Aims: To highlight an uncommon situation during stenting for obesity surgery complications. Place and Duration of Study: 1st Propaideutic Surgical Unit, Hippokration Hospital, Athens between December 2008 and November 2010. Results: 2 cases of obese patients are presented where the placing of metal stents in esophagogastric region after leakage in the postoperative period of sleeve gastrectomy, resulted in formation of papilloma at the edge of these stents. Conclusion: May be these cases are two of the very few reports in the medical literature which describe mucosal hyperplasia in the esophagus at the edge of a covered metal stent placed for a benign condition.
Background: Both vitamin D deficiency and Gestational diabetes (GDM) are common among Saudis. The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to several diseases. Studies on association between VDR polymorphisms and risk of GDM in Saudi populations are yet inconclusive. Objective: to evaluate the association between Vitamin D receptor gene polymorphisms and genetic susceptibility to gestational diabetes (GDM) in pregnant Saudis. Subjects & Methods: thirty pregnant Saudi women with diabetes (17 GDM and 13 type 2 diabetes (T2DM) with past history of GDM) were compared to 14 pregnant women with normal glucose tolerance. Patients and controls were recruited at their third trimester from Taibah University medical unit from January to July 2010. Genomic DNA was extracted and the genotyping related to vitamin D receptor BsmI gene single – nucleotide polymorphisms was carried out by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The gene frequency, allele frequency and carriage rate of the VDR polymorphism BsmI did not differ between patients and controls with no significant association with any clinical parameters. The 25 hydroxyl Vitamin D level but not the gene frequency was a significant predictor of history of abortion among diabetics (OR=-0.29, 95% CI -0.081-0.0, p=0.047). Conclusions: Vitamin D receptor BsmI gene polymorphisms is not associated with gestational diabetes among Saudis. Further studies of other Vitamin D receptor gene polymorphism in combination are required.
Objective: To evaluate the association between low serum levels of 25 (OH)2 D and the risk of breast cancer among the female population. Methods: A prospective case control study was done, which recruited female patients with newly diagnosed breast cancer, follow up cases of treated breast cancers, and recurrent or metastatic breast cancer (Group A). Another group of control volunteers, presenting with benign breast diseases, in the surgical clinics was incorporated (Group B). Serum vitamin D levels of both groups were compared. Results: 50 patients were included in each group. Age ranged 21-76 years with a mean of 47.6 years. The levels of vitamin D in Group A were significantly lower than those in Group B (Odd ratio 55.5); two-tailed p value <0.05. This signified a substantial difference of vitamin D levels between the patients with established breast cancer and those not suffering from breast cancer. Conclusion: There is significant relation between breast cancer disease and low levels of vitamin D. This finding testifies the hypothesis that low serum levels of vitamin D plays an important role in the pathogenesis of breast cancer.
Aims: Soluble cytokeratin (CK) fragments and inflammatory interleukins (ILs) in bone marrow (BM) aspirates of colorectal cancer (CRC) patients are expected to indicate presence of disseminated tumor cells (DTCs) and anticancer response of the host, respectively. The present study investigated the relations of CK18 fragment M65, IL6, IL8, and IL17A in BM samples to the presence of DTCs and prognosis. Place and Duration of Study: Department of Medicine (Medical Unit II) and Department of Surgery, Donauspital Vienna, between 2002 and July 2005. Methodology: BM aspirates were obtained immediately prior to and one and two years after tumor surgery, respectively, and M65 and cytokines were quantified by ELISA assays. Results: 16/66 patients revealed tumor-positive BM aspirates, and 10/46 evaluable patients relapsed within five years. M65 levels exhibited no relation to either positive biopsies, relapses or methylation status of O6-methyl guanine methyl transferase (MGMT). In contrast, IL17A concentrations of BM aspirates were elevated in non-relapsed versus relapsed, as well as MGMT-wildtype versus MGMT-methylated patients. Due to large individual variations, IL6 and IL8 levels of BM showed no significant differences for non-relapsed versus relapsed patients. Conclusion: M65 levels of BM samples of CRC patients exhibited no correlation with micrometastases or disease recurrence, respectively; however, patients who achieved disease-free survival revealed increases of IL17A in BM aspirates, possibly indicating immune response to tumor cells.
