A rare cause of chronic mesenteric ischemia from fibromuscular dysplasia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chronic mesenteric ischemia is a condition that is classically associated with significant atherosclerosis of the abdominal arteries, causing postprandial abdominal pain out of proportion to physical examination. The abdominal pain is exacerbated after meals due to the shunting of blood away from the intestines to the stomach, causing relative ischemia. More than 95% of chronic mesenteric ischemia cases are due to atherosclerosis. We report the first known case of chronic mesenteric ischemia from fibromuscular dysplasia. To the best of our knowledge, this is also the first known case in the literature where postprandial abdominal pain was the presenting symptom of fibromuscular dysplasia.</p> <p>Case presentation</p> <p>A 44-year-old Caucasian woman with a history of hypertension and preeclampsia, who had taken oral contraceptive pills for 15 years, presented with an intractable, colicky abdominal pain of two weeks duration. This abdominal pain worsened with oral intake. It was also associated with diarrhea and vomiting. Physical examination revealed stage III hypertension out of proportion to her risk factors and diffuse abdominal pain without peritoneal signs. An abdominal computed tomography scan, completed in the emergency room, revealed nonspecific colitis. Laboratory work revealed leukocytosis with a left shift, an erythrocyte sedimentation rate of 79 and a C-reactive protein level of 100. She was started on intravenous flagyl and intravenous ciprofloxacin. However, all microbial cultures were negative including three cultures for clostridium difficile. Urine analysis revealed nephritic range proteinuria. The laboratory profile was within normal limits for perinuclear-anti-neutrophil cytoplasmic antibody, cytoplasmic-anti-neutrophil cytoplasmic antibody, anti-saccharomyces cerevisiae antibody, antinuclear antibody test, celiac profile, lactate, carbohydrate antigen-125 and thyroid stimulating hormone. A colonoscopy was completed, which revealed diffuse colonic lymphoid reactive hyperplasia. A small bowel series was negative for any inflammation. An indium scan, pan-computed tomography scan and transvaginal ultrasound were also negative. Magnetic resonance angiography of her abdomen revealed proximal superior mesenteric artery stenosis, which was confirmed by computed tomography angiogram findings of severe proximal and distal superior mesenteric artery stenosis, consistent with the appearance of fibromuscular dysplasia on angiography in the absence of vasculitis or atherosclerotic disease. The patient's superior mesenteric artery stenosis was subsequently angioplastied suboptimally and had to be stented with an Angioplus stent. One month after she was admitted, her abdominal pain and tolerance to oral feeds improved tremendously.</p> <p>Conclusion</p> <p>Fibromuscular dysplasia most commonly presents with renal artery stenosis, which rarely causes abdominal pain. This case illustrates how fibromuscular dysplasia can present as a rare cause of chronic mesenteric ischemia, similar to chronic mesenteric ischemia from atherosclerosis.</p

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Immunomodulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in a Swine Hemi-Facial Allotransplantation Model

BACKGROUND: In this study, we investigated whether the infusion of bone marrow-derived mesenchymal stem cells (MSCs), combined with transient immunosuppressant treatment, could suppress allograft rejection and modulate T-cell regulation in a swine orthotopic hemi-facial composite tissue allotransplantation (CTA) model. METHODOLOGY/PRINCIPAL FINDINGS: Outbred miniature swine underwent hemi-facial allotransplantation (day 0). Group-I (n = 5) consisted of untreated control animals. Group-II (n = 3) animals received MSCs alone (given on days -1, +1, +3, +7, +14, and +21). Group-III (n = 3) animals received CsA (days 0 to +28). Group-IV (n = 5) animals received CsA (days 0 to +28) and MSCs (days -1, +1, +3, +7, +14, and +21). The transplanted face tissue was observed daily for signs of rejection. Biopsies of donor tissues and recipient blood sample were obtained at specified predetermined times (per 2 weeks post-transplant) or at the time of clinically evident rejection. Our results indicated that the MSC-CsA group had significantly prolonged allograft survival compared to the other groups (P<0.001). Histological examination of the MSC-CsA group displayed the lowest degree of rejection in alloskin and lymphoid gland tissues. TNF-α expression in circulating blood revealed significant suppression in the MSC and MSC-CsA treatment groups, as compared to that in controls. IHC staining showed CD45 and IL-6 expression were significantly decreased in MSC-CsA treatment groups compared to controls. The number of CD4+/CD25+ regulatory T-cells and IL-10 expressions in the circulating blood significantly increased in the MSC-CsA group compared to the other groups. IHC staining of alloskin tissue biopsies revealed a significant increase in the numbers of foxp3(+)T-cells and TGF-β1 positive cells in the MSC-CsA group compared to the other groups. CONCLUSIONS: These results demonstrate that MSCs significantly prolong hemifacial CTA survival. Our data indicate the MSCs did not only suppress inflammation and acute rejection of CTA, but also modulate T-cell regulation and related cytokines expression

Confirmed malaria cases among children under five with fever and history of fever in rural western Tanzania

