Long-term clinical, radiological, and histological follow-up after complex ventral incisional hernia repair using urinary bladder matrix graft reinforcement: a retrospective cohort study.

BACKGROUND: Complex ventral incisional hernia repair represents a challenging clinical condition in which biologically derived graft reinforcement is often utilized, but little long-term data inform that decision. Urinary bladder matrix (UBM) has shown effectiveness in diverse clinical settings as durable reinforcement graft material, but it has not been studied over a long term in ventral incisional hernia repair. This study evaluates the clinical, radiographic, and histological outcome of complex incisional hernia repair using UBM reinforcement with 12-70 months of follow-up. METHODS: A single-arm, retrospective observational study of all ventral incisional hernia repairs utilizing UBM reinforcement over a 6-year time frame by a single surgeon was performed. Patients were assessed in long-term follow-up clinically and with the Carolina Comfort Scale. A subset of patients was assessed with abdominal wall ultrasound or CT scan. Three patients had abdominal wall fascial biopsies years after the incisional hernia repair with UBM graft, and the histology is analyzed. RESULTS: 64 patients underwent repair of complex incisional hernias with UBM graft reinforcement by a single surgeon. 42 patients had concomitant procedures including large or small bowel resection, excision of infected mesh, evacuation of abscess or hematoma, cholecystectomy, or panniculectomy with abdominoplasty. 16 patients had ostomies at the time of repair. Median follow-up time is 36 months, with a range of 12-70 months. Nine patients (14%) have required surgical repair of a recurrent hernia, and a tenth patient has a recurrence that is managed non-surgically, for a total recurrence rate of 15.6% over the entire time frame. Median time to recurrence was 32 months, and a Kaplan-Meier freedom from recurrence curve is depicted. 28 patients have undergone ultrasound or CT assessments of the abdominal wall which demonstrate radiographic fascial integrity 12-70 months after repair. Three patients have been re-explored for unrelated reasons in the years following ventral incisional hernia repair with UBM, and full thickness fascial biopsies demonstrate a robust remodeling response histologically similar to native myofascial tissue. No patients have developed graft infection, fistulization to the graft, or required graft explantation. Carolina Comfort Scale assessment of 45 patients 3 years after the repair averaged 16 out of a possible 115. CONCLUSION: In 64 patients undergoing complex ventral incisional hernia repair with UBM reinforcement, all have experienced successful resolution of complex clinical conditions and 15.6% of these repairs have recurred at a median follow-up of 3 years. Three full-thickness biopsies of the repaired fascia years later shed light on a promising remodeling response which may signal strength and durability comparable to native fascia.

The role of high-sensitivity C-reactive protein for assessing coronary artery disease severity and left ventricular end diastolic pressure in patients with suspected coronary artery disease.

OBJECTIVE: Much attention has recently been focused on the underlying role of circulating inflammatory biomarkers such as high-sensitivity C-reactive protein for predicting cardiovascular disease progression. We therefore set out to assess the relationship between the value of high-sensitivity C-reactive protein and (i) coronary artery disease severity, and (ii) left ventricular end diastolic pressure. DESIGN: A cross-sectional study. SETTING: The Shafa hospital in Kerman, Iran. PATIENTS: A total of 107 consecutive patients referred for coronary angiography from January 2008 to January 2009 were prospectively studied. INTERVENTION AND MAIN OUTCOME MEASURES: All patients underwent coronary angiography. They all had undergone left ventricular end diastolic pressure measurement, involving a 6-Fr pigtail catheter and a properly zeroed fluid-filled pressure transducer. For each patient, the level of high-sensitivity C-reactive protein was also determined using enzyme-linked immunosorbent assay kits. RESULTS: The high-sensitivity C-reactive protein levels could strongly predict increased left ventricular end diastolic pressure (standardised beta=1.010; P=0.008), with other patient variables being confounders, but there was no significant association between these levels and Gensini scores. Multiple linear regression analysis showed that among the study parameters, systolic hypertension (standardised beta=1.611; P=0.047) and a family history of coronary artery disease (standardised beta=1.911; P=0.005) were the main predictors of high Gensini scores in study patients. CONCLUSION: High-sensitivity C-reactive protein level is a clinical parameter that could predict left ventricular end diastolic pressure and left ventricular dysfunction, but was not associated with the severity of coronary artery disease.