The study was undertaken to evaluate the possible role of Androgen Receptor (AR) in relation to tumor grade, age, sex and urinary bladder cancer risk. Expression of AR detected by immunohistochemistry in 125 Transitional Cell Carcinoma and 100 control cases. Expression of AR was noticed in 28.8% cases. AR increased with increasing tumor grade. Expression of AR was seen to be significantly higher in male in the age group ≥ 50 years (p < 0.05). AR expression was found to be associated significantly with the tumor grades, age and sex suggesting that AR may be used as prognostic markers in the treatment of urinary bladder carcinomas.
Paclitaxel (Ptx) is a taxane anticancer mitotic inhibitor, widely used in oncology for the last 20 years. Poor solubility of Ptx, as a consequence using of toxic solvents such as Cremofor EL, high affinity to P-glycoprotein are associated with serious side effects due to hypersensitivity reactions, low bioavailability and low therapeutic index. Development of new delivery solvent-free forms of Ptx is one of the key research problems in modern cancer chemotherapy. Ptx loaded into polylactic-co-glycolic acid (PLGA) nanoparticles (Ptx-PLGA-Nps) (size 200-300 nm) have been prepared using nanoprecipitation method. Impact of technological parameters on Ptx encapsulation efficacy and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Citotoxic activity and cell accumulation of nanosomal formulation of Ptx was studied on multiresistant cell line Jurkat WT (cells of human Ð¢-limphoblastic leucosis). Obtained results suggest that formulation of PLGA Ptx nanoparticles have above 90-98% drug encapsulation efficacy, higher cell accumulation and cytotoxic activity.
Aim: To evaluate the prevalence of symptoms of posttraumatic stress disorder (PTSD), depression and anxiety among children and adolescents exposed to the 2007 fire disaster in Greece along with the relationships of these symptoms with disaster-related stressors and sociodemographic characteristics four months after the fire. Methodology: A sample of 343 youths aged 9-18 years from schools in an area severely affected by the fire completed self-reported questionnaires. The Children’s Post-Traumatic Stress Disorder-Reaction Index-Revised (CPTSD-RI-R), the Children’s Depression Inventory (CDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were used to assess relative symptoms, while fire-related stressors were also examined in respondents. Results: The estimated prevalence rates of high levels of PTSD, depressive and anxiety symptoms four months after the disaster were approximately 45%, 34% and 32%, respectively. Staying without both parents after the fire was strongly associated with more PTSD symptoms, while housing adversity and loss of property were most strongly associated with elevated depressive symptoms. Life-threatening experience of a loved one and worry for a loved one predicted higher levels of PTSD symptomatology, whereas injury of a loved one was associated with high levels of depressive and anxiety symptoms. Conclusion: A significant proportion of children and adolescents exposed to 2007 Greek forest fires experienced mental health problems four months after the fire. Different types of stressors were associated with PTSD, depressive and anxiety symptoms. These findings highlight the importance of preventive and treatment mental health services in the aftermath of similar disasters.
Aims: To describe: 1) our cohort of patients diagnosed with NCPH in a HIV academic clinic in North America, and 2) longitudinal follow-up and outcomes of patients following NCPH diagnosis. Study design: Retrospective case series Place and Duration of Study: Owen clinic, University of California, San Diego, United States, between October 1990 and December 2010. Methodology: We describe a cohort of patients diagnosed with NCPH in a HIV academic clinic with emphasis on their follow-up and outcomes after NCPH diagnosis. Results: During the study period, eight HIV-infected men were diagnosed with NCPH. All patients were exposed to Didanosine (ddI) for a median of 37 months. One patient died soon after NCPH diagnosis due to a condition unrelated to NCPH. The other seven patients have received B-blocker therapy and annual esophago-gastro-duodenectomy screenings with banding of esophageal varices when indicated and remain still alive. Three patients were on ddI at the time of NCPH diagnosis. In one patient ddI was discontinued shortly after NCPH diagnosis. The other two patients continued to use ddI after NCPH diagnosis and developed recurrent upper gastrointestinal bleeding in the subsequent 2 years, requiring revascularization interventions. The four patients that were already off ddI at the time of NCPH diagnosis have been followed for a median of 6 years. These four patients remained minimally symptomatic for up to 16 years of follow-up from NCPH diagnosis. Conclusion: When ddI was discontinued before portal hypertension was clinically apparent the progression of NCPH appeared to subside without major clinical complications.