The World Health Organization recommends that malaria treatment should begin with parasitological diagnosis. This will help to control misuse of anti-malarial drugs in areas with low transmission. The present study was conducted to assess the prevalence of parasitologically confirmed malaria among children under five years of age presenting with fever or history of fever in rural western Tanzania. A finger prick blood sample was obtained from each child, and thin and thick blood smears were prepared, stained with 10% Giemsa and examined under the light microscope. A structured questionnaire was used to collect each patient's demographic information, reasons for coming to the health center; and a physical examination was carried out on all patients. Fever was defined as axillary temperature ≥ 37.5°C. A total of 300 children with fever or a history of fever (1 or 2 weeks) were recruited, in which 54.3% (163/300, 95%CI, 48.7-59.9) were boys. A total of 76 (76/300, 25.3%, 95%CI, 22.8 - 27.8) of the children had fever. Based on a parasitological diagnosis of malaria, only 12% (36/300, 95%CI, 8.3-15.7) of the children had P. falciparum infection. Of the children with P. falciparum infection, 52.7% (19/36, 95%CI, 47.1-58.3) had fever and the remaining had no fever. The geometrical mean of the parasites was 708.62 (95%CI, 477.96-1050.62) parasites/μl and 25% (9/36, 95%CI, 10.9 -- 39.1) of the children with positive P. falciparum had ≥ 1001 parasites/μl. On Univariate (OR = 2.13, 95%CI, 1.02-4.43, P = 0.044) and multivariate (OR = 2.15, 95%CI, 1.03-4.49) analysis, only children above one year of age were associated with malaria infections. Only a small proportion of the children under the age of five with fever had malaria, and with a proportion of children having non-malaria fever. Improvement of malaria diagnostic and other causes of febrile illness may provide effective measure in management of febrile illness in malaria endemic areas

Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage

<p>Abstract</p> <p>Background</p> <p>Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.</p> <p>Methods</p> <p>Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.</p> <p>Results</p> <p>954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.</p> <p>Conclusion</p> <p>There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.</p

Single Molecule Analysis Research Tool (SMART): An Integrated Approach for Analyzing Single Molecule Data

Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data

Ca2+ Permeable AMPA Receptor Induced Long-Term Potentiation Requires PI3/MAP Kinases but Not Ca/CaM-Dependent Kinase II

Ca2+ influx via GluR2-lacking Ca2+-permeable AMPA glutamate receptors (CP-AMPARs) can trigger changes in synaptic efficacy in both interneurons and principle neurons, but the underlying mechanisms remain unknown. We took advantage of genetically altered mice with no or reduced GluR2, thus allowing the expression of synaptic CP-AMPARs, to investigate the molecular signaling process during CP-AMPAR-induced synaptic plasticity at CA1 synapses in the hippocampus. Utilizing electrophysiological techniques, we demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460, and found to be dependent on postsynaptic Ca2+ ions through calcium chelator (BAPTA) studies. Surprisingly, Ca/CaM-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDA-receptor dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDA-receptor dependent LTP in control studies. In contrast, inhibitors for PI3-kinase (LY294002 and wortmannin) or the MAPK cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Similarly, postsynaptic infusion of tetanus toxin (TeTx) light chain, an inhibitor of exocytosis, also had a significant inhibitory effect on this form of LTP. These results suggest that distinct synaptic signaling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain

Prescribing practice for malaria following introduction of artemether-lumefantrine in an urban area with declining endemicity in West Africa

<p>Abstract</p> <p>Background</p> <p>The decline in malaria coinciding with the introduction of newer, costly anti-malarials has prompted studies into the overtreatment for malaria mostly in East Africa. The study presented here describes prescribing practices for malaria at health facilities in a West African country.</p> <p>Methods</p> <p>Cross-sectional surveys were carried out in two urban Gambian primary health facilities (PHFs) during and outside the malaria transmission season. Facilities were comparable in terms of the staffing compliment and capability to perform slide microscopy. Patients treated for malaria were enrolled after consultations and blood smears collected and read at a reference laboratory. Slide reading results from the PHFs were compared to the reference readings and the proportion of cases treated but with a negative test result at the reference laboratory was determined.</p> <p>Results</p> <p>Slide requests were made for 33.2% (173) of those enrolled, being more frequent in children (0-15 yrs) than adults during the wet season (p = 0.003). In the same period, requests were commoner in under-fives compared to older children (p = 0.022); however, a positive test result was 4.4 times more likely in the latter group (p = 0.010). Parasitaemia was confirmed for only 4.7% (10/215) and 12.5% (37/297) of patients in the dry and wet seasons, respectively. The negative predictive value of a PHF slide remained above 97% in both seasons.</p> <p>Conclusions</p> <p>The study provides evidence for considerable overtreatment for malaria in a West African setting comparable to reports from areas with similar low malaria transmission in East Africa. The data suggest that laboratory facilities may be under-used, and that adherence to negative PHF slide results could significantly reduce the degree of overtreatment. The "peak prevalence" in 5-15 year olds may reflect successful implementation of malaria control interventions in under-fives, but point out the need to extend such interventions to older children.</p

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study

BACKGROUND: Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). METHODS: We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. DISCUSSION: In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. TRIAL REGISTRATION: Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT0015093