[Show abstract][Hide abstract] ABSTRACT: Problem
To check whether there is a relationship between stem cell transplantations of malignant and non malignant hematological diseases with HLA disparity as source of complication and rejection.
Over the last decade, we have seen a significant increase in the use of umbilical cord blood (UCB) as a source of hematopoietic stem cells (HSCs) for allogeneic transplantation. Though UCB transplantation (UCBT) is widely used to treat malignant and non-malignant diseases, the spectrum of success
has been varied with geographical boundaries. Currently there are 7 million registered donors typed for HLA-A, HLA-B, and HLA-DR available through marrow donor registries around the world, while more than 30% of patients requiring transplant therapy are still unable to find a donor. For individuals receiving unrelated donor marrow, a single major or minor HLA disparity has clearly shown to increase the risk of treatment-related mortality (TRM).
In the current study we have tried to figure out what percent of stake does successful UCBT really takes in hematological transplantable diseases and individually, whether a comparison could be established on the success rate of UCBT in malignant and non-malignant diseases.
Since we were aiming for global figure, therefore we restrained form retrospective single hospital based analysis. Methodologies included data mining,
analysis of reviews and original articles. Further the study design included only diseases with well-established transplant therapy.
• Sickle cell disease
Congenital or Acquired
• Aplastic anemia,
Primary Immunodeficiency Diseases (PIDs)
• Chronic Granulomatous Disease,
• Wiskott–Aldrich syndrome (WAS)
Inherited Metabolic Disorders (IMDs)
• Acute lymphocytic leukemia (ALL)
• Acute myeloid leukemia (AML)
• Chronic lymphocytic leukemia (CLL)
• Chronic myeloid leukemia (CML)
• Hodgkin's lymphomas
• Non-Hodgkin's lymphomas
• Multiple Myeloma (MM)
The myelodysplastic syndromes (MDS)
[Show abstract][Hide abstract] ABSTRACT: Problem
There is significant growth on the diseases that can be treated by cord blood stem cells. In middle east especially in Saudi Arabia, there are two cord blood banks, however there has not been any representation from southern region . We do not have a cord blood bank or feasibility of one such bank in the high altitudes of the southern region. In the current study we have explored the possibility of the cord blood units and stem cells from high altitudes for the quality and feasibility to bank on the hills of Asser regions. Further there has not been a single point information available on the necessity of the cord blood banks in these regions.
Southern Saudi Arabia is the wide region within the peninsula with approximately entire south eastern part covered with harsh inhabitable desert. The south western part is mountainous region covered with scanty vegetation and comprises some of the highest part of elevation in the entire kingdom. The concept of cord blood either public or private is comparatively new and there are currently two public cord blood banks located in the Riyadh region. In the current study we investigated the scope and feasibility of the cord blood bank in Aseer region where the elevations reach up to 2200m above the sea level.
Aseer and adjoining mountainous region in the southern part of KSA has been long known for low oxygen tension. While the populations have been adjusted to live in such environment, most cases of cerebral palsy and developmental disorders are reported from this region. We investigated the quality of the stem cells on par with blast formation and differentiation capability and check whether the natural hypoxia prevailing would affect the functional aspects of the progenitor cells.
We collected initially about 40 UCB samples from normal and cesarean cases after due consent. The blood was collected in ACD sampler immediately after placental delivery by gravity feed. The samples were processed on the same day the mononuclear cells phenotypes were cryofreezed. The cells were
then investigated for proliferation, blast formation and differentiation assessment and analyzed.
