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Biomedical subjects

G Adams

Publications and source records attributed to G Adams.

At least 55 records · Page 3Linked to original sources
PubMed1997

Quality of life following bone marrow transplantation: a comparison of patient reports with population norms.

All surviving patients who had received an allogeneic bone marrow transplant at the Princess Margaret Hospital were asked to participate in a health-related quality of life (HQL) study using the Medical Outcomes Survey-Short Form 36 (MOS SF-36), the Satisfaction with Life Domains Scale-Bone Marrow Transplantation (SLDS-BMT) and a current symptoms checklist. The main objective was to compare the health status of BMT survivors with age-adjusted population norms. Of the 251 patients contacted, 93% returned questionnaires. The median follow-up after BMT was 40 months, ranging from 1-253 months. On average, survivors had some diminished HQL relative to the health status of the population in general. Time since transplant had a significant influence on HQL; those less than 3 years from transplant experienced considerable impairment while those who had survived beyond this point were indistinguishable from the normal population in most domains and significantly better in certain psychosocial aspects of health. Many patients still reported symptoms months after BMT; some were mildly affected while others experienced more troublesome symptoms. However, 81% of patients were satisfied with the HQL outcome that they had achieved and 94% would recommend a transplant for someone in similar circumstances.

Adult↗
PubMed1997

Pathogenic lymphoid cells engineered to express TGF beta 1 ameliorate disease in a collagen-induced arthritis model.

Collagen-induced arthritis in DBA/1 mice is a model of rheumatoid arthritis with marked synovitis and erosions. The disease can be adoptively transferred to SCID mice with arthritogenic splenocytes from DBA/1 mice injected with bovine collagen type II. However, infection of arthritogenic splenocytes with a retrovirus expressing TGF beta 1 inhibits development of arthritis in SCID mice. When DBA/1 mice, at onset of arthritis have additional arthritogenic splenocytes transferred, exacerbation occurs, reflected in a rapid increase in the number of arthritic joints, increased paw swelling and higher levels of anti-collagen antibody. By infecting arthritogenic splenocytes ex vivo with TGF beta 1 retrovirus, this exacerbation was inhibited. TGF beta 1 was effective in lowering inflammation of joints with already established arthritis and inhibiting the spreading of the disease to other joints. Transient reduction in anti-collagen antibody levels could also be obtained using purified T cells infected with TGF beta 1 retrovirus. In addition, expression of TGF beta 1 in lymphocytes reduced the levels of gelatinase (MMP2) activity in inflamed joints.

Animals↗
PubMed1997

Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group.

PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.

Actuarial Analysis↗
PubMed1996

Immunohistochemical staining for markers of future neoplastic progression in the larynx.

We performed a retrospective, longitudinal study to determine whether abnormalities in immunohistochemical staining for the epidermal growth factor receptor (EGFR), p53, or cyclin D1 occur before the development of laryngeal carcinoma. Staining was performed on 63 paraffin-embedded biopsies from 18 patients who subsequently developed carcinoma in situ (CIS) or invasive carcinoma of the larynx. These were compared to 71 biopsies from 20 patients who did not develop CIS/cancer (minimum follow-up period, 4 years). Also studied were the 34 biopsies containing CIS and/or carcinoma from those patients who progressed and 22 biopsies obtained concurrently. The two patient groups did not differ significantly in terms of tobacco and alcohol use. Distinct patterns of staining correlated with malignant progression. These included EGFR staining of two thirds or more of the epithelium thickness, a linear basal p53 staining pattern, and strong (3+) staining for cyclin D1 (P < 0.01 for each). These staining patterns also correlated with increasing atypia. In our study population, linear basal staining for p53 and strong staining for cyclin D1 had higher specificity for progression than did EGFR overexpression, which was also seen in association with inflammation and chronic irritation. Marked site-to-site variation was seen in the immunohistochemical staining and in the degree of atypia, suggesting that multiple biopsies are necessary to properly assess risk. These immunohistochemical staining patterns may be clinically useful to predict patients at risk for neoplastic progression.