Rituximab is Indispensable for Pediatric Heart Transplant Recipients Developing Post Transplant Lymphoproliferative Disorders.

Rituximab, an anti-CD20 agent, has been suggested as an effective strategy to deal with post transplant lymphoproliferative disorders (PTLD). In the current study, we aim to evaluate the efficacy of rituximab therapy in heart transplant population developing PTLD. A comprehensive search of the literature was performed to gather the available data on lymphoproliferative disorders occurring in heart transplant patients. Finally, data of 125 patients from 26 previously published studies were included into the study. Patients who underwent rituximab therapy had significantly worse tumoral histopathology features (P-value= 0.003). Survival analyses showed no significant difference regarding receiving rituximab therapy for heart recipients; however, when the analysis was repeated only including data of pediatric patients, significant beneficial effects for pediatric were found for rituximab therapy. In fact, no children undergoing rituximab therapy died during the follow up. In conclusion, this study showed that rituximab therapy in pediatric heart transplant recipients with PTLD represents surprisingly excellent results, making rituximab an indispensable agent in the management of the disease. To define feasibility of rituximab therapy in adult recipients of heart graft with PTLD, randomized controlled trials are needed.

Coronary Artery Disease Risk Factors in an Urban and Peri-urban Setting, Kerman, Southeastern Iran (KERCADR Study): Methodology and Preliminary Report.

BACKGROUND: This article was to present the sampling and measurements methods and the main preliminary findings of the KERCADR cohort study (first round) in an urban and peri-urban setting, Kerman, southeastern Iran 2009-11. METHOD: 5900 (3238 female) people aged between 15 to 75 years were recruited in the household survey by non-proportional to size one-stage cluster sampling. Trained internal specialists, general practitioners, clinical psychologists and dentists have assessed the study subjects by person-assisted questionnaires regarding different NCD risk factors including cigarette and opium smoking, physical activity, nutrition habits, anxiety, depression, obesity, hypertension and oral health. Blood samples were also collected for determining FBS, HbA1c, cholesterol and triglyceride. Weighted standardized prevalence estimates were calculated by STATA 10 survey analysis package. RESULTS: The participation rate was more than 95% in all subgroups. Cigarette smoking (18.4% vs. 1.2%), opium use (17.8% vs. 3.0%) and triglyceridemia (16.1% vs. 12.0%) were significantly higher among men than women. In contrast, women were presented with higher level of sever anxiety (29.1% vs. 16.7%), obesity (16.8% vs. 9.2%), low-physical activity (45.1% vs. 39.2%) and uncontrolled diabetes (60.2% vs. 31.0%). More than 68% of all subjects have presented with moderate to severe gingival index scores. CONCLUSION: The first round of the KERCADR cohort with sufficient sample size and response rate provided precise estimates for the main clinical and para-clinical NCD risk factors. These evidences need to be translated into public health interventions and monitored in the next rounds of the cohort.

A biomechanical study comparing plate fixation using unicortical and bicortical screws in transverse metacarpal fracture models subjected to cyclic loading.

The use of bicortical screws to fix metacarpal fractures has been suggested to provide no added biomechanical advantage over unicortical screw fixation. However, this was only demonstrated in static loading regimes, which may not be representative of biological conditions. The present study was done to determine whether similar outcomes are obtained when cyclic loading is applied. Transverse midshaft osteotomies were created in 20 metacarpals harvested from three cadavers. Fractures were stabilised using 2.0 mm mini fragment plates fixed with either bicortical or unicortical screw fixation. These fixations were tested to failure with a three-point bending cyclic loading protocol using an electromechanical microtester and a 1 kN load cell. The mean load to failure was 370 N (SD 116) for unicortical fixation and 450 N (SD 135) for bicortical fixation. Significant differences between these two constructs were observed. A biomechanical advantage was found when using bicortical screws in metacarpal fracture plating.

Anemia after kidney transplantation in adult recipients: prevalence and risk factors.

