[Exposure to noise in the general population and hypertension: results from a pilot case-control study in Rome]. / Esposizione a rumore nella popolazione generale ed iperten- sione arteriosa: risultati di uno studio pilota caso-controllo nella città di Roma.

The aim of the study was to assess the impact of noise pollution on blood pressure values of a sample population in the metropolitan area of Rome. A case-control study was carried out. Cases were patients with hypertension recruited at the Hypertension Center of the Teaching Hospital "Agostino Gemelli" in Rome, whereas controls were healthy people recruited at the same center. Noise exposure was assessed using place of residence of participants, and this related to monitoring air pollution data of Rome. 241 individuals entered the study, 161 cases (80 males and 81 females) and 80 controls (42 males and 38 females), aged on average 55,65 (+/- 12.66) and 57.08 (+/- 14.64) year, respectively. Multivariate analysis showed that being a case is directly associated to increasing age (the risk increases of 5% for each increase of 1 year), salt use (OR = 2.76; 95% CI: 1.18 - 8.48), exposure to a noise level over 65 dBA (OR = 2.09; 95% CI: 1.01 - 4.47), and inversely to physical activity (OR = 0.49; 95% CI: 0.23 - 1.00). These results, could be considered in city and urban green planning, having the last element a mitigating effect on population health.

Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as consolidation therapy in patients undergoing bone marrow transplantation for acute lymphoblastic leukemia.

We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic recovery to 38 patients undergoing autologous or allogeneic marrow transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12 of 22 receiving allogeneic and 12 of 16 receiving autologous transplants) received between one and 12 doses of PEG-L-A, including nine who completed the planned 12 doses of therapy. The toxicities encountered were similar to those observed in non-transplanted patients undergoing therapy with PEG-L-A and included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low levels of anti-thrombin III. Of the 24 who received the drug, eight remain in remission. Of 12 patients in second remission at the time of transplantation who received PEG-L-A, five of seven who received allogeneic and two of five who received autologous transplants remain in remission, 16+ to 46+ months from transplant. While PEG-L-A could be administered to most of the patients undergoing marrow transplantation for ALL, most patients either relapsed while receiving the drug or developed toxicities which resulted in abbreviated courses. At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.

The use of partially HLA-mismatched donors for allogeneic transplantation in patients with mucopolysaccharidosis-I.

Allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling appears to improve survival and diminish some of the physiologic derangements seen in children with mucopolysaccharidosis (MPS)-I (Hurler Syndrome), an inherited metabolic storage disease resulting from the lack of alpha-L-iduronidase enzyme activity. Death is usually expected in the first decade of life. Unfortunately, most patients lack an HLA-matched sibling donor and alternative donors have been identified for transplant. This study reports on a five-year median follow-up (range: 985-2,355 days) in 11 Hurler Syndrome patients who underwent allogeneic BMT from partially mismatched related donors (PMRDs). The median age was 20 months (range: 11-44 months). The overall survival rate was 64% (95% CI 34-94%). The overall graft failure rate (36%) was higher than reported with matched sibling BMT. All patients with sustained engraftment experienced improvement in physical manifestations, such as corneal opacity, gum and tongue hypertrophy, hepatosplenomegaly and joint mobility. Skeletal abnormalities, such as dysostosis-multiplex, were stabilized but not reversed. Some patients have continued to show decline in neuropsychometric testing, while others appear to stabilize and one has demonstrated improvement. Until better methods for replacing enzyme activity are developed, BMT from a matched sibling of alternative donors can be considered a viable intervention for Hurler Syndrome patients to achieve partial improvement or stabilization from the deterioration caused by substrate storage, particularly in minimally affected patients early in life.

High-dose chemotherapy with autologous stem-cell rescue in patients with recurrent and high-risk pediatric brain tumors.

PURPOSE: We treated 49 patients with recurrent or poor-prognosis CNS malignancies with high-dose chemotherapy regimens followed by autologous marrow rescue with or without peripheral-blood stem-cell augmentation to determine the toxicity of and event-free survival after these regimens. PATIENTS AND METHODS: Nineteen patients had medulloblastomas, 12 had glial tumors, seven had pineoblastomas, five had ependymomas, three had primitive neuroectodermal tumors, two had germ cell tumors, and one had fibrosarcoma. Thirty-seven received chemotherapy with cyclophosphamide 1.5 g/m2 daily x 4 and melphalan 25 to 60 mg/m2 daily x 3. Nine received busulfan 37.5 mg/m2 every 6 hours x 16 and melphalan 180 mg/m2 (n = 7) or 140 mg/m2 (n = 2). Three received carboplatin 700 mg/m2/d on days -7, -5, and -3 and etoposide 500 mg/m2/d on days -6, -4, and -2. All patients received standard supportive care. RESULTS: Eighteen of 49 patients survive event-free 22+ to 55+ months (median, 33+) after transplantation, including nine of 16 treated before recurrence and nine of 33 treated after recurrence. There was one transplant-related death from pulmonary aspergillosis. Of five patients assessable for disease response, one had a partial remission (2 months), one has had stable disease (55+ months), and three showed progression 2, 5, and 8 months after transplantation. CONCLUSION: The toxicity of these regimens was tolerable. Certain patients with high-risk CNS malignancies may benefit from such a treatment approach. Subsequent trials should attempt to determine which patients are most likely to benefit from high-dose chemotherapy with autologous stem-cell rescue.

