Parent Expectations of the School Health Program in Nebraska

This article presents findings from the first phase of a comprehensive evaluation plan for the school health program in Nebraska public schools. The evaluation utilized the Targeting Outcomes of Programs (TOP) framework to gather parents' perspectives about the benefits of the school health program, and a ranking of important health activities and role providers. A survey was distributed to 1,200 parents randomly selected from 60 school districts. Of these, 450 (38%) were returned: 96% supported funding of health programs; 88% believed families benefited from school health; 92% viewed the health programs as "essential" to the educational mission; 64% preferred a ratio of 1 nurse/500 students; and 89% believed all students needed access to a professional school nurse. The nurse was the only clearly defined role in the health program and had activities rated as "extremely important." Results were reported to the Nebraska legislature for support of state funding for school health nursing.     

Secondary mania in patients with HIV infection: are antiretrovirals protective?

A case-control study of 19 patients with HIV-associated mania and 57 HIV-seropositive control patients matched by CD4 cell count, age, and year of treatment was undertaken to investigate associations with risk factors for human immunodeficiency virus (HIV) infection, treatment, and disease. There was no significant difference between groups for HIV exposure category, baseline health status, or drugs other than antiretrovirals. Zidovudine therapy provided a significant protective effect against the development of mania, whether administered at or prior to diagnosis of mania. In a 3-year follow-up study, incident AIDS dementia was significantly more common in patients with mania, despite no apparent difference in survival between cases and controls. These findings strengthen the evidence of an etiological association of HIV neuropathology with AIDS mania by demonstrating a protective effect of an antiretroviral agent able to penetrate the central nervous system.     

Measurement of in vitro cellular pharmacokinetics of 5-fluorouracil in human and rat cancer cell lines and rat hepatocytes using a flow-through system

Summary A flow-throught system was used to study the cellular pharmacokinetics of 5-fluorouracil (5-FU) in four human cell lines (squamous-cell carcinoma HEp-2, colon carcinoma WiDr, hepatoma Hep G2, and breast carcinoma MCF-7) as well as in the rat hepatoma H35 cell line and in freshly isolated rat hepatocytes. The system made it possible to restrict the decrease in the concentration of 5-FU in the medium, to keep the volume in which the metabolites accumulated relatively small, and to study the dynamics of a response during and after a change in the composition of the eluent. Clearance of 5-FU from the eluent was achieved predominantly (>95%) by its catabolism to dihydrofluorouracil in the tumor cell lines and to 2-fluoro--alanine in the hepatocytes. Not only rat hepatocytes but also HEp-2 cells showed relatively high clearance values. A concentration-dependent 5-FU elimination was observed, indicating saturation of 5-FU elimination according to Michaelis-Menten kinetics (K_m 14–22 M). The maximal velocity (V_max) values ranged from 0.025 to 0.13 nmol 5-FU/10⁶ cells per minute. For HEp-2 cells, high-concentration pulse injections of 5-FU, thymine, uridine, or uracil immediately led to a reduction in 5-FU conversion, followed by recovery within 5 min. The flow-through system proved to be adequate for the study of the non-linear pharmacokinetics of 5-FU in different intact cells and for the comparison of various manipulations of these pharmacokinetics.Abbreviations 5-FU 5-fluorouracil - FUR 5-fluorouridine - F-DHU dihydrofluorouracil - F--ala 2-fluoro--alanine - F-UPA -fluoroureidopropionic acid - HEPES 4-(2-hydroethyl)-1-piperazine-ethane sulfonic acid - MEM modified minimal essential medium - HBSS Hanks' balanced salt solution - HPLC high-performance liquid chromatography Supported by grant IKA 87-16 from the Netherlands Cancer Foundation. One author (G. J. P.) is the recipient of a senior research fellowship from the Royal Netherlands Academy of Arts and Sciences (KNAW)     

Perinatal support programs: A strategy for the primary prevention of child abuse

Perinatal support programs are offering new hope for the prevention of child abuse. This article reviews the research stimulating these programs, details the prescribed components of perinatal programs according to the Interprofessional Task Force on Health Care of Women and Children and the National Committee for Prevention of Child Abuse, and discusses four demonstration projects currently being conducted.Ellen B. Gray is Program Associate for Primary Prevention and Director of the project, Collaborative Research and Community and Minority Group Action to Prevent Child Abuse, at the National Committee for Prevention of Child Abuse. Reprint requests may be addressed to the author at the National Committee for Prevention of Child Abuse, 332 South Michigan Avenue, #1250, Chicago, Illinois 60604.     