OBJECTIVE: To evaluate the prevalence of anemia and appraise its risk factors at 6 months after renal transplantation. MATERIALS AND METHODS: This retrospective study was performed between 2008 and 2010 in 2713 adult kidney transplant recipients to determine the prevalence of posttransplantation anemia. Anemia was defined as hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men. RESULTS: The prevalence of posttransplantation anemia was 52.7%, with severe anemia (hemoglobin≤11 g/dL) detected in 24.4% of patients. Impaired renal function was the only risk factor associated with anemia (odds ratio, 3.6; P=.047). However, severe anemia after kidney transplantation was correlated with female sex (P=.001), renal allograft dysfunction (P=.00), and cytomegalovirus infection (P=.002). CONCLUSION: The present study demonstrated a quite high prevalence of posttransplantation anemia, in particular associated with impaired renal allograft function. Severe anemia was correlated with female sex, degree of kidney graft dysfunction, and cytomegalovirus infection.

Three-dimensional magnetic focusing of superparamagnetic beads for on-chip agglutination assays.

We present a new method for three-dimensional (3D) magneticfocusing of magnetic microparticles in a microfluidic system. On-chip magnetic particle manipulation in the microchannel is achieved by a high-gradient magnetic field generated by means of a micromachined field concentrator. The system allows retention of functionalized beads in a dense plug while flowing through buffer or analyte. Slowly reducing the magnetic retention force in the presence of a flow results in controlled release of the particles into a fine streamline with regular longitudinal interparticle spacing. Alignment at half-height of the channel is readily obtained through the symmetry of the magnetic field. A single lateral sheath flow is required to provide full 3D focusing of the microparticles in the middle of the microchannel with a maximum deviation of ±5 µm from the center position. With the use of this system, a new approach for performing an immunoagglutination assay on-chip has been implemented. Three-dimensional focusing allowed reliable counting of singlets and agglutinated doublets. We demonstrate the potential of the agglutination assay in a microfluidic format using a streptavidin/biotinylated bovine serum albumin (bBSA) model system. A detection limit of about 400 pg/mL (6 pM) is achieved.

Attitude and Willingness towards Tissue Donation in Iranian High School Students: Bone Marrow and Blood.

BACKGROUND: Tissue donation has been promising in prolonging the lives of people with life-threatening diseases. OBJECTIVE: To assess the attitude and willingness of high school students towards bone marrow (BM) and blood (as tissue) donation for maintaining a safe and adequate pool. METHODS: This cross-sectional study was conducted among the high school girls, aged 15-18 years, who studied in natural sciences, mathematics and humanities. All participants filled a questionnaire consisting of age, religion, education levels and study branch, attitude and willingness towards BM and blood donation according to a Likert scale. RESULTS: Out of 416 students, with the mean±SD age of 16.3±1.2 years, 31% studied in grade I, 27% in grade II (25% natural sciences, 27% mathematics, and 48% humanities), 26% in grade III (30% natural sciences, 34% mathematics, and 36% humanities), and 16% in pre-university level (college) (32% natural sciences, 42% mathematics, and 6% humanities). The students had highly positive attitudes toward BM and blood donation (mean±SD score of 4.2±0.54). The willingness for BM and blood donation was declared respectively, in 87% and 71% of respondents. Moreover, 16% of students wanted to donate only to their relatives and 84% to all persons in need of therapy. There was no significant correlation between the donation willingness and educational levels and study branch; however, these variables significantly correlated with attitude towards tissue donation (p=0.02, p=0.01, respectively). CONCLUSION: Despite positive attitude towards BM and blood donation, willingness for BM donation is lesser than blood which may be attributed to insufficient information about this type of tissue donation. An organized educational program for high school students in all aspects of tissue donation seems necessary.

Effects of aerobic exercise and resistance training on lipid profiles and inflammation status in patients on maintenance hemodialysis.

