Successful treatment of rheumatic chorea with carbamazepine

Carbamazepine has been used successfully in the treatment of different movement disorders and was recently reported to be effective for nonhereditary chorea. In view of the significant side effects associated with the drugs currently used to treat chorea, we sought to further evaluate the efficacy of carbamazepine in children with rheumatic chorea. The study was prospective and included 10 children with chorea (eight females and two males; age range = 7-16 years) referred to our Pediatric Rheumatology Clinic between 1995 and 1999. Nine had rheumatic fever and one had antiphospholipid antibody syndrome that later evolved to systemic lupus erythematosus. All were treated with carbamazepine. Improvement was evident within 2-14 days of initiation of low doses of carbamazepine (4-10 mg/kg daily). The plasma drug levels were 2.8-8.2 microg/mL (therapeutic antiepileptic range = 8-12 microg/mL). The chorea disappeared within 2-12 weeks. The duration of treatment was 1-15 months. No side effects were observed. Recurrence was observed in three patients who received a second trial of carbamazepine with a good response. We suggest that carbamazepine may serve as a first-line treatment for rheumatic chorea.     

Geographic variation in groundwater iodine and iodine deficiency in Israel, The West Bank and Gaza

BACKGROUND: Iodine deficiency during pregnancy and infancy is the world's most common preventable cause of mental retardation. Previous studies have shown a high incidence of goiter and low groundwater iodine concentrations in northern Israel. OBJECTIVE: We examined the relationship between low groundwater iodine and iodine deficiency in pregnant women and schoolchildren. SUBJECTS AND METHODS: We measured the urinary iodine excretion of school-children in the West Bank and Gaza and rural and urban pregnant women in Western Galilee (an area known to have low groundwater iodine concentrations). We also measured iodine concentrations in groundwater in various locations in the West Bank and Gaza. RESULTS: Lower urinary iodine excretion was found among pregnant Arab women living in rural Western Galilee (101+/-7 microg iodine/g creatinine). 20% of them excreted <50 microg I/g creatinine. This is relatively less than found among pregnant Jewish women living in cities in the same area (154+/-13 microg I/g creatinine). Low iodine concentrations (<5 microg/l) were found in groundwater in the Nablus, Ramallah, Bethlehem highlands, as compared to normal concentrations in the lowland districts of the West Bank and Gaza. In a cohort of 728 schoolchildren aged 8-10, 10% (range 8-13%) of children from areas of low groundwater iodine had low levels of urinary iodine excretion, as compared to only <5% of those from districts with groundwater iodine concentrations >10 microg/l. CONCLUSIONS: Lower concentrations of groundwater iodine are related to low urinary iodine excretion in Israel, the West Bank and Gaza.     

Prevalence of hypothyroidism and diabetes mellitus in elderly kibbutz members

The aim of this study was to determine the prevalence of hypothyroidism and diabetes mellitus (DM) in elderly (aged 65–92 years) kibbutz members in Northern Israel. Method: The medical records of 1096 elderly (642 females and 454 males) residing in 11 kibbutzim were reviewed for data regarding thyroid function tests (TSH and FT4) and fasting blood glucose. Fasting blood glucose levels above 7.8 mmol/l was considered diagnostic for diabetes mellitus. Results: The prevalence of hypothyroidism was 14% (9.7% in males and 18.2% in females) and that of DM was 11.5% (12.1% in males and 11.1% in females). In 74% of the diabetics the diagnosis was made after the age of 60 years. Distribution of treatment modalities in diabetics was as follows: diet only 42%, oral hypoglycemic agents 52% and Insulin 6%. Subclinical hypothyroidism (serum TSH levels above 4.5 mU/L with normal FT4 levels) was detected in 38% of all the hypothyroid subjects. Conclusion: The data suggest that diabetes mellitus and primary hypothyroidism are common disorders in elderly subjects. DM in the elderly can usually be handled with diet and oral hypoglycemic drugs. Since the clinical features of hypothyroidism in the elderly are often atypical, we suggest that elderly subjects should be screened for hypothyroidism.     

East and South East Asian Ethnicity and Moderate-to-Severe Endometriosis

Study Objective

To investigate ethnic differences for moderate-to-severe endometriosis.

Retrofitting implant overdenture attachments: A clinical report

The remake of implant-overdenture prostheses on preexisting implants can present the clinician with a challenge, especially when the prosthetic components used initially cannot be replaced. The difficulty of remaking the prosthesis may be further increased by implant attachments designed to be cemented to the implant itself--a feature that complicates future replacement. This clinical report describes the restoration of worn implant attachments using retrofit components.     

The crystal structure of the complex of the anticancer prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11) with Torpedo californica acetylcholinesterase provides a molecular explanation for its cholinergic action

The anticancer prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino-]carbonyloxycamptothecin (CPT-11) is a highly effective camptothecin analog that has been approved for the treatment of colon cancer. It is hydrolyzed by carboxylesterases to yield 7-ethyl-10-hydroxycamptothecin (SN-38), a potent topoisomerase I poison. However, upon high-dose intravenous administration of CPT-11, a cholinergic syndrome is observed that can be ameliorated by atropine. Previous studies have indicated that CPT-11 can inhibit acetylcholinesterase (AChE), and here, we provide a detailed analysis of the inhibition of AChE by CPT-11 and by structural analogs. These studies demonstrate that the terminal dipiperidino moiety in CPT-11 plays a major role in enzyme inhibition, and this has been confirmed by X-ray crystallographic studies of a complex of the drug with Torpedo californica AChE. Our results indicate that CPT-11 binds within the active site gorge of the protein in a fashion similar to that observed with the Alzheimer drug donepezil. The 3D structure of the CPT-11/AChE complex also permits modeling of CPT-11 complexed with mammalian butyrylcholinesterase and carboxylesterase, both of which are known to hydrolyze the drug to the active metabolite. Overall, the results presented here clarify the mechanism of AChE inhibition by CPT-11 and detail the interaction of the drug with the protein. These studies may allow the design of both novel camptothecin analogs that would not inhibit AChE and new AChE inhibitors derived from the camptothecin scaffold.