Hematopoiesis occurs via proliferation and differentiation of a small number of pluripotent stem cells into progressively restricted progenitors populations and ultimately into terminally differentiated cells. During this process there are large numbers of maternal/neonatal and environmental factors which can affect these processes and there by result in neonatal disease or growth disorders. In the current study we investigated a natural hypoxia condition which can grossly affect the proliferation, differentiation of the progenitor cells. The results of the in-vitro assay to enumerate differentiation into various hematopoietic cellular lineages such as CFU-E, BFU-E, CFU-GM and CFU-GEMM were comparable with the samples collected along the side of the sea level (Control samples). The differentiation of the HPC’s to neuronal and chondrogenic lineages were consistent with control samples while few samples showed delayed differentiation. Colony forming unit assay was performed for hematopoietic stem cells after brief cryostorage. The results of the current study were comparable with samples from sea level. However we do find a delay in differentiation in some high altitude samples. Since the sample size was small, we need more samples to decide whether the delays in differentiation in few samples are due to factors such as natural hypoxia or any other storage or procession
[Show abstract][Hide abstract] ABSTRACT: Problem
In the last decade, there was a huge growth of public and private cord blood banks globally with a new emphasis on banking of umbilical cord lining, cord blood mesenchymal cells, menstrual blood etc. In reality how much of these cells are going to be useful for organ regeneration? and currently what is the success rate of organ regeneration using progenitor stem cells?
For the past four decades the umbilical cord blood as the source of hematopoietic progenitor cells is used in transplantation. There have been many private and public umbilical cord blood banks all around the globe with increasing promise to cure the incurable. In recent years a huge emphasis had been given by many private cord blood banks to preserve their, umbilical cord, placental derived progenitor (stromal/endothelial) cells. In some studies, even the foreskin fibroblast derived progenitors after circumcision, progenitors from the menstrual blood, liposuction derived mesenchymal cells are subjects of the storage, yet a fully approved clinical grade or a condition needs to be identified. In all these cases though there are numerous animal, and
few humanized studies pertaining especially to cardiac, islet, liver or brain regenerations, the results of these controlled studies are as usual varied. We do
not know how much an individual in his life time with the current speed of medical advancement will tend to use his stored stem cells from other sources. Therefore in the present study, we investigated the literature approximately for a decade to categorize the use of progenitor stem cells from other sources other than Bone marrow, cord blood and peripheral blood mobilized hematopoietic cells used in the organ regenerations.
We intended to know the success rate of organ regeneration using the progenitor stem cells from sources like, umbilical cord lining, placenta, menstrual
blood, foreskin induced stem cells and liposuction mesenchymal stem cells. We searched and analyzed the literature for three important and well-studied
organ failure models like cardiac (CVD), islet regeneration (T1DM), and neuronal regeneration (ALS/Stroke).
Based on the hypothetical questions raised, we investigated three organ regenerative models exhaustively researched by various basic and biomedical
science groups. We searched for a decade though these areas of the organ regenerations especially heart and islets are one of the oldest areas that have
been investigated. Most well cited papers were scrutinized and analyzed for results on the basis of;
1. Source of stem cells,
2. Route of administration,
3. Success of regeneration
4. Whether tried at multiple studies or centers
5. Number of animal studies that was extrapolated to human trials
6. Comparative enumeration of one source of progenitors with other cells
7. Studies with negative impact over successful studies
Though there are varied observations on the effectiveness of stem cells on the regeneration of the organs, most of the studies or reviews are focused on selecting the best source of progenitor cells. This is as far as cardiac regeneration is considered. In the treatment of diabetes, the studies bifurcate as either direct transplantation of the progenitor cells such as mesenchymal origin or differentiate into insulin producing pancreatic β−cells. Though both
groups of these studies claim exact reversal of diabetes in rat and mouse model, we do not know the long term outcome in non-human primates or clinical trials. The use of cord blood hematopoietic cells and mesenchymal progenitors were cited in the most of neuronal regeneration studies. The use of umbilical cord blood stem cells and mesenchymal stem cells were prominently used.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease (CVD) is among the most major causes of morbidity and mortality worldwide. Great progress has been made in the management of CVD which has been influenced by the use of experimental animal models. These models provided information at cellular and molecular levels and allowed the development of treatment strategies. CVD models have been developed in many species, including large animals (e.g. pigs and dogs) and small animals (e.g. rats and mice). Although, no model can solely reproduce clinical HF, simulations of heart failure (HF) are available to experimentally tackle certain queries not easily resolved in humans. Induced HF may also be produced experimentally through myocardial infarction (MI), pressure loading, or volume loading. Volume loading is useful to look at hormone and electrolyte disturbances, while pressure loading models is helpful to study ventricular hypertrophy, cellular imbalance and vascular changes in HF. Coronary heart disease is assessed in MI animal models. In this review we describe various experimental models used to study the pathophysiology of HF.
