Diarrhetic Shellfish Poisoning,Washington, USA, 2011

Diarrhetic shellfish poisoning is a gastrointestinal illness caused by consumption of bivalves contaminated with dinophysistoxins. We report an illness cluster in the United States in which toxins were confirmed in shellfish from a commercial harvest area, leading to product recall. Ongoing surveillance is needed to prevent similar illness outbreaks.     

Validation of a reference control for an SYBR-Green fluorescence assay-based real-time PCR for detection of bovine herpesvirus 5 in experimentally exposed bovine embryos

The objective of this study was to optimize an internal control to improve SYBR-Green-based qPCR to amplify/detect the BoHV-5 US9 gene in bovine embryos produced in vitro and experimentally exposed to the virus. We designed an SYBR-Green-based binding assay that is quick to perform, reliable, easily optimized and compares well with the published assay. Herein we demonstrated its general applicability to detect BoHV-5 US9 gene in bovine embryos produced in vitro experimentally exposed to BoHV-5. In order to validate the assay, three different reference genes were tested; and the histone 2a gene was shown to be the most adequate for normalizing the qPCR reaction, by considering melting and standard curves (p < 0.05). On the other hand, no differences were found in the development of bovine embryos in vitro whether they were exposed to BoHV-5 reference and field strains comparing to unexposed embryos. The developed qPCR assay may have important field applications as it provides an accurate BoHV-5 US9 gene detection using a proven reference gene and is considerably less expensive than the TaqMan qPCR currently employed in sanitary programs.     

Statin-Associated Polymyositis Following Omeprazole Treatment

Statins are an extensively used class of drugs, and myopathy is an uncommon, but well-described side effect of statin therapy. Inflammatory myopathies, including polymyositis, dermatomyositis, and necrotizing autoimmune myopathy, are even more rare, but debilitating, side effects of statin therapy that are characterized by the persistence of symptoms even after discontinuation of the drug. It is important to differentiate statin-associated inflammatory myopathies from other self-limited myopathies, as the disease often requires multiple immunosuppressive therapies. Drug interactions increase the risk of statin-associated toxic myopathy, but no risk factors for statin-associated inflammatory myopathies have been established. Here we describe the case of a man, age 59 years, who had been treated with a combination of atorvastatin and gemfibrozil for approximately 5 years and developed polymyositis after treatment with omeprazole for 7 months. Symptoms did not resolve after discontinuation of the atorvastatin, gemfibrozil, and omeprazole. The patient was treated with prednisone and methotrexate followed by intravenous immunoglobulin, which resulted in normalization of creatinine kinase levels and resolution of symptoms after 14 weeks. It is unclear if polymyositis was triggered by interaction of the statin with omeprazole and/or gemfibrozil, or if it developed secondary to long-term use of atorvastatin only.     

Superior vena cava obstruction: bypass using spiral vein graft.

BACKGROUND: Previous midterm experience with the composite spiral saphenous vein graft to bypass the obstructed superior vena cava (SVC) has been favorable. This study looks at the long-term results in patients followed for up to 23 years. METHODS: Sixteen patients aged 17 to 68 years had operation for obstruction of the SVC with SVC syndrome caused by benign disease. Eleven patients had fibrosing mediastinitis with or without caseous necrosis, 4 had thrombosis caused by a catheter or a pacemaker electrode, and 1 had spontaneous thrombosis. All operations were performed using a composite spiral vein graft constructed from the patient's own saphenous vein. Graft diameter ranged from 9.5 to 15.0 mm. Ten grafts were from the left innominate vein, and six grafts were from the right or left internal jugular vein. The grafts were placed to the right atrial appendage in all patients except 1. Follow-up extends from 1 month to 23 years 8 months (mean follow-up, 10.9 years). RESULTS: Fourteen of 16 grafts remain patent for up to 23 years, and all patients but 1 are free from SVC syndrome. One patient required revision of the graft for thrombosis 4 days after operation. Two grafts closed during the first year after operation: one because of recurrence of spontaneous venous thrombosis and the other because of aggressive fibrosing mediastinitis requiring operation for graft revision three times over a 12-year period prior to death. CONCLUSIONS: These data demonstrate that a spiral vein bypass graft for treatment of the obstructed SVC relieves SVC syndrome and has excellent long-term patency.     

Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation

Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.     

