Lung health consequences of reported accidental chlorine gas exposures among pulpmill workers

The long-term consequences of accidental chlorine gas exposure have been investigated, mainly in the community setting, among persons exposed as a result of a nearby chlorine spill. This circumstance is not analogous to the more frequent chlorine or chlorine dioxide gas overexposures that occur commonly in pulpmills over a background of a low level of gas exposure. To investigate the respiratory health consequences of these accidental exposures ("chlorine gassing") in the industrial setting, we carried out a cross-sectional respiratory health survey among workers at a British Columbia coastal pulpmill and a nearby rail maintenance yard. A greater proportion of pulpmill workers were unavailable for study because of illness (10.5% versus 2.4% in the railyard, p less than 0.01). Procedures involved simple spirometry, respiratory symptom assessment, and measurement of average levels of air contaminants. Average chlorine levels in the pulpmill were below 1 ppm; however, 60% of the pulpmill workers reported one or more accidental "chlorine gassing" incidents. Pulpmill workers who reported being "gassed" were significantly more likely to report wheezing on occasion than were other pulpmill workers and railyard workers (rate for these three groups: nonsmokers: 8, 2, 1%; ex-smokers: 17, 11, 7%; current smokers: 42, 21, 19%; p less than 0.05). No significant lung function differences were found between the overall pulpmill group and the railyard workers; however, nonsmoking and formerly smoking pulpmill workers who reported being "gassed" had significantly lower average midmaximal flow rate and FEV1/FVC ratio than did their counterparts in the remainder of the pulpmill population (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

An analysis of the effects of implementing the teaching-family model in two community-based group homes

The effects of implementing the Teaching-Family Model in two community-based group homes were assessed through a series of pre-post measures. Data analysis indicates substantial positive change in youth social skills, program quality, youth and staff satisfaction levels, social climate, and staff accountability for care of the children.Requests for reprints, samples of the Staff Accountability Scale, and other forms or the questionnaires in this study should be addressed to Kurt Scheider at The Maryville Academy, 1150 North River Road, Des Plaines, IL 60016     

Staged TRAM Breast Reconstruction: Combining the Advantages of Tissue Expansion with Surgical Delay

The TRAM flap has become the gold standard in breast reconstruction but suffers from the disadvantages of poor color match, different texture, and impaired sensation compared to the normal breast. This study reports on a two-stage procedure to address these problems. The first stage consists of insertion of a tissue expander and surgical delay of the TRAM flap. The second stage consists of removal of the tissue expander and transposition of a deepithelized TRAM flap into the tissue expanded cavity. (The capsule is excised.) Four cases of breast reconstruction are reported. The advantage of this procedure is that it offers the benefits of tissue expansion, viz., normal color match, texture, and sensation, and in addition, reconstruction is achieved with autologous tissue by a pedicled TRAM flap. The vascularity of the TRAM is enhanced by a surgical delay procedure.     

Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.     

“Amnesia” for Summer Camps and High School Graduation: Memory Work Increases Reports of Prior Periods of Remembering Less

Claims regarding amnesia for childhood sexual abuse have often been based on studies of adults' responses to questions of the form, “Was there ever a period of time when you remembered less of the abuse than you do now?” In this experiment, 43 adult (mean age = 42) participants rated their current and prior memories of several nontraumatic childhood/adolescent events. Reports of prior periods of less memory were fairly common. Participants then engaged in “reminiscence” or “enhanced” retrieval activities directed toward remembering more about a selected target event. Following retrieval, 35% of the reminiscence condition participants reported prior poor memory for the target event, as did 70% of the enhanced condition. These results highlight the need for appropriate control conditions in retrospective studies of amnesia for childhood trauma.     

Azoxymethane-induced colon tumors and aberrant crypt foci in mice of different genetic susceptibility

Azoxymethane (AOM) is an organotropic colon carcinogen that is commonly used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbred mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) and AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a week for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3±1.1 and 36.4±2.4, respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also assessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J mice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the other strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that ACF in resistant mice are persistent but do not progress to tumors.     

Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV.

UK-427,857 (4, 4-difluoro-N-[(1S)-3-[exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl]cyclohexanecarboxamide) is a novel CCR5 antagonist undergoing investigation for use in the treatment of human immunodeficiency virus (HIV) infection. Pharmacokinetic and metabolism studies have been performed in mouse, rat, dog, and human after single and multiple administration by oral and intravenous routes. The compound has physicochemical properties that are borderline for good pharmacokinetics, being moderately lipophilic (log D(7.4) 2.1) and basic (pK(a) 7.3), possessing a number of H-bonding functionalities, and with a molecular weight of 514. The compound was incompletely absorbed in rat (approximately 20-30%) but well absorbed in dog (>70%). Based on in vitro studies in Caco-2 cells, UK-427,857 has relatively poor membrane permeability, and transcellular flux is enhanced in the presence of inhibitors of P-glycoprotein. Further evidence for the involvement of P-glycoprotein in restricting the oral absorption of UK-427,857 was obtained in P-glycoprotein null mice (mdr1a/mdr1b knockout). In these animals, AUC after oral administration was 3-fold higher than in control animals. In oral dose escalation studies in humans, the compound demonstrated nonlinear pharmacokinetics, with increased dose-normalized exposure with increased dose size, consistent with saturation of P-glycoprotein. The oral dose-exposure relationship of UK-427,857 in humans was not reflected in either rat or dog. In animal species and humans, UK-427,857 undergoes some metabolism, with parent compound the major component present in the systemic circulation and excreta. Elimination of radioactive dose was primarily via the feces. In rat, parent compound was secreted via bile and directly into the gastrointestinal tract. Metabolites were products of oxidative metabolism and showed a high degree of structural consistency across species.     

Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089.

PURPOSE: In 1990, fluorouracil (FU) plus levamisole for 1 year became standard adjuvant treatment for patients with high-risk stages II and III colon cancer. Intergroup (INT) 0089 assessed the relative contributions of leucovorin and levamisole in such patients. PATIENTS AND METHODS: From 1988 to 1992, 3,794 patients were randomly assigned. Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks. The control arm was levamisole plus FU (LEV) for 1 year. RESULTS: After a median follow-up of 10 years, of 3,561 eligible patients, 1,691 (47%) have died and 1,330 (37%) have experienced disease recurrence; 137 (10%) of those experiencing recurrence are still alive. A total of 481 patients (13%) died without evidence of recurrence, and 1,723 (48%) are alive and disease free. Although there were toxicity differences among the four arms, none was statistically superior in disease-free or overall survival. CONCLUSION: The 6- to 8-month regimens of LDLV and HDLV without levamisole used in this trial, rather than the previous standard regimen of 12 months of LEV, have become widely used. INT-0089 has long-term follow-up of the largest clinical trial of patients with high-risk colon cancer, documenting not only the durability of the treatment effects, but also the natural history of patients with high-risk colon cancer, and analyses of treatment based on age, race, and comorbid conditions such as obesity, diabetes, and second primary cancers.