Brucella bacteremia in patients with acute leukemia: a case series

<p>Abstract</p> <p>Background</p> <p>Brucellosis may cause serious infections in healthy individuals living in countries that are endemic for the infection. However, reports of brucella infections in immunocompromised hosts are relatively rare.</p> <p>Case Presentations</p> <p>Reported here are two patients with acute leukemia who developed <it>Brucella melitensis </it>bacteremia during their follow up at the Armed Forces Hospital in Riyadh. The first patient developed <it>B. melitensis </it>bacteremia during the transformation of his myelodysplasia into acute myeloid leukemia. The second patient developed <it>B. melitensis </it>bacteremia while his acute lymphoblastic leukemia was under control. Interestingly, he presented with acute cholecystitis during the brucella sepsis. Both brucella infections were associated with a marked reduction in the hematological parameters in addition to other complications. The bacteremic episodes were successfully treated with netilmicin, doxycycline and ciprofloxacin.</p> <p>Conclusion</p> <p>Brucellosis can cause systemic infections, complicated bacteremia and serious morbidity in patients with acute leukemia living in endemic areas. These infections may occur at the presentation of the leukemia or even when the leukemia is in remission. Nevertheless, the early diagnosis of brucellosis and the administration of appropriate antimicrobial therapy for sufficient duration usually improves the outcome in these immunocompromised patients.</p

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Optimization Based Machine Learning Methods for Business Analytics

The growing availability of data and recent developments in optimization methods and machine learning have led to a revolution in modern business analytics. In this Ph.D. dissertation, we propose two frameworks based on mixed-integer optimization that advance business analytics in the context of two important problems: product design with market share maximization and learning optimal decision trees.In the first problem, we aim to find a product, as defined by its attributes, that maximizes market share, which is a weighted sum of logistic probabilities when we assume each customer segment follows a logit choice model to make a purchase. At first glance, this problem appears hopeless: one must optimize an objective function that is neither convex nor concave over an exponentially-sized discrete set of attribute combinations. Surprisingly, we show that this problem can be reformulated as a mixed-integer convex program by exploiting an economic model. We further propose an exact methodology for solving this problem based on modern integer, convex, and conic optimization techniques. Using synthetic problem instances and instances derived from real conjoint data sets, we show that our methodology can solve large problem instances to provable optimality or near-optimality within operationally feasible time frames.In the second problem, we propose a mixed-integer program that learns optimal decision trees from data. While decision trees are among the most widely-used machine learning methods, their learning algorithms are usually based on top-down heuristics and cannot incorporate side constraints arising from real-world business operations. We show that our proposed mixed-integer formulation is theoretically stronger than other formulations in the literature by exploring its relaxation properties. We also develop a large-scale solution method based on constraint generation. Based on computational studies on real-world data sets, we show that our proposed model is significantly more tractable than alternative mixed-integer optimization models and our large-scale method based on constraint generation can further improve the solution time in several data sets.Overall, we contribute to business analytics by proposing exact solution methods based on optimization to two significant but computationally challenging problems and developing efficient algorithms that make them more practical to use

Joubert syndrome: review and report of seven new cases

Joubert syndrome (JS) is an autosomal-recessive disorder, characterized by hypotonia, ataxia, global developmental delay and molar tooth sign on magnetic resonance imaging. A variety of other abnormalities have been described in children with JS, including abnormal breathing, abnormal eye movements, a characteristic facial appearance, delayed language, hypersensitivity to noise, autism, ocular and oculomotor abnormalities, meningoencephaloceles, microcephaly, low-set ears, polydactyly, retinal dysplasia, kidney abnormalities (renal cysts), soft tissue tumor of the tongue, liver disease and duodenal atresia. Even within siblings the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of JS. We review the clinical characteristics of seven cases that fulfill the criteria of JS

Rubella-associated hemophagocytic syndrome in an infant

Hemophagocytic syndrome (HPS) is a fulminant disorder characterized pathologically by multiple-organ infiltration of hemophagocytic histiocytes in the lymphoreticular tissues. The characteristic pathologic feature is reactive histiocytic hyperplasia with leukoerythrophagocytosis in a variety of organs. This disorder occurs most often in patients in whom the immune system is compromised and has been associated with a variety of infectious agents, including viruses, bacteria, mycobacteria, spirochetes, fungi, and parasites. The authors describe a 2.5-month-old girl with rubella-associated HPS, demonstrated by postmortem liver necropsy

