Institutional research evaluation model [IREM]: a framework for measuring organizational research trends and impact and its application in medical academia in Saudi Arabia

Increased financial and human resource constraints for research and development [RandD] imply rigorous research evaluation to guide the research policy for wise allocation of resources. In this study, we developed a conceptual framework called the ''Institutional Research Evaluation Model" [IREM] to evaluate the quality of research and its determinants. The IREM was then applied to a medical institution to study its applicability in Saudi Arabia. The IREM consists of five levels: duration decision; choice of research quality indicators [impact factor [IF], article influence scores [AIS], citations per paper [CPP], and publication in indexed journal]; trend indicators [numbers of publications, study design, subject]; data extraction; and statistical techniques to determine the factors affecting impact of research. Application of the IREM to the College of Medicine, King Saud University [CMKSU] for research evaluation from 2003 to 2013 revealed that during this duration, 1722 studies were published, the highest in 2013 [n = 314] and 85.5% [n = 1472] in indexed journals [p < 0.001]. The mean IF was 2.6, mean AIS 1.16, and mean CPP 10.06. IF was positively associated with duration, indexation, CPP, and subject being human genetics at multivariable linear regression. The IREM is an applicable basic tool for institutional research evaluation which can guide the research policy

Epidemiological, clinical, and biochemical characteristics of Saudi patients with nonalcoholic fatty liver disease: a hospital-based study

The estimated prevalence of nonalcoholic fatty liver disease [NAFLD] in Saudi Arabia is 7% to 10%. Despite the high prevalence of risk factors including diabetes, obesity, and hyperlipidemia, no recent epidemiological studies have measured the disease burden. We aimed to determine the characteristics of Saudi NAFLD patients attending a university hospital, and study factors affecting alanine aminotransferase [ALT] levels. A prospective study among patients referred for ultrasonography in King Khalid University Hospital in Riyadh, Saudi Arabia from February to May 2009. NAFLD was defined as an appearance of fatty liver on routine abdominal ultrasound in the absence of coexisting liver disease and alcohol consumption. Patients were classified into normal and high ALT [ALT >60 U/L] level groups for analysis. The prevalence of NAFLD was 16.6% [218/1312]. Patients with normal ALT had the mean [SD] age of 45.9 [10.6] years and the mean body mass index of 34.5 [7.9] kg/m2. Forty percent of the 151 patients with normal ALT had diabetes, 66.2% were obese, and 29.1% had hypertension. Forty-three patients [23%] had high ALT levels. These patients had significantly lower age [P=.003] and fasting blood sugar [P=.03] than the normal ALT group. Non-diabetic patients [odds ratio 0.30, 95% CI 0.1-0.8], men [female OR 0.23, 95% CI 0.1-0.5], lower cholesterol [P=.001], high-density lipoprotein [P=.006], and low-density lipoprotein [P=.008] levels were more likely to be observed among patients with high ALT levels. In a multivariate analysis, younger age [OR 0.96, 95% CI 0.93-0.99], being male [OR 0.23, 95% CI 0.09-0.57], and a lower cholesterol level [OR 0.55, 95% CI 0.37-0.82] were significant predictors of high ALT levels. Based on the high prevalence of obesity and diabetes, the prevalence of NAFLD will continue to be high, unless awareness is inculcated among the local population

Recurrence of hepatitis C virus genotype-4 infection following orthotopic liver transplantation: natural history and predictors of outcome

There are few reports on hepatitis C virus genotype 4 [HCV-4] recurrences after orthotopic liver transplantation [OLT]. Therefore, we undertook a study to determine the epidemiological, clinical and virological characteristics of patients with biopsy-proven recurrent HCV infection and analyzed the factors that influence recurrent disease severity. We also compared disease recurrence and outcomes between HCV-4 and other genotypes. All patients who underwent OLT [locally or abroad] for HCV related hepatic cir-rhosis from 1991 to 2006 and had recurrent HCV infection were identified. Clinical, laboratory and pathological data before and after OLT were collected and analyzed. Of 116 patients who underwent OLT for hepatitis C, 46 [39.7%] patients satisfied the criteria of recur-rent hepatitis C. Twenty-nine [63%] patients were infected with HCV genotype 4. Mean [SD] for age was 54.9 [10.9] years. Nineteen of the HCV genotype 4 patients [65.5%] were males, 21 [72.4%] received deceased donor grafts, and 7 [24.1%] developed >1 acute rejection episodes. Pathologically, 7 [24.1%] and 4 [13.8%] patients had inflammation grade 3-4 and fibrosis stage 3-4, respectively. Follow-up biopsy in 9 [31%] HCV genotype 4 patients showed stable, worse and improved fibrosis stage in 5, 2 and 2 patients, respectively. Of the 7 patients in the recurrent HCV group who died, 6 were infected with genotype 4 and 4 of them died of HCV-related disease. This analysis suggests that HCV recurrence following OLT in HCV-4 patients is not significantly different from its recurrence for other genotypes

