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Biomedical subjects

J J Spinelli

Publications and source records attributed to J J Spinelli.

At least 37 records · Page 2Linked to original sources
PubMed1999

The cost of obesity in Canada.

BACKGROUND: Almost one-third of adult Canadians are at increased risk of disability, disease and premature death because of being obese. In order to allocate limited health care resources rationally, it is necessary to elucidate the economic burden of obesity. OBJECTIVE: To estimate the direct costs related to the treatment of and research into obesity in Canada in 1997. METHODS: The prevalence of obesity (body mass index of 27 or greater) in Canada was determined using data from the National Population Health Survey, 1994-1995. Ten comorbidities of obesity were identified from the medical literature. A population attributable fraction (PAF) was calculated for each comorbidity with data from large cohort studies to determine the extent to which each comorbidity and its management costs were attributable to obesity. The direct cost of each comorbidity was determined using data from the Canadian Institute of Health Information (for direct expenditure categories) and from Health Canada (for the proportion of expenditure category attributable to the comorbidity). This prevalence-based approach identified the direct costs of hospital care, physician services, services of other health professionals, drugs, other health care and health research. For each comorbidity, the cost attributable to obesity was determined by multiplying the PAF by the total direct cost of the comorbidity. The overall impact of obesity was estimated as the sum of the PAF-weighted costs of treating the comorbidities. A sensitivity analysis was completed on both the estimated costs and the PAFs. RESULTS: The total direct cost of obesity in Canada in 1997 was estimated to be over $1.8 billion. This corresponded to 2.4% of the total health care expenditures for all diseases in Canada in 1997. The sensitivity analysis revealed that the total cost could be as high as $3.5 billion or as low as $829.4 million; this corresponded to 4.6% and 1.1% respectively of the total health care expenditures in 1997. When the contributions of the comorbidities to the total cost were considered, the 3 largest contributors were hypertension ($656.6 million), type 2 diabetes mellitus ($423.2 million) and coronary artery disease ($346.0 million). INTERPRETATION: A considerable proportion of health care dollars is devoted to the treatment and management of obesity-related comorbidities in Canada. Further research into the therapeutic benefits and cost-effectiveness of management strategies for obesity is required. It is anticipated that the prevention and treatment of obesity will have major positive effects on the overall cost of health care.

Adult↗
PubMed1999

Regimen-related toxicity and non-relapse mortality with high-dose cyclophosphamide, carmustine (BCNU) and etoposide (VP16-213) (CBV) and CBV plus cisplatin (CBVP) followed by autologous stem cell transplantation in patients with Hodgkin's disease.

This analysis compares the regimen-related toxicity (RRT) and overall non-relapse mortality (NRM) in Hodgkin's disease patients conditioned with either CBV (cyclophosphamide, BCNU (carmustine), and VP16-213 (etoposide)) (26 patients) or CBVP (CBV + cisplatin) (68 patients) followed by autologous stem cell transplantation (ASCT). CBVP included a continuous infusion rather than intermittent doses of etoposide, a lower BCNU dose and the addition of cisplatin. RRT and NRM were determined for each regimen and compared; risk factors for each were examined by multivariate analysis. Grade IV (fatal) RRT occurred in five patients (pulmonary in two, cardiac in two, and central nervous system in one). Eighteen patients experienced grade II-III pulmonary RRT, consistent with BCNU damage in 15. Prior nitrosourea exposure was the main risk factor for pulmonary RRT. Grade II mucosal and hepatic RRT occurred less often after CBVP vs CBV (P = 0.031 and 0.0003, respectively). In addition, three other early and eight late non-relapse deaths were seen. Median follow-up of the entire group is 5.1 (range 2.8-10.2) years. The probability of overall NRM was 26% (95% confidence interval (CI) 13-50%) with CBV vs 23% (95% CI 12-41%) with CBVP (P = 0.40). The progression-free survival and relapse rates were similar. Although the rates of fatal RRT, pulmonary RRT and overall NRM were similar with CBV or CBVP, CBVP produced less mucosal and liver RRT with a comparable antitumor effect. As many autografted patients are cured, future efforts should include measures to decrease NRM.

Adult↗
PubMed1999

Identification of occupational cancer risks in British Columbia. Part I: Methodology, descriptive results, and analysis of cancer risks, by cigarette smoking categories of 15,463 incident cancer cases.