Adult↗
PubMed1996

Characterization of the radical trapping activity of a novel series of cyclic nitrone spin traps.

alpha-Phenyl-tert-butyl nitrone (PBN) is a nitrone spin trap, which has shown efficacy in animal models of oxidative stress, including stroke, aging, sepsis, and myocardial ischemia/reperfusion injury. We have prepared a series of novel cyclic variants of PBN and evaluated them for radical trapping activity in vitro. Specifically, their ability to inhibit iron-induced lipid peroxidation in liposomes was assessed, as well as superoxide anion (O2(-.)) and hydroxyl radical ((.)OH) trapping activity as determined biochemically and using electron spin resonance (ESR) spectroscopy. All cyclic nitrones tested were much more potent as inhibitors of lipid peroxidation than was PBN. The unsubstituted cyclic variant MDL 101,002 was approximately 8-fold more potent than PBN. An analysis of the analogs of MDL 101,002 revealed a direct correlation of activity with lipophilicity. However, lipophilicity does not solely account for the difference between MDL 101,002 and PBN, inasmuch as the calculated octanol/water partition coefficient for MDL 101,002 is 1.01 as compared to 1.23 for PBN. This indicated the cyclic nitrones are inherently more effective radical traps than PBN in a membrane system. The most active compound was a dichloro analog in the seven-membered ring series (MDL 104,342), which had an IC50 of 26 mum, which was 550-fold better than that of PBN. The cyclic nitrones were shown to trap (.)OH with MDL 101,002 being 20 25 times more active than PBN as assessed using 2-deoxyribose and p-nitrosodimethylaniline as substrates, respectively. Trapping of (.)OH by MDL 101,002 was also examined by using ESR spectroscopy. When Fenton's reagent was used, the (.)OH adduct of MDL 101,002 yielded a six-line spectrum with hyperfine coupling constants distinct from that of PBN. Importantly, the half-life of the adduct was nearly 5 min, while that of PBN is less than 1 min at physiologic pH. MDL 101,002 also trapped the O2(-.) radical to yield a six-line spectrum with coupling constants very distinct from that of the (.)OH adduct. In mice, the cyclic nitrones ameliorated the damaging effects of oxidative stress induced by ferrous iron injection into brain tissue. Similar protection was not afforded by the lipid peroxidation inhibitor U74006F, thus implicating radical trapping as a unique feature in the prevention of cell injury. Together, the in vivo activity, the stability of the nitroxide adducts, and the ability to distinguish between trapping of (.)OH and O2(-.) suggest the cyclic nitrones to be ideal reagents for the study of oxidative cell injury.

Animals↗
PubMed1996

Organism isolation and serum bactericidal titers in oral antibiotic therapy for pediatric osteomyelitis.

Isolation of the etiologic organism and monitoring of serum bactericidal titers are considered necessary in oral antibiotic therapy for osteomyelitis. Over a 5-year period, 26 pediatric patients with hematogenous osteomyelitis were treated with sequential parenteraloral therapy. No organism was isolated in 9 cases, and bactericidal titers were determined in only 7 cases. All patients did well, raising questions about the conventional prerequisites invoked for oral treatment of skeletal infections.

Administration, Oral↗
PubMed1995

Differences in work activities between private and community health centre general practitioners.

OBJECTIVE: To investigate differences in the characteristics of general practitioners (GPs) and patients, referral rates, rates of prescribing and ordering of tests and x-rays, and types of counselling and consultation, between private and community health centre (CHC) GPs in Victoria. METHOD: All 51 full-time Victorian CHC GPs were invited to enrol in the Australian Morbidity and Treatment Survey (AMTS) developed by the Family Medicine Research Unit at the University of Sydney in 1992. The control group comprised the 114 Victorian GPs involved in this survey in 1991. RESULTS: Thirty-nine CHC GPs (76%) provided complete data. CHC GPs were more likely to be younger, female, and to have less experience in general practice. Patient age and gender distributions were similar. CHC GPs had higher rates of offering counselling and advice and of referral to allied health professionals, but similar rates of referral to medical specialists to those of private GPs. We found no differences in prescribing after multivariate analysis. CONCLUSIONS: Counselling, and referral to allied health professionals, were the only striking differences after multivariate analysis. It may be that any movement toward non-throughput-related remuneration may, in isolation, have less impact on general practitioner work patterns than imagined. Patient throughput was not measured, and this would be important in any future global assessment of the cost-effectiveness of CHC and private general practitioners.

