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.     

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.     

Can a leukocyte depletion filter (LDF) reduce the risk of reintroduction of hepatocellular carcinoma cells?

During liver transplantation for hepatocellular carcinoma (HCC) patients, HCC could theoretically be introduced into the systemic circulation when salvaged blood is used with an autotransfusion device. Several reports have shown that some types of leukocyte depletion filters (LDFs) could completely reduce the risk for reintroducing some types of tumor cells. In this study, we tested the ability of the LDF (RCEZ1T, Pall Biomedical Co, NY, USA) to reduce the risk for reintroducing HCC cells in vitro by using a very sensitive detection method. We divided the test group into 6 groups: group I was 10 cells, group II was 20 cells, group III was 2 x 10(3) cells, group IV was 2 x 10(5) cells, group V was 2 x 10(6) cells, and group VI was 2 x 10(7) cells. The counted cells in 200 mL saline were passed through the RCEZ1T using the force of gravity. To identify the presence of cells, the pellet was resuspended, and polymerase chain reaction (PCR) was performed. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene, was used as a primer. In groups I and II, the HCC cells were completely filtered in all experiments. However, in groups III, IV, and V, the HCC cells were not completely filtered in a few of the repeated experiments, with the unfiltered rate of tumor cells being between 8% and 20%. In group VI, the HCC cells were not completely filtered in all the repeated experiments. In conclusion, the RCEZ1T filter markedly reduced the risk for reintroduction of HCC cells. However, at high HCC cell load the filter cannot completely remove all the tumor cells. Further studies are required to assess the impact in clinical settings.     

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.     

Severe Malnutrition Associated with α-Heavy Chain Disease: Response to Tetracycline and Intensive Nutritional Support

A 20-yr-old black male was admitted with a 5-month history of profound weight loss and diarrhea. Appetite and dietary intake had been remarkably well preserved up until the week before admission. The severity of his depletion was evidenced by a body weight of only 38% of standard, multiple electrolyte deficiencies, and reduced metabolic expenditure, protein turnover, protein synthesis, and pancreatic function. Immunological defects included diminished lymphocyte numbers, lymphocyte transformation, gamma-globulin concentration, and cell-mediated immunity. A diagnosis of alpha-heavy chain disease (alpha-HCD) was made on endoscopic duodenal biopsy and serology--lymphoma being excluded by scanning and laparotomy. Treatment consisted initially of intravenous nutrition (because of the extreme malnutrition, severe diarrhea, and malabsorption of fluid, electrolytes, carbohydrates, and fat) and oral tetracycline. Response was dramatic, with a doubling of body weight within 6 wk, and resolution of malabsorption. He was discharged on a normal diet and long-term oral tetracycline (250 mg/day), and at 1-yr follow-up, nutritional status and gut function were normal despite persistence of duodenal mucosal abnormalities and markers of alpha-HCD and bacterial overgrowth. These results suggest that the malabsorption initially identified in this patient was not due simply to the mucosal abnormalities that characterize alpha-HCD, but was more a consequence of the superimposition of nutrient maldigestion and absorption resulting from the extreme state of protein deficiency and its effects on gut and pancreatic function.     

A system for tissue-specific gene targeting: transgenic mice susceptible to subgroup A avian leukosis virus-based retroviral vectors.

Avian leukosis viruses (ALVs) have been used extensively as genetic vectors in avian systems, but their utility in mammals or mammalian cell lines is compromised by inefficient viral entry. We have overcome this limitation by generating transgenic mice that express the receptor for the subgroup A ALV under the control of the chicken alpha sk-actin promoter. The skeletal muscles of these transgenic animals are susceptible to efficient infection by subgroup A ALV. Because infection is restricted to cell lineages that express the transgene, the method has utility for studies of development and oncogenesis and will provide models for tissue-specific gene therapy.