Primary sources document Dr. Saul Hertz (1905 - 1950) as conceiving and developing radioiodine (RAI) as a diagnostic tool and as a therapy for thyroid diseases. Dr. Hertz was the first and foremost person to develop the experimental data on RAI and apply it to the clinical setting.
Saul Hertz was born on April 20,1905 to Jewish parents who had immigrated to Cleveland, Ohio. He received his A.B. from the University of Michigan in 1925 with Phi Beta Kappa honors. After graduating from Harvard Medical School in 1929, at a time of quotas for outsiders, he fulfilled his internship and residency at Cleveland’s Mt. Sinai Hospital.
In 1931, he came back to Boston to join the newly formed Thyroid Unit at The Massachusetts General Hospital serving as the Chief from 1931 - 1943.
Natural killer (NK) cells, the third population of lymphoid cells, comprise 5%-25% of peripheral blood (PB) lymphocytes and represent the first line of defense against infections and tumors [1-7]. They can be derived from: bone marrow, PB, cryopreserved umbilical cord blood (UCB), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and various cell lines such as NK-92 and KHYG-1 [1]. NK cells; which have been divided into cytotoxic, tolerant, and regulatory subsets; are classified into: (1) naïve CD56 bright CD 16 dim CD 3 dim cells, (2) mature CD56 dim CD16 bright CD3 dim cells, and (3) lymphoid tissue-resident CD69+/CXCR6+ NK cells [1,2,8-11]. Although NK cells have been traditionally considered as part of the innate immune system, they have recently been shown to exhibit many of the features associated with adaptive immunity [8,12]. The functions of NK cells which are influenced by several cytokines include: elimination of infected cells, destruction of cancer cells, reducing the incidence of graft versus host disease (GVHD) following hematopoietic stem cell transplantation (HSCT), and regulation of pregnancy outcome [10,11,13].
Mesenchymal stem cells (MSCs) conditioned medium (CM) has a promising prospect towards skin regeneration. Therefore, human dental pulp and adipose stem cells (DPSCs and ADSCs) were isolated, propagated and evaluated for their stemness and genetic stability over time in culture before making CM. We aimed to characterize the applicability of lyophilized ADSCs and DPSCs derived CM (AD-CM and DP-CM) at 5 mg, 10 mg and 20 mg for wound healing process. The ability of wound closure was assessed by direct human dermal fibroblast cell scratch assay, treated with variable concentrations of AD-CM and DP-CM in vitro. Additionally, we also assessed the expression of different cytokines and growth factors secreted from ADSCs and DPSCs in the CM relevant to the wound healing by cytokine array analysis. Our data demonstrates a significant effect of both the AD-CM and DP-CM in wound healing within 24 hrs compared to that in control.
Natural killer cells represent the first line of defense against infections and tumors and can be derived from various sources including: bone marrow, peripheral blood, specific types of human stem cells, and certain cell lines. The functions of natural killer cells are influenced by: several cytokines, activating and inhibitory receptors, as well as other immune cells such as dendritic cells and mesenchymal stem cells.
Natural killer cells are attractive candidates for adoptive cellular therapy in patients with hematologic malignancies and solid tumors in addition to recipients of various forms of hematopoietic stem cell transplantation as they enhance antitumor effects without causing graft versus host disease. Several clinical trials have shown safety and efficacy of natural killer cell products obtained from autologous as well as allogeneic sources and used in conjunction with cytotoxic chemotherapy, monoclonal antibodies and novel agents.
The following review, which includes extensive literature review on several aspects of natural killer cells, will give particular attention to: the rising role of natural killer cell therapies in patients with malignant hematological disorders, solid tumors and in recipients of stem cell therapies; preparation and manufacture of natural killer cell products; challenges facing the utilization of this form of cellular therapy including evolution of resistance; and maneuvers that can be employed to enhance the efficacy of natural killer cell therapies as well as suggested solutions to resolve the remaining challenges.
In recent years, stem cells technology have been used widely in basic and clinical science researches LIPUS (low-intensity pulsed ultrasound) is another technique commonly used in conjunction with stem cells that can have complications after applications. One of the important issues in using this modern technique is the occurrence of opportunistic infections and inflammatory reactions in the rejection or destruction of these cells and in turn making ineffective of its applications, which have been reviewed in the following.
ystemic sclerosis (SScl) is an autoimmune disorder of unknown aetiology, characterised by fibrosis and microvascular injury of the affected organs. The hallmark of the disease is thickening and tightness of the skin and the subcutaneous tissue. SScl can affect virtually any organ systems, most importantly the skin, blood vessels, lungs, kidneys, gastrointestinal tract, and the heart [1].
