Chronic progressive multiple sclerosis: double-blind controlled study of plasmapheresis in patients taking immunosuppressive drugs

Fifty-four patients with chronic progressive multiple sclerosis received prednisone plus oral low-dose cyclophosphamide and either true plasmapheresis (PP) or "sham" PP weekly for 20 weeks in a double-blind controlled study. Immunosuppressive drug therapy alone (sham PP group, n = 29) was associated with improvement (greater than or equal to one step in Kurtzke Disability Status Scale [DSS]; mean change of 1.5) in 8 and stabilization of MS in 18 patients, with this status sustained in 23 patients at follow-up, 11 months after entry. In contrast, 14 of 26 patients who received "true" PP improved (greater than or equal to one step in DSS; mean change of 2.6), and 11 more were stable, with these changes sustained in 23 of 26 patients at follow-up. These differences, overall, between the PP and sham PP groups were significant at p less than 0.007.     

Effects of the co-carcinogen catechol on benzo[a]pyrene metabolism and DNA adduct formation in mouse skin

We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene)on the metabolic activation of [³H] benzo[a]pyrene (BaP) inmouse skin, in vivo and on the binding of BaP metabolites toDNA and protein at intervals from 0.5–24 h. Upon topicalapplication of 0.015 mg [³H]BaP and 0.25 or 0.5 mg catecholper mouse, catechol had little effect on the total amount of[³H]BaP metabolized in mouse skin, but it affected the relativeproportions of [³H]BaP metabolites. Catechol (0.5 mg/mouse)decreased the proportion of watersoluble [³H]BaP metabolites,ethyl acetate-soluble polar metabolites and quinones, but doubledthe levels of unconjugated 3-hydroxy-BaP at all measured intervalsafter treatment. Catechol also caused a small increase in thelevels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP0.5 h after treatment. Two hours after treatment, the levelsof these metabolites subsided to those of the controls. Catecholdid not affect the levels of glutathione conjugates of BaP.However, it caused a decrease in glucuronide and sulphate conjugateformation from BaP. Catechol caused an 2-fold increase in theformation of anti-7, 8-dihydroxy-9, 10-epoxy-7, 8, 9, 10-tetrahydroBaP(BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNAadducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivityassociated with epidermal proteins after [³H]BaP application.Because catechol increased levels of 3-hydroxyBaP, we consideredthe possibility that 3-hy-droxyBaP might enhance the tumor initiatingactivities of BaP or BPDE in mouse skin; a bioassay demonstratedthat this was not the case. The results of this study indicatethat one important effect of catechol related to its co-carcinogenicityis its ability to enhance formation of anti-BPDE-DNA adductsin mouse skin.     

A strategy to reduce drug expenditures with a drug utilization review program

This paper describes a potential strategy for implementing a Drug Utilization Review (DUR) program aimed at reducing hospital drug expenditures. The importance of this type of program is underscored by the spiraling rise in health care expenditures and the influence of a new drug technology on this rise. The program described here consists of a utilization review program for high cost drugs for which a lower cost alternative exists. An initial retrospective usage and cost analysis must be undertaken to identify those drugs which should be reviewed initially. As the DUR program progresses, additional drugs can be added to the review program. Once the drugs to be reviewed are identified, the first step is to develop usage criteria. This can be accomplished through a review of the literature and consultation with medical and other specialists. Appropriate medical administrative staff approval and endorsement of the criteria should be obtained utilizing various committee structures and other input. The pharmacy staff must also be inserviced on the approved drug usage criteria. After the criteria are finalized, staff pharmacists will contact a DUR pharmacist daily upon receipt of any physician orders for the review drugs. This pharmacist will then compare the prescribed drug use to the approved criteria and contact the prescriber when the usage appears questionable. A lower cost therapy will then be recommended when appropriate. In order to assess the impact of this intervention strategy on drug expenditures, the cost of the initially prescribed therapies must be compared to the recommended therapies. Data should also be obtained on overall drug usage and expenditures to detect shifts in therapy and drug costs. The success or failure of this concurrent DUR program will be highly dependent upon a team approach and cooperation. A program of this type could have a significant impact on hospital drug expenditures in those hospitals where it can be successfully implemented.     

Risks in Management of Enteral Nutrition in Intensive Care Units: A Literature Review and Narrative Synthesis

Critically ill patients in the intensive care unit (ICU) have a high risk of developing malnutrition, and this is associated with poorer clinical outcomes. In clinical practice, nutrition, including enteral nutrition (EN), is often not prioritized. Resulting from this, risks and safety issues for patients and healthcare professionals can emerge. The aim of this literature review, inspired by the Rapid Review Guidebook by Dobbins, 2017, was to identify risks and safety issues for patient safety in the management of EN in critically ill patients in the ICU. Three databases were used to identify studies between 2009 and 2020. We assessed 3495 studies for eligibility and included 62 in our narrative synthesis. Several risks and problems were identified: No use of clinical assessment or screening nutrition assessment, inadequate tube management, missing energy target, missing a nutritionist, bad hygiene and handling, wrong time management and speed, nutritional interruptions, wrong body position, gastrointestinal complication and infections, missing or not using guidelines, understaffing, and lack of education. Raising awareness of these risks is a central aspect in patient safety in ICU. Clinical experts can use a checklist with 12 identified top risks and the recommendations drawn up to carry out their own risk analysis in clinical practice.     

Postmortem Stability of SARS-CoV-2 in Nasopharyngeal Mucosa

Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem.     

Experimental SARS-CoV-2 Infection of Bank Voles

After experimental inoculation, severe acute respiratory syndrome coronavirus 2 infection was confirmed in bank voles by seroconversion within 8 days and detection of viral RNA in nasal tissue for up to 21 days. However, transmission to contact animals was not detected. Thus, bank voles are unlikely to establish effective transmission cycles in nature.     

Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology,Germany, 2018–2020

Human bornavirus encephalitis is a severe and often fatal infection caused by variegated squirrel bornavirus 1 (VSBV-1) and Borna disease virus 1 (BoDV-1). We conducted a prospective study of bornavirus etiology of encephalitis cases in Germany during 2018–2020 by using a serologic testing scheme applied along proposed graded case definitions for VSBV-1, BoDV-1, and unspecified bornavirus encephalitis. Of 103 encephalitis cases of unknown etiology, 4 bornavirus infections were detected serologically. One chronic case was caused by VSBV-1 after occupational-related contact of a person with exotic squirrels, and 3 acute cases were caused by BoDV-1 in virus-endemic areas. All 4 case-patients died. Bornavirus etiology could be confirmed by molecular methods. Serologic testing for these cases was virus specific, discriminatory, and a practical diagnostic option for living patients if no brain tissue samples are available. This testing should be guided by clinical and epidemiologic suspicions, such as residence in virus-endemic areas and animal exposure.     

Analysis of odontoblast gene expression using a novel approach,laser capture microdissection

Studying the mechanisms of molecular interactions in developing tissues demands sensitive molecular biological in vivo and in vitro techniques. Laser capture microdissection (LCM) allows for the isolation of mRNA in histological sections even from single cells, thus enabling the identification of in vivo gene expression products in closely circumscribed tissue areas. The aims of this study were to assess the optimal fixation, processing, and staining conditions to retrieve RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha 1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA isolated from day 0 and day 3 captured odontoblasts was sufficient in quantity and quality. Our results indicate that individual odontoblasts obtained by LCM are morphologically intact and chemically unaltered, allowing accurate molecular and biochemical analyses.