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Biomedical subjects

C Canning

Publications and source records attributed to C Canning.

30 records · Page 2Linked to original sources
PubMed2000

Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia.

The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation is a clear demonstration of the graft-versus-leukemia (GVL) effect. T cells are critical mediators of GVL, but the antigenic targets of this response are unknown. To determine whether patients who respond to DLI also develop B-cell immunity to CML-associated antigens, we analyzed sera from three patients with relapsed CML who achieved a complete molecular remission after infusion of donor T cells. Sera from these individuals recognized 13 distinct gene products represented in a CML-derived cDNA library. Two proteins, Jkappa-recombination signal-binding protein (RBP-Jkappa) and related adhesion focal tyrosine kinase (RAFTK), were recognized by sera from three of 19 DLI responders. None of these antigens were recognized by sera from healthy donors or patients with chronic graft-versus-host disease. Four gene products were recognized by sera from CML patients treated with hydroxyurea and nine were detected by sera from CML patients who responded to IFN-alpha. Antibody titers specific for RAFTK, but not for RBP-Jkappa, were found to be temporally associated with the response to DLI. These results demonstrate that patients who respond to DLI generate potent antibody responses to CML-associated antigens, suggesting the development of coordinated T- and B-cell immunity. The characterization of B cell-defined antigens may help identify clinically relevant targets of the GVL response in vivo.

Antibodies, Neoplasm↗
PubMed2000

Effect of muscle length on strength and dexterity after stroke.

OBJECTIVE: The effect of muscle length on strength and dexterity after stroke was investigated. The aim was to determine if poor function at a particular muscle length could be attributed solely to differential weakness at this joint angle or whether an additional problem of differential dexterity exists. DESIGN: This descriptive research study measured elbow flexor and extensor strength as well as dexterity at three elbow joint angles: 30 degrees , 60 degrees and 90 degrees flexion. Dexterity was measured independently of strength. SUBJECTS: Fifteen (seven female, eight male) chronic stroke patients (mean age 67 years) who could actively flex and extend their affected elbow participated. Ten neurologically normal control subjects (mean age 67 years) acted as controls. MAIN OUTCOME MEASURES: Strength was measured as peak elbow flexor and extensor torque at three angles; and dexterity was measured as coherence for slow and fast tracking also at three angles. RESULTS: Dexterity was not affected by muscle length but strength was and this finding was the same for both stroke and controls. While the magnitude of the torque-angle curves was not significantly different between stroke and controls, the shape of torque-angle curves was altered after stroke so that both the elbow flexors (p < 0.05) and extensors (p < 0.05) tested weaker in the testing position where they were shortest. CONCLUSION: Since there was no differential loss of dexterity, it appears that differential loss of strength, especially in the shortened range, may explain the clinical observation of poorer function at one muscle length than another after stroke. Specific training to strengthen the muscles in these ranges is therefore of clinical importance for rehabilitation.

Aged↗
PubMed1999

Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy.

OBJECTIVES: To evaluate the validity of patient report, pharmacy dispensing records, and pill counts as measures of antihypertensive adherence using electronic monitoring as the validation standard. METHODS: The study was conducted among 286 members of Harvard Pilgrim Health Care, a managed care organization, who were at least 18 years of age, on monotherapy for hypertension, and had prescription drug coverage. Prescription refill adherence during the 12 months before enrollment was determined from their automated pharmacy dispensing records. Participants were interviewed about their medication adherence before and after a 3-month electronic monitoring period during which pill counts were also performed. Adherence to both recommended number and timing of doses was estimated from electronic monitoring data. Data analysis was based on statistical correlation and analysis of variance. RESULTS: Electronic adherence monitoring revealed that the proportion of prescribed doses consumed was higher (0.92) than the proportion of doses taken on time (0.63). The correlation between adherence to quantity and timing of doses was 0.32. Concurrent pill counts and earlier refilling patterns were moderately correlated with electronic monitoring (pill count: r = .52 with quantity and r = .17 with timing; refill adherence r = .32 with quantity and r = .22 with timing). There was considerable misclassification of adherence reported by patients, although nonadherence was generally accurately reported. CONCLUSIONS: Deviation from recommended timing of doses appears to be greater than from prescribed number of doses. Pharmacy dispensing records demonstrate predictive validity as measures of cumulative exposure and gaps in medication supply. Adherence levels determined from pill counts and pharmacy dispensing records correlate more closely with quantity than with timing of doses. Nonadherence reported by patients can serve as a qualitative indicator and predictor of reduced adherence.

