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Biomedical subjects

K A Guthrie

Publications and source records attributed to K A Guthrie.

16 recordsLinked to original sources
PubMed2005

Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after non-myeloablative conditioning.

We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3(-)/CD56(+)), NKT (CD3(+)/CD56(+)), DC1, and DC2 cells] of granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSC) on early T-cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)-matched related grafts after non-myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m(2) fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post-transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T-cell chimaerism (P = 0.03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft-versus-host disease (P = 0.05). Higher numbers of CD14(+) cells were associated with worse overall survival (P = 0.03), while higher numbers of CD34(+) cells showed better survival (P = 0.03). The addition of fludarabine or autologous HCT predicted higher early T-cell chimaerism (P = 0.001), while advanced donor age predicted lower chimaerism (P < or = 0.02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression-free and overall survival (P < 0.01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post-HCT after non-myeloablative conditioning.

Adult↗
PubMed2003

Outcome following haematopoietic cell transplantation in patients with myelodysplasia and del (5q) karyotypes.

The deletion (5q) karyotype [del (5q)] in patients with myelodysplastic syndrome (MDS) is considered a good risk feature, while the impact of del (5q) combined with other karyotypic abnormalities [del (5q)+] is less well defined. We analysed the outcome of haematopoietic cell transplants (HCT) in patients with MDS with del (5q) or del (5q)+. Fifty-seven patients, aged 6-72 years, with MDS and del (5q) abnormalities received HCT from related (n = 32) or unrelated (n = 25) donors. By French-American-British (FAB) criteria, 27 patients had refractory anaemia (RA), 10 RA with excess blasts (RAEB), eight RAEB in transformation (RAEB-T) and 12 acute myeloid leukaemia evolving from MDS (tAML). Non-relapse mortality at 1-year post-transplantation was 30% for del (5q) and 38% for del (5q)+ patients. Relapse occurred in one of 20 del (5q) patients and 15 of 37 del (5q)+ patients (P = 0.001). After adjusting for del (5q) status, blast count (<5%) was the only factor significantly associated with relapse-free survival. Patients with del (5q), either as a '5q- syndrome' or with MDS in general, had better outcomes than did patients with del (5q)+. The indication for transplantation in patients with del (5q) was generally severe cytopenias, compared with disease progression to a more advanced FAB stage in patients with del (5q)+. Conceivably, outcome for patients with del (5q)+ would be improved with transplantation earlier in the disease course.

Acute Disease↗
PubMed2001

Stature loss following treatment for Wilms tumor.

BACKGROUND: The study was designed to estimate reduction in adult stature induced by megavoltage radiation therapy (RT) of the spine in children treated for Wilms tumor and to ascertain whether the dose reduction in successive National Wilms Tumor Study Group (NWTSG) trials has mitigated late effects of RT in these children. PROCEDURE: Effects of RT dose, age at treatment, and chemotherapy on stature of 2,778 children with Wilms or another solid tumor of the kidney were analyzed using statistical models accounting for the dependence of height on gender and advancing age. Model predictions were validated by descriptive analysis of heights measured at 17 to 18 years of age for 205 patients. RESULTS: Radiation-induced reductions below normal height depended on dose, portal size, and age at treatment and were not augmented by doxorubicin or cyclophosphamide. Younger children were more strongly affected. Predicted height deficit at age 18 years was 1.8 cm for a child treated with 10 Gy to the flank at age 4 years. Observed height deficits at age 1 7 to 18 years were 4.1 cm for 57 patients who received 15-24 Gy at a mean age of 55 months and zero for 16 children who received RT doses under 15 Gy at a mean age of 83 months. CONCLUSIONS: Reduction in stature following RT to the pediatric spine is dose- and age-dependent, persists into adulthood, and is not exacerbated by doxorubicin or cyclophosphamide. Average height deficits observed at maturity for children receiving doses currently recommended by the NWTSG are clinically nonsignificant.

Adolescent↗
PubMed2000

Magnetic resonance imaging appearances of the Mirena and GyneFix intra-uterine contraceptive devices: a report of two cases.

We report here two cases which illustrate the magnetic resonance imaging (MRI) appearance of the Mirena levonorgestrel releasing intra-uterine system and the GyneFix copper intra-uterine contraceptive implant. The MRI appearance of these devices has not to our knowledge been reported to date, and as increasing numbers of women choose to use these devices for treatment of gynaecological conditions and contraception, it becomes increasingly important to recognise their appearance on pelvic imaging.

Adult↗
PubMed1999

Significance and management of computed tomography detected pulmonary nodules: a report from the National Wilms Tumor Study Group.