Neonatal hepatitis in 2 siblings with Seckel syndrome

Seckel syndrome was described as the prototype of the primordial bird-head type of dwarfism. We report 2 cases of Seckel syndrome in siblings. Both cases showed peculiar phenotypic features. Autopsy was performed and microscopic examination of the livers displayed histologic features of neonatal hepatitis. Tn addition, our younger patient had central nervous system anomalies such as agenesis of corpus callosum, cerebral cyst, and primitive convolutional pattern. No previous reports of liver disease exist in patients with Seckel syndrome. The pathologic findings of such an unusual association and a review of literature are presented

Serum leptin levels in patients with childhood immune thrombocytopenic purpura

Acute immune thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Recent studies suggested that T helper immune response is responsible for the pathogenesis of chronic ITP. Despite several studies that were carried out, we do not have a clue as to what triggers the autoimmunity. Leptin is a 16-kd protein secreted from the adipose tissue. Leptin is structurally similar to interleukin (IL)-2, IL-6, and IL-15. The structural similarities between leptin receptor and hernatopoietic cytokine receptors suggested that leptin could play a role in hematopoiesis and immune function. Recent studies suggested that leptin could play an important role in autoimmunity. We made a prospective analysis of a series of 39 newly diagnosed acute childhood ITP in a year period. Serum leptin levels were obtained after diagnosis and before treatment and all patients were followed up at least 6 months to designate acute or chronic event. We conclude that in childhood acute ITP, leptin did not play a role in the pathophysiology of the disease. Further investigations are needed to examine what triggers T cells and how the autoimmune disease became

The Relationship between Abdominal Aortic Intima-Media Thickness and Lipid Profile in Neonates Born to Mothers with Preeclampsia

Neonates born to mothers with preeclampsia are known to be associated with lipid alterations that might increase the risk for cardiovascular disease in adult life. The aim of this study was to investigate the effect of preeclampsia on lipid metabolism, aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 60 neonates of mothers with preeclampsia (group I; 30 neonates of mothers with preeclampsia and group II; 30 neonates of mothers with severe preeclampsia) and 30 healthy neonates (group III). Maternal and cord serum lipid profiles were determined in all groups. Mean abdominal aIMT measurements were higher in the neonates born to mothers with preeclampsia (group I; 0,36 +/- 0,03 mm and group II; 0,36 +/- 0,04 mm) compared with the control group (group III; 0,33 +/- 0,03 mm, p=0,006). Serum triglyceride levels were significantly higher in the neonates born to mothers with preeclampsia (group I; 39,2 +/- 42,0 mg/dl and group II; 39,5 +/- 56,5 mg/dl) compared with the control group (group III; 14,9 +/- 18,8 mg/dl, p = 0,039). Serum HDL cholesterol levels were significantly lower in the neonates born to mothers with precclampsia (group I; 17,3 +/- 12,3 mg/dl and group II; 17,1 +/- 12,8 mg/dl) compared with the control group (group III; 27,6 +/- 13,0 mg/dl, p = 0,002). In conclusion; neonates of mothers with preeclampsia have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.Neonates born to mothers with preeclampsia are known to be associated with lipid alterations that might increase the risk for cardiovascular disease in adult life. The aim of this study was to investigate the effect of preeclampsia on lipid metabolism, aortic intimamedia thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 60 neonates of mothers with preeclampsia (group I; 30 neonates of mothers with preeclampsia and group II; 30 neonates of mothers with severe preeclampsia) and 30 healthy neonates (group III). Maternal and cord serum lipid profiles were determined in all groups. Mean abdominal aIMT measurements were higher in the neonates born to mothers with preeclampsia (group I; 0.36 +/- 0.03 mm and group II; 0.36 +/- 0.04 mm) compared with the control group (group III; 0.33 +/- 0.03 mm, p = 0.006). Serum triglyceride levels were significantly higher in the neonates born to mothers with preeclampsia (group I; 39.2 +/- 42.0 mg/dl and group II; 39.5 +/- 56.5 mg/dl) compared with the control group (group III; 14.9 +/- 18.8 mg/dl, p = 0,039). Serum HDL cholesterol levels were significantly lower in the neonates born to mothers with preeclampsia (group I; 17.3 +/- 12.3 mg/dl and group II; 17.1 +/- 12.8 mg/dl) compared with the control group (group III; 27.6 +/- 13.0 mg/dl, p = 0.002). In conclusion; neonates of mothers with preeclampsia have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.</p