Experience with 122 consecutive liver transplant procedures at king Faisal specialist hospital and research center

Saudi Arabia is a leading country in the Middle East in the field of deceased-donor liver transplantation [DDLT] and living-donor liver transplantation [LDLT]. We present out experience with DDLT and LDLT at King Faisal Specialist Hospital and Research Center [KFSHRC] for the period from April 2001 to January 2007. We performed 122 LT procedures [77 DDLTs and 45 LDLTs] in 118 patients [4 re-transplants] during this period of time. The number of adult and pediatric procedures was 107 and 11, respectively. The overall male/female ratio was 66/52 and the median age of patients was 43 years [range, 2-63 years]. In the DDLT group, the median operating time was 8 hours [range, 4-19], the median blood transfusion was 6 units [range, 0-40], and the median hospital stay was 13 days [range, 6-183]. In the DDLT group, after a mean follow-up period of 760 days [range, 2-2085], the overall patient and graft survival rate was 86%. In the LDLT group, the median opera ting time was 11 hours [range, 7-17], the median blood transfusion was 4 units [range, 0-65], and the median hospital stay was 15 days [range, 7-127]. In the LDLT group, and after a mean follow-up period of 685 days [range, 26-1540], the overall patient and graft survival rates were 90% and 80%, respectively with no significant difference in patient and graft survivals between groups. Biliary complications were significantly higher in LDLT compared to DOLT [P<0.05]. Vascular complications were also significantly higher in LDLT compared DDLT [P<0. 05]. Both DDLT and LDLT are being successfully performed at KFSHRC with early experience indicating a higher rate of biliary and vascular complications in the LDLT group

Effect of peritoneal dialysis and hemodialysis on oxidation end products in end stage renal disease patients

Chronic renal failure [CRF] is a worldwide public health problem. It is a progressive disease characterized by gradual and persistant impairment of both glomrerular filtration and tubular functions, so the kidneys are no longer able to keep normal internal environment. Oxidative and carbonyl stresses are considered among the mechanisms involved in the pathogenesis of CRF. Oxidative stress is known as imbalance between reactive oxygen species and antioxidants in favour of the former, while carbonyl stress is characterized as an overload of reactive carbonyl compounds [RCOs]. Both oxidative stress and carbonyl stress can cause damage to important biological structures e.g. proteins, carbohydrates, lipids, and nucleic acids resulting in the generation of new compounds and modified structures which can serve as markers of these mechanisms such as advanced glycation end products [AGEs] and advanced oxidation protein products [AOPPs]. AOPPs are proteins, predominantly albumin and its aggregates, that are damaged by oxidative stress. The present work aimed to study the effects of two different renal replacement modalities, peritoneal dialysis [PD] and hemodialysis [HD], on oxidation products of glucose, lipids, and proteins in patients with end stage renal disease [ESRD.] It also aimed at studying the effects of these therapies on the antioxidant defenses of these patients. The present study was conducted on 20 patients with ESRD. Patients were divided into two groups; group I consisted of 10 patients maintained on continuous intermittent peritoneal dialysis [PD] thrice weekly, and group II consisted of 10 patients maintained on bicarbonate hemodialysis [HD] thrice weekly. 10 healthy volunteers of matched age and sex served as a control group. All patients and control subjects were subjected to the following investigations; serum malondialdehyde [MDA] serum AOPPs, blood glutathione [GSH], erythrocyte glutathione peroxidase [GPx] and superoxide dismutase [SOD] activities, plasma vitamins A and C, serum vitamin E and beta carotene. For all patients, these markers were measured before the start of dialysis and 4 weeks after the first dialysis session. For control volunteers, these markers were measured only once. There was significant increase in the predialysis values of MDA and AOPPs when all ESRD patients were compared with the control group. There was also significant decrease in the predialysis values of GSH, GPx, SOD, vitamins A, E, and C, and beta carotene when all ESRD patients were compared with the control group. There was significant increase in the postdialysis values of MDA and AOPPs and significant decrease in the postdialysis values of GSH, GPx, SOD, vitamins A, E, and C, and beta carotene compared to their corresponding predialysis values in both PD and HD groups. There was no significant percentage change in all studied markers between PD and HD except GPx and vitamin C where the percentage change was significant. This study also revealed significant positive correlation between serum levels of MDA and AOPPs and significant negative correlation between each of them in one hand and all the antioxidant markers except for vitamin E in the post dialysis phase in the other hand. It is concluded that both PD and HD therapies, as practiced currently, are associated with increased oxidative stress. AOPPs are new uremic toxins that appear to be important components in the complex pathophysiology of oxidative stress and inflammation and therefore should be taken as a potential target to interrupt the vicious circle of oxidation and inflammation in uremia. AOPPs can be also used as a marker of oxidative stress. Prevention of oxidative stress in dialysis patients might focus on improving the biocompatibility of the dialysis system and supplementation of deficient patients with antioxidants

