Selective inactivation of viruses in the presence of human platelets: UV sensitization with psoralen derivatives.

Inactivation of viruses in blood products requires that the method employed display selectivity in its action for viral elements while not affecting the biological entity of interest. Several methods have been developed for the treatment of human plasma or products derived from human plasma. An effective technique for the treatment of the cellular components of blood has been lacking, in part due to the inability to develop agents capable of selectively targeting viral agents in the milieu of cellular material. In this paper, we examine the behavior of a group of viral sensitizers designed to be added to cellular samples and be activated upon exposure to UVA light. Upon activation, these agents are capable of disrupting nucleic acids of the virus in a manner that renders them inactive for proliferation. The selectivity observed in this inactivation is determined by the chemical structure of the sensitizer, which can be varied to increase viral killing capacity while diminishing collateral damage to cellular and protein constituents.     

Candidaemia: a 10-year study in an Indian teaching hospital

Retrospective evaluation of candidaemia patients was performed in an Indian teaching hospital over a 10-year period. The incidence of patients with candidaemia increased eleven-fold in the second half of the study period (55 patients) compared with the first half (5 patients). Haematological malignancies (11 patients), neonatal septicaemia (9), cardiac abnormalities and cardiac surgery (9) were the commonest underlying diseases in these patients. Candida albicans (50%), C. guilliermondii (17%), C. tropicalis (15%) and C. parapsilosis (8%) were the most common fungal pathogens isolated from blood culture. Therapy with two or more antibiotics (92%), corticosteroid administration (25%), intravascular catheter use for over 24 h (78%) and neutropenia (48%) were the accountable predisposing factors. Prolonged hospitalization (mean average 22.2 days as compared with 11.2 days in other patients) was an added risk factor in these patients.     

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.     

The association between non-melanoma skin cancer and osteoporotic fractures—a population-based record linkage study

Summary We studied the association between osteoporotic fractures and prior non-melanoma skin cancer (NMSC, a biomarker for cumulative sun exposure). The risk of prior NMSC in our fracture cohort was significantly reduced (standardised incidence ratio 0.69, 95% CI 0.61, 0.78). Adequate lifetime sun exposure may be necessary to protect against osteoporotic fractures in later life. Introduction The relationship between cumulative sun exposure and osteoporotic fractures is uncertain. We aimed to study the association between non-melanoma skin cancer (NMSC), a marker of cumulative sun exposure, and osteoporotic fractures in an older cohort. Methods A retrospective cohort study in southern Tasmania in people aged at least 50 years with incident radiographic fracture (n = 2,283) was carried out. By record linkage to the Tasmanian Cancer Registry the cohort was followed backwards through time until the occurrence of NMSC or end-of follow-up. Relative risk was estimated by the standardised incidence ratio (SIR) using sex-, age- and calendar year-specific cancer incidence rates in southern Tasmania as reference. Results The incidence of prior NMSC in the fracture cohort was 31% lower than for the general population (SIR 0.69, 95% CI 0.61, 0.78). This effect was significant for most fracture subtypes except pelvic and wrist fractures and observed for both NMSC subtypes, squamous cell carcinoma and basal cell carcinoma. Conclusions Older people with osteoporotic fractures may have had lifestyles linked to lower cumulative sunlight exposure. Achieving a balance between adequate lifetime sun exposure and protection against its adverse effects (such as fractures and skin cancer) may require assessment of individual risks.     

The validity of brief screening cognitive instruments in the diagnosis of cognitive impairment and dementia after first-ever stroke

INTRODUCTION: Brief cognitive tests such as the Mini-mental State Examination (MMSE) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) have been used to detect cognitive impairment and dementia in studies of stroke patients. However, there are few data on their validity for such use. We have evaluated their validity in detecting cognitive impairment not dementia (CIND) and dementia in a community-based sample of first-ever stroke patients. METHODS: The standardized MMSE (S-MMSE) and the 16-item IQCODE were administered to 79 patients 1 year after a first-ever stroke. CIND and dementia were diagnosed independently using a comprehensive cognitive battery. The performances of the two tests were evaluated using receiver operating characteristic (ROC) analyses. Combined performance was evaluated when their scores were used in parallel (the "or rule"), in series (the "and rule") or as a weighted sum (the "weighted sum rule"). RESULTS: Both tests were extremely poor at detecting CIND individually and in combination. For dementia, at traditional cut-points, the S-MMSE (< or =23) was insensitive (0.50, 95% CI 0.16-0.84) and the IQCODE (> or =3.30) nonspecific (0.63, 95% CI 0.51-0.75). An acceptable balance between sensitivity and specificity was achieved for dementia using the "or rule" combination, but with only modest positive predictive value. CONCLUSIONS: The S-MMSE and the IQCODE were individually poor at detecting CIND and dementia after a nonaphasic first-ever stroke. The combination was useful in detecting dementia but it does not replace the need for detailed neuropsychological tests.     