Aim: To determine the effects of a Mediterranean-style low-glycemic load diet alone or in combination with a medical food (MF) on insulin resistance and inflammation in women with metabolic syndrome (MetS). Study design: Two groups, Parallel study with control. Place and Duration of Study: Department of Nutritional Sciences, University of Connecticut, Storrs, CT; Department of Emergency Medicine, University of Florida, Jacksonville, FL; Department of Medicine, University of California, Irvine, CA. The study was carried out from September of 2009 to May 2010. Methodology: Eighty three women (20-75 y) with MetS. Participants were randomly allocated to consume diet alone (control group) or the diet plus the MF (MF group) for 12 wk. Body composition was measured at baseline, week 8 and week 12 by use of bioelectrical impedance in all participants while Dual-emission X-ray absorptiometry was used for 37 of the subjects. Insulin resistance, plasma insulin, leptin, adiponectin and the inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), adhesion molecules, sICAM-1 and sVCAM-1, were measured at the same time points. Results: Independent of group allocation, women had decreases in body mass index (p < 0.0001) and body and trunk fat (p < 0.0001). Plasma insulin, insulin resistance, and leptin were also significantly decreased over time (p < 0.0001), while plasma adiponectin levels did not change. Regarding inflammatory markers, significant reductions were found in TNF-α (p < 0.0001) and sICAM-1 levels (p < 0.001), but not in IL-6 or sVCAM-1. At 12 wk, sICAM was reduced only in the MF group (p<0.05 vs control). Conclusion: A Mediterranean-style diet, in combination with a MF, are a viable option to decrease factors associated with increased risk for type 2 diabetes and coronary heart disease.
Aims: To estimate the oxidant/antioxidant status in type 2 diabetic patients with retinopathy; and to correlate a number of independent variables (age, gender, education, body mass index, duration of diabetes, glycosylated haemoglobin, hypertension) to development of retinopathy. Study design: Case-control study. Place and Duration of Study: Research laboratories, Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University from April 2010 to April 2011. Methodology: One-hundred diabetic patients with retinopathy recruited from King Fahad Specialist Hospital- Buraidah were included in the study. The control groups were: control group 1 consisted of sixty type 2 diabetic patients without retinopathy recruited from Diabetes and Endocrinology Center, KFSH, Buraidah, KSA; and control group 2 consisted of sixty healthy "non diabetic subjects" recruited from public places, i.e. Estarahes (party lounges). Plasma, serum, and erythrocyte lysate were prepared from blood of each subject. Human serum 8-OHdG, plasma MDA, and erythrocyte lysate Cu-Zn SOD were estimated by using commercial kits supplied by Northwest, U.S.A. Data was analyzed using SPSS software and Win Episcope software. P- values < 0.05 were considered significant. Results: Age, education, duration of diabetes, poor glycaemic control, and hypertension were consistently associated with development of retinopathy (OR 5.891, 4.44, 10.420, 1.699, 1.820 respectively). Moreover, increased plasma MDA, increased serum 8-OHdG levels, decreased Cu-Zn SOD activity were observed in diabetic patients with retinopathy compared to subjects in control groups. In addition, negative correlations were found between plasma MDA and Cu-Zn SOD activity, HbA1c & Cu-Zn SOD activity as well in all subjects. Conclusion: This report emphasizes the important role of oxidative stress in the development of retinopathy in type 2 diabetes suggesting that blocking of oxidative stress is a crucial step for delayed progression of diabetic retinopathy and hence the need for antioxidant supplements to postpone the severity of diabetic retinopathy.
