Systematic review of factors contributing to penicillin treatment failure in Streptococcus pyogenes pharyngitis.

OBJECTIVE: Review the evidence for various explanations for microbiologic treatment failure following use of penicillin in group A streptococcal (GAS) tonsillopharyngitis. DATA SOURCE: Systematic review of the literature based on Medline and EMBASE searches, and review of reference lists of included studies. RESULTS: The explanations for penicillin treatment failure in GAS tonsillopharyngitis include 1) carrier state, 2) lack of compliance, 3) recurrent exposure, 4) in vivo copathogenicity of beta-lactamase-producing normal pharyngeal flora, 5) in vivo bacterial coaggregation, 6) poor antibiotic penetration to tonsillopharyngeal tissue, 7) in vivo eradication of normal protective flora, 8) early initiation of antibiotic therapy resulting in suppression of an adequate host immune response, 9) intracellular localization of GAS, 10) GAS tolerance to penicillin, 11) contaminated toothbrushes or orthodontic appliances, and 12) transmission from the family pet. There is very little type I or II evidence to support any of the above-cited explanations for treatment failure in GAS tonsillopharyngitis; available studies are mostly observational (in patients) or laboratory-based without clinical confirmation. CONCLUSION: Multiple explanations have been offered by investigators to explain penicillin treatment failures in GAS tonsillopharyngitis, but the evidence base to support the proposed explanations is generally weak by current standards. Further research is needed to better understand the mechanism(s) of penicillin treatment failure in GAS tonsillopharyngitis.     

Effect of “wet nights” on daytime behavior during concurrent treatment of enuresis and conduct problems

The case study reported in this paper focuses on the relationship between bedwetting and misconduct after the implementation of behavior therapy for both problems. A 6 -year-old girl was treated for enuresis and subsequently for conduct problems (lying, aggressiveness). After both bedwetting and misconduct displayed substantial and stable improvement, it was found that occasional nightly relapses in bedwetting were strongly associated with the occurence of misconduct the following day. Implications of this finding are discussed.     

Rurality, remoteness and the change process: evidence from a study of maternity services in the north of Scotland.

There is a wealth of material on 'how to do' change plus empirical work revealing change process complexity. In health care, the relevance of context is highlighted, but studies of rural health-care change have focused on community impacts. There is little to inform health-care managers of how remoteness and rurality impact upon change processes. This study considered Scottish maternity units and aimed to identify issues in the change process associated with rurality and remoteness. Six units were purposively selected and 131 interviews were conducted with managers, staff and community members over 15 months. Analysis induced themes pertinent to remoteness and rurality. These included: perceived 'distance' between senior managers imposing change and the wider community of staff and residents; perceptions of community vulnerability; and tensions arising from working in small teams and living in small communities. The study provides useful insights for rural managers at a time of considerable service reconfiguration.     

UVB radiation induces phosphorylation of the epidermal growth factor receptor, decreases EGF binding and blocks EGF induction of ornithine decarboxylase gene expression in SV40-transformed human keratinocytes

Abstract We previously demonstrated that epidermal growth factor (EGF) induces a several-fold increase in ornithine decarboxylase (ODC) activity and the steady-state level of ODC mRNA in cultured SV40-transformed human keratinocytes (1). Pretreatment of cell cultures with ultraviolet B (UVB) radiation resulted in a reduction of EGF-induced ODC activity. To determine whether UVB inhibits the accumulation of ODC mRNA by EGF, cells were pretreated with 20 mJ/cm² UVB or sham-irradiated and then incubated with 100 ng/ml EGF. Northern blot analysis revealed that UVB irradiation entirely blocked the EGF induction of ODC mRNA. Since the binding of EGF to its plasma membrane receptor is the first step in initiating a biological response, the effect of UVB on EGF binding was evaluated. UVB treatment of cultured keratinocytes resulted in an immediate and dose-dependent reduction of EGF binding. Scatchard analysis revealed thai the reduction of EGF binding was due to a 52% decrease in the number of available receptors, from 6.2 × 10⁴/cell to 3.0 × 10⁴/cell. However, UVB decreased the EGF-binding affinity very little (Kd = 0.60 nM in control and Kd=0.75 nM in UVB-treated Z114 cells). In addition, UVB did not alter the rate of EGF internalization. These data suggest that UVB blocks the signal transduction pathway of EGF that is involved in regulation of ODC gene expression. Immunoblot analysis of extracts from irradiated cells showed that UVB induced tyro-sine phosphorylation of EGFR and that the quantity of EGFR protein was unaffected by UVB treatment. Phosphorylation of EGFR may be responsible for decreased binding of EGF to its receptor.     

