Infant developmental milestones: a 31-year follow-up

This study examined the association between infant developmental milestones and educational level at 31 years of age in the Northern Finland 1966 Birth Cohort ( n =12 058). Developmental data (age at standing, walking, speaking, and measures of bowel and bladder control) were gathered from children's welfare centres. Information on type of schooling at 14 years of age was reported by children and parents. School achievement at 16 years of age and educational level at 31 years were obtained from national registers. Those who reached infant developmental milestones sooner in their first year of life had significantly better ( p <0.05) mean scores in teacher ratings at 16 years, and at 31 years they were more likely to have achieved a better educational level than slower developers. The adjusted odds ratios for individuals who developed more slowly to remain at a basic educational level (7 to 16y) ranged significantly from 1.1 to 1.3. The possibility of advancing from secondary to tertiary level was 1.4 times greater in faster developers than in slow developers. In conclusion, those who develop faster during their first year of life tend to attain higher levels of education in adolescence and adulthood.     

Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage

Free radicals are involved in neurodegenerative disorders, such as ischemia and aging. We have previously demonstrated that treatment with diets enriched with blueberry, spinach, or spirulina have been shown to reduce neurodegenerative changes in aged animals. The purpose of this study was to determine if these diets have neuroprotective effects in focal ischemic brain. Adult male Sprague-Dawley rats were fed with equal amounts of diets (blueberry, spinach, and spirulina) or with control diet. After 4 weeks of feeding, all animals were anesthetized with chloral hydrate. The right middle cerebral artery was ligated with a 10-O suture for 60 min. The ligature was later removed to allow reperfusional injury. Animals were sacrificed and brains were removed for caspase-3 enzymatic assays and triphenyltetrazolium chloride staining at 8 and 48 h after the onset of reperfusion. A subgroup of animals was used for locomotor behavior and biochemical assays. We found that animals which received blueberry, spinach, or spirulina enriched diets had a significant reduction in the volume of infarction in the cerebral cortex and an increase in post-stroke locomotor activity. There was no difference in blood biochemistry, blood CO2, and electrolyte levels among all groups, suggesting that the protection was not indirectly mediated through the changes in physiological functions. Animals treated with blueberry, spinach, or spirulina had significantly lower caspase-3 activity in the ischemic hemisphere. In conclusion, our data suggest that chronic treatment with blueberry, spinach, or spirulina reduces ischemia/reperfusion-induced apoptosis and cerebral infarction.     

Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: a single-blinded, randomized, and controlled trial

BACKGROUND: Warts occur commonly in humans. Destructive modalities are generally the first physician-administered therapy. Other treatment options include immunotherapy. Intralesional immunotherapy using mumps, Candida, or Trichophyton skin test antigens has proved efficacy in the treatment of warts. OBJECTIVES: To determine rates of wart resolution in response to injection of antigen alone, antigen plus interferon alfa-2b, interferon alfa-2b alone, and normal saline; and to compare response according to viral type, major histocompatibility complex antigens, and peripheral blood mononuclear cell proliferation to autologous human papillomavirus antigen before and after injection. DESIGN: Randomized, single-blinded, placebo-controlled, clinical trial. SETTING: Medical school-based dermatology department. PATIENTS: Two hundred thirty-three patients clinically diagnosed as having 1 or more warts.Main Outcome Measure Clinical resolution of warts in response to intralesional immunotherapy. RESULTS: Responders were observed in all treatment arms, but were significantly more likely to have received antigen (P<.001). Resolution of distant untreated warts was observed, and was significantly more likely in subjects receiving antigen (P<.001). Interferon did not significantly enhance the response rate (P = .20) and did not differ from normal saline (P = .65). No viral type or major histocompatibility complex antigen correlated with response or lack of response (P>.99 and P = .86, respectively). A positive peripheral blood mononuclear cell proliferation assay result (2 times pretreatment levels) was significantly more likely among responders (P = .002). While there was no significant difference in response based on sex (P = .56), older subjects (>40 years) were less likely to respond (P = .01). CONCLUSIONS: Intralesional immunotherapy using injection of Candida, mumps, or Trichophyton skin test antigens is an effective treatment for warts, as indicated by significantly higher response rates and distant response rates in subjects receiving antigen. Viral type and major histocompatibility complex antigens did not seem to influence treatment response. Response is accompanied by proliferation of peripheral blood mononuclear cells to human papillomavirus antigens, suggesting that a human papillomavirus-directed cell-mediated immune response plays a role in wart resolution.     