To identify occupational cancer risk factors, lifetime occupational, smoking, and alcohol-consumption histories were collected by means of a self-administered questionnaire from 15,463 male cancer patients aged 20 years and over as ascertained from the British Columbia population-based cancer registry; all cases were histologically confirmed. The study methodology, descriptive results, and cancer risks from cigarette smoking are reported. Assessment of questionnaire validation and reliability showed very high correlations between all variables analysed. Non-response bias, assessed among 221 non-responders and 432 matched controls, revealed no statistically significant differences for smoking status, education, or for 11 usual (longest-held job) occupational groups, except for managerial occupations and for four pooled groups that represented 6.7% of all occupations. Except for pancreatic cancer, a significant relationship was found for all cancer sites known to be strongly associated with cigarette smoking.

Adult↗
PubMed1999

alpha1-antitrypsin genotypes and the acute-phase response to open heart surgery.

A mutation in the 3' region of the alpha1-antitrypsin (alpha1-AT) gene is associated with chronic obstructive pulmonary disease (COPD). However, the reason for this association is unknown. The mutation does not cause alpha1-AT deficiency but in vitro studies suggest it could attenuate the rise in alpha1-AT levels during the acute-phase response. Therefore, we sought an association between the 3' mutation and a reduced rise in alpha1-AT levels following open heart surgery, a known trigger of the acute-phase response. We genotyped 198 patients and identified 31 with the 3' mutation. Their alpha1-AT rise was compared with the remaining 167 wild type subjects. Multiple linear regression analysis identified sex, urgency of surgery, and surgical pump time as significant independent predictors of the rise in alpha1-AT. However, we found no association between the 3' mutation and a reduced rise in alpha1-AT. We also identified patients who had the Z and S alpha1-AT deficiency mutations and found a significant reduction in the rise in alpha1-AT in individuals who were heterozygous for the Z mutation compared with wild type subjects. However, when the rise in alpha1-AT was expressed as a percentage of the basal level, there was no significant difference between individuals who had the S or Z mutations compared with wild type. Therefore, an attenuated alpha1-AT acute-phase response does not explain previous associations of the 3' and S mutations with COPD. However, a deficient acute-phase rise in alpha1-AT may contribute to the susceptibility to COPD associated with the Z mutation.

Acute-Phase Reaction↗
PubMed1999

Z and S mutations of the alpha1-antitrypsin gene and the risk of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) has been associated with heterozygosity for the Z and S alleles of the alpha1-antitrypsin gene in some studies, but these observations have not been confirmed by others. Cigarette smoking is the major risk factor for COPD and may have been a confounding factor in many of the previous studies. We investigated whether the Z or S alleles were more prevalent in a group of heavy smokers with COPD than in a group of nonobstructed smokers. Forced expiratory volume in 1 s and forced vital capacity were derived for 266 patients undergoing lobar or lung resection. These lung-function measurements were used to divide the patients into a COPD group and a group of nonobstructed control subjects. The subjects were typed for the Z and S alleles of the alpha1-antitrypsin gene using a polymerase chain reaction-based technique. In the COPD patients, 12 of 193 (6%) were heterozygous for the Z allele (MZ) compared with 0 of 73 control subjects, which gave a P value of 0.04 after correction for age, gender, and smoking history. There was no association of the S allele with COPD. The results indicate that the Z, but not the S, allele is a risk factor for COPD in the heterozygous state.

Aged↗
PubMed1998

Admission of bone marrow transplant recipients to the intensive care unit: outcome, survival and prognostic factors.

