Provider-reported illness and absence due to illness among children attending child-care homes and centers in San Diego, Calif

PURPOSE: To compare the incidence of provider-reported illness and absence due to illness among children attending small child-care homes, large child-care homes, and child care centers in a large metropolitan area. METHODS: From July 6, 1992, through January 28, 1994, we collected information from child-care providers on illness and absence due to illness at 64 small and 58 large child-care homes and 41 child-care centers. This included 113 446 child-weeks of information on 5360 children. RESULTS: Providers reported 14 474 illness episodes (6.6 episodes per child-year) and 8593 days of absence due to illness (3.9 days per child-year). The incidence of illness episodes was greatest in children who were younger than 1 year, white, or enrolled in small child-care homes. The incidence of absence due to illness was greatest in children who were 1 year of age, Hispanic, or enrolled in child-care centers. Respiratory symptoms were most commonly associated with illness episodes and absence due to illness. CONCLUSIONS: Children in child-care homes had a greater incidence of provider-reported illness than did those in centers. This risk varied by the type of facility and was greatest in small child-care homes. The increased risk for absence due to illness among children in child-care centers reflects exclusion and attendance patterns. It may be possible to reduce the incidence of absence due to illness and subsequent economic impact of child-care-associated illness by educating providers on exclusion guidelines.     

Antitumour activity of 3-chlorodeoxylapachol, a naphthoquinone from Avicennia germinans collected from an experimental plot in southern Florida

As part of an ongoing collaborative effort to discover new anticancer agents from plants, an extract obtained from the leaves and twigs of Avicennia germinans, collected in a coastal area of southern Florida, was identified as possessing cytotoxic activity in a panel of human cancer cell lines. Fractionation of the petroleum ether partition, using cytotoxicity to guide the fractionation, led to the isolation of 3-chlorodeoxylapachol. The antitumour potential of 3-chlorodeoxylapachol was demonstrated with the in-vivo hollow fibre assay, a model of antitumour activity using human cancer cell-filled fibres implanted into mice. The possibility that this compound is an artefact of the isolation procedure was ruled out by liquid chromatography-mass spectrometry analysis of extracts prepared without the use of chlorinated solvent. In conclusion, 3-chlordeoxylapachol, a secondary metabolite obtained from the chloroform-soluble extract of a mangrove tree, was cytotoxic in a panel of human cancer cells, and active against KB human cancer cells in the murine hollow fibre antitumour model, with selectivity in KB cells for the intravenous site at lower doses, indicating possible metabolic activation.     

Transient ischemic attacks: a prospective study of 225 patients

Between the years 1964 and 1973, 225 patients with transient ischemic attacks (TIAs) due primarily to atherosclerosis were evaluated and treated. They have now been followed for from 3 to 14 years (average 5.5 years). As of 1976, 82 of the 225 patients were dead, 21 from cerebral infarction, 52 from heart disease and nine from other causes. Of the 56 untreated patients, 11 (19 percent) had cerebral infarctions, four (7 percent) of which were fatal; six (11 percent) were still having TIAs. Of the 45 patients medically treated, 10 (24 percent) had cerebral infarctions, three (7 percent) of which were fatal; 11(25 percent) still experienced TIAs. In the surgical group of 124, 27 (21 percent) had postoperative cerebral infarctions, seven (6 percent) of which were fatal; 23 (18 percent) had cerebral infarctions during follow-up, of which seven (6 percent) were fatal; and 15 (12 percent) were still having TIAs. No statistically significant differences (p less than 0.05) related to cerebral infarction or TIAs developed among the three groups. The majority (23 percent) eventually succumbed to myocardial infarction, leading us to conclude that great emphasis must be placed upon TIAs as a warning for cardiac as well as cerebrovascular disease.     

A newborn with severe liver failure,cardiomyopathy and transaldolase deficiency

Summary This paper describes the second patient found to be affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2). Clinically, this patient presented in the neonatal period with several signs of severe liver failure: severe coagulopathy, low serum protein, elevated blood ammonia, and hypoglycaemia. She had generalized oedema, moderate muscular hypotonia, and dysmorphic signs. Liver size was decreased, and the spleen was moderately enlarged. There was severe cardiomegaly. The clinical course was characterized by intractable liver failure and progressive myocardial hypertrophy. The child died at the age of 18 days from respiratory failure. In urine, elevations of erythritol, arabitol and ribitol were found, suggesting a deficiency of transaldolase. Enzyme studies in cultured fibroblasts showed undetectable transaldolase activity. DNA sequence analysis of the TALDO1 gene showed a homozygous missense mutation (575G>A), resulting in an amino acid alteration at position 192 (arginine to histidine, R192H). This amino acid is part of the catalytic site of the transaldolase protein. Discovery of this second patient affected with transaldolase deficiency and liver failure suggests that this disorder has a heterogenous clinical presentation with highly variable severity.     

