Membrane separation of indigenous noroviruses from sewage sludge and treated wastewater.

In this study, feasibility of membrane separation for the removal of indigenous noroviruses (NVs) is evaluated. The indigenous NV gene was never detected from ultrafiltration (UF) permeates of sewage sludge and treated wastewater. Indigenous NV gene was also not detected from permeates of sewage sludge and treated wastewater by microfiltration (MF) with a pore size of 0.1 microm (MF0.1). Even though the pore size of MF (0.1 microm) was much larger than the diameter of virus particle (approximately 30-40nm), more than 4-log10 reduction value (LRV) at maximum was achieved by membrane separation with MF0.1. NV genes were often detected from permeates of sewage sludge and treated wastewater by MF with a pore size of 0.45 microm (MF0.45), although the maximum log10 reduction values were more than 3.59 for sewage sludge and more than 2.90 for treated wastewater. It is important to verify factors determining the removal efficiency of viruses with MF membranes.     

Retinal vessel dilatation and elongation precedes diabetic macular oedema

Rolandic discharge (RD), noted in the electroencephalography (EEG) of patients with benign epilepsy in childhood with centrotemporal spikes (BECCT) has several unique features. One feature is that the amount or frequency of RDs does not correlate well with the incidence of seizures in BECCT although it is a key finding in the diagnosis of this epileptic syndrome. In this study, we examined the efficacy of antiepileptic drugs focusing on the disappearance of RDs in relationship with seizure control. Forty patients with BECCT who were not medically treated prior to this study were randomly sorted into three groups. Twenty patients were assigned for clonazepam (CZP) treatment, 10 patients for valproate (VPA) and the remaining 10 patients for carbamazepine (CBZ). Each drug was administered for 4 consecutive weeks. EEGs were recorded twice during the study, before and 4 weeks after the medication trial. The effects of each treatment on RDs were assessed. RDs disappeared in 15 of the 20 cases treated with CZP (75%) within 4 weeks while the same was observed in only one of the 10 cases treated with VPA (10%). CBZ failed to demonstrate any effect on RD. In the group treated with CZP, there were no differences in seizure incidence, seizure type and blood concentration of CZP between the patients whose RDs disappeared and those whose RDs remained.     

Facial myokymia and spastic paretic facial contracture as the result of anaplastic pontocerebellar glioma

The case of a 36-year-old man who sought treatment of right facial myokymia and spastic paretic facial contracture is reported. Computed tomography and magnetic resonance imaging revealed a tumor located in the right cerebellar peduncle and the right dorsal pons bulging into the fourth ventricle. After microsurgical partial resection of the mass, which was verified histologically as an anaplastic glioma, facial myokymia initially ceased. The vermicular rippling movements were less intense upon recurrence and could be controlled by low-dose dexamethasone in the further course, when magnetic resonance imaging showed an interstitial pontine edema after percutaneous radiation therapy. It is assumed that facial myokymia and spastic paretic facial contracture were generated by ectopic activity due to alterations in the microenvironment at the intrapontine portion of the axons of the seventh nerve caused by the compressive effect of the tumor and later by edema.     

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

Development of a monoclonal antibody to 6 beta-hydroxycortisol and its application in an enzyme-linked immunosorbent assay (ELISA) for 6 beta-hydroxycortisol in urine

A novel monoclonal antibody to 6 beta-hydroxycortisol (6 beta-OHC) was generated and incorporated into an antigen-coated indirect enzyme-linked immunosorbent assay (ELISA) using 6 beta-OHC-protein conjugate as the steroid-coating antigen. The monoclonal antibody is specific to 6 beta-OHC and 6 beta-OHC-3-carboxymethyloxime. Cross-reactivity with other structurally related steroids such as cortisol, cortisone, and 6 beta-hydroxycortisone was less than 10%. Two different clones (clone 5C1 and 19F) of the monoclonal anti-6 beta-OHC antibody have been developed, each with slightly different sensitivity and specificity. The sensitivity of the MAb clones was not significantly improved when compared to the rabbit polyclonal antibodies in this study, but still within the accepted detection limit for 6 beta-OHC in both human and laboratory animals. The assay had a detection limit of 200 ng/ml, an intraassay variation of 6.4% and an interassay variation of 7.3%. The application of the anti-6 beta-OHC-MAb-based-ELISA was tested by measuring the urinary output of 6 beta-OHC in human before and after enzyme induction by rifampicin treatment. The mean 24-h urine output of 6 beta-OHC in human subjects was 485 +/- 100 micrograms and 1478 +/- 281 micrograms before and after rifampicin administration, respectively. In conclusion, the monoclonal anti-6 beta-OHC antibody developed in this study has the required specificity and sensitivity as an alternative method for measuring urinary 6 beta-OHC in the detection of enzyme induction or enzyme inhibition of CYP3A in humans and laboratory animals.     

CEO summit. Building the new health care delivery alliance, Part III. Roundtable discussion

In cooperation with McManis Associates, Hospitals & Health Networks recently convened a CEO summit on physician/hospital integration activities. In the third report of a three-part series on the summit, leading health care executives discuss investor capital needs, strategic information management needs, and the management competencies required for capitated managed care success.     

Association of INAD with NORPA is essential for controlled activation and deactivation of Drosophila phototransduction in vivo

Visual transduction in Drosophila is a G protein-coupled phospholipase C-mediated process that leads to depolarization via activation of the transient receptor potential (TRP) calcium channel. Inactivation-no-afterpotential D (INAD) is an adaptor protein containing PDZ domains known to interact with TRP. Immunoprecipitation studies indicate that INAD also binds to eye-specific protein kinase C and the phospholipase C, no-receptor-potential A (NORPA). By overlay assay and site-directed mutagenesis we have defined the essential elements of the NORPA-INAD association and identified three critical residues in the C-terminal tail of NORPA that are required for the interaction. These residues, Phe-Cys-Ala, constitute a novel binding motif distinct from the sequences recognized by the PDZ domain in INAD. To evaluate the functional significance of the INAD-NORPA association in vivo, we generated transgenic flies expressing a modified NORPA, NORPAC1094S, that lacks the INAD interaction. The transgenic animals display a unique electroretinogram phenotype characterized by slow activation and prolonged deactivation. Double mutant analysis suggests a possible inaccessibility of eye-specific protein kinase C to NORPAC1094S, undermining the observed defective deactivation, and that delayed activation may similarly result from NORPAC1094S being unable to localize in close proximity to the TRP channel. We conclude that INAD acts as a scaffold protein that facilitates NORPA-TRP interactions required for gating of the TRP channel in photoreceptor cells.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.