Study of islet cell autoantibodies in serum of siblings of type 1 diabetics

Type 1 diabetes is an autoimmune disease that accounts for approximately 15% of the diabetic population. The pathogenesis of Type 1 diabetes could be divided into six stages. Stage I is genetic susceptibility which requires the presence of a triggering event [stage Il] that initiate the development of autoimmunity [stage Ill] which is characterized by lymphocytic infiltration of the islet cells and production of anti-islet autoantibodies e.g. islet cell cytoplasmic autoantibodies [ICCA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], and autoantibodies against irisulinoma-associated-2 autoantigen [IA-2A]. In stage IV, there is progressive loss of insulin secretion despite normal blood glucose level. Stage V develops when overt diabetes is first recognized. In stage VI, there is complete beta cell destruction. Since the clinical onset of Type 1 diabetes does not occur until 80-90% of the insulin-producing pancreatic beta cells have been destroyed, this prediabetic stage may last for a long time during which the immunologic disease markers are present and measurable. The present study aimed to determine the prevalence of the islet cell autoantibodies in siblings of type I diabetics for the presence of islet autoantibodies in an attempt to allow the opportunity for prediction and/or the prevention the clinical onset of the disease. 108 healthy siblings of Type 1 diabetic children [group I] and 100 healthy control subjects [group II] of matched age and sex were enrolled in the present study. IAA, GADA, and IA-2A autoantibodies were assayed in serum of all subjects by radioimmunoassay. Eight of the control subjects had autoantibodies in their sera which were of the IAA type only. In siblings of Type 1 diabetic children, the prevalence of GADA seropositivity showed the highest percentage [25%], followed by IAA [14.81%], then IA-2A [2.78%]. There was significant association between the brotherhood to Type 1 diabetic children and the presence of GADA alone [i.e. no concomitance with any other autoantibody], total GADA [GADA alone and in combination with other autoantibodies], and GADA+IAA [P=0.000, 0.000, and 0.018 respectively]. IAA+GADA+IA-2A or for IAA+lA-2A combinations were not detected in sera of siblings of Type 1 diabetic children. None of the siblings of Type 1 diabetics had lA-2A autoantibodies alone in the serum. From the present results it could be concluded that some degree of islet cell autoimmunity might develop in siblings of type 1 diabetic children as evidenced by the significant association between the presence of GADA or GADA+IAA and the brotherhood to type 1 diabetics. The present results also revealed that GADA is the most frequent autoantibody in serum of siblings of type 1 diabetics. They also showed that the presence of GADA per se conferred the highest significant association with the brotherhood to Type I diabetic children. However, a larger prospective study is recommended to ascertain the importance of the assay of these immunologic markers for the prediction and possible prevention of type 1 diabetes in individuals at risk e.g. sibling, parents, and offspring of Type 1 diabetics

Study of the relationship between adiponectin, myeloperoxidase enzyme activity and severity of coronary artery disease

