Physiologic and pharmacologic approaches to spasticity

The term spasticity is used to describe many relatively unrelated syndromes and, because they share few common pathophysiologic mechanisms, it is not possible to define the physiology or pharmacology of spasticity. In patients with spastic paresis, it is the latter negative symptom (rather than the spasticity) that accounts for almost all the functional disability. Clinical neurophysiologic techniques are useful for categorization of patients with clinically identical syndromes into subgroups which respond to different therapies. Fusimotor or spindle primary afferent hyperactivity have not been demonstrated in spastic patients; reduction in central inhibitory mechanisms probably accounts for spastic hyper-reflexia. Increased passive muscle stiffness may also be clinically significant. Therapies for spasticity include elimination of causative or enhancing factors, frequent muscle stretching, surgical approaches and chemotherapy. The latter includes dantrolene (which weakens muscles), baclofen (particularly useful for reduction of flexor spasms and flexor dystonia in patients with spinal lesions) and diazepam.     

A placebo-controlled trial of light treatment for winter depression.

We studied 32 patients with winter seasonal affective disorder (SAD) in a counterbalanced crossover design comparing 1 h of morning light treatment (about 7000 lux) to 1 h of morning placebo treatment (deactivated negative ion generator). Both treatments significantly reduced depression ratings, but there was no difference between the antidepressant response to light and to placebo. Several possible explanations for this result were discussed including an inadequate 'dose' of light (e.g., ineffective duration or intensity), an unusual sample of patients, and a placebo mechanism.     

Artifacts due to stimulus correlated motion in functional imaging of the brain

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.     

Enteric microbial flora, bacterial overgrowth, and short-bowel syndrome.

Small intestinal bacterial overgrowth (SIBO) occurs commonly in short-bowel syndrome (SBS) and, in some instances, may result in significant problems. SIBO is characterized by a variety of signs and symptoms resulting from nutrient malabsorption caused by an increased number and/or type of bacteria in the small intestine. The anatomic and physiologic changes that occur in SBS together with medications commonly used in these patients facilitate the development of SIBO. Because many aspects related to SIBO in the SBS population remain poorly understood, it was our aim to review the current understanding of the gut flora and issues related to SIBO occurring in SBS.     

The association of cancer survival with four socioeconomic indicators: a longitudinal study of the older population of England and Wales 1981–2000

Background  

Many studies have found socioeconomic differentials in cancer survival. Previous studies have generally demonstrated poorer cancer survival with decreasing socioeconomic status but mostly used only ecological measures of status and analytical methods estimating simple survival. This study investigate socio-economic differentials in cancer survival using four indicators of socioeconomic status; three individual and one ecological. It uses a relative survival method which gives a measure of excess mortality due to cancer.     

The immunomodulatory effects of 3-monochloro-1,2-propanediol on murine splenocyte and peritoneal macrophage function in vitro.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. To evaluate the immunomodulatory effect of MCPD on murine splenocyte and macrophage in vitro, we investigated splenocyte blastogenesis by concanavalin A (Con A), anti-CD3, and lipopolyssacharide (LPS), the production of cytokines from splenocyte, and the activity of mouse peritoneal macrophages. There was a significant decrease in lymphocyte blastogenesis to Con A or anti-CD3 at subtoxic dose of MCPD. A significant decrease in splenocyte blastogenesis to LPS was also observed. The production level of interferon (IFN)-gamma on splenocyte culture with Con A was significantly reduced at the higher concentration than 1.0mM of MCPD. The levels of interleukin (IL)-4 and IL-10 were also decreased at high concentrations of MCPD. There was a significant decrease in production of nitric oxide (NO) by peritoneal macrophages treated with MCPD. MCPD also inhibits tumor necrosis factor (TNF)-alpha production of stimulated macrophages. These results indicate that MCPD might be able to reduce the functionality of lymphocytes and peritoneal macrophages in vitro.     

Transdermal permeation-enhancing activities of some inorganic anions

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inorganic anions were roughly proportional to lyotropic Hofmeister swelling abilities of the anions; F^?<SO₄ ^2?<Cl^? <ClO₄ ^?<NO₃ <SCN^? <Br <I^?, i.e. l, Br and SCN increased the flux of drugs through the mouse skin, while F^?, SO₄ ^2?, Cl^?, ClO₄ ^? and NO₃ ^? decreased or did not affect the flux. In invivo experiment using the rabbit as the test animal, the plasma concentration of salicylic acid of the rabbit to which 10%-salicylic acid ointment containing 5%-Nal or NaBr was applied was significantly higher than that of the rabbit to which the ointment without the electrolytes was applied. The amounts of sterol leached out of stratum corneum sheet when the sheet was immersed in aqueous solutions of Nal, NaBr, or NaSCN were much more than that of stratum corneum immersed in aqueous solutions of the other inorganic anions. The FTIR/ATR spectroscopy showed that the peaks at 2853 cm^?1 and 2924 cm^?1 in the IR absorption spectrum of the stratum corneum sheet of the mouse were shifted to higher frequencies by the anions which enhanced the transdermal drug permeation, while not shifted by the anions which did not have any permeation-enhancing activities or have permeation-reducing activities. These results suggest that sodium salts of some anions such as iodide, bromide and thiocyanate enhance transdermal permeation of salicylic acid through swelling and perturbation of the skin structure by these anions.