The role of ICU support in BMT patients is controversial. In an era of constrained resources, the use of prognostic factors predicting outcome may be helpful in identifying patients who are most likely (or unlikely) to benefit from this intervention. We attempted to define the survival of patients admitted to ICU following autologous or allogeneic BMT and to identify those factors important in determining patient outcome. A retrospective study of all adult BMT recipients admitted to intensive care over a 6 year study period was performed to determine overall and prognostic indicators of poor outcome. Pre-treatment, pre-ICU admission and ICU admission data were analyzed to identify factors predicting long-term survival. 116 patients were admitted to ICU on 135 separate occasions with the primary reasons for admission being respiratory failure (66%), sepsis associated with hypotension (10%), and cardiorespiratory failure (8%). No pre-ICU characteristics were predictive of survival. Univariate analysis identified the number of support measures required, the need for ventilation or hemodynamic support, the APACHE II score, the year of ICU admission and the serum bilirubin as significant predictors of post-discharge survival. On multivariate analysis the year of ICU admission, the need for hemodynamic support and the serum bilirubin remained significant. The APACHE II score significantly underestimated survival in the 46% of patients with scores less than 35, and could only be used to predict 100% mortality when it exceeded 45. Twenty-three percent of all BMT patients admitted to the ICU and 17% of ventilated patients survived to hospital discharge. Of the 27 patients surviving to leave hospital, 16 remain alive with a median follow-up of 4.2 years and a mean Karnofsky performance status of 90. Although mortality in BMT recipients admitted to ICU is high our results indicate that intensive care support can be lifesaving and that the outcome in patients requiring ventilation and ICU support may not be as poor as has been previously reported. No single variable was identified which could be used to predict futility but patients requiring both hemodynamic support and mechanical ventilation, and those with an APACHE II score greater than 45 have a very poor prognosis and are unlikely to benefit from lengthy ICU support.

Adolescent↗
PubMed1998

Vitamin D binding protein variants and the risk of COPD.

Although the development of chronic obstructive pulmonary disease (COPD) in smokers shows genetic susceptibility, only alpha1-antitrypsin deficiency has been identified as a definite genetic risk factor. There have been three previous studies in which associations between Gc-globulin phenotypes and COPD have been investigated. Although some data suggest an association, the results were inconclusive. Because smoking is the major risk factor for COPD, it may have been a confounding factor in previous studies. We have investigated Gc-globulin genotypic frequencies among 75 COPD patients and 64 nonobstructed controls. Both groups had significant smoking histories: pack-years (mean +/- SD) of 52 +/- 30 and 48 +/- 27, respectively. The results show that homozygosity for the Gc2 allele is protective against COPD (OR = 0.17, 95% CI = 0.03 to 0.83). There were no differences between genotypes for lung elastic recoil values or for the level of upstream airway resistance. Gc-globulin can enhance complement (C5a)-mediated neutrophil chemotaxis. Because neutrophils play a role in parenchymal destruction and airway inflammation, we examined whether Gc-globulin's ability to enhance neutrophil chemotaxis varied with genotype. We found no difference among genotypes with respect to neutrophil chemotaxis suggesting that the protective effect of the Gc2 allele is mediated through a different mechanism.

Airway Resistance↗
PubMed1997

Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer.

BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.

Adult↗
PubMed1997

Validation of a high-performance liquid chromatographic assay method for pharmacokinetic evaluation of busulfan.

The development and validation of a high-performance liquid chromatographic (HPLC) assay for determination of busulfan concentrations in human plasma for pharmacokinetic studies is described. Plasma samples containing busulfan and 1,6-bis(methanesulfonyloxy)hexane, and internal standard, were prepared by derivatization with sodium diethyldithiocarbamate (DDTC) followed by addition of methanol and extraction with ethyl acetate. The extract was dried under nitrogen and the samples reconstituted with 100 microl of methanol prior to HPLC determination. Chromatography was accomplished using a Waters NovaPak octadecylsilyl (ODS) (150 x 3.9 mm I.D.) analytical column, NovaPak ODS guard column, and mobile phase of methanol-water (80:20, v/v) at a flow-rate of 0.8 ml/min with UV detection at 251 nm. The limit of detection was 0.0200 microg/ml (signal-to-noise ratio of 6) with a limit of quantitation (LOQ) of 0.0600 microg/ml for busulfan in plasma. Calibration curves were linear from 0.0600 to 3.00 microg/ml in plasma (500 microl) using a 1/y weighting scheme. Precision of the assay, as represented by C.V. of the observed peak area ratio values, ranged from 4.41 to 13.5% (13.5% at LOQ). No day-to-day variability was observed in predicted concentration values and the bias was low for all concentrations evaluated (bias: 0 to 4.76%; LOQ: 2.91%). The mean derivatization and extraction yield observed for busulfan in plasma at 0.200, 1.20 and 2.00 microg/ml was 98.5% (range 93.4 to 107%). Plasma samples containing potential busulfan metabolites and co-administered drugs, which may be present in clinical samples, provided no response indicating this assay procedure is selective for busulfan. This method was used to analyze plasma concentrations following administration of a 1 mg/kg oral busulfan dose.