The pandemic of COVID-19 has adversely affected the world in many aspects. The health and economic sectors suffer most of the repercussions of this disease. The search for a cure for this rapidly spreading virus which is causing massive life losses worldwide requires clear understanding of the immunopathogenesis of this virus so as to develop pinpointed targeted therapies rather than relying mainly on supportive care measures and drug repurposing to fight this life-threatening virus infection.
Neutrophils, neutrophil extracellular traps (NETs), and NETosis are not well studied not only in COVID-19, but also in coroviruses in general. The review will shed lights on the functions of neutrophils, NETs, and NETosis in various infectious complications as well as in sepsis and acute lung conditions in an attempt to understand their actual roles and in order to help in designing targeted therapies in the near future.
Infectious diseases are a leading cause of death worldwide [1,2]. The Mid-20th century witnessed most of the antimicrobial discoveries but recently there is dramatic shortage of new classes of antimicrobial agents due to failure to build a sustainable antimicrobial discovery platform [1-4]. For example, antibiotics comprise ˂ 1.5% of the compounds under investigation at the major pharmaceutical and biotechnology companies [1,5].
Objectives: The aim of this study was to assess the knowledge, attitude and motivation toward stem cell donation among Saudi population in Riyadh, Saudi Arabia.
Methods: This is a cross-sectional study that was conducted at different malls in Riyadh. Selection of malls was done randomly according to the geographical distribution of Riyadh, in which sample size was calculated and distributed equally. The participants were asked to complete a questionnaire that addressed their knowledge, attitude and motivation toward stem cell transplantation and donation.
Results: Results of this study showed that population knowledge about stem cell transplantation and donation is considered to be low. Only (37.8%) has enough information about stem cell transplantation and donation. There is a positive correlation between level of education and participant’s knowledge regarding stem cell transplantation and donation. The study revealed that 39.3% of participants have willingness for stem cell donation.
Conclusion: It has been found that two third of population expressed lack of knowledge about stem cell transplantation and donation. Also, only 40% of participants showed willingness for donation, and the most common reason for not donating stem cell was the lack of information about stem cell and the value of donation While, increasing level of education was associated with better understanding of stem cell donation and its role in therapy and saving lives. Therefore, suitable campaign, advertising and counseling program for population is recommended to increase level of knowledge and motivation toward stem cell donation.
The oocyte is the female gamete that contributes not only half of the genetic material but also all of the cytoplasm to the zygote, supplying the transcripts, proteins, mitochondria and other components necessary for early embryonic development. The intrinsic oocyte quality is one of the main factors affecting the embryo yield, the implantation rate and the rate of healthy offspring. It is obvious that a fertilized oocyte must reach the blastocyst stage within 6–9 days in the proper culture conditions to have a significant chance of inducing a pregnancy and producing an offspring. The ability to sustain the first week of embryonic development is clearly influenced by the follicular status from which the oocyte is obtained indicating that this developmental potential is inherent within certain oocytes. Since most early embryos that do not reach the blastocyst stage are blocked at or close to the maternal to zygotic transition (MZT)-stage, which occurs at the eight-cell stage in cattle, one could speculate that incompetent oocytes fail to appropriately activate the embryonic genome. Oocyte selection based on glucose-6-phosphate dehydrogenase (G6PDH) activity has been successfully used to differentiate between competent and incompetent bovine oocytes. Recently, molecular regulation of genes regulating biological process of Brilliant Cresyl Blue staining (BCB) selected oocytes and embryos was investigated to explain their variation in quality and developmental potentiality. This short review will highlights some of these efforts that have been done in this interesting area of research.
We present a case of hypocomplementemic urticarial vasculitic syndrome (HUVS) who developed severe renal failure requiring ICU-level care. Our patient is a 66-year-old man who presented with abdominal pain, rash, confusion, oliguria, and shortness of breath. He was found to be in acute renal failure with leukocytosis and elevated lactate. Work-up for infectious, autoimmune, and hematologic malignant diseases was negative. The presence of chronic urticaria, abdominal pain, hypocomplementemia, and leukocytoclastic vasculitis on skin biopsy confirmed the diagnosis of HUVS. He required hemodialysis for renal failure as well as gastrostomy tube placement for nutritional support secondary to the development of mucosal ulcers, a rare finding in HUVS. He recovered with several months of high-dose steroids and hemodialysis. This case highlights the effectiveness of steroids for initial treatment of HUVS, and the relapsing and remitting nature of the disease. Providers should also be aware of the broad range of presenting symptoms such as mucosal lesions that may require nutritional support. Interestingly, unlike many previously reported cases of HUVS, our patient had not yet developed signs and symptoms of systemic lupus erythematosus, which often overlaps with HUVS.