Full-text · Article · Feb 2015 · Current Vascular Pharmacology
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To produce an effective recombinant streptokinase (rSK) from pathogenic Streptococcus pyogenes isolate in yeast, and evaluate its potential for thrombolytic therapy.
METHODS: This study was conducted from November 2012 to December 2013 at King Khalid University, Abha, Kingdom of Saudi Arabia (KSA). Throat swabs collected from 45 pharyngitis patients in Asser Central Hospital, Abha, KSA were used to isolate Streptococcus pyogenes. The bacterial DNA was used for amplification of the streptokinase gene (1200 bp). The gene was cloned and in vitro transcribed in an eukaryotic expression vector that was transformed into yeast Pichia pastoris SMD1168, and the rSK protein was purified and tested for its thrombolytic activity.
RESULTS: The Streptococcus pyogenes strain was isolated and its DNA nucleotide sequence revealed similarity to other Streptococcus pyogenes in the Gene bank. Sequencing of the amplified gene based on DNA nucleotide sequence revealed a SK gene closely related to other SK genes in the Gene bank. However, based on deduced amino acids sequence, the gene formed a separate cluster different from clusters formed by other examined genes, suggesting a new bacterial isolate and accordingly a new gene. The purified protein showed 82% clot lysis compared to a commercial SK (81%) at an enzyme concentration of 2000 U/ml.
CONCLUSION: The present yeast rSK showed similar thrombolytic activity in vitro as that of a commercial SK, suggesting its potential for thrombolytic therapy and large scale production.
Full-text · Article · Dec 2014 · Saudi medical journal
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular manifestations are one of the major complications of type 1 diabetes mellitus (T1DM) and supersede the slow progression of DM in most cases as the leading cause of mortality. There have been many studies and trials in regenerating the functional β-cells of islets from mesenchymal stem cells (MSCs) with varied success. The effect of MSCs ex vivo differentiated to mimic functional insulin-secreting β-cells of islets and their impact on restoration of diabetic complications and transplantation via systemic delivery have not been well studied. In the current study, bone marrow MSCs differentiated to insulin-secreting β-cells are used to treat STZ-induced diabetic rats. The post-homing effects of the differentiated MSCs (dMSCs) were endogenous with definite reversal of diabetic parameters. Consequently, the altered cardiac functions like heart beat rate, left ventricular performance, contractility index and physiological body weight gain due to hyperglycemia were amelorated into normacy. The primary onset cardiac perfomance and the endothelial activation were well evidenced by high fibrinogen levels and systolic blood pressure (SBP) being reversed on the treatment by dMSCs. Further high basal [Ca(2+)]c in isolated endothelial cells and thereby increased ROS confirmed the endothelial activation. The levels of pro-apoptotic makers p53 and Bax were highly expressed in the diabetic groups indicating oxidative stress through ROS induced by high cytosolic calcium skewing the cells towards apoptosis. The expression of the anti-apoptotic marker Bcl-2 was observed to be low in the diabetic group further augmenting the stress state of endothelial cells (ECs) in T1DM. Restoration of [Ca(2+)]c chelates ROS and the subsequent reversal of pro- and anti-apoptotic markers after the successful treatment of dMSCs proved that endogenous reconstitution of insulin secretion improves diabetic-induced cardiac manifestations.
Full-text · Article · Nov 2014 · Cell and Tissue Research
[Show abstract][Hide abstract] ABSTRACT: Ricin intoxication is a fatal and an uncommon medical condition. We report a case of ricin poisoning in a 42-year-old Saudi male patient who ingested a herbal medicine mixture containing ricin bean powder, after which he presented with gastrointestinal symptoms followed by gastrointestinal bleeding and hypotension. The patient then passed into a state of shock with respiratory failure followed by cardiac arrest and death. Public health awareness of self-prescribed herbal medications is necessary.