PURPOSE: To define the optimal treatment for children with Wilms tumor who have pulmonary nodules identified on chest computed tomography (CT) scan, but have a negative chest radiograph, we evaluated the outcome of all such patients randomized or followed on National Wilms Tumor Study (NWTS)-3 and -4. PATIENTS AND METHODS: We estimated the event-free and overall survival percentages of 53 patients with favorable histology tumors and pulmonary densities identified only by CT scan (CT-only) who were treated as Stage IV with intensive doxorubicin-containing chemotherapy and whole-lung irradiation, and compared these to the event-free and overall survival percentages of 37 CT-only patients who were treated less aggressively based on the extent of locoregional disease with 2 or 3 drugs, and without whole-lung irradiation. RESULTS: The 4-year event-free and overall survival percentages of the 53 patients with CT-only nodules and favorable histology Wilms tumor who were treated as Stage IV were 89% and 91%, respectively. The 4-year event-free and overall survival percentages for the 37 patients with CT-only nodules and favorable histology who were treated according to the extent of locoregional disease were 80% and 85%, respectively. The differences observed between the 2 groups were not statistically significant. Among the patients who received whole-lung irradiation, there were fewer pulmonary relapses, but more deaths attributable to lung toxicity. CONCLUSIONS: The current data raise the possibility that children with Wilms tumor and CT-only pulmonary nodules who receive whole lung irradiation have fewer pulmonary relapses, but a greater number of deaths due to treatment toxicity. The role of whole lung irradiation in the treatment of this group of patients cannot be definitively determined based on the present data. Prolonged follow-up of this group of patients is necessary to accurately estimate the frequency of late, treatment-related mortality.

Adolescent↗
PubMed1999

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.

OBJECTIVE: To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA: Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS: Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS: The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS: This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.

Child, Preschool↗
PubMed1999

Nuclear morphometry and prognosis in favorable histology Wilms' tumor: A prospective reevaluation.

PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MV(f) = (0.02 x AGE) + (1.17 x SNRF) + (90.6 x LEFD) - 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of "MV(f) is greater than -0.35" as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of "MV(f) is greater than -0.35" were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.

Child↗
PubMed1990

Information systems and audit in antenatal care.

The obstetric record as initiated at the antenatal booking clinic essentially identifies the degree of risk engendered in that pregnancy so that consequent obstetric and paediatric management is tailored appropriately. Whether carried by the patient or based in the hospital with a summary carried by the patient (shared-care card), this record should be exhaustive, the emphasis being on quality, not quantity, of information recorded. To obviate human error in history-taking, patient management or record transcription, we believe on-line computerization of patient records with spin-off paperwork to be the only patient management system to fulfil the above criteria. User-friendly software can be designed with highly branching programmes which provide clinical action suggestions in high-risk cases. Various 'error traps' enhance the accuracy of information recorded. Such systems can be operated by medical and midwifery staff with minimal keyboard skills and are well accepted by patients and staff. Inexpensive and versatile microcomputer networks are excellent for such systems. The operational effects are discussed. Audit means different things to different people and one's view on the subject depends on which definition is selected. Obstetricians are quick to take credit for instituting audit in the form of local and national data collection exercises, such as statistics on perinatal mortality, birthweight, etc. While these exercises certainly constitute observational studies, they cannot be used to make conclusions about the quality of care. There is no sound inference that can be made from a review of information contained in amalgamated databases of hospital statistics. Audit, as properly defined, hinges on inference: the inference that the quality of care was or was not of a high standard. Descriptive statistics, therefore, can be used to generate hypotheses but should not be used as a form of audit, at least not in obstetrics. Auditing the quality of care involves a study of process. It therefore depends on the assumption that we know which practices maximize beneficial outcomes. This exercise is therefore only relevant when we have good evidence linking the process of care with these outcomes. In some cases the accepted standard against which the process of care can be compared is very obvious. In other cases, however, the accepted standard should itself be audited to ensure that it is based on sound evidence.

Confidentiality↗
PubMed1989

Audit of medical response to antenatal booking history.

A retrospective review of 600 obstetric case-notes, covering the years 1978 to 1984, was performed independently by two assessors. The medical response to 22 risk factors, recorded at booking by the midwife, was assessed. The medical staff recognized 69% of the risk factors recorded at booking and responded appropriately to 82% of these. The standard of care improved over the period studied. The accuracy of our conclusions was greatly enhanced by carrying out each assessment in duplicate with arbitration by a third assessor when necessary, and it is proposed that all audits of medical practice should themselves be audited in this way.

England↗
PubMed1983

Fetal growth achievement and elevated maternal serum alpha-fetoprotein.

Maternal serum alpha-fetoprotein (AFP) was measured by radioimmunoassay in 7223 unselected patients between 16 and 20 weeks gestation. In 141 patients an elevated AFP level (greater than 2.5 multiples of the median for gestation) was found in the absence of a primary cause. When the birthweights of the 137 liveborn infants were corrected for maternal height and weight, sex and birth rank, 37 (27%) fell below the 10th centile of normal birthweight standards. No excess of premature deliveries was found, but there was a significant association with primiparity. Patients delivered of their second infant showed a significant decrement in mean birthweight when compared with their first-born infants and with a matched control group (normal maternal serum AFP levels). There was a highly significant association between elevated serum AFP and subsequent placental abruption.

Abruptio Placentae↗