Adolescent↗
PubMed1999

Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion.

PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.

Adult↗
PubMed1998

Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant.

Donor lymphocyte infusions (DLI) can induce remissions in patients who have relapsed after allogeneic bone marrow transplantation (BMT). However, DLI frequently also result in significant acute and/or chronic graft-versus-host disease (GVHD). Several clinical and experimental lines of evidence have suggested that CD8(+) T cells play a critical role in the pathogenesis of GVHD. To develop methods to reduce the incidence of GVHD associated with DLI, we administered defined numbers of CD4(+) donor T cells after ex vivo depletion of CD8(+) lymphocytes to 40 patients with relapsed hematologic malignancies after allogeneic BMT. Cohorts of patients received 0.3, 1.0, or 1.5 x 10(8) CD4(+) cells/kg. Overall, 12 of 38 patients (32%) evaluable for toxicity developed acute or chronic GVHD. However, 6 of 27 patients (22%) receiving 0.3 x 10(8) CD4 cells/kg developed GVHD compared with 6 of 11 patients (55%) who received >/=1.0 x 10(8) CD4 cells/kg (P = .07). Treatment-related mortality was low (3%), with 1 death related to infection in the setting of immunosuppression for GVHD. Disease responses after CD4(+) DLI were documented in 15 of 19 patients (79%) with early-phase chronic myelogenous leukemia (CML) relapse, 5 of 6 patients (83%) with relapsed multiple myeloma, and 1 patient with myelodysplasia. For patients with early-phase CML relapse, the Kaplan-Meier probability of achieving complete cytogenetic remission was 87% and the probability of complete molecular response was 78% at 1 year after DLI. The median time to complete cytogenetic response and molecular response in patients with CML was 13 weeks (range, 9 to 30 weeks) and 34 weeks (range, 10 to 56 weeks), respectively. The median time to response in patients with multiple myeloma was 26 weeks (range, 15 to 62 weeks). All patients in this trial who developed GVHD demonstrated tumor regression, but the presence of GVHD was not required for patients to achieve a response, because 48% of responding patients never developed evidence of GVHD. Two patients with CML who did not respond at dose level 1 subsequently achieved complete cytogenetic remission after a second infusion of CD8-depleted cells at dose level 2. In patients with evidence of mixed hematopoietic chimerism who achieved a complete remission after DLI, cytogenetic analysis of marrow cells also demonstrated conversion to complete donor hematopoiesis in all evaluable patients. These studies suggest that relatively low numbers of CD8-depleted donor lymphocytes are effective in inducing complete remissions in patients with stable-phase CML and multiple myeloma who have relapsed after allogeneic BMT. Because of the relatively low risk of toxicity associated with the infusion of defined numbers of CD4(+) donor cells, further studies can be undertaken in the setting of persistent minimal residual disease to prevent relapse after allogeneic BMT.

Adult↗
PubMed1998

Evaluating screening policies for the early detection of retinopathy in patients with non-insulin dependent diabetes.