No preview · Article · May 2012 · Annals of Saudi medicine
[Show abstract][Hide abstract] ABSTRACT: Identifying risk factors for acute coronary syndrome (ACS) is important for both diagnostic and prognostic purposes. Abnormal platelet parameters, mainly platelet count (PC), mean platelet volume (MPV) and platelet distribution width (PDW) are thought to be among these risk factors. In this study, the associations between PC, MPV and PDW and ACS were investigated in patients admitted to the tertiary care hospital in the south west region of Saudi Arabia.
A retrospective cohort of 212 patients with the diagnosis of ACS admitted to Aseer Central Hospital during the period extending from February 1, 2008 to October 31, 2008 were included. The control group consisted of 49 matched subjects who were admitted for chest pain investigation and subsequently found to be non-cardiac chest pain after performing relevant investigations. Blood samples were taken at the time of admission for platelet parameters. Statistical analysis was made using SPSS software and P-values were considered significant if <0.05.
A total of 212 patients with acute coronary syndrome (80 patients with MI and 132 patients with UA) and 49 matched controls were studied. The PC was not statistically different among the three groups (283.3 ± 94.8 × 10(9) L(-1) for MI cases, 262 ± 60.8 × 10(9) L(-1) for UA cases and 275.8 ± 58.9 × 10(9) L(-1) for controls). The MPV was significantly larger in MI cases compared to controls (8.99 ± 1.5 fl vs. 8.38 ± 0.51 fl, respectively, P < 0.009), similarly, the MPV was significantly larger in UA cases compared to controls (9.23 ± 1.19 fl vs. 8.38 ± 0.51 fl, respectively, P < 0.001). The PDW was significantly higher in MI cases compared to controls (15.88 ± 1.5 fl vs. 11.96 ± 1.8 fl, respectively, P < 0.001), similarly, the PDW as also significantly larger in UA cases compared to controls (18.1 ± 18 fl vs. 11.96 ± 1.8 fl, respectively, P < 0.019).
Platelet parameters mainly MPV and PDW are readily available and relatively simple and inexpensive laboratory tests which we detected to be significantly raised in patients who have suffered an acute coronary syndrome compared with controls.
[Show abstract][Hide abstract] ABSTRACT: We aimed to evaluate demographic data, underlying cardiac abnormalities, clinical profile, microbiological features, treatments and complications of infective endocarditis (IE) in a tertiary hospital in Aseer region, Saudi Arabia.
A retrospective study of all cases with the diagnosis of definite endocarditis according to modified Duke Criteria admitted to ACH between May 2002 and April 2007. Data were reviewed on demographic and clinical data, underlying cardiac disease, microbiological findings, treatments and complications of IE.
The study included 44 patients (28 males and 16 females; mean age 31.1 ± 16 years; range 13-65 years). Infective endocarditis developed on a native valve in 31 (70.5%), a mechanical prosthetic valve in 10 (22.7%), mitral valve prolapse in 2 (4.5%) and ventricular septal defect in 1 (2.3%). Rheumatic heart disease in 31 cases (70.5%) was the most common preexisting valvular abnormality in native valve endocarditis. The mitral valve was the most commonly affected valve 28 (63.6%). Fever occurred in 40 (90.9%) of the cases. Electrocardiography was abnormal in 34 cases (77.3%). Trans-thoracic and/or trans-esophageal echocardiography showed a vegetation in 22 (50%). Staphylococci in 10 cases (22.7%) and Streptococci in 8 cases (18%) were the most common causative agents and cultures were negative in 20 cases (45.5%). Twenty-two patients (50%) underwent surgical treatment. Congestive heart failure occurred in 16 (36.4%) cases, atrial fibrillation in 6 (13.6%) cases, and cerebrovascular accidents in 4 (9%) cases.
Our data reflects the clinical and microbiological profiles of IE in a tertiary hospital in Aseer region, Saudi Arabia.
[Show abstract][Hide abstract] ABSTRACT: Gender differences in the clinical presentation and management of patients with acute coronary syndrome (ACS) have been reported in different parts of the world with contradicting results. We aimed at investigating the presence of gender bias in patients admitted with ACS to Aseer Central Hospital (ACH).