Development and pharmacological characterization of a modified procedure for the measurement of carbonic anhydrase activity.

Carbonic anhydrases (CAs) are a family of zinc metalloenzymes of molecular mass 30-60 kDa; seven different isoenzymes belong to this family (Okuyama et al., 1992, Proc Natl Acad Sci USA 89:1315-1319). They may be broadly recognized according to the efficiency with which they catalyze the reversible interconversion of CO2 and HCO3-, and they differ in physicochemical properties, in sensitivity to various inhibitors and in their subcellular localization; cytoplasmic (CA I, CA II, CA III, and CA VII), cell-surface membrane (CA IV), and mitochondrial (CA V) and secretory (CA VI) isoenzymes have been described. Several methods are reported in the literature for the measure of CA enzymatic activity; they may be broadly divided into two categories: those based on the measure of pH variation (pH-stat and colorimetric assays) (Wu et al., 1993, J Ocular Pharm 9:97-108; Maren, 1991, Molec Pharmacol 41:419-426) and the ones in which CO2 production is measured through pCO2 sensors (Botrè and Botrè, 1990, Anal Biochem 185:254-264).

Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.

BACKGROUND: Transplantation of bone marrow from unrelated donors is limited by a lack of HLA-matched donors and the risk of graft-versus-host disease (GVHD). Placental blood from sibling donors can reconstitute hematopoiesis. We report preliminary results of transplantation using partially HLA-mismatched placental blood from unrelated donors. METHODS: Twenty-five consecutive patients, primarily children, with a variety of malignant and non-malignant conditions received placental blood from unrelated donors and were evaluated for hematologic and immunologic reconstitution and GVHD. HLA matching was performed before transplantation by serologic typing for class I HLA antigens and low-resolution molecular typing for class II HLA alleles. In donor-recipient pairs who differed by no more than one HLA antigen or allele, high-resolution class II HLA typing was done retrospectively. Fordonor-recipient pairs who were mismatched for two HLA antigens or alleles, high-resolution typing was used prospectively to select the best match for HLA-DRB1. RESULTS: Twenty-four of the 25 donor-recipient pairs were discordant for one to three HLA antigens. In 23 of the 25 transplant recipients, the infused hematopoletic stem cells engrafted. Acute grade III GVHD occurred in 2 of the 21 patients who could be evaluated, and 2 patients had chronic GVHD. In vitro proliferative responses of T cells and B cells to plant mitogens were detected 60 days after transplantation. With a median follow-up of 12 1/2 months and a minimal follow-up of 100 days, the overall 100-day survival rate among these patients was 64 percent, and the overall event-free survival was 48 percent. CONCLUSIONS: HLA-mismatched placental blood from unrelated donors is an alternative source of stem cells for hematopoietic reconstitution in children.

Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant.

Most patients requiring allogeneic bone marrow transplantation (BMT) lack a human leukocyte antigen genotypically identical sibling and require an alternative donor. This carries an increased risk of graft failure and acute graft-versus-host disease (GVHD). We sought to overcome these problems with transplants by using grafts obtained from the most readily available source: the haploidentical, partially mismatched, related donor. This study of 40 patients used a novel approach combining in vitro and in vivo T cell depletion with T lymphocyte targeted monoclonal antibodies (mAb) and intensified conditioning therapy, including fractionated total body irradiation before etoposide, cytoside arabinoside, cyclophosphamide, and methylprednisolone. Grafts were treated with T10B9.1A-31 mAb, directed against the alpha-beta heterodimer of the T cell receptor, and rabbit complement. In vivo depletion was attempted with an anti-CD5 mAb-Ricin A-chain (H65-RTA) immunotoxin (IT). Study patients were compared with a historical control group of 17 patients not given H65-RTA. Rates of engraftment were not significantly different (93% vs. 100%, P=0.12), although patients receiving IT engrafted more rapidly. The incidence of > grade I GVHD was significantly lower in the study group (36% vs. 100%, P=0.0001), as well as for severe grade III-IV GVHD (19% vs. 92%, P=0.0001). Five-year survival tended to be improved in the study group (40% vs. 18%, P=0.21). Transplant from haploidentical family members is indicated for patients without a matched sibling in whom allogeneic BMT offers the best opportunity to achieve cure.

Capitalizing on the hidden job market.

As nurses expand their roles, job opportunities become less overt and in fact may actually be hidden from the casual job seeker. The purpose of this article is to describe how nurse practitioners can use two marketing techniques to become cognizant of those jobs in their expanded role that are not advertised. Informational interviewing and skills identification are two methods nurse practitioners can use to capitalize on this hidden job market.