Objective: During aging, an ineffective perfusion of tissues/organs is a major risk factor for several diseases. Age-induced oxidative stress has been proposed to correlate with this age-related microvascular dysfunction including angiogenesis impairment. It has been demonstrated that exercise training could ameliorate oxidative damage, as well as, enhance angiogenesis in various organs. Therefore, the present study aims to investigate whether exercise training can prevent alterations of capillary vascularity in brain and bone during aging. Design and method: Male Wistar rats were divided into three groups: sedentary-young (aged 4-6 months), sedentary-aged (aged 20-22 months) and train-aged (aged 20-22 months). The exercise program included swimming training 5 days/week for 8 weeks. We directly observed microvasculature of brain and bone by using a laser scanning confocal microscopic system. The microvascular networks were visualized by fluorescein isothiocyanate labeled dextran and were analyzed for capillary vascularity by image analysis software. Blood was collected to determine the level of malondialdehyde, an indicator of oxidative stress. Results: In sedentary-aged group, the malondialdehyde level was significantly increased, whereas capillary vascularities in brain and bone were significantly decreased when compared to the sedentary-young group (P<0.05). In train-aged group, capillary vascularities in brain and bone were significantly higher, whereas the malondialdehyde level was significantly lower when compared to the sedentary-aged group (P<0.05). Besides, the result also showed a linear correlation between capillary vascularity and malondialdehyde level. Conclusion: The exercise training could attenuate age-induced suppression of capillary vascularity in brain and bone, closely related to exercise-ameliorated oxidative stress during aging.
Aims: This study was to investigate the cytotoxicity of both plant extracts from Ficus deltoidea (locally known as Mas Cotek), aqueous and ethanolic extracts on human ovarian carcinoma cells using standard colometric MTT assay. Study design: Cell based assay Place and Duration of Study: Institute of Bioproduct Development and Department of Bioprocess Engineering, Universiti Teknologi Malaysia, Johor Bahru, Malayisa between January 2007 and December 2009. Methodology: The biochemical responses of cells after plant sample treatment were observed and have been reported through several assays such as trypan blue exclusion assay for cell viability, analysis of glucose uptake and lactate release, cell survival evaluation and genomic assay through DNA fragmentation. Results: Both aqueous and ethanolic extracts of the plant sample gave IC50 value of 224.39 + 6.24 µg/ml and 143.03 ± 20.21 µg/ml, respectively. The detachment capability of the plant aqueous extract was observed in the cell viability assays. DNA fragmentation was not observed in the aqueous extract, but in ethanolic extract (1000 µg/ml). The DNA was fragmented around 200 Kbp. Morphological observation was carried out and apoptosis body was observed at 1000 µg/ml of both extract. Conclusion: A2780 cancer cells behaved differently on cell growth profile upon treating with different concentrations of the aquoues and ethanolic extracts of F. deltoidea. Even though both extracts could cause apoptosis at 1000 µg/ml, the aqueous extract prompted to promote cell detachment, and the ethanolic tried to inhibit cell proliferation through DNA fragmentation.
Aims: To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. Study design: Prospective study. Place and Duration of Study: Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. Methodology: We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock’s criteria. Results: Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. Conclusion: These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2).
Aims: Ovarian cancer has the highest mortality of any gynaecological malignancy; this is due to rapid peritoneal spread of tumour cells and neovascularization. Understanding the mechanisms underlying this is critical to developing early diagnostic or treatment strategies. We devised a pilot study to examine the role of γ-SYNUCLEIN (γ-SYN), oestrogen receptor (ER)α, and the splice variant ERαΔ3. Methodology: With ethical approval, ovarian tissue was collected from patients (n=24) undergoing oopherectomy for non-ovarian pathology or primary surgery for suspected ovarian cancer. Quantitative gene expression analysis was employed for γ-SYN, ERα, and ERαΔ3. To identify the in situ localization, immunofluorescence for γ-syn was carried out. Results: Ovarian tumour tissue exhibited an elevated expression of γ-SYN and high-grade tumours had an elevated ERαΔ3:ERα ratio compared with benign tissue. The majority of previous studies point to the γ-syn protein being present in epithelial cells of high-grade disease. Our study supports this, but additionally we conclusively identify its presence in the endothelial cells of vasculature surrounding low-grade disease; immunofluorescence was strongest in the apical cells surrounding the lumen. Conclusion: Our results demonstrate for the first time that there are readily-expressed levels of γ-SYN and ERαΔ3 in normal ovarian tissue and ovarian tumours. In high-grade disease, γ-syn and an elevated ERαΔ3:ERα ratio might confer metastatic potential to the tumourigenic cells and promote neoangiogenesis. Future in vitro studies might be necessary to delineate such a mechanism, which could potentially be the basis of early intervention.