A retrospective cohort of all consecutive patients admitted to ACH with the diagnosis of ACS, during the period between the 1st of June 2007 and the 31st of May 2009 was studied. Data on demographic and clinical profiles, management and outcomes of ACS patients were collected and compared for both genders.
The present study included 148 females and 397 males. Females were significantly older than males (62.9 ± 14.2 vs. 60 ± 13.4, respectively, P < 0.03), were less likely ever to have smoked (0.7% vs. 26.2%, respectively, P < 0.001), less likely to have had a history of hyperlipidemia (10.8% vs. 22.2%, respectively, P < 0.003) or family history of ischemic heart disease (10.1% vs. 18.9%, respectively, P < 0.014). Female patients presented more with atypical presentation (42.6% vs. 28.9%, respectively, P < 0.003), more with unstable angina (72.3% vs. 50.4%, respectively, P < 0.001), and less with ST-elevation myocardial infarction (18.9% vs. 40.8%, respectively, P < 0.001). Furthermore, they had significantly lower levels of hemoglobin compared to males (12.9 ± 2.3 vs. 14.5 ± 2.2 g/L, respectively, P < 0.001), and higher levels of high density lipoprotein (1.1 ± 0.4 vs. 0.98 ± 0.4 mmol/L, respectively, P < 0.008). Left ventricular ejection fraction was significantly higher in female patients compared to males (50.9 ± 14 vs. 45.8 ± 14, respectively, P < 0.003). Coronary angiography showed a higher rate of normal findings (29.3% vs. 8.9%, respectively, P < 0.001) and less severe disease (46.7% vs. 60.3%, respectively, P < 0.027) in women, however, they were less likely to undergo invasive revascularization procedures (31% vs. 42.8%, respectively, P < 0.013). No significant differences were found between both sexes regarding in-hospital mortality or re-infarction rates.
We documented gender differences in both clinical presentation as well as management of patients admitted with ACS to ACH. However, there were no significant differences between both genders regarding the clinical in-hospital outcomes. Emphasis should be made to avoid such bias in the future.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate the clinical and therapeutic profiles of heart failure (HF) cases admitted to Aseer Central Hospital (ACH), Saudi Arabia.
A retrospective cohort of 300 consecutive patients admitted with the diagnosis of HF to ACH from 1 June 2007 to 31 May 2009 were included in the study. Data on demographic variables, aetiologic factors, risk factors, and therapeutic profiles of patients with HF were collected and analysed.
The patients' mean age was 67.4 ± 13.7 years and 68.7% of them were male. The commonest aetiologies for HF were ischaemic heart disease (IHD) and hypertension in 38.3% and 33.3% of patients, respectively. A total of 61.3% of patients were diabetics. Other risk factors for HF included renal failure in 9.7%, atrial fibrillation in 13%, and anaemia in 48.3% of patients. Echocardiography was performed in 98.7% of cases: the average ejection fraction (EF) was 33% ± 17. Angiotensin converting enzyme inhibitors (ACEI) or angiotensin 2 receptor blockers were used in 68.3% of cases, β-blockers in 51.6% of cases and digoxin in 28.3% of cases.
The major causes of HF in our study were IHD and hypertension. Diabetes and anaemia were common risk factors. The cohort constituted an intermediate HF risk group (ejection fraction (EF) 33%). Important therapeutic agents like angiotensin converting enzyme inhibitor I, β-blockers and digoxin were underutilised. Fostering such therapy in practice will lead to a better outcome in the management of HF patients. Anaemia was a significant risk factor in our HF patients and should be managed properly.
Preview · Article · May 2011 · Sultan Qaboos University medical journal
[Show abstract][Hide abstract] ABSTRACT: Heart failure (HF) is a common medical problem with a high impact on public health. Evidence of gender difference in management of HF is scarce. We conducted a retrospective study to evaluate the presence of gender difference in management of HF patients admitted to the tertiary care hospital in the Aseer region/Saudi Arabia.
A chart review was conducted at Aseer Central Hospital (ACH) on consecutive patients admitted with the primary diagnosis of HF between Jun 2007 and May 2009. Data were collected on clinical and management profiles and analyzed for the presence of gender difference in HF management.