Adult↗
PubMed1995

Tolerance induced by direct inoculation of donor antigen into the thymus in low and high responder rodents.

A novel approach to tolerance induction in rats was recently described where donor antigen is inoculated directly into the thymus along with a brief period of immunosuppression in a pretransplant strategy. To develop a strategy that has more clinical appeal, we evaluated the timing of donor antigen inoculation in relation to allografting, the use of frozen bone marrow as the antigen, and the dose response of purified T cells as the antigen in a low responder heterotopic heart allograft combination. Additionally, the success of this pretransplant strategy in different low and high responder strain combinations was defined. In tolerant low responder animals we evaluated in vitro and in vivo cellular immunity. Tolerant host strain naive CD8+ T cell responses to donor and third party stimulators were compared to determine if tolerance is related to the strength of the response of the T cell subsets to donor antigen. Frozen bone marrow can induce tolerance in a low responder combination. Additionally, the dose of purified T cells necessary for tolerance induction was 5 x 10(5) cells. The pretransplant strategy was successful in two low responder strain combinations, Lewis into Wistar Furth and Lewis into DA, but unsuccessful in all high responder strain combinations evaluated. Low responder animals unresponsive to donor heart allografts demonstrate intact cell-mediated immunity and donor-specific tolerance in vivo by rejecting third party but not second donor strain hearts. The in vitro responses of tolerant animals demonstrated donor-specific suppression of the MHC class II response but an intact (normal) response to third party stimulators by proliferation assays and IFN-gamma production, suggesting suppression at the CD4+ T cell subset level.

Animals↗
PubMed1995

Results of a multicenter trial using the BTA test to monitor for and diagnose recurrent bladder cancer.

OBJECTIVES: We compare the Bard BTA (bladder tumor antigen) test to voided cytology studies in patients undergoing surveillance cystoscopy for recurrent bladder cancer. MATERIALS AND METHODS: A prospective, blinded, multicenter trial was performed. RESULTS: A total of 499 patients underwent 1,014 cystoscopic examinations and tumor was identified in 151. The bladder tumor antigen test was more sensitive than cytology studies in detecting recurrent cancer (p < 0.001), being positive in 61 cases versus 25 for cytology. The trial in healthy volunteers and nonurological patients estimates bladder tumor antigen test specificity to be 95.9%. CONCLUSIONS: The bladder tumor antigen test is a simple, rapid and inexpensive adjunct to cystoscopy, and the results are equivalent or superior to those of voided cytology as performed in this trial.

Adult↗
PubMed1995

A controlled double blind study of azathioprine in the management of Crohn's disease.

While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7% receiving placebo), p = 0.001. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p = 0.02). There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease.

Adolescent↗
PubMed1995

Cervical lymph node status and survival in laryngeal carcinoma: prognostic factors.

Elective cervical lymphadenectomy often is performed for laryngeal carcinoma to eliminate metastatic disease that escapes clinical and radiographic detection. We investigated characteristics of the primary tumor that might predict cervical lymph node status. We obtained archival tissue from 88 laryngectomies--65 with concurrent cervical lymphadenectomies. Of the 40 clinically negative necks that were dissected, 17% showed lymph node metastasis by pathologic examination. The primary tumors were examined immunohistochemically for expression of epidermal growth factor receptor (EGFR), p53, cathepsin D, proliferating cell nuclear antigen (PCNA), and Ki-67-specific antigen, and by flow cytometry for DNA ploidy-cell cycle analysis. Seventy-seven percent of the cases showed aberrant p53 staining, 99% expressed EGFR, 40% produced cathepsin D, 29% were aneuploid, and 54% had a moderate or high synthesis phase fraction (SPF). High grade, aneuploidy, and tumor vascular invasion independently predicted cervical node metastasis (p < .04 each). Supraglottic locale (p < .16) and a raggedly infiltrating invading margin (p < .13) were weakly associated with node positivity. Advanced clinical T status, the expression of EGFR, p53, and cathepsin D, the PCNA and Ki-67 indices, and SPF did not correlate with node metastasis. The presence of cervical node metastasis predicted poor disease-free (p < .005) and overall survival (p < .04). Advanced clinical T status correlated with brief overall survival (p < .02). Tumor site, histopathologic parameters, ploidy, SPF, PCNA and Ki-67 indices, and the expression of p53, EGFR, and cathepsin D did not affect survival. The presence of vascular invasion, high grade, and aneuploidy may help identify which patients would benefit from elective cervical lymphadenectomy. The correlation of cervical lymph node status and clinical T category with survival confirms the results of previous studies.