Objectives: To facilitate early detection of chronic kidney disease, many organizations now recommend reflex reporting of estimated glomerular filtration rate (eGFR) whenever serum creatinine (Cr) is measured. To compare two widespread eGFR equations with creatinine clearance (CrCl) calculated through a timed urine collection. Methodology: Laboratory data of subjects’ ≥ 18 years tested for CrCl from October 2010 to December 2010 was retrieved from laboratory information system of Aga Khan University Hospital. Statistical comparison of eGFR using Cockcroft Gault (CG) and 4-variable Modification of Diet in Renal Disease (MDRD) formulae with CrCl was performed. Results: Six hundred and seventy subjects with CrCl were studied. Mean age of the group was 51 ±15 years, 55.7 % being males. Mean glomerular filtration rate using CrCl, MDRD and CG were 57.1 (±35.9), 57.8 (±33.6) and 68.7 (±41.5) ml/min respectively. Deming regression analysis generated MDRD = 5.23 + 0.92 (CrCl) and CG = 0.23 + 1.2 (CrCl) for comparison of CrCl results with those of MDRD and CG respectively. Comparing MDRD and CrCl, Bland Altman revealed acceptable agreement with a minimal bias of 0.65 ml/min. Conclusion: We suggest that automatic reporting of eGFR using MDRD can be implemented in clinical laboratories when serum Cr is reported.
Aims: Collagen induced arthritis in rats is an important model for human rheumatoid arthritis. This study was designed to improve and refine this model by use of infrared thermography by measuring surface temperature of hind feet. Our hypothesis is that the local temperature on the feet correlates with other clinical parameters such as clinical score and edema and may serve as a method for quantification of the degree of inflammation. Study design: Experimental animal study. Place and Duration of Study: Institute of Biomedicine, University of Aarhus, Denmark between February and March 2010. Methodology: Arthritis was induced with collagen immunization in sixteen Lewis rats. Four of the animals were treated with dexamethasone to function as negative controls. Clinical scores were based on the magnitude of paw edema. The mean temperature of the hind feet (region covering the metatarsus and tarsus) was normalized with a reference area on the back of the same rat. The temperature index were compared with the clinical score index, edema index, and bodyweight of the rats Results: The mean hind feet temperatures increased with increasing clinical severity in the acute stage of the disease. There were positive correlation between temperature and clinical scores.
Conclusion: The thermographic response appeared prior to the clinical signs, suggesting that thermography may be used as a predictive sign for the development of disease. This technique could be a non-invasive, objective, rapid, and reproducible method for evaluation of the degree of inflammation and effect of therapeutic interventions.
Rachele Fornari, Paolo Sgro, Emanuela Greco, Davide Francomano, Antonio Aversa, Mario Marini, Carla Lubrano, Chiara Marocco, Francesco Conti, Giovanni Spera, Luigi Di Luigi, Andrea Lenzi, Silvia Migliaccio
Aims: Osteogenesis imperfecta (OI) is a rare inherited disorder causing low bone density and increased fragility. Bisphosphonates (BP) are a treatment of choice for OI. Few studies have investigated the long-term effects of BP in OI patients. Thus, aim of our study was to follow up adults affected by OI to evaluate changes in metabolic, clinical situation and safety of long-term neridronic acid therapy, BP authorized for OI treatment. Study design: Longitudinal observational study. Place and duration of the Study: Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition. Year: 2004 - October 2010. Methodology: 68 patients underwent clinical examination, laboratory endocrine/ metabolic, pro-inflammatory cytokines screening, ECG at baseline and every 3 months and bone mineral density evaluation, by DEXA, once a year. Results: Skeletal evaluation showed a significant increase of BMD through follow up. Patients were evaluated for metabolic and cardiovascular risk factors, which were unmodified by long-term therapy. Conclusion: Long-term neridronic acid treatment increases bone density, does not alter metabolic parameters indicating that this therapy can be considered safe and a valid therapeutic option for OI patients.