Busulfan↗
PubMed1997

Importance of the day 7 bone marrow biopsy as a prognostic measure of the outcome in children with acute lymphoblastic leukemia.

The presence of > or = 25% blasts in a marrow aspirate obtained on day 7 of induction followed by a remission at day 28 has been associated with a poor prognosis in children with acute lymphoblastic leukemia (ALL). We evaluated whether a day 7 marrow biopsy may be used to more accurately assess therapeutic reduction of leukemia tumor burden. Studied were 76 children with ALL enrolled on CCG protocols at B.C's Children's Hospital who received both a day 7 aspirate and biopsy and were in remission by day 28. Evaluation for the correlation of the percentage aspirate blasts on day 7 with the biopsy demonstrated a moderate correlation with the percentage biopsy blasts (R = 61), but not correlation with the biopsy cellularity. We saw a similar prediction of outcome by the percentage blasts on day 7 marrow aspirate in the study as reported previously although it was not significant. Outcome analysis was done using leukemia burden as measured by the day 7 absolute blast index-aspirate (ABI-aspirate) calculated as the product of the biopsy cellularity with the percentage blasts on the aspirate. The ABI-aspirate significantly predicted patient outcome with 83% survival in those with an ABI-aspirate of < .06 compared to 51% in those > or = .06 (P = .01) and was highly significant when analyzed as a continuous predictor (P = .004). This is the first study to demonstrate that information gained from the day 7 marrow biopsy can improve prediction of outcome in children with ALL. Based on this preliminary study, we recommend that large population ALL therapy trials evaluate the role of the day 7 marrow biopsy for outcome prediction in children with ALL.

Adolescent↗
PubMed1997

Mutation in the 3' region of the alpha-1-antitrypsin gene and chronic obstructive pulmonary disease.

A mutation in the 3' flanking region of the alpha-1-antitrypsin gene has been reported to be associated with chronic obstructive pulmonary disease (COPD). We have investigated the prevalence of this mutation in a group of 185 patients with airway obstruction and in 69 non-obstructed controls. The subjects were selected on the basis of their development of lung cancer and therefore had similar exposure to cigarette smoke, the major risk factor for COPD. In the majority of subjects, the level of airway inflammation and loss of elastic recoil was known, and therefore we were able to test whether the mutation was associated with one of these pathological mechanisms. The prevalence of heterozygotes for the mutation was 10% in both the obstructed group and controls. The mutation was not associated with increased airway inflammation or loss of elastic recoil. This result indicates that the 3' mutation is not a significant risk factor for COPD in this population, and suggests heterogeneity in the pathogenesis of the disease.

Female↗
PubMed1997

Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners).

Aged↗
PubMed1997

Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives.

OBJECTIVES: This study examined the association between exposure to chlorophenates and the risk of soft tissue sarcoma; non-Hodgkin's lymphoma; Hodgkin's disease; and cancers of the lung, nose, and nasopharynx. METHODS: A retrospective cohort study was conducted of 26487 workers employed for at least 1 year between 1950 and 1985 in 11 chlorophenate-using and 3 non-using sawmills in British Columbia, Canada. Exposures by job were ascertained with interviews of senior employees. RESULTS: Probabilistic record linkage to the Canadian Mortality Data Base and the British Columbia Cancer Registry found 4710 deaths between 1950 and 1990, and 1547 incident cases of cancer between 1969 and 1989. None of the cancers of interest had elevated mortality related to chlorophenate exposure. Non-Hodgkin's lymphoma incidence (n = 65) increased with increasing chlorophenate exposure hours, yielding the following standardized incidence ratios: less than 120 hours 0.68; 120 to 1999 hours, 0.59; 2000 to 3999 hours, 1.04; 4000 to 9999 hours, 1.02; and 10000 or more hours, 1.30. CONCLUSIONS: These results are consistent with the borderline positive associations seen in other recently reported studies of chlorophenate-exposed workforces.

British Columbia↗
PubMed1997

Induction failure in de novo acute myelogenous leukemia is associated with expression of high levels of CD34 antigen by the leukemic blasts.