Physical function limitation is a common disorder in chronic hemodialysis (HD) patients, relating to increased morbidity and mortality. The aim of this study was to determine the effects of aerobic and resistance trainings on blood lipids and inflammation status in HD patients. Out of 30 volunteer males who had been undergoing conventional maintenance HD within an HD unit in Tehran, 21 subjects were enrolled. They were randomly assigned into aerobic exercise group - resistance training group undergoing an 8-week intradialytic exercise program (three times/week) and control group (n = 7, each). Training program consisted of 10-30 min stationary cycling at an intensity of 12-16 out of 20 at the rate of perceived exertion (RPE) of Borg scale in aerobic group and using ankle weights for knee extension, hip abduction and flexions at an intensity of 15-17 out of 20 at the RPE of Borg scale in resistance group. Fasting blood samples for serum biochemistry were drawn at baseline and 8 weeks. The age, HD duration, and physical activity score were 51.6±18.9yrs; 25.1±13.9 mo, and 19.2±7.6, respectively. Diabetes mellitus (43%), hypertension (28%), and obstructive uropathy (14%) were the most common underlying diseases. Aerobic and resistance exercises were correlated with serum creatinine (P< 0.0001 and P<0.001) and hs-CRP levels (P=0.005 and P=0.036) reduction so that aerobic exercise induced more reduction. These exercises had no influence on weight, Kt/V values, serum urea, albumin, hemoglobin, and lipid levels (P>0.05). Both intradialytic aerobic and resistance exercises showed beneficial effects on inflammation status without any influences on serum lipid levels probably due to short duration of the study which was not accompanied with body weight changes. Solute removal had no change during exercise programs. There is a need for more investigation on the role of exercise in HD patients.

Survey of medical students of Shahed University in Iran about attitude and willingness toward organ transplantation.

BACKGROUND: Transplantation is a successful procedure that prolongs the lives of people suffering from debilitating diseases. The purpose of this study was to assess medical students' attitude toward organ donation. METHODS: The study population consisted of 262 medical students with a mean age of 22.1 +/- 2.5 years who were surveyed using a reliable questionnaire that examined their attitudes and willingness. All data analyses were performed using Chi-square and analysis of variance tests with SPSS. RESULTS: The medical students had highly positive attitude toward organ donation (mean score 4.34 +/- 0.46) and a great willingness. Participants were more willing to donate their own organs than those of a deceased relative (85% vs 49.2%) to help others more than to develop science (91.2% vs 8.8%). The greatest willingness among students was kidney (84%) donation. There was no correlation between age, gender, education levels, and attitude toward organ donation. CONCLUSION: These findings necessitate an organized education program of medical students in all aspects of organ and tissue donation.

Outcomes of two different polytetrafluoroethylene graft sizes in patients undergoing maintenance hemodialysis.

Arteriovenous access creation is mandatory for maintenance hemodialysis. If native fistula placement was not possible or failed, a prosthetic conduit would be the best substitute. The purpose of this prospective study was to compare outcomes of two different sizes of polytetrafluoroethylene (PTFE) grafts, in hemodialysis patients, at the Mustafa Khomeini Hospital in Iran. The study population consisted of 586 end-stage renal disease referrals for vascular access construction (January 2003 to January 2007) of which eventually 102 subjects were candidates for PTFE graft who were followed for one year. Data were collected by a questionnaire and analyzed using the SPSS, life table, Kaplan- Meier and Log-Rank tests. Out of 102 PTFE implantation candidates (mean value of age 51.7 +/- 17.06 yrs), 56% were male and 44% female. PTFE grafts of 8 mm and 6 mm sizes were randomly placed in 57 and 45 subjects, with distribution of 83%, 12% and 5% in arm, forearm and thigh. The most underlying diseases were hypertension and diabetes. There was a significant difference in complication rates between patients with and without underlying diseases [42% vs. 10% (P = 0.03)]. One-year patency rates were 42.2% and 36.5% for 6 mm and 8 mm grafts and 28.2% vs. 52% in patients with and without underlying diseases respectively. Despite more complication frequency in 8 mm grafts, the patency and complication rates of two graft groups did not significantly differ. Hypertension and diabetes could have contributory roles in graft complication rate, which may be preventable. Non-tapered grafts of 6 mm and 8 mm sizes have not significant different outcomes. Further research is recommended with larger sample size and longer duration.

Allergic asthma: a tale of many T cells.

Asthma is a common immune-mediated disorder characterized by reversible airway inflammation, mucus production, and variable airflow obstruction with airways hyperresponsiveness (AHR). In most cases the airway inflammation characteristic of asthma is thought to result from an allergic-type reaction to an inhaled substance from the environment (so-called allergic asthma). In allergic asthma, allergen exposure stimulates eosinophilic inflammation of the airways associated with infiltration of T cells. Although the recruitment of eosinophils into the airways is an important component in the pathogenesis of asthma, the trafficking of T lymphocytes into the airways is now believed to establish and orchestrate the asthmatic inflammatory response. This review explores the roles of various T cell subsets in the pathogenesis of allergic airway inflammation and highlights the contributions of these cells in regulating asthma.