Aims: To analyze various degrees of psychological status of ischemic stroke in the young population with different age, sex, degrees of education, injured regions and ways of medical expense payment. Study design: Cross-sectional study. Place and Duration of Study: Department of Neurology, People’s Hospital of Ningxia Hui Autonomous Region and Department of Rehabilitation, the Second Affiliated Hospital of Qingdao University Medical College, between March 2008 and March 2010. Methodology: We included 90 patients (58 men, 32 women; age range 21-45 years) with ischemic stroke. Psychological distress was evaluated with Symptom Distress Checklist (SCL-90, Chinese version). The 90 patients with ischemic stroke at the acute stage have completed the SCL-90 and the scores were analyzed statistically against the national Norm of China. Results: Compared with the national norm of China, there were great differences in almost all aspects such as depression, anxiety, somatization, phobia and psychoticism (P <0.01, P<0.001, respectively) except for obsessiveness-compulsiveness, hostility and paranoid ideation (P>0.05 respectively). Among 90 stroke patients, the occurrence of Depression/Anxiety was 39 (43.33%). Female patients took up 75%, while male for 25% (P<0.01). Education levels made no difference (P > 0.05). Different payments brought out marked differences; the occurrence of Depression/Anxiety was 29.2% for the group where the medical expense paid by medical insurance, but 66.7% paid at one’s own expense (P< 0.05). Different injured regions brought out marked difference in the psychological reaction (P< 0.05), the occurrence of Depression/Anxiety was 75% with bilateral hemispheres injures. Conclusion: The psychological reactions of the young to the ischemic stroke are depression, anxiety, somatization, interpersonal sensitivity, phobic anxiety, and psychoticism except for obsessive-compulsiveness, hostility and paranoid ideation. Ischemic stroke in the young of different sex, payment method and injured regions resulted in different psychological reactions.
A set of embryonic proteins - potential markers for ovarian tumors is presented. More than ten new embryonic proteins have been tested, but no one strictly specific protein marker for diagnosis of ovarian tumors has been revealed. SOVA-1 is the most perspective marker for today. The special attention is given to peculiarities of evolution and mechanisms of early distribution of the tumor process. The role of pregnancy and “pregnancy specific glycoprotein”- PSG as a way of the ovary tumor disease prevention is discussed. An attempt to realize sources and logic of the disease is undertaken in the present work.
This project investigated genomic epidemiology of congestive heart disease, the clinical and non-invasive techniques for diagnosis and the modifiable and non-modifiable risk factors associated with the disease were explored. Trends in the morbidity and mortality of CHD revealed an increase in the disease frequency with minor drop in its’ trajectory into the twenty-first century. While the modifiable risk factors were discussed with suitable interventions, the non-modifiable risk factors demand prompt medical diagnosis and treatment if any. The genes incriminated were listed. The relevance of pharmacogenomics cannot be overstated in the age of genomic medical science. But by far most important is the consumption of food items rich in phyto-nutrients to maximize public health and minimize the impact of dangerous lipids in our diet.
The incidence of obesity has significantly increased worldwide. Surgery has proven to be the most effective long-term treatment for sustained weight loss and improvement of co-morbidities in morbidly obese patients. Laparoscopic sleeve gastrectomy (LSG) is a relatively new procedure for weight loss with lower surgical risks, which is particularly suitable for those patients at highest risk for surgery, either because of their co-morbidities or their weight. LSG is being explored as a viable surgical option for treating morbid obesity, after simply being considered the first step of a staged procedure in super-obese/high-risk patients to allow some weight loss before a laparoscopic Roux-en-Y gastric bypass or biliopancreatic diversion-duodenal switch procedure. With the revelation that patients experience safe weight loss after LSG, interest in using this procedure as a bridge to more definite surgical procedures has risen. Outright reported benefits of LSG include the low rates of complications, the avoidance of foreign material, the maintenance of normal gastro-intestinal continuity, the absence of malabsorption, and the reduction of gherlin producing mass, accounting for its superiority to other restrictive bariatric surgical procedures. Although early results after LSG are promising in terms of short-term weight loss, more studies are required to evaluate the long-term durability of LSG especially effective weight loss, maintenance of weight loss, resolution of co-morbidities, and the potential of gastric tube dilatation with weight regain.
