Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

Is cholic acid responsible for embryo-toxicity of the post-receptive uterine environment?

HPLC analysis of the embryo-toxic fraction of human uterinefluid, collected between the 22nd and 25th days of the menstrualcycle, revealed the presence of cholic acid at high concentrations.It is suggested that cholic acid could be responsible for theembryo-toxicity of the uterine environment, which follows thereceptive period for implantation.     

A combined immunohistochemical and histochemical approach on the differential diagnosis of giant cell epiphyseal neoplasms

The histological similarities and the common localization are the main causes of difficulties concerning the differential diagnosis between giant cell tumor of bone and chondroblastoma. The purpose of the present study was to detect whether histochemistry and/or immunohistochemistry could help to make the distinction between these two entities easier. The study was based on cases of chondroblastoma and giant cell tumor of bone from patients in the 2nd and 3rd decades of life. Histochemical detection of special intracellular and extracellular components (glycogen, glycosaminoglycans) as well as immunohistochemical investigation using various tumor markers (S-100, NSE, a-1-ACT, lysozyme, fibronectin) were performed on parallel paraffin sections. The presence of abundant intracytoplasmic glycogen granules and the immunoreactivity of the cells of chondroblastoma with S-100 and NSE, together with the presence of acidic sulfated glycosaminoglycans in the stroma, could help the differential diagnosis of this tumor from giant cell tumor of bone.     

Potential roles of protease inhibitors in Alzheimer's disease

Recently, protease inhibitors have been recognized as potential contributors to the pathogenesis of Alzheimer's disease. In this role, they could mediate an exaggerated regenerative response in the brain, participate as acute phase reactants, or be involved in the aberrant proteolytic processing of the amyloid proteins. Protease inhibitors are, therefore, attractive targets for drug intervention in Alzheimer's disease.     

Cytoskeletal rearrangement by oxidative stress

The cytoskeleton is susceptible to oxidative stress and this occurs prior to membrane blebbing and cell lysis. Vimentin intermediary filaments in rheumatoid synoviocytes are more susceptible than in normal synoviocytes and this may have pathological significance. They are however no more susceptible to heat shock than other cell types.     

Modulation of spontaneous motility by GABAA receptor antagonism in the guinea pig isolated ileum

Rhythmic neurally mediated spontaneous contractions of the longitudinal muscle in the isolated ileum of the guinea pig, sensitive to tetrodotoxin and atropine, were depressed and most often abolished by the GABAA receptor antagonists, bicuculline methiodide, RU 5135, and picrotoxin, a Cl- -ionophore blocker, as well as by GABA desensitization. 3-Mercaptopropionic acid, known to prevent GABA release, also reduced these naturally occurring spontaneous contractions. All these strongly indicate a physiological involvement of endogenous GABA in the control of spontaneous rhythmic activity in the intestine.     

The projection pattern of forepaw nerves to the cuneate nucleus of the raccoon

The transganglionic transport of horseradish peroxidase (HRP) was used to determine the projection pattern within the cuneate nucleus of the 4 major nerves innervating the forepaw of the raccoon, a carnivore noted for its tactile and manipulative abilities. The two nerves innervating the dorsal, hairy skin and claws (the radial and dorsal ulnar nerves) projected to the marginal rim of the cuneate nucleus, but not to the middle cluster region or to the caudal region of the nucleus. The two nerves innervating glabrous skin (median and ulnar) projected heavily to the cluster region as well as to rostral and caudal levels of the nucleus. This organization, with dorsal nerves ending above the ventral nerves, is similar in the raccoon, rat and tree squirrel, but reversed in the cat. However, the medio-lateral topography is similar in all species with the ulnar and dorsal ulnar nerves projecting medially within the nucleus compared to the median and radial nerves.