A total of 206 male patients and 94 female patients with HF were reviewed. Ischemic and dilated cardiomyopathy etiologies were significantly higher in male patients (42.7 vs. 28.7%, P < 0.021) and (13.1% vs. 3.2%, P < 0.008), respectively. Renal failure and atrial fibrillation were significantly higher in female patients with HF (20.2 vs., 5.3% P < 0.001) and (20.2 vs. 10.2%, P < 0.018), respectively. Smoking was significantly higher in male patients (11.7 vs. 0%, P < 0.001). Echocardiography was performed equally for both genders and ejection fraction was significantly higher in female patients (38.2 ± 16.9% vs. 30.4 ± 16.6%, P < 0.001). Beta-blockers were prescribed significantly less to female patients (36.2 vs. 57.8%, P < 0.001), while ACE inhibitors and digoxin were prescribed significantly less to male patients (64.1 vs.75.5%, P < 0.049) and (24.8 vs. 36.2%, P < 0.042), respectively.
Gender differences were detected in clinical presentation and management of HF. Female patients with HF had less ischemic etiology and smoking, but more atrial fibrillation and renal dysfunction. Female patients were under-treated by Beta-blockers while male patients were under-treated by ACE inhibitors and digoxin. Both genders were investigated equally, and female patients had a better ejection fraction.
[Show abstract][Hide abstract] ABSTRACT: Increased concentrations of estrogen metabolites (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact patho-etiology remains elusive.
The binding of antibodies from the sera of RA patients and control subjects to native and modified DNA was studied by direct binding and inhibition ELISA, quantitative precipitin titration. Experimentally induced antibodies were also checked to detect oxidative lesions in the DNA as well as for the estimation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in different fluids of RA.
Anti-DNA IgG from RA sera, exhibited increased recognition of modified DNA than native DNA (nDNA; P < 0.001). The relative affinity of anti-DNA antibodies for modified and nDNA was in the order of 1.85 × 10(-7), 1.23 × 10(-7), and 1.2 × 10(-6). Samples of DNA from RA patients showed a significant inhibition in the induced antibody activity in comparison to DNA isolates from controls (P < 0.001). The concentration of 8-OHdG evaluated by induced antibody in RA patients was found to be significantly higher than controls ((P < 0.0001, P < 0.01, P < 0.05).
High binding of modified DNA with the IgG from RA patient might explain possible antigenic role of 4-OHE(2)-modified DNA in the production of anti-DNA antibodies. In addition, the induced antibodies have been shown to represent an alternative immunochemical probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG levels in different body fluid of RA patients, which may be used as marker in the diagnosis of the disease.
No preview · Article · Feb 2011 · Journal of Clinical Immunology
[Show abstract][Hide abstract] ABSTRACT: Acute coronary syndrome (ACS) is the most prevalent cardiac disorder. Adjunctive pharmacotherapy has proved to be safe and effective in treating patients with this syndrome. Underutilization of such pharmacotherapy was reported in different studies.
In this study, we evaluated the underutilization of these pharmacotherapies on patients admitted to Aseer Central Hospital (ACH) with ACS, find out factors that may predict utilization of these therapies, and determine the effect of such pattern of drug utilization on survival at discharge.
A retrospective cohort of 562 patients admitted with the diagnosis of ACS to ACH during the period from March 2007 to February 2009 was studied.
β-blockers (B-blocker) and angiotensin-converting enzyme inhibitors (ACEI) were used in only 69 and 59% of cases, respectively. Aspirin, clopidogrel, and statin were used in 98.4, 82.6, and 89.3% of cases, respectively. The presence of diabetes predicts the use of ACE inhibitors, whereas the diagnosis of unstable angina and ST-elevation myocardial infarction predict the use of statin. Survival rate at discharge was 95.6%. Use of statin and aspirin improved survival.
Certain adjunctive pharmacotherapies were underutilized in ACS patients in Southwest region, Saudi Arabia, specifically β-blockers and ACEI. Standard of care should be revised and updated, aiming to improve adherence to guidelines of management of patients with ACS.