Retroviral vectors based upon the Moloney murine leukemia virus (MLV) have been used due to their high efficiency of stable gene transfer. Core binding factors (CBF) are heterodimeric transcription factors containing a DNA binding Runx 1, Runx 2, or Runx 3 subunit, along with a non DNA binding CBF subunit. All four subunits are required at one or more stages of hematopoiesis. This review describes the role of Runx1 and CBF ß in the initiation of hematopoiesis in the embryo, and in the emergence of hematopoietic stem cells. The core site in the Moloney murine leukemia virus (Moloney MLV) enhancer was previously shown to be an important determinant of the T-cell disease specificity of the virus. Mutation of the core site resulted in a significant shift in disease specificity of the Moloney virus from T-cell leukemia to erythro-leukemia. It has been shown that a protein that binds the core site, one of the core-binding factors is highly expressed in thymus and is essential for hematopoiesis in stem cells. Earlier studies suggest that CBF plays a critical role in mediating pathogenesis of Moloney MLV in vivo. Spontaneous leukemia was not observed either upon CBF expression, consistent with a model in which the increase in HSC and progenitor populations represents a pre-leukemic state, and additional mutations are required for progression to leukemia.
This review brings together and analyzes the problem of zinc effects on the body through apoptosis, also affecting the latest data in the study of process itself apoptosis. Also, the possibility of using zinc and its derivatives and its complexes in cancer treatment are discussed. The review also focuses on the biochemical problems that lead to various diseases occurring in conditions of excess or deficiency of intracellular zinc. Review includes more than 300 references and contains research over the past ~ 15 years, focusing on the latest data.
This project reviewed gene mutations which are associated with BRCA1 and BRCA2. From epidemiological perspective, the escalating cost of breast cancer management is due to the aging phenomenon of the female cohort in United States population. Innovative genomic sequencing techniques could continue to augment gene mutations beside the BRCA1/BRCA2 and TP53, PTEN, ST11/LKB1, CDH1, CHEK2, and ATM among others. To reduce the escalating cost of breast cancer management, the application of pharmacogenomic techniques, use of electronic health record and the most appropriate software could be applied for both primary prevention and chemoprevention. Physicians and other clinicians must hone their skills in advanced Mendelian genetics to become proficient in using statistical risk analysis and the appropriate IT software to recommend primary prevention to at risk breast cancer patients.
Aims: There is considerable interest in the potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the management of musculoskeletal injuries. This review aims to summarise the information in the literature on the evolving role of these cells in the management of these complex heterogenous injuries. Study design: Review Article. Place and Duration of Study: University College London Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, Middlesex, HA7 4LP, United Kingdom. Methodology: We reviewed the literature to identify studies on the use of BM-MSCs for the management of musculoskeletal injuries. Results: There is an increasing and encouraging body of evidence to suggest that BM-MSCs have a significant role in the management of musculoskeletal injuries involving muscles, tendons, ligaments, bone, cartilage, menisci and nervous tissue. Conclusion: Several characteristics of BM-MSCs make them ideal candidates in managing musculoskeletal injuries. Bone marrow is easy to obtain requiring minimal donor site morbidity, invasiveness and anaesthetic. Their autologous nature eliminates the issue of immunoreactions and ethical problems. The majority of studies in the literature however use small animal models, and further work in larger animals and ultimately ethically approved clinical trials should be explored before any significant clinical relevance can be assessed.
