Tumor Necrosis Factor Alpha Gene ?376 Polymorphism and Susceptibility to Multiple Sclerosis: An Egyptian Study

Tumor necrosis factor alpha, a proinflammatory cytokine, plays an important role in the clinical activity of relapsing?Cremitting multiple sclerosis and the development of progression. Dysregulation in the expression of tumor necrosis factor gene had been suggested in the pathogenesis of multiple sclerosis. Our aim was to investigate the relationship between tumor necrosis factor ???376 polymorphism with disease susceptibility and course of multiple sclerosis in Egyptian patients. Polymerase chain reaction and restriction fragment length polymorphism were carried out on 36 primary progressive multiple sclerosis patients, 36 age- and sex-matched remitting relapsing multiple sclerosis patients (diagnosed according to McDonald??s Diagnostic criteria) and 30 age- and sex-matched healthy controls. The GG genotype and the guanine allele (G) were detected significantly more often in the primary progressive (p?=?0.02; p?=?0.004, respectively) and remitting relapsing (p?=?0.015; p?=?0.024, respectively) multiple sclerosis groups as compared with the healthy control group. The G allele in the examined position in tumor necrosis factor alpha might have a role as regards susceptibility in both remitting relapsing and primary progressive multiple sclerosis.     

Incidence of anterior pituitary deficiency after radiotherapy at an early age: study in retinoblastoma

Thirty-one patients treated for retinoblastoma in the first few years (3 months to 3 years and 6 months) of life were studied 2 to 15 years later. Radiotherapy delivered 1 300 to 6 500 rads to the hypothalamo-pituitary area. Growth deficiency was documented in 30% of all cases. Other pituitary deficiencies were the exception. The critical dose for GH insufficiency is between 2 000 and 3 000 rads, as in older children or adults. Our study does not support the hypothesis that the hypothalamo-pituitary area is more sensitive to radiation at an early age. Furthermore, conservative therapy of retinoblastoma leads to double lateral irradiation and will increase the number of GH deficient children after retinoblastoma.     

Heel pain triad (HPT): the combination of plantar fasciitis, posterior tibial tendon dysfunction and tarsal tunnel syndrome

Between 1996 and 1999, we evaluated 286 patients with chronic heel pain. We identified 14 patients who were diagnosed and surgically treated for a unique combination of plantar fasciitis, posterior tibial tendon dysfunction and tarsal tunnel syndrome. We postulate that failure of the static (plantar fascia) and dynamic (posterior tibial tendon) support of the longitudinal arch of the foot has resulted in traction injury to the posterior tibial nerve, i.e., tarsal tunnel syndrome. The combination of plantar fasciitis, posterior tibial tendon dysfunction and tarsal tunnel syndrome was recognized and treated. We have called this combination the "Heel Pain Triad (HPT)." Using the AOFAS hindfoot rating system, retrospective chart review and patient examination revealed marked improvement in 85.7% of patients. Follow-up was done four to 33 months (mean follow-up was 17.1 months). Marked improvement was noted in the categories of pain, activity level, walking distance, walking surface and limp. Improvement was statistically significant for all categories.     

Spastic hemiplegia in a quadriplegic patient: treatment with phenol nerve block

A quadriplegic patient with a C6 lesion had a stroke with aphasia and right hemiplegia 20 years after his cervical cord injury. The combination of hemiplegia and quadriplegia created unusual rehabilitation problems, the most disabling of which was a painful flexion contracture of the right elbow that prevented any useful right arm function. A sequence of phenol nerve blocks produced almost complete resolution of this contracture and was a key factor in his successful return to independent living. Although phenol block is much less commonly performed in the upper than lower extremities, its judicious use in carefully selected cases may be beneficial to the patient's functional outcome.     

Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids

BACKGROUND: CYP3A5 and MDR1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements. The aim is to determine whether these polymorphisms also affect sirolimus trough concentrations and dose requirements after kidney transplantation. METHODS: Eighty-five renal transplant recipients receiving sirolimus were included. Twenty-four were treated with a combined sirolimus-tacrolimus regimen. Eighty-one patients received steroids. Sirolimus and tacrolimus were adjusted to a target therapeutic window. CYP3A5 (intron 3) and MDR1 (exons 12, 21, 26) genotypes were correlated to the adjusted trough concentrations and dose requirements for both sirolimus and tacrolimus. RESULTS: There were no significant correlation between adjusted sirolimus trough concentrations or dose requirements and genetic polymorphisms. In a multiple regression model, adjusted-prednisone dose was involved with a positive or negative effect when considering sirolimus dose requirements or adjusted concentrations, respectively. In the subgroup of patients treated by tacrolimus and sirolimus, adjusted tacrolimus doses were higher in patients carrying at least one CYP3A5 *1 allele (median 0.083 vs. 0.035 mg/kg for CYP3A5*3/*3 patients, P<0.05). Adjusted-prednisolone dose and CYP3A5 polymorphism explained up to 61% of the variability in tacrolimus dose requirements. CONCLUSIONS: Unlike tacrolimus, sirolimus adjusted trough concentrations and dose requirements seem not affected by CYP3A5 and MDR1 polymorphisms. Adjusted-prednisone dose has a significant impact on tacrolimus and sirolimus dose requirements.     

Cohort mortality study among French asphalt workers

BACKGROUND: In conjunction with the European cohort study among asphalt workers coordinated by the International Agency for Research on Cancer (IARC), we studied the mortality of 15,011 French men who were followed for 17 years for a total of 175,062 persons-years. This group contained 2,506 subjects who had ever been employed as asphalt workers: they contributed 30,692 person-years of risk. A reference group was composed of 6,675 subjects (i.e., 61,856 persons-years) who had been employed only in building or ground construction. METHODS: Mortality ratios standardized for age and period were computed with their 95% confidence intervals (CI) from the age and period mortality rates of all French men for the years covered by the study (1979-1996). We also compared the mortality of exposed workers and the reference group with Poisson regression models after adjustment for age, calendar period, and either duration of employment or length of follow-up. RESULTS: Mortality from lung cancer was equivalent to the expected rate [SMR = 1.01 95% CI (0.6-1.6)], but was 40% greater than among the non-exposed reference group [RR = 1.4 95% CI (0.7-2.8)]. We also found an excess of gastrointestinal cancers, especially of the esophagus [SMR = 1.94, 95% CI (0.9-3.6)] and stomach [SMR = 2.2, 95% CI (0.8-4.7)]. Comparison with the internal reference group confirmed these findings, especially for stomach cancer [RR = 2.8, 95% CI (0.7-11.4)]. CONCLUSIONS: Although our results are not statistically significant, they suggest that road-paving workers may have a slightly higher rate of lung cancer and a moderately higher rate of stomach cancer than their non-exposed counterparts. The excess of lung cancer may be due to potential confounding factors, including the occupational risk factor of coal tar exposure and the lifestyle risk factor of smoking. A nested case-control study is under way that will make it possible to control for smoking and other potential carcinogenic exposures; this is necessary before any definitive conclusions can be drawn.     

Immunization coverage of Australian-born children of Arabic-speaking background in Central Sydney

OBJECTIVES: To examine the immunization coverage rates of 12-36-month-old Australian-born children from an Arabic-speaking background in Central Sydney as determined by parental report and documentary evidence. METHODOLOGY: Eligible children were identified by examination of the records of five hospitals. Eligibility criteria were that the mother gave an Arabic speaking country of birth and a Central Sydney post code (as her place of residence) and the child was born between 1 May 1994 and 30 April 1996. Parents of all eligible children were invited to participate, either by a special appointment to answer a structured questionnaire, or by telephone survey. Of the 1157 eligible children identified from hospital birth records, only 641 could be contacted, of whom 584 (91.1%) agreed to participate. Full information on age appropriate immunization rates, as reported by parents and documented in records, could be assessed for 403 children. RESULTS: Parents reported that 97.6% of children were fully immunized. When the child's immunization status could be verified from either the child's personal health record and/or the service provider, the rate of full, age-appropriate immunization was 94.3% (95% confidence intervals 92.0-96.6) compared to a parent-reported rate of 98.0%. General practitioners provided 76.2% of immunizations. CONCLUSION: While a substantial proportion of children identified from birth records could not be contacted, comparisons with census data and other analyses indicate that this sample is likely to be representative of the general population of 12-36-month-old Australian-born children from an Arabic-speaking background. This group appeared to be highly immunized. Further studies examining why the rates for this ethnic group are high in Central Sydney may determine strategies which will enhance immunization rates in other communities.