Genetic association studies

We review the rationale behind and discuss methods of design and analysis of genetic association studies. There are similarities between genetic association studies and classic epidemiological studies of environmental risk factors but there are also issues that are specific to studies of genetic risk factors such as the use of particular family-based designs, the need to account for different underlying genetic mechanisms, and the effect of population history. Association differs from linkage (covered elsewhere in this series) in that the alleles of interest will be the same across the whole population. As with other types of genetic epidemiological study, issues of design, statistical analysis, and interpretation are very important.     

Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain

Polymorphism of the insulin gene (INS) variable number of tandem repeats (VNTR; class I or class III alleles) locus has been associated with adult diseases and with birth size. Therefore, this variant is a potential contributory factor to the reported fetal origins of adult disease. In the population-based Avon Longitudinal Study of Pregnancy and Childhood birth cohort, we have confirmed in the present study the association between the INS VNTR III/III genotype and larger head circumference at birth (odds ratio [OR] 1.92, 95% CI 1.23-3.07; P = 0.004) and identified an association with higher cord blood IGF-II levels (P = 0.05 to 0.0001). The genotype association with head circumference was influenced by maternal parity (birth order): the III/III OR for larger head circumference was stronger in second and subsequent pregnancies (OR 5.0, 95% CI 2.2-11.5; P = 0.00003) than in first pregnancies (1.2, 0.6-2.2; P = 0.8; interaction with birth order, P = 0.02). During childhood, the III/III genotype remained associated with larger head circumference (P = 0.004) and was also associated with greater BMI (P = 0.03), waist circumference (P = 0.03), and higher fasting insulin levels in girls (P = 0.02). In addition, there were interactions between INS VNTR genotype and early postnatal weight gain in determining childhood BMI (P = 0.001 for interaction), weight (P = 0.005), and waist circumference (P = 0.0005), such that in the approximately 25% of children (n = 286) with rapid early postnatal weight gain, class III genotype-negative children among this group gained weight more rapidly. Our results indicate that complex prenatal and postnatal gene-maternal/fetal interactions influence size at birth and childhood risk factors for adult disease.     

Computer-assisted surveillance for detecting clonal outbreaks of nosocomial infection

Whole-house surveillance for healthcare-associated infection is no longer the recommended practice because of the large personnel time investment required. We developed a computer-based tracking system using microbiologic data as an aid in detecting potential outbreaks of healthcare-associated infections on a hospital-wide basis. Monthly total isolates of 25 clinically significant hospital pathogens were tallied from 1991 to 1998 to form a database for future comparison. Two different algorithm tools (based on increases of organism numbers over baseline) were applied to determine alert thresholds for suspected outbreaks using this information. The first algorithm (2SD) defined an alert as two standard deviations above the mean monthly number of isolates. The second (MI) defined an alert as either a 100% increase from the baseline organism number over 2 months or a >/=50% increase (compared to baseline) during a three-consecutive-month period. These two methods were compared to standard infection control professional surveillance (ICP) for the detection of clonal outbreaks over 12 months. Overall, a total of seven clonal outbreaks were detected during the 1-year study. Using standard methods, ICP investigated nine suspected outbreaks, four of which were associated with clonal microbes. The 2SD method signaled a suspected outbreak 15 times, of which three were clonal and ICP had detected one. The MI method signaled a suspected outbreak 30 times; four of these were clonal, and ICP had detected one. The sensitivity and specificity values for ICP, 2SD, and MI for detecting clonal outbreaks were 57, 43, and 57% and 17, 83, and 67%, respectively. Statistical methods applied to clinical microbiology laboratory information system data efficiently supplement infection control efforts for outbreak detection.     

Anthrone and oxanthrone C-glycosides from Picramnia latifolia collected in Peru

Cytotoxicity-based, bioassay-guided fractionation of the chloroform-soluble extracts of both the roots and leaves of Picramnia latifolia led to the isolation of two new anthrone C-glycosides, picramniosides G (1) and H (2), two new oxanthrone C-glycosides, mayosides D (3) and E (4), and a new benzanthrone natural product, 6,8-dihydroxy-10-methyl-7H-benz[de]anthracen-7-one (5), together with 10 known compounds, 6,8-dihydroxy-4-methyl-7H-benz[de]anthracen-7-one (6), nataloe-emodin (7), chrysophanein, chrysophanol, 1,5-dihydroxy-7-methoxy-3-methylanthraquinone, pulmatin, 7-hydroxycoumarin, 7-hydroxy-6-methoxycoumarin, beta-sitosterol, and beta-sitosterol glucoside. The structures of 1-5 were established by spectroscopic methods, including 1D and 2D NMR, HRMS, and CD data interpretation. The cytotoxic activity of all isolates was evaluated in a small panel of human cancer cell lines. Compound 7 exhibited significant in vitro cytotoxic activity in the tested cell lines, but no significant activity was observed with an in vivo hollow fiber model at doses of 6.25, 12.5, 25, and 50 mg/kg/injection.