Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.     

Provider attitudes regarding use of an immunization information system to identify children with asthma for influenza vaccination.

OBJECTIVES: Despite longstanding national guidelines, many children with asthma do not receive annual influenza vaccinations. Information from Medicaid-administrative claims data was integrated into the Michigan Care Improvement Registry (MCIR) to prompt providers regarding influenza vaccination among children with high-risk conditions such as asthma. The attitudes of pediatric primary care providers regarding the implementation of this system were assessed. METHODS: A survey was sent in February 2006 to office-based general pediatricians (n = 300) and family physicians (n = 300) in Michigan. The survey focused on influenza vaccination during the 2005-2006 influenza season and attitudes regarding a reminder system for providers using the MCIR. RESULTS: Overall response rate was 67 percent. MCIR participation was high (91%) among respondents, and most (83%) had MCIR information available to them prior to visits with pediatric patients. Most physicians (75%) considered the MCIR high-risk indicator for influenza vaccination a feature that they would find helpful. Some respondents reported concerns that the reminder system is limited to Medicaid patients only (44%) and regarding the completeness of Medicaid data to identify children with asthma (24%). CONCLUSIONS: Physicians have a positive overall view of a statewide registry-based automated reminder system to assist in identifying children with asthma for influenza vaccination, albeit with specific areas of concern.     

African histoplasmosis masquerading as carcinoma of the colon

A case of African histoplasmosis primarily affecting the large bowel—a very unusual manifestation—is reported. In the absence of classical clinical features, pathognomonic of large bowel histoplasmosis, the macroscopic appearance at surgery was confused with large-bowel cancer. The diagnosis was, therefore, retrospective and based on demonstration of large yeast cells ofHistoplasma capsulatum var.duboisii in tissue sections of the lesions.     

Mortality in neonatal septicemia with involvement of mother in management.

In most Special Care Neonatal Units (SCNUs) in India, mothers are excluded from the care of their sick babies for fear of over-crowding and dislocation. We have attempted to study the feasibility of involving mothers in the care of their babies admitted for neonatal septicemia and to analyse whether this changed the sepsis related case fatality rate. The study material consisted of 158 neonates with blood culture positive neonatal septicemia whose mothers were actively involved in their care during their stay in the SCNU of LNJPN Hospital throughout 1987-88. The mothers lived in with their sick neonates and were extremely useful in feeding, cleaning, and monitoring for some important signs and symptoms. There were no epidemics of infection in the nursery during this period. All the babies discharged were receiving breast feeds, and the mothers were confident in taking care of them before discharge. The mortality in this group was 43%. The onset of septicemia was most often in the first week (36%) being 25.9% in second week, 26.6% in the third, and 11.4% in the fourth. Mortality was maximum (64.5%) when the onset of illness was in the first 3 days. Klebsiella and S. aureus were commonly isolated organisms (38.6 and 21.5%, respectively). Gram negative organisms were isolated in 66.5% cases with higher mortality in this group. Nearly 46% of the babies weighed 2 kg or less, with a mortality of 60.2% compared to 28.2% in those more than 2 kg. Only 3 to 5% and 40 to 66.7% of Gram negative and 23 and 70% of Gram positive organisms were sensitive to ampicillin and gentamicin, respectively.