Predictive factors of excess body weight loss 1?year after laparoscopic bariatric surgery

Background

Bariatric surgery (BS) is widely accepted for the treatment of patients with morbid obesity (MO). We aimed to determine presurgical predictors of and surgical technique-related differences in excess weight loss (EWL) 1?year after BS.

Methods

This retrospective study included 407 subjects (F/M 3:1, median age?=?44?years) who underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n?=?307) or sleeve gastrectomy (SG, n?=?100) at our University Hospital and were evaluated 1?year after surgery.

Results

Baseline median (min–max) body mass index (BMI) was 47?kg/m² (range?=?36–71). BMI was higher in the SG than in the RYGB group (53 vs. 46?kg/m², p?p?p?=?0.2), was lower in diabetic than in nondiabetic subjects (71?±?17% vs. 79?±?17%, p?p?p?=?0.4) after taking into account baseline BMI. Multiple regression and logistic analysis showed that younger individuals with lower BMI but higher WC, and lower HbA1c and TG, had higher EWL and a higher rate of successful (EWL?≥?60%) weight loss.

Conclusions

Our data indicate that some of the characteristics that would have subjects referred early for BS were associated with higher weight loss. Therefore, the timing of laparoscopic BS might be an important factor for MO individuals in which medical weight loss intervention has failed.     

Clinical patterns of spontaneous recovery of paralyzed triceps brachii associated with C5 to C7 injuries of the brachial plexus

Some patients who sustain C5 to C7 nerve root injuries may demonstrate a natural recovery of elbow extension via the lower trunk; however the surgical effect of the reinnervation of the triceps brachii in such cases is still unknown. This study aims to determine the incidence of spontaneous recovery of the tricipital function and to identify the clinical and/or radiological predictors of poor spontaneous functional rehabilitation of elbow extension resulting from injuries of the upper roots of the brachial plexus. We conducted a review of the charts of 24 subjects sustaining an upper trunk syndrome with complete elbow extension palsy and who did not undergone any intervention for reinnervation of the triceps brachii in the primary brachial plexus surgery. Two years posttrauma, the muscle was scored as M0 in 12 patients (50%), M1 in 3 (12.5%), M2 in 1 (4.1%), M3 in 4 (16.6%), and M4 in 4 subjects (16.6%). The number of avulsed roots and the preoperative power of the latissimus dorsi did not demonstrate any significance in predicting the outcome of spontaneous elbow extension recovery; whereas the preoperative paralysis of the muscles for wrist extension was determined to be reliable predictive parameter for poor natural recovery of tricipital function.     

Racial differences in rate of decline in bone mass in older men: the Baltimore men's osteoporosis study.

Older black men have higher adjusted BMD than older white men. Using data from a longitudinal cohort study of older men followed for a mean of 18.8 +/- 6.5 (SD) months, we found that older black men have a higher rate of decline in femoral neck and total hip BMD and femoral neck BMAD than older white men. INTRODUCTION: Older black men have higher adjusted BMD compared with older white men. The difference in BMD may be caused by having attained higher peak bone mass as young adults and/or having a slower rate of decline in bone mass as adults. There are few published longitudinal data on change in bone mass in older white men and no published data for older black men. MATERIALS AND METHODS: Three hundred forty-nine white men and 119 black men 65 of age (mean age, 75 +/- 5.7 and 72 +/- 5.6 years, respectively) who participated in the longitudinal component of the Baltimore Men's Osteoporosis Study returned for a second visit after a mean of 18.8 +/- 6.5 (SD) months and were not taking medications used to treat low bone mass at either visit. BMD was measured at the femoral neck and total hip by Hologic-certified technicians using a QDR 2000 at the baseline visit (V1) and QDR 4500 at the first follow-up visit (V2). Participants also completed self-administered and interviewer-administered questionnaires and underwent standardized clinic examinations. Bone mineral apparent density (BMAD) at the femoral neck was calculated as an estimate of volumetric BMD. Annual crude and multiple variable adjusted percent changes in BMD and BMAD were calculated. RESULTS: In univariate analyses, black men had lower percent decline in femoral neck and total hip BMD and femoral neck BMAD than white men. In addition, older age at baseline, lower baseline weight, current smoking, and lower baseline BMD were associated with greater percent decline per year in femoral neck BMD; older age at baseline, current smoking, and lower baseline BMD were associated with greater percent decline per year in total hip BMD; and older age at baseline and lower baseline femoral neck BMAD were associated with greater percent decline per year in femoral neck BMAD. Racial differences in bone loss persisted in multiple variable models that controlled for other factors associated with change in BMD and BMAD. CONCLUSIONS: Older black men seem to lose bone mass at a slower rate than older white men. These differences in the rate of bone loss may account, in part, for the racial disparities in BMD and BMAD and risk of osteoporotic fractures among older men.     