Diaphragmatic stimulation: a case of atrial lead dislodgement and right atrium perforation.

We report a 48 year old male who presented with diaphragmatic stimulation. The biventricular implantable cardioverter and defibrillator (CRT-D) was implanted two weeks before admission and active fixation lead caused perforation of the right atrial wall. Echocardiography did not demonstrate pericardial effusion but Chest X-ray and computed tomography (CT) visualized the atrial screw helix outside the right atrial wall, penetrating through the right lung middle lobe. There was no atrial capture. After changing the pace mode DDDR to VVIR, diaphragmatic stimulation was disappeared. The atrial lead was repositioned and fixed again. During the hospital admission and after that the patient was well and free of any symptoms.

Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear factor kappaB activity.

Nuclear factor kappaB (NF-kappaB) and the Rel family of proteins are pleiotropic transcription factors that play central roles in the immune and inflammatory responses, as well as apoptosis. Here, we identified a serine/threonine protein phosphatase X (PPX; also called protein phosphatase 4 (PP4)) that specifically associated with c-Rel, NF-kappaB p50, and RelA. The amino acid sequences of human and mouse PPX are 100% identical, and the PPX gene was mapped to human chromosome 16 p11.2. Overexpression of PPX, but not catalytically inactive PPX mutants, stimulated the DNA-binding activity of c-Rel and activated NF-kappaB-mediated transcription. These results suggest that PPX is a novel activator of c-Rel/NF-kappaB.

Synthesis, cytotoxic and antiviral activity of uracils containing 5-(1-hydroxy-2-haloethyl)- and 5-(1-methoxy-2-haloethyl) substituents.

5-(1-Hydroxy-2-haloethyl)- (4), 5-(1-methoxy-2-haloethyl)- (5) and 5-(1-hydroxy-2-methoxyethyl)uracils (6) (see Figure 2 for structures) were synthesized to investigate the effect of the C-5 substituents on cytotoxic and antiviral activity. The bromo compounds (4b and 5b) exhibited greater cytotoxic activity than the chloro or iodo analogues in the in vitro L1210 assay. Replacement of the hydroxyl substituent of 4b (bromo) and 4c (iodo) by a methoxyl substituent (5b-c), or substitution of their halogen substituents by methoxyl (providing 6) increased the potency. However, the cytotoxic activity of all the compounds was weak, the most active (6) producing a 45% decrease in cell survival at a concentration of 50 micrograms/ml, as compared with a 97% decrease when the reference standard (melphalan) was tested at 1 microgram/ml. They were inactive antiviral agents against herpes simplex virus type 1 (HSV-1) infected Vero cells at 10 micrograms/ml; in the same test, the reference standard (acyclovir) exhibited an ID50 of 0.01 micrograms/ml.

Synthesis of 5-[1-hydroxy(or methoxy)-2-bromo(or chloro)ethyl]-2'-deoxyuridines and related halohydrin analogues with antiviral and cytotoxic activity.

A series of new 5-(1-hydroxy-2-haloethyl)-2'-deoxyuridines (3, 6, 8) were synthesized in 60-70% yields by addition of HOX (X = Br, Cl, I) to the vinyl substituent of the respective 5-vinyl-2'-deoxyuridines (2, 5, 7). Treatment of 3a,b with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-haloethyl)-2'-(deoxyuridines (4a,b). The 5-(1-hydroxy-2-chloroethyl) (3b), 5-(1-methoxy-2-bromoethyl) (4a), 5-(1-hydroxy-2-bromo-2-(ethoxycarbonyl)ethyl) (6a), and 5-(1-hydroxy-2-iodo-2-(ethoxycarbonyl)ethyl) (6b) derivatives exhibited in vitro antiviral activity (ID50 = 0.1-1 microgram/mL range) against herpes simplex virus type 1 (HSV-1). 5-(1-Hydroxy-2-bromo-2-(ethoxycarbonyl)-ethyl)-2'-deoxyuridine (6a) was the most active cytotoxic agent in the in vitro L1210 screen exhibiting an ED50 of 11 micrograms/mL relative to melphalan (ED50 = 0.15 micrograms/mL).