Care of kidney transplant recipient remains complex and long-term graft survival is not seen in every transplant recipient. Due to reduced supply and increased demand of human organs, more transplants are carried out using marginal grafts on emergency lists. Transplant recipients have altered physiology due to known end-stage renal disease, recent surgery and the use of potent analgesic and immunosuppressive medications. Amongst the known surgical complications, urine leak remains the most common. It can result from poor graft preparation due to excessive peri ureteric or lower pole dissection or damage to lower polar artery resulting in ischemic necrosis. In addition, poor surgical technique, bladder outflow obstruction, iatrogenic injury to bladder or renal pelvis may contribute to urine leak. Ongoing urine leak may manifest itself as swelling, pain, high drain output, sepsis, ileus and eventual graft loss. Early identification, localisation and quantification of leak remain essential in management of these patients. In addition, sepsis should be identified and treated promptly as these patients are highly susceptible to infections. Early recognition of this complication can significantly reduce hospital stay, improve quality of life and reduce graft loss and mortality. In this article, we aim to develop an evidence-based management approach to a patient with urine leak using a clinical scenario.
Liver cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD) is a rare but life-threatening complication. Diagnosis and treatment remain challenging. We report the case of a 64-year-old kidney transplant patient presenting with fever and abdominal pain. The diagnosis of liver cyst infection was made by positron emission tomography scan (PET/CT). Moreover, the course of our patient illustrates the interest of subsequent PET/CT during follow-up as our patient failed on antibiotherapy and required liver cyst drainage.
Brucellosis is a zoonotic infection that is endemic in some Mediterranean countries, North Africa and the Middle East. Brucella is a rare cause of peritonitis in Peritoneal Dialysis (PD) population and in non-dialysis patients alike. We report here a challenging case of PD-related Brucella peritonitis in a 45-year-old Saudi male with late peritonitis that delivered some key learning throughout its course from presentation, diagnosis and treatment to catheter salvage attempts so as to circumvent PD failure. We provide an in-depth review of limited published literature on PD-related Brucella peritonitis (seven cases, and present case) and summarized the data on key clinical characteristics, management and PD technique outcome to benefit nephrologists when encountered with this rare presentation.
Purpose: Deficiency of Fetuin A, as a calcification inhibitor, is assumed to be involved in vascular calcification in patients on maintenance hemodialysis (MHD). This study examined the relationship between serum Fetuin-A and vascular and valvular calcification in a cohort of MHD patients.
Methods: The study was conducted on 122 MHD patients. Serum levels of calcium, phosphorus, parathormone, and Fetuin-A were tested. Intima-media thickness (IMT) ≥0.8 mm and the presence of stenosis>50% or plaques in carotid doppler sonography were considered as vascular calcification. Calcification of cardiac valves or mitral annular calcification in two-dimensional echocardiography, were considered as cardiac valvular calcification. The presence of any or both of the two conditions was defined as cardiovascular calcification (CVC).
Results: Fetuin-A was lower than normal in 37% of 122. Totally 106 patients (87%) had CVC, who were older (61±14 vs. 38±14 years, P<0.001), more affected by diabetes (54% vs. 13%, P=0.007), had a longer dialysis vintage (median 5 vs. 2 years, P=0.006), lower levels of creatinine (8.9±2.8 vs. 11.9±3.1 mg/dL, P<0.001) and higher levels of calcium (8.7±0.7 vs. 8.4±0.5 mg/dL, P=0.026). There was no significant difference in mean Fetuin-A level between the two groups (P=0.101). In logistic regression increased age (OR=1.1, CI 95%=1.1 - 1.2) and serum calcium (OR=2.8, CI 95%=1.1- 7.6), and diabetes mellitus (OR=7.4, CI 95%=1.1 - 47.4) were risk factors.
Conclusion: This study showed that 87% of our patients had vascular and/or valvular calcification. Increased age and calcium level and diabetes were the predictors of CVC, whereas Fetuin-A was not.
Background: Chronic Kidney Disease is no longer considered just a health burden today but a major health priority owing to its high treatment costs and poor outcome. World Kidney Day and International Women’s Day in 2018 coincided, thus offering an opportunity to reflect on the importance of women’s health, and specifically their kidney health. The current study aims to identify chronic kidney disease in women through a cross sectional screening in hospital based camp in Varanasi on World Kidney Day.