Relation between myelin area and axon diameter in the aortic depressor nerve of spontaneously hypertensive rats

The hypothesis that the aortic depressor nerve (ADN) from spontaneously hypertensive rats (SHR) does not show the expected correlation between myelin sheath area and the axonal diameter of myelinated fibers detected in normotensive rat myelinated fibers was tested by means of regression analysis. Proximal and distal segments of ADN from 13 normotensive Wistar-Kyoto rats (WKY) and nine SHR were prepared for light microscopy study. With an image analysis system, the area of the myelin sheath and the axonal diameter of all myelinated fibers in each nerve were automatically measured. Regression lines were calculated for all nerve segments from each group. Differences between the regression lines were tested for slope and intercept and differences between the correlation coefficients were also tested. Regression lines for WKY data showed no differences between the proximal and distal segments either for slope or intercept. Proximal and distal SHR regression lines were not coincident between segments or when compared to WKY data. These results agree with previous observations that there are morphological differences between WKY and SHR myelinated fibers of the ADN suggesting that the SHR depressor nerve fibers present characteristics of axonal atrophy and/or remyelination.     

Protecting RNA in fixed tissue: an alternative method for LCM users

RNA degradation is a major drawback in most common fixation protocols in techniques that require both RNA integrity and preserved morphology, such as laser capture microdissection (LCM) followed by RT-PCR. Moreover, RNA isolation kits especially developed for LCM samples are very expensive. Our aim was to determine an easy protocol that ideally must provide an acceptable morphology, allow proper laser capture of selected cells and improve RNA yield and quality. In this study, retinas were dissected, briefly incubated in a RNA preservative and fixed in 2% paraformaldehyde before being cut on a cryostat. LCM was carried out in retinal sections for immediate RNA isolation, by using TRIzol common protocol with minor modifications. Real-time PCR was performed next in order to compare availability of RNA from samples submitted to different protocols. The use of the RNA preservative followed by a fast fixation did not jeopardize tissue morphology, allowing microdissection of selected cells, combined to minor modifications in usual RNA isolation procedures, significantly improved RNA yield and quality. Furthermore, only LCM samples submitted to our protocol provided amplifiable mRNA, as determined by real-time PCR. Taken together, the combination of the described procedures resulted in a reliable alternative for LCM users.     

Muscle fiber-type distribution as a predictor of blood pressure: a 19-year follow-up study

The known association between physical activity and low blood pressure may be influenced by inherited characteristics. Skeletal muscle consists of type I (slow-twitch) and type II (fast-twitch) muscle fibers, with proportions highly variable between individuals and mostly determined by genetic factors. A high percentage of type I fibers (type I%) has been associated with low blood pressure in cross-sectional studies. We investigated whether type I percentage predicts future blood pressure levels and explains part of the association between physical activity and blood pressure. At baseline, in 1984, muscle fiber-type distribution, physical activity, and body mass index (BMI) were determined in 64 healthy men (age, 32 to 58 years). At follow-up, in 2003, blood pressure, physical activity, and BMI were determined in these men. In subjects without antihypertensive medication (n=43), type I percentage accounted for 5%/18% of the variation in systolic/diastolic blood pressure. A high type I percentage predicted, independent of both baseline (in 1984) and follow-up (in 2003), physical activity, BMI, and low systolic and diastolic blood pressure. Adjusted for all baseline covariates, a 20-unit higher type I percentage predicted a 11.6-mm Hg lower systolic blood pressure (P=0.018) and a 5.0-mm Hg lower diastolic blood pressure (P=0.018). High levels of physical activity in 1984 predicted low diastolic blood pressure, but this association was lost when type I percentage was included into the model. A high proportion of type I fibers in skeletal muscle is an independent predictor of low blood pressure and explains part of the known association between high levels of physical activity and low blood pressure.     

Specific risk factors for Clostridium difficile-associated diarrhea: a prospective, multicenter, case control evaluation

BACKGROUND: Clostridium difficile is a toxin-producing bacterium that is responsible for toxicity to the colonic mucosa, causing inflammation, necrosis, and, in some extreme cases, intestinal dilation and perforation. C difficile-associated diarrhea (CDAD) occurs when patients have a reduction in their natural gastrointestinal flora that allows for the proliferation of and toxin production by C difficile. METHODS: Using a multicenter, prospective observational case control study, we assessed and quantified risk factors associated with the development of diarrhea caused by Clostridium difficile, with particular attention to antibiotic use. All hospitalized patients with diarrhea requiring a C difficile toxin test as part of their routine clinical workup were considered for study inclusion. Patients with a negative specimen (controls) were considered for enrollment if matched (by age, sex, length of stay, and institution) to a case. Variables associated with CDAD were identified using univariate analysis. Significant factors were then entered into multivariate logistic regression analysis to identify independent factors. RESULTS: There were no significant differences in antibiotic use between cases and controls. Patient severity, classified by Horn's Index, was significantly different between cases and controls (P = .0022). No other significant variables were identified. CONCLUSION: The severity of illness of the cases was classified as more severe than the controls, but no significant differences in antibiotic use were identified between the groups. The negative C difficile toxin studies on the well-matched control patients indicate a different etiology of diarrhea (such as antibiotic-associated diarrhea), which may have developed in the presence of similar antibiotic use as the cases.