APACHE-II scoring system in perforative peritonitis

BACKGROUND: Prospective assessment of the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) scoring system of stratification of disease severity has been shown to provide objective discrimination between low-risk and high-risk groups of patients with intra-abdominal sepsis. The current study was undertaken to evaluate the performance of APACHE-II score in prediction of mortality risk in patients with peritonitis due to hollow viscus perforation. STUDY DESIGN: Fifty patients admitted to a teaching hospital with peritonitis due to hollow viscus perforation were prospectively studied over a 2-year period. APACHE-II points were assigned to all patients in order to calculate their individual risk of mortality before undergoing emergency surgery. The accuracy in outcome prediction of the APACHE-II system was assessed by means of receiver operating characteristic (ROC) curve and the Pearson correlation coefficient and its significance test. RESULTS: Of the 50 patients admitted during the study period, there were 42 (84%) survivors and 8 (16%) nonsurvivors. Mean APACHE-II score of the study population was 11.38 with a range of 1 to 23. The predicted death rate was 23% and the observed death rate was 16%. Mean APACHE-II score in survivors was 9.88, whereas in nonsurvivors it was 19.25. Using ROC analysis, the area under the curve was found to be .984. Correlation of APACHE-II score and predicted death rate showed perfect correlation, with r = .99 and P <.001 [R2 = .9993]. APACHE-II score between 11 and 15 showed a sensitivity and specificity of 100% and 73.8%, respectively, and APACHE-II score of 16 to 20 had a sensitivity and specificity of 87.5% and 100%, respectively. CONCLUSION: APACHE-II score between 11 and 20 was shown to be a better predictor of risk of mortality in patients with peritonitis due to hollow viscus perforation. Predicted mortality did not correlate with observed mortality in patients with APACHE-II scores of 1 to 10 and greater than 20. The APACHE-II scoring system can be used to assess group outcomes in patients with peritonitis due to hollow viscus perforation. However, it does not provide sufficient confidence for outcome prediction in individual patients.     

Computed Tomography Patterns in Small Bowel Obstruction after Open Distal Gastric Bypass

Background: Life-threatening small bowel obstruction (SBO) after Roux-en-Y gastric bypass can present with surprisingly minimal laboratory and plain x-ray findings. Based on a 10-year (1994-2003) experience of 1,409 open distal gastric bypasses, we present clinical and radiological findings in 29 patients with unusual forms of bowel obstruction. Methods: A retrospective chart review was conducted. A radiologist experienced in reviewing these in gastric bypass patients reviewed all computed tomography (CT) scans. Results: CT findings: The normal appearance and 7 recurring patterns of small bowel obstruction were identified. These include: 1) intussusception, 2) internal hernia through Petersen's space, 3) through Petersen's space and the mesenteric defect at enteroenterostomy, 4) through the mesenteric defect from the entero-enterostomy, 5) isolated biliary limb obstruction, 6) segmental non-anastomotic ischemia, and 7) internal hernia through bands. Clinical findings: 1 had peritonitis, and 1 had free air on plain film. WBC count was normal in 20/27 patients (74%) including 5/6 (83%) with dead bowel. 9/14 patients (62%) had "non-specific" findings on x-rays. 7 of these had an internal hernia (2 with volvulus and 2 with dead bowel), 1 had biliopancreatic limb obstruction, and 1 had peritonitis. Conclusion: Patients with SBO after distal gastric bypass may present with vague complaints and confusing laboratory and non-specific findings on x-rays. Delayed diagnosis can have catastrophic consequences. CT imaging with oral and intravenous contrast can be life-saving, and should be obtained in all gastric bypass patients with abdominal pain, particularly when all other parameters seem "normal". Unexplained abdominal pain should prompt exploration.     

Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion

BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain viability of non-heart-beating donor (NHBD) livers that have undergone significant warm ischemic injury. However, the logistics of clinical organ retrieval are complex, and a period of cold storage before warm preservation would simplify the process. We have investigated the effects of short duration of cold preservation before normothermic preservation on the function of porcine NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm ischemia and then assigned to the following groups: group W (n=5), normothermic preservation for 24 hours; and group C (n=4), cold preservation in University of Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours (total preservation time 24 hours). Outcome parameters that were measured included bile production, serum transaminases and hyaluronic acid levels (cellular damage), and base deficit and glucose use (metabolic function). RESULTS: Group W livers had superior bile production, metabolic activity (base deficit and greater glucose use), and less evidence of hepatocellular damage (alanine aminotransferase, aspartate aminotransferase), and sinusoidal endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater necrosis and destruction of architecture on histology. CONCLUSION: Normothermic perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia and 4 hours of cold preservation. Even a short period of cold ischemia is significantly deleterious to the function of ischemically damaged (NHBD) livers.