Cardiomyopathies with particular reference to the diagnostic relevance of endomyocardial biopsies

A distinction is made between heart muscle diseases with a known cause, or occurring as part of a systemic disease, and those of unknown cause. The first category is termed "specific heart muscle disease". The term "cardiomyopathy" is then limited to the latter category. Cardiomyopathies are categorized as dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy. The pathology of dilated cardiomyopathy depends on the clinical stage of the disease. Basically, the histology shows hypertrophic myocytes, often with degenerative signs, and interstitial fibrosis. Lymphocytes may be observed, particularly in cases studied shortly after the onset of symptoms. Endocardial thickening may occur in time. The role of endomyocardial biopsies in the clinical setting is limited and relates mainly to excluding other diseases, such as myocarditis. The pathology of hypertrophic cardiomyopathy is characterized by myocardial wall thickening, either asymmetric or symmetric, and disorganization of the normal myocardial texture. The latter phenomenon should be distinguished from disarray, since it may occur as a natural phenomenon. The differentiation between these two may be extremely difficult on the basis of only small tissue samples, as with endomyocardial biopsies. This, therefore, poses serious limitations in the use of endomyocardial biopsies. The pathology of restrictive cardiomyopathy also depends on the stage of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adult-onset rod disease with abundant intranuclear rods

Summary The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of -actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of -actinin as the pathogenetic basis of the rod formation.     

Analysis of DNA adducts in putative premalignant hepatic nodules and nontarget tissues of rats during 2-acetylaminofluorene carcinogenesis

Exposure of rats to a standard four-cycle feeding regimen of 0.06% 2-acetylaminofluorene (AAF) results in the formation of putatively premalignant hepatic nodules, but the types and magnitude of DNA adducts formed in these nodules has not been previously examined. By using a sensitive 32P-adduct assay (R. C. Gupta, Cancer Res., 45: 5656-5662, 1985), we analyzed the DNA adduct lesions in individual hepatic nodules at various times during and after exposure to AAF. Kidney, spleen, and testis were included as nontarget tissues. No qualitative difference was observed in the DNA adducts found in hepatic nodules and nontarget tissues; however, quantitative differences occurred. At least one unknown and two known (dG-C8-AF and dG-N2-AAF) DNA adducts were detected, with dG-C8-AF being predominantly (96-98%) formed, in all tissues examined. At the end of the first three weeks of AAF feeding, the concentration of the deacetylated adduct dG-C8-AF in liver (223 fmol/micrograms DNA) was found to be about 2, 6, and 5 times higher than in kidney, spleen, and testis, respectively. The concentration of the N2-acetylated adduct in liver (4.5 fmol/micrograms DNA) was 4-fold higher than in kidney and strikingly higher (51- and 42-fold, respectively) than in spleen and testis. At the end of the fourth feeding cycle, total DNA adducts measured in the hepatic nodules ranged from 30-100 fmol/micrograms DNA, while the "surrounding liver," kidney, spleen, and testis showed 235, 218, 62, and 28 fmol adducts/micrograms DNA, respectively. Sixty days following the cessation of AAF, the binding in both the persistent nodules and liver had decreased to 7% of their respective levels measured at the end of the fourth cycle, while adducts in kidney, spleen, and testis were 32%, 18% and 19%. After 88 days, the binding levels in the nontarget tissues declined further, but no additional adduct removal occurred in the nodules. Our data indicate that (a) although the metabolic apparatus for activation of AAF is diminished in the hepatic nodules, a significant level of adduct formation occurs in the cells of this putative, premalignant lesion, and (b) unlike in the nontarget tissues, repair processes in the premalignant nodules may not be operative several weeks after the cessation of AAF exposure.     