The prognostic significance of CD34 antigen expression in acute myelogenous leukemia (AML) is controversial. Most studies to date have reported on CD34 positivity and not the level of antigen present. In this study of 62 patients with de novo AML, 48 (77%) patients were CD34+ in varying levels (0-85 mean channels of fluorescence (MCF)). Forty seven of 62 were treated with combination chemotherapy and 39 (83%) of them achieved complete remission (CR). Patients with CD34- blasts were more likely to achieve CR; however, this trend was not statistically significant (p = .11). On the other hand, patients with higher levels of CD34 antigen on the blasts were less likely to attain CR (p < 0.001, multivariate analysis). The patients who achieved CR expressed lower levels of CD34 (0-57; median 9 MCF) as compared to those who did not achieve CR (15-85; median 30 MCF). Of the other antigens tested, partial or complete absence of CD33 (CD33 absent in > or =25% blasts) correlated with failure to achieve CR (p = 0.0029). These results are in keeping with the hypothesis that more primitive AML blasts with high levels of CD34 are chemoresistant.

Adult↗
PubMed1996

Acyclovir prophylaxis of oral herpes virus during bone marrow transplantation.

Oropharyngeal shedding of herpes viruses (herpes simplex, cytomegalovirus) was assessed in patients on standard acyclovir prophylaxis during bone marrow transplantation (BMT) to determine the frequency of viral shedding and to assess possible oropharyngeal complications that may be associated with viral reactivation in these patients. We conducted a prospective assessment of 83 patients receiving BMT. Patients were evaluated weekly and oral surveillance cultures were completed. Shedding of herpes simplex virus (HSV) was detected in the oropharynx of 2.9% of seropositive patients on prophylactic acyclovir, and only one case of clinical oral herpetic infection was seen. Cytomegalovirus (CMV) was cultured from the oropharynx in 13.3% of CMV seropositive patients provided with prophylactic acyclovir, but no oropharyngeal lesions were attributed to CMV reactivation. No correlation was seen between HSV and CMV pretransplant serology and severity of oral mucositis and acute graft versus host disease. No effect on time to engraftment was detected. This study supports the continuing use of acyclovir prophylaxis in HSV seropositive patients receiving BMT. Acyclovir prophylaxis was effective in preventing viral shedding in all but 2.9% of patients, and only one case of clinical infection was diagnosed. The frequency of CMV shedding was approximately four times that of HSV; however, no oral lesions were attributed to CMV.

Acyclovir↗
PubMed1996

Chemotherapy of Mediterranean abdominal lymphoma. Retrospective comparison of chemotherapy protocols in Iranian patients.

Retrospectively, 41 Iranian patients with Mediterranean abdominal lymphoma (MAL) were studied; 21 patients had received anthracycline-based protocols, and 20 patients had been treated with regimens lacking anthracyclines. The study groups were comparable with respect to several factors, including age, performance status, histology of lymphoma, stage of disease, and the average relative dose intensity of their protocols. Our first group had a complete remission (CR) rate of 62%, mean disease-free interval (DFI) of 16.3 months and a 71% overall survival at 30 months. The second group showed a CR rate of 40%, mean DFI of 11.2 months, and a 35% overall survival at 30 months. The differences were significant in survival (P = .012) and DFI (p < .001). The incidence of serious toxicities and complications was similar.

Adult↗
PubMed1996

Criteria for marrow engraftment: comparison of reticulocyte maturity index with conventional parameters.

Reticulocyte maturity index (RMI) has recently been proposed as an early indicator of marrow engraftment. We compared the RMI with conventional bone marrow engraftment criteria including total leukocyte count (WBC), absolute neutrophil count (ANC), reticulocyte count (RC) and the day of last platelet transfusion required to maintain the platelet count (PC) > or = 20 x 10(9)/l in 37 patients undergoing allo- or autologous BMT. There was no discrepancy in predicting engraftment between RMI, ANC, WBC and RC. RMI indicated engraftment earlier (median day 17, range 10-63 days) than the ANC (median day 19, range 8-63 days), WBC (median day 19, 9-71), RC (median day 19, 11-125) or PC (median day 29, 11-237). RMI heralded engraftment preceded ANC, WBC, RC or PC in 22, 21, 34 and 32 patients, respectively. RMI signal occurred 6 days prior to the rise in ANC in patients who engrafted later than 25 days (n = 7). Trend analysis showed that ANC fluctuated more frequently (6/37 patients) than RMI (1/37). Combined use of ANC and RMI (whichever increased first) predicted engraftment earlier (median 15 days) and more confidently (no false starts) than either used alone.

Bone Marrow Transplantation↗