation of oral intake); B (patients started on oral diltiazem upon initiation of oral intake without prior intravenous diltiazem); and C (patients receiving no diltiazem). A comparison of postoperative rates of atrial fibrillation was made between the 3 (demographically balanced) groups using logistic regression. Results. Two hundred and eighty seven patients met inclusion criteria. The incidence of postoperative atrial fibrillation in the entire sample was 19.9% (57/287). Incidence of postoperative atrial fibrillation within each group was: A - 16.3% (22/135); B = 12.7% (7/55); C = 28.9% (28/97). Statistical significance was demonstrated for the following comparisons: A versus C (p = 0.0451) and B versus C (p =0.0065). In an alternate model groups A and B were combined and compared to C (p - 0.0181). Conclusion. A lower incidence of atrial fibrillation following CABG was observed in patients treated prophylactically with diltiazem. Differences were statistically significant whether the drug was administered intravenously and orally (A) or only orally (B). Diltiazem, which has an established role in the management of atrial fibrillation, may prove to be well suited for prophylaxis due to low cost and relative safety.

Testicular histopathological diagnosis as a predictive factor for retrieving spermatozoa for ICSI in non-obstructive azoospermic patients.

Abstract: Objective: Histological testicular pattern has a predictive role in the possibility of finding spermatozoa for ICSI in cases of non-obstructive azoospermia because some individuals could show residual spermatogenic sites in the testis. The aim of this study was to evaluate the sperm retrieval rate in each of the histopathological groups (hypospermatogenesis-Hypo, spermatogenic maturation arrestMA, Sertoli cell only-SCO and testicular hyalinization) in patients assisted in our clinic. Materials and Methods: Retrospective study from March 1997 to October 2002. We analyzed 14 patients with mean age of 34.3 ± 0.7, with non-obstructive azoospermia. All patients were submitted to previous diagnostic biopsy (Bx) elsewhere and came to our institution for treatment. After an average of 12 months (8 - 20), they were submitted to a new Bx procedure to retrieve sperm. Results: Previous diagnostic Bx showed the following histopathological results: 5 patients with MA, 4 with Hypo and 5 SCO. In the following Bx (for sperm retrieval) spermatozoa was found in 33% of the procedures in patients with MA, 50% in patients with Hypo and 40% of the procedures in patients with SCO. Conclusion: Previous diagnostic Bx can help in patient counseling concerning the result of sperm retrieval.