Methods: 138 females attending a health camp were screened for clinical parameters like serum creatinine, random blood sugar, and pregnancy complications. Demographic and anthropometric parameters were noted. Ordinal logistic regression analysis was used to find the predictors of chronic kidney disease stages.
Results: The median age of the participants was 36 years. The prevalence of chronic kidney disease was 6.4% with 1.4% of Stage 1, 2.1% of Stage 2, 1.4% of Stage 3 and 1.4% of Stage 4. Women with diabetes were nearly 4 times at a greater risk of developing higher stages of chronic kidney disease compared to women without it. With a unit increase in serum creatinine levels, women were nearly 13 times more likely to develop higher stages of chronic kidney disease.
Conclusion: Serum creatinine levels and diabetes were the significant predictors for the development of higher stages of chronic kidney disease. Early screening for kidney diseases in women could reduce the load of health care delivery system that is involved in renal replacement therapies.
We present below a mechanistic molecular approach for development of Anti-Inflammatory biomarkers of Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses arrroaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory bathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary componenents on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.
Prednisone-sensitive hypocomplementemia, renal insufficiency, and kidney biopsy demonstrating severe tubulointerstitial nephritis (TIN), storiform fibrosis, and tubulointerstitial immune deposits are typical of IgG4-related tubulointerstitial nephritis and hypocomplementemic interstitial nephritis. A diagnosis of hypocomplementemic interstitial nephritis requires clinical and pathologic exclusion of IgG4-related tubulointerstitial nephritis. We describe a patient with hypocomplementemic interstitial nephritis who did not develop diagnostic features of IgG4 related disease (RD) over 2-year follow-up. We conclude that hypocomplementemic interstitial nephritis could be on a biologic spectrum with IgG4-related disease, but not all cases will develop the abundance of IgG4-positive plasma cells, systemic manifestations, or elevated immunoglobulin levels characteristic of IgG4-RD.
Introduction: Chronic kidney disease is a costly and burdensome public health concern. Delayed recognition and treatment of CKD may predispose patients to unfavorable future outcomes and burden the healthcare services. The early detection of disease via screening programs is widely recommended. The present study is a hospital camp-based screening for detecting patients with chronic kidney disease in Varanasi from 2014-18.
Methods: The study subjects constituted 436 apparently healthy adults (age ≥18 years) of Varanasi. Information on socio-demographic profile, personal characteristics and clinical investigations were recorded. Stepwise binary logistic regression analysis was applied to find the significant predictors of chronic kidney disease.
Results: Median age of the study subjects was 40.5 years. There were 39.7% males and 60.3% females. Chronic kidney disease was found in 23.9% subjects. Underweight, diabetes mellitus, hypertension, smoking status and higher creatinine levels came out as significant predictors of chronic kidney disease.
Conclusion: We screened apparently healthy individuals and found very high percentages of chronic kidney disease and its predictors. Henceforth, understanding the preventable and modifiable risk factors of chronic kidney disease becomes a prerequisite to intervene before risk populations reaches to irreversible stages of adverse future outcomes.
Background: Haemodialysis is the commonest method of Renal Replacement Therapy in Nigeria. Despite an advancement in the technicality and better understanding of haemodialysis, a number of complications are known to be associated with this procedure..
Objective: We aimed to highlight our experiences and share some of the uncommon complications encountered during haemodialysis and present the outcome of our patients.
Subjects and methods: A retrospective review of 101 patients during the last two years was done. Data extracted include: sociodemographic characteristic, aetiology of kidney disease, type of vascular access, intradialytic complication and outcome of treatment.
Results: The total number of dialysis session during the period was 823. Males constituted a higher proportion (64.4%) and were found to be older than female patients 49.8 vs 42.8 years (P=0.001).
Majority (89.1%) had chronic kidney disease while chronic glomerulonephritis was the main cause of CKD as seen in about 45% of the patient.
Due to the cost implication, only 2(1.98%) were able to undergo 3 sessions of dialysis per week for up to 1 month.
Vascular access was femoral (66.3%), internal jugular vein (25.7%), while only 2% used Artero-venous-fistula and one patient had femoral vessel pseudoaneurysm from frequent cannulation.
The commonest complication was hypotension which was present in 15.8%. Twenty-eight deaths were recorded, 44(43%) were either lost to follow up or absconded while 5% were transplanted at a referral centre.
Conclusion: Challenges of renal replacement therapy is overwhelming in our country due to poor human and financial resources. Early diagnosis and adequate government support are advocated.
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