Adult↗
PubMed1995

The prevalence and severity of microvascular complications in pancreatic diabetes and IDDM.

OBJECTIVE: To investigate and compare the prevalence, associations, and severity of retinopathy and nephropathy in patients with pancreatic diabetes (PD) and insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Thirty patients with PD due to alcohol-induced chronic pancreatitis were matched for age, sex, and duration of diabetes with 30 patients with IDDM. Retinopathy was assessed by fluorescein angiography using the Wisconsin classification. Renal function was assessed by albumin excretion rates (AERs) in at least two timed overnight urine collections and glomerular filtration rates (GFRs) by single injection of 51Cr-EDTA. Microalbuminuria was defined as AER 20-200 micrograms/min and nephropathy as AER > 200 micrograms/min. RESULTS: Retinopathy was found in 33% of patients with PD and in 40% with IDDM. The spectrum of disease was similar in the two groups. The geometric mean of AER was 15 micrograms/min (range 1-1,541) in the PD group and 24 micrograms/min (2-2,288) in the IDDM group. Nephropathy was found in 7 PD and in 5 IDDM patients, and a reduced GFR was present in 8 (26%) and 4 (13%) of the two groups, respectively. Microalbuminuria occurred in 9 (33%) and hyperfiltration in 3 (10%) in each group. These differences were insignificant. Retinopathy correlated with AER in both groups. Retinopathy and AER correlated with duration of diabetes in the IDDM but not in the PD group. CONCLUSIONS: Microvascular complications are equally common and severe in PD and IDDM, and improved glycemic control should be the goal in both.

Albuminuria↗
PubMed1995

The delivery of insulin from aqueous and non-aqueous reservoirs governed by a glucose sensitive gel membrane.

A self regulating delivery device, responsive to glucose, has been shown to operate successfully in vitro. This comprises a gel membrane which determines the delivery rate of insulin from a reservoir. The gel consists of a synthetic polysucrose and the lectin, concanavalin A. The mechanism is one of displacement of the branched polysaccharide from the lectin receptors by incoming glucose. The gel loses its high viscosity as a result but reforms on removal of glucose, thus providing the switch controlling the drug diffusion rate. The drug does not require to be chemically modified and thus the device is adaptable to other anti-hyperglycaemic drugs. However, results here indicate that the molecular weight of the solute may be an important parameter. Others include path length, gel formulation and temperature. It had been hypothesised that the reversal might be improved by the use of a non-aqueous reservoir of insulin. However, with the use of insulin, the switching off was found to be superior to that found with other test solutes used in previous studies, irrespective of the reservoir solvent. The advantages in the use of the non-aqueous system include, however, more reproducibility in the magnitude of response and a reduced temperature sensitivity.

Concanavalin A↗
PubMed1995

Inhibition of transfer of collagen-induced arthritis into SCID mice by ex vivo infection of spleen cells with retroviruses expressing soluble tumor necrosis factor receptor.

Collagen-induced arthritis can be transferred into severe combined immunodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. The development of arthritis in SCID animals can be prevented by infection ex vivo of DBA/1 spleen cells with retroviruses expressing the monomeric soluble human p75 tumor necrosis factor (TNF) receptor (TNF-R). In addition, a vector engineered to express a polycystronic mRNA with TNF-R and the herpes simplex virus thymidine kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect which could be blocked by treating the animals with ganciclovir. A retroviral vector expressing the HSVtk gene alone had no effect on this arthritis transfer model with or without ganciclovir. Serum levels of TNF-R did not correlate with clinical signs, however, lower anti-collagen antibody levels corresponded with lack of clinical symptoms. These results indicate that local production of cytokine inhibitor is essential for therapeutic purposes while systemic levels may not be required.

