Medical management of rheumatoid arthritis

The overall management of RA is multifaceted. It includes rest, both systemic and articular; physical therapy; utilization of the techniques and appliances of occupational therapy; drugs, both those that suppress inflammation and those that are capable of altering the disease course itself; a knowledge of specific articular and nonarticular complications; and the ability to refer for appropriate surgical management. Judicious, energetic application of these principles can favorably affect the outcome of rheumatoid disease in most patients.     

The role of central muscarinic and nicotinic receptors in the regulation of sodium and potassium renal excretion

The effect of intraseptal injection of carbachol and nicotine on urinary output of Na+ and K+ in untreated rats as well as in animals pretreated with locally injected atropine, hexamethonium, dibenamine and propranolol was studied in order to evaluate the relative role played by central muscarinic and nicotinic receptors in the regulation of salt and water renal excretion. The injection of 30-250 nmol of nicotine into the medial septal area caused a dose-dependent increase in Na+ and K+ urinary output whereas urine volume was little affected. The effect of 30 nmol of nicotine was blocked by pretreatment with 100 nmol of hexamethonium. In addition, pretreatment with 5 nmol of either hexamethonium or atropine partially antagonized the natriuretic and kaliuretic effect of 1 nmol of carbachol. Also the alpha-blocking agent, dibenamine (150 nmol) antagonized, while the beta-blocker, propranolol (100 nmol) significantly enhanced the effect of carbachol. Propranolol (100 nmol) alone caused a small, but significant increase in Na+ and K+ renal excretion. These results indicate that stimulation of both muscarinic and nicotinic receptors in the septal area, as caused by carbachol, elicits increased disposition of Na+ and K+ by the kidneys. Also, part of the effects of carbachol appear to be mediated by the release of endogenous catecholamines, acting on central alpha receptors to increase Na+ and K+ urinary excretion. On the other hand, simultaneous activation of beta-receptors by the released amines would partially inhibit this effect.     

Anti-tuberculous initial drug resistance of Mycobacterium tuberculosis in Kenya: a ten-year review

Our experience at the Respiratory Diseases Research Unit (RDRU), over the last 10 years (1981-1990) on the initial drug resistance pattern, focusing on three drugs viz: isoniazid (H), streptomycin (S) and rifampicin (R) is presented. Records on all isolates of M. tuberculosis from one specimen of every newly diagnosed patient recruited countrywide between 1981-1990 were reviewed. We analyzed records of 6,514 isolates and found that total resistance to the three drugs had increased from 8.9% to 14.4%. Resistance to H alone increased from 6.8% to 10.2% while that of S alone from 0.8% to 1.8%. Resistance to R was between 0.1% and 0.3%. Generally, the increase in the resistance trend to both H and S was statistically significant (p = < 0.05 and 0.03, respectively). Although in our analysis we did not address the possible impact of HIV infection, we hope that these findings form a basis for evaluation of this and other possible factors on the emergence of anti-TB drug resistance in future studies.     

Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats

Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn.     

Alpha-1-thymosin and transcatheter arterial chemoembolization in hepatocellular carcinoma patients: a preliminary experience

BACKGROUND/AIMS: To evaluate the tolerability and therapeutic potential of the immunostimulating adjuvant alpha-1-thymosin in patients with hepatocellular carcinoma. METHODOLOGY: Twelve patients with hepatocellular carcinoma were treated with alpha-1-thymosin (900 micrograms/m2 subcutaneously twice per week for 6 months) and transcatheter arterial chemoembolization and compared to a historical control group (matched for gender, age, Okuda staging, Child's score, alpha-fetoprotein serum levels and viral infection) treated with transcatheter arterial chemoembolization alone. RESULTS: No severe side effects were recorded in the 2 treatment groups. The combination of alpha-1-thymosin plus transcatheter arterial chemoembolization resulted in a longer survival that reached statistical significance 7 months after the end of treatment (p < 0.05). Patients receiving combined treatment demonstrated a significant increase in peripheral blood mononuclear cells expressing CD3 (p < 0.05) and CD8 (p < 0.025) 3 months after beginning treatment. They also had a significant increase (p < 0.05) in CD16+ and CD56+ cells after 1 month, and a slight reduction in mononuclear cells expressing CD25, a marker for cell activation. No alterations in the response to phytohemagglutinin stimulation were seen during the alpha-1-thymosin treatment. CONCLUSIONS: The absence of toxicity and the favourable effects observed in this open study call for a double blind control study to confirm the efficacy of the combined treatment.