Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

Meta-analysis of randomized controlled trials in dacryocystorhinostomy with and without silicone intubation

Objective

To determine the effect of bicanalicular silicone intubation (SI) on dacryocystorhinostomy (DCR) success rate in adult primary acquired nasolacrimal duct obstruction.

Folate intake, serum homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T genotype are not associated with oral cancer risk in Puerto Rico

We examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Structured questionnaires were used to collect information on demographic factors, usual adult diet, and tobacco and alcohol use. Oral epithelial cells and blood samples were collected from a subset of subjects. Analyses were conducted by logistic regression, adjusting for age, sex, lifetime smoking and lifetime alcohol intake, with the following numbers of cases/controls, respectively: dietary data (341/521); MTHFR genotype (148/149); and homocysteine (60/90). Although increased folate intake was associated with decreased oral cancer risk [adjusted odds ratio (OR) in highest vs. lowest quartile = 0.6, 95% confidence interval (CI): 0.4, 1.0, P(trend) = 0.05)], this finding was due almost entirely to folate intake from fruit (adjusted OR = 0.4, 95% CI: 0.2, 0.6; P(trend) = 0.0001), whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant (TT) genotype had a nonsignificantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking, although the power to detect significant associations in subgroups of these variables was low. Risks for oral cancer are not folate specific; preventive recommendations for this disease should emphasize the importance of a healthy diet, including substantial intake of fruits.     

Changes in body temperature and urinary cortisol after routine immunization in babies with intrauterine growth retardation

Aim : To investigate whether infants with intrauterine growth retardation (IUGR) experience different changes in temperature and cortisol excretion after routine immunization compared with normal healthy infants. Methods : Overnight deep body temperature and urinary cortisol to creatinine ratios were measured on the night after immunization and a control night in normal and IUGR infants. Results : In 60 normal infants, first vaccination at about 10 wk of age led to a significant increase in minumum overnight temperature compared to the control night, mean rise 0.25°C (95% CI, 0.12 to 0.38). In 35 IUGR infants the mean rise in temperature between immunization night and control night was 0.35°C (95% CI, 0.15 to 0.55). The increases in minimum temperature did not differ significantly between the normal and IUGR infants ( p = 0.11). Cortisol to creatinine ratios measured from overnight urine samples showed that 23 IUGR infants had consistently higher levels than 39 normal infants; control night medians 34 and 15 ( p = 0.01) and immunization night medians 56 and 26 ( p= 0.02), respectively. However, the percentage increase did not differ significantly between the IUGR infants and the normal infants. A smaller number of second immunizations were studied, but no significant differences were found.

Conclusion : These results suggest that although the impact of immunization is the same for IUGR and normal infants, because IUGR infants are less mature and at greater stress before immunization, the absolute levels that they experience after immunization are higher than those for normal infants.     

Accuracy and comparability of long-term measurements of cholesterol

Laboratories of the Lipid Research Clinics Program (LRC) maintained the accuracy of their measurements of total cholesterol by using seven pooled serum calibrators supplied by the Centers for Disease Control (CDC). Over the 11-year life of the LRC, each calibrator was prepared in succession and a target value was assigned by the CDC reference method for cholesterol. The results of a special experiment in which six of the seven calibrators were analyzed simultaneously demonstrated that the target values were accurately assigned. Deviations of the target values from the experimental means ranged from zero to 1.7% of the original target value. The experiment revealed no evidence of drift in the bias of the reference method over the life of LRC and demonstrated the accuracy, consistency, and the comparability of the values assigned to the successive calibrator pools used by the LRC laboratories during more than eight years. It demonstrated the reliability of a reference method and the suitability of frozen serum pools for maintaining an accurate measurement base for serum cholesterol.     

A procedural guide to the modification of a Canon Auto Ref R-1 for use as a continuously recording optometer

We have recently reported on the modification of the Canon AutoRef R-1 for use as a continuously recording optometer, while retaining its capacity to measure in 'single-shot' mode. Although the principles of the modification and performance of the dual mode of operation have been described in previous publications, this technical not aims to provide sufficient detail for research laboratories wishing to implement the modification.     

A study in human subjects using a new device designed to mimic the protrusive functional appliances used previously in monkeys

A new appliance is described that mimics in function the protrusive jaw-positioning devices used previously in monkeys. The appliance consists of maxillary and mandibular posterior biteplates separated by a sharp vertical interface perpendicular to the occlusal plane. Function of the appliance was evaluated in 35 consecutively treated patients and compared against matched controls. The patients, who ranged in age from 9 to 14 years, accepted the appliance readily and wore it 24 hours each day, even while eating. Although cephalometrics was the primary assessment tool, tomograms and/or transcranial x-ray films and models were also obtained. The rate of mandibular length increase, measured from articulare, was comparable to or better than that found in monkeys using similar devices. The dentoalveolar effects were also similar to those found in monkeys, including anterior migration of the mandibular dentition and posterior movement of the maxillary dentition. The mandibular molars moved forward 4.8 mm of which 73% was determined to have come from increased anterior movement of the mandible. Subtracting normal growth, the net mandibular length increase was 2.2 mm during the 9.4-month average treatment interval.