The Complex Nature of Interactive Neuroregeneration-Related Molecules

We review the growing list of molecules that may be involved in wound healing in the central nervous system (CNS). It is known that many of these molecules are present during normal development and neoplastic growth in both neural and nonneural tissues, often in areas where pattern formation or tissue remodeling is evident; however, their functional roles are often quite elusive. In order to understand the changes that occur in and around a brain wound, we review proposed functions of neuroregeneration-related molecules in in vitro and in vivo preparations, as well as note their expression in other healing tissues including skin. A hypothesis that wound healing events in the CNS supersede neuritic growth around a lesion is presented. In contrast to the classical view of failed regeneration, there may be significant amounts of circuit reorganization that occur following injury, and such plasticity may be further enhanced by manipulating the molecular environment around a brain wound and in synaptically related structures.     

Platelet satellitism: experimental studies

Platelet satellitism (PS), the in vitro phenomenon of platelets rosetting about nonlymphocytic leukocytes, is an uncommon and poorly understood finding reported in the ethylenediaminetetra-acetic acid (EDTA)-anticoagulated blood of patients with a wide variety of clinical conditions. This report presents experimental studies investigating the nature of this phenomenon by utilizing the blood of patients with platelet satellitism. Wet preparation studies and electron microscopy (transmission and scanning) demonstrated the morphologic sequences involved in the phenomenon, including eventual phagocytosis of platelets by neutrophils. The results of varying conditions such as time, temperature, and anticoagulant are described. All of five patients tested were found to have cryofibrinogenemia. Certain blood components from all of three patients tested were capable of inducing PS in normal whole blood, whereas components from normal subjects usually were not. In one patient (A), the PS-inducing capability appeared to be present in both plasma and platelets. In another patient (B) the PS-inducing capability was present in platelets (in both 1966 and 1975) and also in the cryosupernate of serum and plasma; among various antisera, antifibrinogen had the greatest ability to reduce the degree of PS in patient blood; addition of moderate amounts of CaCl2 and/or MgCl2 did not diminish the phenomenon; and two sisters and two daughters demonstrated no PS. In a third patient (C) the PS-inducing capability appeared to be largely concentrated in the cryoprecipitable fraction of plasma. These studies suggest that there are different factors in the patients' blood resulting in PS. Further studies showed PS could be induced in normal blood by adding certain nonprimate antihuman antisera (anti-IgM, antialbumin or antifibrinogen) and also by adding some preparations of normal washed platelets to the same individuals's normal whole blood. This indicates that the phenomenon of PS can be produced by factors other than those specifically present in patients with PS. Antigen-antibody complexes, either formed in vivo (mixed cryoglobulinemia) or in vitro, did not result in PS when mixed with normal blood. These and other studies suggest that PS can result from the presence of several different factors, usually proteins (in conjunction with EDTA), which probably attach to the surface of platelets apparently resulting in some alteration (such as change in surface charge) causing the platelets to be attracted to and phagocytosed by neutrophils.     

Craniosynostosis and congenital heart anomalies associated with a maternal deletion of 15q15-22.1

We report an infant with multiple congenital anomalies, including craniosynostosis, tetralogy of Fallot variant, and limb anomalies associated with a maternal deletion of 15q15-22.1. Only two other patients have been reported with a similar deletion, but the deletion was paternal in both cases. We review our patient's findings and compare them to previously reported individuals with similar 15q abnormalities. Our patient allows an expansion of phenotype associated with mid-15q deletions to include severe craniosynostosis, congenital heart disease, and limb anomalies. This will assist in prenatal counseling and predicting postnatal outcome for other affected individuals. The specific breakpoints in our patient and the other patients with similar deletions may also assist in determining a critical region for suture formation.     

A simple plaque assay for influenza A2 viruses and its application to antiviral screening

Summary Influenza A₂/Singapore and A₂/Hong Kong virus strains formed plaques in monolayers of monkey kidney and dog kidney cells. Using a serum-free overlay containing Earle's balanced salt solution with 1% lactalbumin hydrolysate, 1.4 g/1 sodium bicarbonate and 0.6% agarose, plaque formation occurred in 4–7 days. By incorporating compound in the overlay, plaque inhibition was demonstrated by Amantadine, Rimantadine and the isoquinoline derivatives designated Pfizer UK-2054, UK-2617, UK-2762 and UK-2888.