The aim of the present work was to study the possible relationships between each of plasma adiponectin level, myeloperoxidase [MPO] activity, serum nitric oxide [NO] metabolites and the occurrence and the severity of coronary atherosclerosis. It also aimed to detect potential interaction among these factors and to find if there is relationship between these factors and some of the traditional CAD risk factors. In order to achieve this goal, 48 male subjects were evaluated and divided into 4 groups who had coronary angiography to evaluate the severity of coronary atherosclerosis if present; group I consisted of 12 CAD patients with single vessel disease, group II consisted of 12 CAD patients with double vessel disease, group III consisted of 12 CAD patients with multivessel disease, and group IV [control group] consisted of 12 individuals of matched age and sex presented with chest pain with normal coronary angiography. Following proper selection of patients and control subjects, the following laboratory tests were performed for all of them: determination of plasma adiponectin concentration, estimation of MPO activity, determination of serum NO metabolites concentrations [nitrite / nitrate] and determination of serum lipids concentration [total cholesterol, triglycerides [TG], high density lipoprotein-cholesterol [HDL-ch], and low density lipoprotein-cholesterol [LDL-ch]]. The result of the present study showed significant association between the occurrence of CAD and each of low adiponectin level, high MPO activity, low nitrite level, low nitrate level, high total cholesterol level, high TG level, high LDL-ch level, low HDL-ch level and high LDL/HDL-ch ratio. They may all be regarded as predictors or risk factors for CAD. Furthermore, adiponectin, MPO activity, nitrite, total cholesterol, LDL-ch and LDLJHDL-ch ratio were the factors that affected the severity of coronary atherosclerosis. Significant correlation was found between low adiponectin level and atherogenic lipid profile. Moreover, the present study showed significant decrease in adiponectin level in hypertensive and cigarette smoking CAD patients compared to normotensive and non cigarette smoking CAD patients suggesting that low adiponectin level might interact with these traditional risk factors to induce oxidative stress and endothelial dysfunction, thereby promoting atherosclerosis. Furthermore, significant correlation was found between high MPO activity and each of cigarette smoking and atherogenic lipid profile in CAD patients suggesting a possible interaction between MPO and these risk factors to induce and promote oxidative stress and vascular inflammatory process in coronary atherosclerosis. However, there was no significant correlation between MPO activity and hypertension. Another point of interest in the results of the present study was the significant correlation of both low adiponectin level and high MPO activity with NO metabolites [nitrite / nitrate] level. Such correlation suggests that NO could be a link parameter and a common mediator for the action of adiponectin and MPO activity. The latter result highlights the importance of NO as both diagnostic tool and therapeutic target in atherosclerosis. The present study supports the hypothesis that endothelial dysfunction, vascular inflammation, and oxidative stress are primary interacting mediators in the pathogenesis of coronary atherosclerosis. It also highlights the importance of adiponectin as a marker for the presence and extent of CAD. MPO might serve as a marker of a general capacity for oxidative damage to the vasculature rather than functioning solely through direct consumption of NO. Furthermore, NO can act as a predictor of CAD severity, a mediator of coronary atherosclerosis and a common mediator of the action of adeponectin and MPO

Biochemical study of duchenne muscle dystrophy

The present work aimed to study dystrophin gene mutations in DMD patients and to investigate some of the biochemical mechanisms that might be involved in the pathogenesis of muscle wasting in this disease. The present study was conducted on 40 male subjects divided into two groups: Group 1: included 30 patients with the firm diagnosis of DMD as confirmed by negative immunohistochemical staining of muscle biopsies for dystrophin protein. Group 2 included 10 healthy male volunteers of matched age. All individuals were subjected to measurements of serum creatine kinase [CK], RANTES, and MDA. A soleus muscle biopsy was taken from every individual and was subjected to measurement of intracellular Ca[2+]concentration [[Ca2+]i], and assays of PLA[2], calpain, calpastatin, and caspase-3 activities in muscle tissue homogenates. DNA was extracted from peripheral blood leukocytes and exons 19, 44, and 50 were amplified by isolated polymerase chain reaction [PCR] technique. The amplified exons were then subjected to agarose gel electrophoresis for detection of exon mutations. The present study showed that 7/30 of the DMD patients had mutations in the form of exon deletions. Exon 50 showed the highest frequency of deletions [4/30]. The study also showed that 5/30 of the patients had deletions of only one exon, whereas 2/30 of them had combined 2 exon deletions. None of the patients had combined 3 exon deletions. The present study also revealed significant increase in serum levels of CK, RANTES, and MDA in DMD patients as compared to the control. It also revealed significant increase in soleus muscle [Ca2+]i], in the activities of PLA[2], calpain, and caspase-3 in muscle tissue homogenates, and in the ratio of calpain/calpastatin activities in the DMD patients as compared to the control group. On the contrary, this study showed a significant decrease in calpastatin activity in DMD patients in comparison to the control group. From the present work it could be concluded that DMD is a complex disease and that dystrophin deficiency is necessary, but not sufficient on its own to fully account for the pathophysiology of the disease which entails the interplay of several factors and mechanisms. Accordingly, secondary modifiers must play an important role in determining the ultimate fate of dystrophin-deficient fibers e.g. cytosolic calcium overload, increased activities of PLA[2] and of the calpain system, and enhanced oxidative stress and apoptosis. Moreover, the inflammatory response within the diseased muscle is one likely candidate among potential disease-modifying factors. Therefore, although there is currently no effective therapy for this fatal muscle disease, various strategies should be developed driven by the increasing understanding of the molecular mechanisms involved in the progression of muscle wasting. These strategies should include the use of membrane stabilizing agents, Ca[2+] channel blockers, PLA[2] inhibitors, calpain inhibitors, anticaspases, and ROS scavengers