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.     

Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases

A review of the pathological material from 42 children with non-Hodgkin's lymphoma seen over a 44 month period revealed 10 large cell tumours. Of these, six were classified as peripheral T-cell lymphoma, an entity rarely reported in childhood. Three patients were boys and three girls (median age 9.5 years), and extranodal presentation was a feature of two patients. Five had high-grade tumours; of these, three were classified as large cell anaplastic, Ki-1 positive and two as pleomorphic large cell. The remaining patient had a low-grade tumour of angioimmunoblastic type. T-cell subsets were examined in three cases and showed the following phenotypes: CD4-, CD8-; CD4+, CD8-; CD4-, CD8+. Three of the patients with high-grade tumours died, with a mean survival of 22 weeks. The remaining patients are alive and clinically disease-free for between 10 and 24 months after treatment.     

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.     

TRH-induced reflex changes in patients with ALS

A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS). One patient's extensor plantar transiently changed to a flexor plantar reflex after injection, probably due to disproportionate increase in tone of the calf muscles. No significant changes in F-waves or H-reflexes were seen. No increase in useful voluntary strength, or in strength measured by Medical Research Council (MRC) testing or strain gauge isometric strength testing was seen. However, dyspnea was seen within 10 minutes of TRH injection.