Angiographic Embolization for Intraperitoneal and Retroperitoneal Injuries

Angiographic embolization (AE) has been used extensively for bleeding control after injuries to the face and neck. Its role in abdominal trauma requires further exploration. We reviewed the medical records of 137 consecutive patients who underwent angiography with the intent to embolize bleeding sites within the abdomen. Of them, 97 (71%) had blunt and 40 (29%) had penetrating trauma. AE was performed for hemorrhage associated with pelvic fractures (97 patients), liver lacerations (n= 26), renal lacerations (n= 12), splenic lacerations (n= 5), other injuries (n= 9), and multiple injuries (n= 12). On angiography, 102 patients were found to have bleeding sites and underwent AE, with angiographic and clinical bleeding control in 93 (91%). The rate of successful hemostasis by AE was identical in blunt and penetrating trauma patients. There was no major morbidity after AE. No factors predicted patients with a high likelihood to have a positive angiogram. Patients who had AE before or after a period of attempted hemodynamic stabilization in the intensive care unit were no different with respect to hemodynamic parameters immediately before AE or effectiveness of AE for bleeding control. AE is a safe and effective method for controlling bleeding after blunt and penetrating intra- and retroperitoneal injuries. Early AE may be used in selected patients as a front-line therapeutic intervention that offers expeditious hemostasis and prevents delays in definitive bleeding control.     

Unusual Hepatic Tumor with Features of Mesenchymal Hamartoma and Congenital Solitary Nonparasitic Cyst

We report a hepatic tumor in an adolescent that does not fit into any of the described categories of liver tumors. The patient presented with hepatomegaly, abdominal pain, and normal liver function test; the tumor was cystic in imaging studies. The resected specimen, result of a partial hepatectomy, measured 21 cm and was multicystic with solid areas. Microscopically, the cysts were lined by a mucous-producing or intestinal-type epithelium, associated with smooth muscle and small mucous-producing glands. The solid component contained fibrous and adipose tissue, smooth muscle and thick-walled vessels. Aneuploidy was demonstrated by flow cytometry. We interpreted the tumor as having features of a mesenchymal hamartoma and congenital solitary nonparasitic cyst. It is conceivable that the lesions originated with small peribiliary glands with dilatation and intestinal metaplasia.     

Resistance to imatinib (Glivec): update on clinical mechanisms.

Imatinib mesylate, an orally administered 2-phenylaminopyrimidine derivative that inhibits BCR/ABL tyrosine kinase activity, has shown great promise in the treatment of chronic myelogenous leukemia (CML). This small molecule, tyrosine kinase inhibitor, has also been shown to be effective against metastatic gastrointestinal stromal tumors (GISTs) expressing the stem cell factor (SCF) receptor kit. However, the threat of resistance in patients has prompted investigators to uncover the mechanisms whereby malignant cells develop resistance to imatinib, and has also led to the establishment of strategies designed to over-ride imatinib resistance. Here, we provide a comprehensive overview of the effectiveness of imatinib in the treatment of chronic, accelerated and blast crisis-phase CML, Philadelphia chromosome-positive (Ph+) acute lymphoid leukemia (ALL) and metastatic GIST. Established mechanisms of resistance to imatinib are discussed, as are novel therapeutic approaches to improving drug responsiveness by reversing development of imatinib resistance in patients.     

Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry.

There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04-2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer.     

A comparison of the in vitro and in vivo activities of IgG and F(ab')2 fragments of a mixture of three monoclonal anti-Her-2 antibodies.

PURPOSE: We have demonstrated previously that a mixture of three anti-Her-2 monoclonal antibodies (MAbs) that bind to different epitopes on the extracellular domain of Her-2 expressed on a human breast cancer cell line has more potent antitumor activity than the individual MAbs both in vitro and in xenografted severe combined immunodeficient mice. Because the activity of Herceptin is Fc dependent, we determined whether this would also be the case when a mixture of these three anti-Her-2 MAbs was used. EXPERIMENTAL DESIGN: IgG and highly purified F(ab')(2) fragments of the anti-Her-2 MAbs and Herceptin were prepared and evaluated for their ability to induce cell death, inhibit vascular endothelial growth factor secretion, and mediate antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity in vitro. They were also compared for their abilities to induce regression of large BT474 tumors in severe combined immunodeficient mice. RESULTS: All of the F(ab')(2) fragments were >95% pure and, as expected, did not mediate antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity in vitro. The in vitro antiproliferative and proapoptotic effects of the IgGs and F(ab')(2) fragments were similar. In contrast, the IgGs had significant antitumor activity in vivo, whereas their F(ab')(2) fragments were only marginally effective even at 5-fold higher doses to offset their shorter half-lives. CONCLUSIONS: These results confirm the importance of the Fc portion of Herceptin for optimal in vivo activity and demonstrate that even a mixture of three anti-Her-2 MAbs that are highly effective at inducing cell death in vitro requires Fc-mediated effector function for optimal in vivo activity.     

Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer.

PURPOSE: The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy. EXPERIMENTAL DESIGN: Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment. RESULTS: Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses. CONCLUSIONS: This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.