The effects of anticholinergics on the photopalpebral reflex, memory and mood

This study investigated central anticholinergic drug effects on: (1) the Randt Memory Test, a relatively new instrument which measures the acquisition and recall of verbal and pictorial information; (2) the averaged photopalpebral reflex (PPR), an electrophysiological parameter, the validity of which needs to be further investigated in pharmacological research and; (3) mood as measured by a 16-item visual analogue scale. Atropine (1 mg and 2 mg), pirenzepine (20 mg) and a placebo were administered intramuscularly in a double-blind cross-over trial in eight healthy volunteers. There were no inter-treatment differences on the Randt Memory Test. This finding is seemingly in contrast to those reported by some authors using other memory tests. In contrast to the reported effects of some benzodiazepines, the anticholinergics used in the present study did not prolong the latencies of the PPR, but reduced the amplitudes. Visual analogue scales indicated central effects for both pirenzepine and atropine. This implies pirenzepine's penetration of the blood-brain barrier and a physiological function for central muscarinic-1-receptors. The significant anticholinergic effects were exclusive to the "alertness" factor.     

Formulation of Vaccine Adjuvant Muramyldipeptides (MDP). 1. Characterization of Amorphous and Crystalline Forms of a Muramyldipeptide Analogue

A relatively nonhygroscopic crystalline form of the glycopeptide, N-acetylmuramyl-L--aminobu-tyryl-D-isoglutamine (I), containing approximately one molecule of water was prepared from amorphous material. The crystalline material, consisting of a mixture of the and anomers, exhibited better physical and chemical stability than the lyophilized amorphous material. The /-anomer ratios of I in both the crystalline and the amorphous state were approximately equal but different from that in solution.     

Advertising and the dental profession. Retrospective and prospective.

"Advertising" has become a very controversial topic, not just among dentists, but among all professionals. That controversy focuses on three questions. First, what are the legal issues surrounding dental advertising and how are these issues being resolved? Second, what are the attitudes toward advertising among practicing dentists and how are these attitudes changing? Finally, how many dentists advertise and what are those advertising dentists actually doing? The purpose of this paper is to neither praise nor excoriate advertising, but to refer to the law and to published research in order to provide dental practitioners with a broader understanding of this topic.     

The respiratory effects of drugs used for conscious sedation and general anesthesia

This review article illustrates that all medications used for conscious sedation can depress ventilation. The dental practitioner should not abandon the use of these agents to control fear and anxiety during dental treatment; rather, the dentist should administer the agents cautiously and monitor respiratory status throughout the dental procedure. In this regard, pulse oximetry is a welcomed advance in monitoring as it acts to warn the unknowing clinician that he is approaching a "cliff" (the steep portion of the oxyhemoglobin curve).     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.     

Asthma deaths during sports: report of a 7-year experience

BACKGROUND: Asthma mortality and the mortality of athletes during sports have been described separately in detail in the medical literature. However, asthma has not been reported as a cause of death in competitive athletes. OBJECTIVE: The object of this study was to raise the awareness of physicians, coaches, trainers, and parents that children and adults can have fatal asthma exacerbations during and immediately after participating in sports. METHODS: The Temple Sports Asthma Research Center identified athletes from 1993 until 2000 who died during or after sporting activity by using the nationwide Burrell's Information Service. Once a possible asthma-related sports death was identified, the autopsy report was requested from the coroner or medical examiner, and an attempt was made to contact the family. Contact with the family was limited to information about the death, medical history, sports involvement, and any medication usage by the person who had died. Secondary sources, including news reports, were used to confirm whether the subject died of asthma during or immediately after a sporting activity. RESULTS: Two hundred sixty-three possible cases were identified. Sixty-one deaths met the criteria for study inclusion. White deaths outnumbered black deaths by 2 to 1. Deaths among male subjects predominated. Most subjects were younger than the age of 20 years, with the most prevalent age group being between 10 to 14 years old. Fifty-one percent (18 of 35) of the competitive athletes had their fatal event while participating in organized sport, 14 in a practice situation and 4 deaths during a game or meet setting. Basketball and track were the 2 most frequent activities performed at the time of the fatal event. CONCLUSION: The subjects who had fatal asthma exacerbations were usually white male subjects between the ages of 10 and 20 years. Mild intermittent or persistent asthma by history was commonly identified. Sudden fatal asthma exacerbations occur in both competitive and recreational athletes and can be precipitated by sporting activity.