Retinopathy is a common complication of insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes, but serious visual loss may be prevented or delayed with sufficiently early diagnosis and treatment. Screening for early signs of retinopathy is clearly beneficial for some people, but there is no established consensus about who should be screened, by whom, by what technique and with what frequency, especially for NIDDM. The model described in this paper simulates the development of eye disease in a population of NIDDM patients and the effects of different screening schemes in terms of years of sight saved and the numbers of people prevented from suffering severe visual loss. The initial results indicate that blanket screening of all NIDDM patients may not be effective.

Adult↗
PubMed1996

Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression.

Several lines of evidence indicate that a subset of murine intestinal intraepithelial lymphocytes (iIEL), particularly those which express the CD8 alpha alpha homodimer, mature extrathymically. This study confirms that a small fraction of adult human iIEL also express the CD8 alpha alpha homodimer and demonstrates that most of these cells in the small intestine are T cells using the alpha beta T-cell receptor (TCR). Whether these cells or other subsets of adult human iIEL mature extrathymically in the intestine was assessed by measuring the expression of terminal deoxynucleotidyltransferase (TdT), an enzyme expressed exclusively by immature lymphocytes. Very low levels of TdT message could be detected by polymerase chain reaction (PCR) amplification in some iIEL samples. The level of TdT expression was assayed by competitive PCR amplification and compared with thymocytes and peripheral blood lymphocytes. These measurements indicated that the number of immature T cells expressing TdT in the intestinal epithelium was less than one cell per 10(7) lymphocytes. This demonstrates that there are few if any TdT expressing immature T cells in the adult human intestinal mucosa and indicates, therefore, that T-cell development in the intestinal mucosa does not contribute significantly to the T-cell repertoire of the adult human intestine.

Adult↗
PubMed1996

Simulation of diabetic eye disease to compare screening policies.

AIMS/BACKGROUND: The purpose of the project was to develop a technique for evaluating screening policies in the treatment of insulin dependent diabetic retinopathy. The study was concerned with patients who contracted the disease, aged under 35 years. Simulation was used to describe the progress of a cohort of patients through disease and treatment. METHOD: Data, derived from a literature survey of European and American population and clinic studies, were used to model as closely as possible the development of retinopathy in all its stages, together with the effects of screening and treatment. The model output was validated against published data. RESULTS: The results showed that where screening sensitivities are high, the frequency of screening makes little difference to the years of sight saved, but it does make a difference if screening sensitivities are close to 50%. CONCLUSIONS: Although annual screening is normally desirable, biannual screening could be considered where patient compliance and screening sensitivities are both high.

Adolescent↗
PubMed1991

Panretinal laser photocoagulation for proliferative diabetic retinopathy: the effect of laser wavelength on macular function.

The effect on macular function of the wavelength of laser light used to treat proliferative diabetic retinopathy was studied. Thirty-six eyes of 25 patients received panretinal photo-coagulation according to a standardised protocol and before and at intervals after the treatment were tested by a battery of macular function tests. Each eye was randomly assigned to treatment with blue-green, yellow, or orange laser. The tests included best corrected visual acuity, colour vision, contrast sensitivity, macular threshold, and central visual fields. There were no significant differences in the results of these tests between the three treatment groups, though there was wide scattering of baseline values within each group. Laser wavelength has not been shown to be an important determinant of central visual function following panretinal photo-coagulation in patients with proliferative diabetic retinopathy within the wavelengths tested.

Adult↗
PubMed1990

[Color vision disturbance in laser operators and patients: comparison of argon and dye lasers].

Color contrast sensitivity was measured in laser operators before and after laser sessions. The tritan threshold was elevated after the sessions in all laser operators who had used argon (blue-green) lasers. No change was observed when lasers with longer wave-lengths were used. Elevation of the tritan threshold to above-normal levels was observed even before laser sessions. The thresholds remained increased even when the laser operator did not use a laser for 3 weeks. Thus, it appears that the damage caused by the argon blue-green laser is cumulative. Elevated tritan thresholds were also observed in patients with peripheral retinal breaks who were treated with an argon (blue-green) laser.

Adolescent↗