Multiple aneurysms in Beh?et's disease

Beh?et's disease is characterized by recurrent ulcers of the mouth and genitalia and relapsing iritis. It is now recognized as a chronic multisystem disease affecting the skin, mucous membranes, eye, joints, central nervous system, and blood vessels. One of the known vascular complications of Beh?et's disease is aneurysm formation or venous thrombosis. The two patients with Beh?et's disease in this report developed multiple aneurysms over a short time span. Vascular surgeons dealing with young adults with peripheral aneurysms must be aware of this uncommon yet challenging clinical entity.     

Characterization of the L-arginine:nitric oxide pathway in human platelets.

1. The activation of the L-arginine: nitric oxide (NO) pathway during aggregation of human platelets by adenosine 5'-diphosphate (ADP), arachidonic acid, thrombin and the calcium ionophore A23187 and its inhibition by NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME) and N-iminoethyl-L-ornithine (L-NIO) were studied. The inhibition of the cytosolic platelet NO synthase by these compounds was also examined. 2. Platelet aggregation induced by ADP (1-10 microM) and arachidonic acid (0.1-10 microM), but not that induced by thrombin (1-30 mu ml-1) or A23187 (1-10 nM), was inhibited by L-, but not D-arginine (1-30 microM). However, in the presence of a subthreshold concentration of prostacyclin (0.1 nM) or of M & B 22948 (1 microM), a selective inhibitor of guanosine 3':5'-cyclic monophosphate (cyclic GMP) phosphodiesterase, L-arginine caused concentration-dependent inhibition of aggregation induced by all of these aggregating agents. 3. L-NMMA, L-NAME and L-NIO (all at 1-30 microM), but not their D-enantiomers, enhanced to the same extent platelet aggregation induced by ADP, arachidonic acid and thrombin without affecting that induced by A23187. 4. In the presence of 300 microM L-arginine, the NO synthase in platelet cytosol was inhibited by L-NMMA, L-NAME and L-NIO with IC50s of 74 +/- 9, 79 +/- 8 and 8.5 +/- 1.5 microM (n = 3), respectively. 5. These results indicate that the L-arginine: NO pathway in human platelets plays a role in the modulation of platelet aggregation.     

Movement disorders and psychological tests of frontal lobe function in schizophrenic patients.

Neuropsychological tests of frontal lobe functions were undertaken in 46 chronic schizophrenic patients who were also rated for movement disorders. Tardive dyskinesia was found to have significant associations with most of these psychological tests. The possible mechanisms are discussed within the context of known neostriatal psychological functions.     

The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine.

The pharmacokinetics of the 5-HT3 receptor antagonist ondansetron following an 8 mg i.v. dose were investigated in 12 subjects previously phenotyped with debrisoquine. Six subjects were poor metabolisers (debrisoquine metabolic ratios 29-131) and six were extensive metabolisers (debrisoquine metabolic ratios 0.45-3.4). There was no significant difference in AUC, Cmax, CL or t1/2 between the poor and extensive metabolisers. It is concluded that ondansetron clearance is not mediated exclusively by cytochrome P-450 2D6.     

Acute Care for Elders Units

Older patients often experience a loss of independent physical functioning during the course of an acute illness that requires hospitalization. Although functional outcomes are not usually the focus of care in the hospital, they may be critical determinants of the quality of life, physical independence, cost of care, and prognosis among older patients.Based on a conceptual model of the dysfunctional syndrome (functional decline associated with hospitalization) we developed, implemented and evaluated a multi-component intervention termed Acute Care for Elders (ACE), in hospital medical units of two urban hospitals. ACE is a model of care that combines the principles of geriatric assessment and quality improvement. The ACE intervention includes a prepared environment (environmental modification), patient-centered care (interdisciplinary assessment), interdisciplinary team rounds and planning for home, and medical care review. Results of randomized clinical trials support the effectiveness of ACE to improve outcomes of hospitalization for older patients. Improved functional status, lower risk of nursing home placement and higher levels of patient and professional satisfaction with care are achievable with ACE.The challenges of establishing an ACE unit in community hospitals can be met through a systematic process of implementation and evaluation.ACE is a multi-component intervention that is potentially transportable to other hospital units, with benefits for patients, health professionals and hospital administrators.     

Guided tissue regeneration--why, when and how?

Chronic periodontitis results in the destruction of the collagen fibre attachment to cementum, apical migration of the epithelial attachment, contamination of the exposed root surface by plaque and loss of alveolar bone. Regeneration can be defined as the restitution of lost tissues to a state which existed before destruction. As such, it is an ultimate and ideal goal and in most circumstances is currently beyond our capabilities. However, research in periodontology over the last 10 years or so has made considerable advances and is perhaps unique in proposing a new and fundamental treatment modality--guided tissue regeneration.     

Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.