Some pharmacological activities of novel adenine-related compounds isolated from a marine sponge Agelas mauritiana.

Agelasimine A and agelasimine B, two novel compounds related to adenine, have been isolated from the orange sponge, Agelas mauritiana, and have been tested for a variety of biological activities. Both compounds inhibited proliferation of cultured L1210 leukemia cells at nanomolar concentrations with accumulation in the G1 stage of the cell cycle. However, no prolongation of life was observed in mice bearing P388 leukemia treated with these compounds. In the rat isolated aorta, micromolar concentrations of agelasimines were very effective in inhibiting contractions elicited by potassium chloride but had little or no effect on responses for prostaglandin F2 alpha and had modest effects on the responses to noradrenaline and significant effects on 5-hydroxytryptamine. Agelsamines A and B appeared to be equipotent in causing relaxation in rabbit jejunum and bovine coronary artery, and they also inhibited nucleoside transport into rabbit erythrocytes in micromolar concentrations.

Synthesis and cytotoxic activity of pyridylthio, pyridylsulfinyl, and pyridylsulfonyl methyl acrylates.

Nineteen 2-pyridylthio (2), 2-pyridylsulfinyl (3) or 2-pyridylsulfonyl (4) derivatives of (Z)-methyl acrylate were synthesized in order to investigate the effect of the oxidation state of the sulfur atom, and the position and nature of pyridyl substituents on cytotoxic activity. Analogous sulfinyl and sulphonyl derivatives were equipotent, and more potent than analogous thio derivatives, in an vitro L1210 screen. In most cases, incorporation of nuclear trifluoromethyl and chloro substituents at various positions of the pyridyl ring of the sulfinyl derivatives (compounds 3b-3h) decreased activity relative to the unsubstituted sulfinyl 3a (ED50 0.43 micrograms/ml). Compounds 3b, 3d and 3i exhibited weak antineoplastic activity in an in vivo P388 screen at a dose of 5 mg/kg.

Synthesis and cytotoxic activity of tetrahydropyridylidene-2- and -4-sulfonamides.

1,2,3,4-Tetrahydropyridylidene-4-sulfonamides, 1,2,3,4-tetrahydropyridylidene-2-sulfonamides, and 1,2,3,6-tetrahydropyridylidene-2-sulfonamides, of structures 10, 12 and 14, respectively (given in Table I), were synthesized in order to investigate the effect of nuclear substituents and the position of the sulfonamido group on cytotoxicity. The relative potency order was 12 greater than 10 greater than 14. Compounds possessing an R1 CONEt2 substituent were more potent than those possessing a R1 CN substituent. The nature of the aryl(alkyl)-sulfonamido substituent was a determinant of activity, the relative potency order being 4-chlorophenyl greater than phenyl, 4-methoxy- or 4-nitrophenyl greater than methyl. 1-Methyl-4-tert-butyl-5-diethylaminocarbonyl-1,2,3,4-tetrahydro pyridylidene- 2-(4-chlorophenyl)sulfonamide (12c) was the most active cytotoxic agent, exhibiting an ED50 of 5.4 micrograms/ml in the L1210 in vitro screen.

Synthesis and cytotoxic activity of 1-(3-oxoprop-1-enyl)-2-pyridones.

1-(3-Oxoprop-1-enyl) derivatives of nuclear substituted 2-pyridones (7a-i), 2-pyridinethione (7j), 1-isoquinolone (9), and the 1,4-dihydropyridine (11) have been synthesized and tested for biological activity. The 2-pyridones (7) and the 1-isoquinolone (9) were all active cytotoxic agents as determined in the in vitro L1210 screen, exhibiting activity in the ED50 0.5-3.5 micrograms/ml range. The nature and position of nuclear substituents present in 7 and 9 did not alter activity significantly. The unsubstituted (7a) and 5-ethoxycarbonyl-2-pyridones (7g), and the 1-isoquinolone derivative (9) were active antineoplastic agents (%T/C = 133-135) in vivo exhibiting activity comparable to 5-fluorouracil.