New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy.

In vitro data have demonstrated a high amount of receptors for various hormones and peptides on malignant cells of neuroendocrine origin. Among these, binding sites for members of the SST-family (hSSTR1-5) are frequently found, and their expression has led to therapeutic and diagnostic attempts to specifically target these receptors. Receptor scintigraphy using radiolabeled peptide ligands has proven its effectiveness in clinical practice. In addition, initial results have indicated a clinical potential for receptor-targeted radiotherapy. Based on somatostatin (SST) receptor (R) recognition, the novel radiopharmaceuticals 111In/90Y-DOTA-lanreotide developed at the University of Vienna as well as 111In/90Y-DOTA-DPhe1-Tyr3-octreotide (NOVARTIS) both have provided promising data for diagnosis and treatment of hSSTR-positive tumors. SSTR scintigraphy using 111In-DTPA-DPhe1-octreotide has a high positive predictive value for the vast majority of neuroendocrine tumors and has gained its place in the diagnostic work-up as well as follow-up of patients. We have used 111In-DOTA-lanreotide scintigraphy in 166 patients since 1997 and have seen positive results in 93% of patients. In 42 patients with neuroendocrine tumors comparative data were obtained. As opposed to 111In-DTPA-DPhe1-octreotide and 111In-DOTA-DPhe1-Tyr3-octreotide, discrepancies in the scintigraphic results were seen in about one third of patients concerning both the tumor uptake as well as tumor lesion detection. Initial results both with 90Y-DOTA-lanreotide as well as 90Y-DOTA-DPhe1-Tyr3-octreotide has pointed out the clinical potential of radionuclide receptor-targeted radiotherapy. This new therapy could offer palliation and disease control at a reduced cost. The final peptide therapy strategy is most probably cheaper than conventional radiotherapies or prolonged chemotherapies. Overall, receptor-mediated radiotherapy with 90Y-DOTA-lanreotide/90Y-DOTA-DPhe1-Tyr3-octre otide might also be effective in patients refractory to conventional strategies.     

Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts

BACKGROUND: Janus Kinase (JAK) 3 is a tyrosine kinase essential for proper signal transduction downstream of selected cytokine receptors and for robust T-cell and natural killer cells activation and function. JAK3 inhibition with CP-690,550 prevents acute allograft rejection. To provide further insight into the mechanisms of efficacy, we investigated the immunomodulatory effects of CP-690,550 in vitro and in vivo in nonhuman primates. METHODS: Pharmacodynamic assessments of lymphocyte activation, function, proliferation and phenotype were performed in three settings: in vitro in whole blood isolated from untransplanted cynomolgus monkeys (cynos), in vivo in blood from untransplanted cynos dosed with CP-690,550 for 8 days, and in vivo in blood from transplanted cynos immunosuppressed with CP-690,550. Cell surface activation markers expression, IL-2- enhanced IFN-gamma production, lymphocyte proliferation and immune cell phenotype analyzes were performed with multiparametric flow cytometry. RESULTS: In vitro exposure to CP-690,550 resulted in significant reduction of IL-2-enhanced IFN-gamma production by T-cells (maximum inhibition of 55-63%), T-cell surface expression of CD25 (50% inhibitory concentration (IC50); 0.18 microM) and CD71 (IC50; 1.6 microM), and T-cell proliferative capacities measured by proliferating cell nuclear antigen expression (IC50; 0.87 microM). Similar results were observed in animals dosed with CP-690,550. In addition, transplanted animals displayed significant reduction of NK cell (90% from baseline) and T-cell numbers whereas CD8 effector memory T-cell populations were unaffected. CONCLUSIONS: Potent in vitro and in vivo immunomodulatory effects of the JAK3 inhibitor CP-690,550 likely contribute to its efficacy in the prevention of organ allograft rejection.