Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: a model of the pathogenesis of severe orthomyxovirus infection

After intranasal, subcutaneous, or intraperitoneal infection with Dhori virus (DHOV), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with H5N1 highly pathogenic avian influenza A virus. Histopathologic findings in lungs of DHOV-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. Extra-pulmonary findings included hepatocellular necrosis and steatosis, widespread severe fibrinoid necrosis in lymphoid organs, marked lymphocyte loss and karyorrhexis, and neuronal degeneration in brain. Similar systemic histopathologic findings have been reported in the few fatal human H5N1 cases examined at autopsy. Because of the relationship of DHOV to the influenza viruses, its biosafety level 2 status, and its similar pathology in mice, the DHOV-mouse model may offer a low-cost, relatively safe, and realistic animal model for studies on the pathogenesis and management of H5N1 virus infection.     

Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications

Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis in vitro. We have now examined whether PF4 regulates megakaryopoiesis in vivo by studying PF4 knockout mice and transgenic mice that overexpress human (h) PF4. Steady-state platelet count and thrombocrit in these animals was inversely related to platelet PF4 content. Growth of megakaryocyte colonies was also inversely related to platelet PF4 content. Function-blocking anti-PF4 antibody reversed this inhibition of megakaryocyte colony growth, indicating the importance of local PF4 released from developing megakaryocytes. The effect of megakaryocyte damage and release of PF4 on 5-fluorouracil-induced marrow failure was then examined. Severity of thrombocytopenia and time to recovery of platelet counts were inversely related to initial PF4 content. Recovery was faster and more extensive, especially in PF4-overexpressing mice, after treatment with anti-PF4 blocking antibodies, suggesting a means to limit the duration of such a chemotherapy-induced thrombocytopenia, especially in individuals with high endogenous levels of PF4. We found that approximately 8% of 250 healthy adults have elevated (> 2 times average) platelet PF4 content. These individuals with high levels of platelet PF4 may be especially sensitive to developing thrombocytopenia after bone marrow injury and may benefit from approaches that block the effects of released PF4.     

Is Patient Outcome Affected by the Administration of Intravenous Fluid During Bowel Preparation for Colonic Surgery?

INTRODUCTION

We have previously shown that Picolax® bowel preparation causes a significant dehydrating effect, which can be minimised by administering a calculated volume of intravenous fluid. The aim of this prospective study was to assess whether peri-operative outcome is affected by administering a calculated volume of intravenous fluid during bowel preparation.

PATIENTS AND METHODS

Patients having bowel preparation (Picolax®: Ferring Pharmaceuticals Ltd, Middlesex, UK) prior to colonic surgery were prospectively randomised to receive no intravenous fluid (group 1) or calculated intravenous crystalloid based on their body weight (group 2), during preparation. In both groups, transfusion was protocol-driven. Outcome variables measured included intra-operative and postoperative intravenous fluid requirement, hourly recorded urine output for 24 h, number of patients transfused, number of units of blood transfused, time to the passage of flatus, time to having their bowels open, time until tolerating a full diet, complications and length of stay in hospital.

RESULTS

Thirty-three patients were recruited – group 1 (n = 18) and group 2 (n = 15). There were 24 men and 9 women, median age 69 years (range, 29–86 years). There was no significant difference between the groups with respect to age, sex, weight, ASA grade, preoperative haemoglobin concentration, duration or type of operation. The total number of patients receiving a transfusion (P = 0.026) and the number of units of blood transfused (P = 0.017) was significantly greater in group 1. The number of units of blood transfused intra-operatively was significantly greater in group 1 (P = 0.029). Significantly fewer patients had a urine output <30 ml/h in the first 24-h after operation (P = 0.046) in group 2. There was no difference between groups in other outcomes measures.

CONCLUSIONS

This study indicates that a calculated volume of intravenous fluid administered during bowel preparation improves patient outcomes with respect to blood transfusion and postoperative oliguria. We advocate calculated intravenous fluid administration in all patients undergoing bowel preparation prior to colonic surgery.     

The pedicled 'policeman' flap salvage of exposed vascular prosthesis - a case report

A case report of a patient with exposed, infected, subcutaneous, extra-anatomical, vascular prosthesis is presented, which was successfully salvaged using pedicled omental flap after other reconstructive procedures had failed.     

Screen for Child Anxiety Related Emotional Disorders (SCARED): psychometric properties in an African-American parochial high school sample

OBJECTIVE: To examine the psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED) for a community sample of African-American high school students. METHOD: The 41-item SCARED was administered to 111 adolescents (57 girls; mean age 15.75) in an urban parochial school. Item frequency, internal consistency, test-retest reliability, and construct validity were assessed. RESULTS: Approximately 30% of the sample had scores high enough to warrant further assessment for anxiety disorders, and girls reported significantly higher anxiety symptoms than boys. Internal consistency (alpha =.89) and test-retest reliability (r = 0.47) over 6 months for the SCARED's total score were good. The SCARED's total score was positively correlated with other measures of anxiety symptoms and inattention and was negatively correlated with perceived self-worth. Unlike the five-factor structure reported for primarily white samples, only three factors emerged for this African-American sample. CONCLUSIONS: The SCARED shows utility as a self-report anxiety screening instrument in a community sample of African-American youths.     

Umstellung von typischen auf atypische Neuroleptika Richtlinien zur ambulanten und stationären Behandlung

The introduction of atypical antipsychotics has presented new options for the pharmacological treatment of schizophrenic patients. It is assumed that in the near future, neuroleptic medication will shift from conventional to atypical antipsychotics for an increasing number of patients. The present article addresses guidelines for the conversion from conventional to atypical neuroleptics in inpatient and outpatient settings.     

Interactions of human Myosin Va isoforms,endogenously expressed in human melanocytes,are tightly regulated by the tail domain

Primary human epidermal melanocytes express six endogenous isoforms of the human actin-associated myosin Va motor protein, involved in organelle transport. As isoforms containing exon F are most abundant in melanocytes, we hypothesized that these isoforms probably have a melanocyte-specific function. To uncover the biologic role of the six isoforms we introduced enhanced green fluorescent protein (eGFP)-myosin Va tail constructs in human melanocytes. We found that the medial tail, undergoing alternative splicing, has to be expressed in combination with the globular tail in order to obtain clear colocalization with organelles. Our data show that isoforms lacking exon F but containing exon D are associated with vesicles near the Golgi area. Myosin Va isoforms containing exon F are able to colocalize with and influence melanosome distribution by indirect interaction with rab27a and direct interaction with melanophilin. These results indicate that the myosin Va medial tail domain provides the globular tail domain with organelle-interacting specificity.     

Update on the safety of itraconazole pulse therapy in onychomycosis and dermatomycoses

As the use of newer antifungal agents becomes more widespread, safety issues surrounding their use have become more important. To date, the safety profile of itraconazole has been well defined by its worldwide use in 50 million patients over the past 13 years. Data from clinical practice and clinical trials indicate that the 1-week pulse regimen of itraconazole is well tolerated and associated with a favourable safety profile. Adverse events are generally mild and transient. Furthermore, a dose increase to 400 mg in the pulse regimen has had no adverse impact on safety.