Two year cumulative incidence of trunk abnormalities in a schoolpopulation in Rotterdam, The Netherlands

We conducted a study of the 2 year cumulative incidence of trunkabnormalities in a cohort of 3,071 11 year old children (1,621boys, 1,450 girls). The following data were recorded: height,weight, signs of puberty and menarche. Trunk abnormality wasassessed in the erect child (asymmetry of shoulders and waistline,imbalance of the trunk, scoliosis, lordosis, kyphosis, swaybackand flexibility) and by the forward bending test (FBT) (ribhump or lumbar prominence, persisting scoliosis, kyphosis anddeviant lateral aspect). A normal FBT both at baseline and atfollow-up was found in 84% of the boys and in 79% of the girls.The 2 year cumulative incidence of an abnormal FBT was 10% inboys and 13% in girls.     

Repair of postinfarction ventricular septal defect using aneurysmal ventricular wall

A new surgical technique is described where a postinfarction ventricular septal defect can be expeditiously repaired using associated aneurysmal left ventricular wall. late     

Complicated migraine and migraine variants.

Curr Pain Headache Rep. 2002;6:233-239.
This article reviews the less frequently encountered varieties of migraine. It is suggested that these disorders be approached by evaluating possible underlying etiologies before positively diagnosing migraine. This decreases the likelihood of "missing" structural or metabolic disorders. The classification, diagnostic evaluation, differential diagnosis, and treatment options of these disorders is reviewed and a selection of references appended for additional information.
Comment: Dr. Rothner is one of the most prominent pediatric neurology headache specialists in the country, and he sees a variety of atypical presentations of migraine. This is an excellent review of such presentations. SJT     

Surgical closure of atrial septal defect in children under two years of age

Infants with atrial septal defects are seldom symptomatic and usually require elective surgery between 2 and 4 years of age. However a small minority is symptomatic and management at this age has been controversial. This study evaluated surgical closure of atrial septal defect below 2 years of age. Eighteen infants with a mean age of 13.4 +/- 5.7 months were operated on for secundum atrial septal defect from 1994 to 2001. Fourteen patients were symptomatic with failure to thrive in 7 and recurrent respiratory infections in 7, one had increasing cardiomegaly, and 3 were operated on early for social reasons. The defect was isolated in 11 patients (61%) and the other 7 (39%) had minor associated lesions requiring additional procedures such as ductal ligation, direct closure of a tiny ventricular septal defect, and inspection of the mitral valve. There were no early or late deaths. The postoperative course was complicated by pulmonary problems in 4 cases. Of the 16 patients available for follow-up, 14 were asymptomatic and 2 were symptomatically improved. Most showed a dramatic improvement in growth and development. These gratifying results indicate that consideration should be given to early surgical closure of atrial septal defect in symptomatic infants.     

Reciprocal interactions between prostaglandin E2- and estradiol-dependent signaling pathways in the injured zebra finch brain

Background

Astrocytic aromatization and consequent increases in estradiol are neuroprotective in the injured brain. In zebra finches, cyclooxygenase-activity is necessary for injury-induced aromatase expression, and increased central estradiol lowers neuroinflammation. The mechanisms underlying these influences are unknown. Here, we document injury-induced, cyclooxygenase-dependent increases in glial aromatase expression and replicate previous work in our lab showing increases in central prostaglandin E2 and estradiol following brain damage. Further, we describe injury-dependent changes in E-prostanoid and estrogen receptor expression and reveal the necessity of E-prostanoid and estrogen receptors in the injury-dependent, reciprocal interactions of neuroinflammatory and neurosteroidogenic pathways.

Methods

Adult male and female birds were shams or received bilateral injections of the appropriate drug or vehicle into contralateral telencephalic lobes.

Results

Injuries sustained in the presence of indomethacin (a cyclooxygenase inhibitor) had fewer aromatase-expressing reactive astrocytes relative to injuries injected with vehicle suggesting that cyclooxygenase activity is necessary for the induction of glial aromatase around the site of damage. Injured hemispheres had higher prostaglandin E2 and estradiol content relative to shams. Importantly, injured hemispheres injected with E-prostanoid- or estrogen receptor-antagonists showed elevated prostaglandin E2 and estradiol, respectively, but lower prostaglandin E2 or estradiol-dependent downstream activity (protein kinase A or phosphoinositide-3-kinase mRNA) suggesting that receptor antagonism did not affect injury-induced prostaglandin E2 or estradiol, but inhibited the effects of these ligands. Antagonism of E-prostanoid receptors 3 or 4 prevented injury-induced increases in neural estradiol in males and females, respectively, albeit this apparent sex-difference needs to be tested more stringently. Further, estrogen receptor-α, but not estrogen receptor-β antagonism, exaggerated neural prostaglandin E2 levels relative to the contralateral lobe in both sexes.

Conclusion

These data suggest injury-induced, sex-specific prostaglandin E2-dependent estradiol synthesis, and estrogen receptor-α dependent decreases in neuroinflammation in the vertebrate brain.

     

The effect of the Fanconi anemia polypeptide, FAC, upon p53 induction and G2 checkpoint regulation

Fanconi anemia (FA) is an autosomal recessive disease marked by developmental defects, bone marrow failure, and cancer susceptibility. FA cells are hypersensitive to DNA cross-linking and alkylating agents and accumulate in the G2 phase of the cell cycle in response to these agents. FA cells also display genomic instability, suggesting a possible defect in the p53 pathway. To test the effect of heterologous expression of FAC cDNA on drug-induced cytotoxicity, G2 accumulation, and p53 induction in FA cells, we compared two isogenic FA cell lines: HSC536N (mock), a FA type C cell line sensitive to mitomycin C (MMC), and the same cell line transfected (corrected) with wild-type FAC cDNA (HSC536N [+FAC]). HSC536N (+FAC) cells showed a 30-fold increase in resistance to MMC concentration. Similarly, increases in resistance were observed following exposure to cisplatin, carboplatin, and cyclophosphamide. In addition, HSC536N (+FAC) cells showed a twofold lower G2 accumulation following MMC treatment. To analyze the possible interaction of FAC with the p53 pathway, we analyzed p53 induction in mock and corrected cell lines following exposure to MMC. HSC536N (mock) cells induced p53 at lower MMC concentrations than HSC536N (corrected). Caffeine, a known G2 checkpoint inhibitor, not only inhibited G2 accumulation seen in both cell lines but also caused the resistant HSC536N (+FAC) to become as sensitive to MMC as HSC536N (mock) cell line. We conclude that the FAC protein has a specific cytoprotective effect and may function as a cell cycle regulator of the G2 phase of the cell cycle.     

Soluble CD4, soluble CD8, soluble CD25, lymphopoieitic recovery, and endogenous cytokines after high-dose chemotherapy and blood stem cell transplantation

Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high- dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. The concentrations of both G- CSF and IL-6 peaked at 7 days after reinfusion of stem cells, and this transient elevation preceded the increase in the white blood cell count by approximately 5 to 7 days. The levels of sCD4 and sCD8 increased to a maximum on day 21, and the time to peak levels coincided with the maximum increase in white blood cell count, absolute neutrophil count, or lymphocytes. The levels of sCD25 were found to be elevated from day 7 to day 21. Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.