Aims: Cartilage is frequently damaged through injury and disease but shows little or no capacity for repair. Injuries that extend to the subchondral level show some capacity for repair due to the release of bone marrow derived mesenchymal stem cells. Focal articular cartilage defects are challenging clinical problems that may progress to more generalised lesions. We reviewed the literature to analyse the results of available non-cell-based and cell-based strategies for the repair of articular cartilage defects in the knee. Study design: Review Article Place and Duration of Study: University College London Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, Middlesex, HA7 4LP, United Kingdom Methodology: We reviewed the literature to identify studies on the use of non-cell-based and cell-based strategies for the repair of articular cartilage defects in the knee. Results: Repair techniques that do not utilise cell therapy include bone marrow stimulating techniques such as microfracture that is effective in small well-contained lesions and has the advantages of being performed arthroscopically as a single stage and cheaper costs compared to cell-based therapies. It also associated with no donor site morbidity unlike mosaicplasty, and perichondrial or periosteal grafting. The evidence suggests that none of the techniques described above consistently produce durable results. There are encouraging mid-term results with Autologous Matrix Induced Chondrogenesis (AMIC) procedures in small number of patients. Although microfracture is appropriate for smaller cartilage defects, Autologous Chondrocyte Implantation (ACI) and Matrix-carried Autologous Chondrocyte Implantation (MACI), as well as other cell carrier systems, are currently used to treat larger full thickness chondral defects in the knee. Although the results are fairly similar, MACI and procedures using other cell carrier systems are amenable to be performed arthroscopically or through a more limited approach. There are a small number of studies using mesenchymal stem cells with promising early results bur further in vitro and in vivo studies are needed before this treatment becomes more routinely available. Conclusion: Focal articular cartilage defects are challenging clinical problems that progress to more generalised lesions. Only cartilage injuries that extend to the subchondral level show some capacity for repair due to the release of bone marrow derived mesenchymal stem cells. Bone marrow stimulating techniques such as microfracture are effective in small well-contained lesions (<2cm2) and have the advantages of being performed arthroscopically as a single stage and cheaper costs compared to cell-based therapies. Mosaicplasty, and perichondrial or periosteal grafting are associated with donor site morbidity. Longer term studies on AMIC may help define the role for this procedure. The best form of non-cell-based treatment for focal articular cartilage defects in the long term is still unknown. ACI and MACI, as well as other cell carrier systems, are currently used in clinical practice to treat larger full thickness chondral defects in the knee. There are a small number of studies using mesenchymal stem cells and further in vitro and in vivo studies are needed before this treatment is optimised.
Two decades of intensive but quite chaotic and decentralized population studies on susceptibility to Graves’ disease (GD) provided a bulk of inconsistent data resulted in finding of proven association only for the HLA class II region that exerts a major effect in the genetics of GD. Using low-resolution microsatellite-based human genome-wide scans revealed several regions of linkage harboring putative susceptibility variants. Further, high throughput genotyping of large population cohorts with help of high dense panels of single nucleotide polymorphisms (SNPs) and application of advanced tools for analysis of extended blocks of linkage disequilibrium within a candidate gene (SNP tagging, etc.) revealed the presence of several susceptibility genes in the regions of linkage on chromosome 2q (CTLA-4), 8q (Tg), 14q (TSHR), 20q (CD40), 5q (SCGB3A2/UGRP1) and, probably, Xp (FOXP3). The list of GD-predisposing loci was then extended with three more genes (PTPN22, IL2RA/CD25, and FCRL3). In the nearest future, implementation of even more robust technology such as whole-genome sequencing is expected to catch any disease-associated genetic variation in the patient’s individual DNA. In this review, the historical development of our knowledge on genetic factors predisposing to GD is considered, with special emphasis on the functional significance of observed associations and discussion of possible mechanisms of their contribution to GD pathogenesis.
Aims: Musculoskeletal injuries are a common injury associated with a reduction in quality of life, increased morbidity and social and financial implications. Although surgical reconstruction is a well established option, outcomes are variable. There is a growing body of interest in the potential of mesenchymal stem cells (MSCs) in the management of tendon and ligament injuries. This review aims to summarise the information in the literature on the evolving role of these. Study design: Review Article. Place and Duration of Study: University College London Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, Middlesex, HA7 4LP, United Kingdom. Methodology: We reviewed the literature to identify studies on the use of MSCs for the management of tendon and ligament injuries Results: There is an increasing and encouraging body of evidence to suggest that MSCs have a significant role in the management of musculoskeletal injuries involving tendons and ligaments. They not only appear to promote healing but can be adapted to have further benefits such as osteointegration at the tendon-bone interfaces. Conclusion: MSCs appear to provide an encouraging treatment option for the treatment, repair and augmentation of tendon and ligament injuries. Their autologous nature make them a safe and viable option, however more studies are needed to evaluate their future role.