Animals↗
PubMed1994

Reduction of intratumoral pH by the mitochondrial inhibitor m-iodobenzylguanidine and moderate hyperglycemia.

The interstitial pH of RIF-1 tumors was selectively lowered by i.p. administration of the mitochondrial inhibitor meta-iodobenzylguanidine (MIBG; 40-100 mg/kg), supported by sustained moderate hyperglycemia (plasma glucose concentration, 14 mM) in rats or by a single i.p. bolus injection of glucose (1.5 g/kg) in mice. Responses were evaluated in a multicenter study by pH measurements with semimicroelectrodes and 31P magnetic resonance spectroscopy, by biochemical analysis of tissue and plasma levels of glucose and lactate, and by positron emission tomography analysis of 2-[18F]fluoro-2-deoxy-D-glucose uptake. In both schedules, treatment with MIBG and glucose reduced the mean intratumoral pH as recorded with semimicroelectrodes to 6.2. In the mouse model, treatment with MIBG plus glucose was accompanied by a 2-3-fold stimulation of 2-[18F]fluoro-2-deoxy-D-glucose uptake and a corresponding increase in tumor glucose content. Responses were maximal in male mice with tumors of 0.2-0.8 g. 31P magnetic resonance spectroscopy analysis revealed no changes in intracellular pH or metabolic status, indicating that only extracellular pH was affected. MIBG was synergistic with bolus or continuous glucose administrations by a dual mechanism. The drug reduced by up to 5-fold the amount of glucose required for effective reduction of intratumoral pH and promoted the availability of (extra) glucose to tumor tissue in a stress-related, sympathomimetic response. Moreover, by converting oxic tumor cells into functionally hypoxic cells, combined treatment resulted in a more homogeneous decrease in intratumoral pH which included better perfused peripheral tumor areas. The effects of combined treatment on tumor glucose metabolism could be monitored noninvasively by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography analysis.

3-Iodobenzylguanidine↗
PubMed1994

Measles-mumps-rubella immunization of susceptible hospital employees during a community measles outbreak: cost-effectiveness and protective efficacy.

OBJECTIVE: To determine cost-effectiveness and protective efficacy of a program to identify and immunize susceptible hospital employees during a measles outbreak. DESIGN: A cost analysis was made of blind measles-mumps-rubella (MMR) immunization versus directed MMR immunization based on 2,000 employees born after December 31, 1956. A directed MMR immunization program for susceptible employees was instituted. Actual costs of the program were calculated at the conclusion of the program. SETTING: A medical center complex with more than 4,000 employees, two acute care community hospitals, and a tertiary care children's hospital. RESULTS: A directed MMR immunization program was projected to be less expensive than blind immunization ($23,106 versus $70,720). MMR vaccine was administered to 169 of 188 susceptible employees. Actual cost of the directed MMR immunization program was $25,384. CONCLUSIONS: The directed MMR immunization program was cost-effective and prevented secondary cases among hospital employees during a community measles outbreak.

Community-Acquired Infections↗
PubMed1993

Multi-level regulation of lysosomal gene expression in lymphocytes.

The expression of the gene coding for the lysosomal enzyme, beta-glucuronidase (Gus), was examined in functionally distinct T, B and plasma cell lines. Each of the different groups of cells had different intracellular levels of active Gus enzyme and numbers of Gus mRNA copies per cell. Analysis of the molecular forms of Gus mRNA and protein by Northern and Western blotting revealed that the different types of cells all produced a single mature 2.7 kb transcript and a 73 kDa polypeptide. However, the utilisation of the Gus mRNA to produce the Gus antigen, and the subsequent posttranslational processing of the polypeptide to generate the mature, enzymically active Gus, were found to be cell type-specific. Control of the functional expression of the Gus gene is thus exerted at both the transcriptional and translational levels, and appears to differ between different types of lymphocyte.

Animals↗