PubMed Health⌕ Search

Biomedical subjects

K J Murray

Publications and source records attributed to K J Murray.

At least 37 records · Page 2Linked to original sources
PubMed2000

Requirements for occupational medicine training in Europe: a Delphi study.

OBJECTIVES: To identify the common core competencies required for occupational physicians in Europe. METHOD: A modified Delphi survey was conducted among members of the European Association of Schools of Occupational Medicine (EASOM), the Occupational Medicine Section of the Union of European Medical Specialities (UEMS), and of the European Network of Societies of Occupational Physicians (ENSOP). An initial questionnaire based on the training syllabus of the United Kingdom Faculty of Occupational Medicine was circulated and respondents were asked to rate the importance of each item. The results were discussed at a conference on the subject of competencies. A further questionnaire was developed and circulated which asked respondents to rank items within each section. RESULTS: There was a 74% response in the first round and an 80% response in the second. Respondents' ratings from most important to least important were; occupational hazards to health, research methods, health promotion, occupational health law and ethics, communications, assessment of disability, environmental medicine, and management. In the second round, among those topics ranked most highly were; hazards to health and the illnesses which they cause, control of risks, and diagnoses of work related ill health. Topics such as principles of occupational safety and selection of personal protection equipment were of least importance. Although the assessment of fitness was regarded as important, monitoring and advising on sickness absence were not highly rated. Management competency was regarded as of low importance. CONCLUSION: This survey identified that respondents had traditional disease focused views of the competencies required of occupational physicians and that competencies were lagging behind the evolving definition of occupational health.

Competency-Based Education↗
PubMed1999

A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein.

A selective cyclic nucleotide PDE5 inhibitor corrected the defective mucin secretion response to the beta-agonist isoproterenol in submandibular acinar cells inhibited by antibody directed against the cystic fibrosis transmembrane conductance regulator. The PDE5 inhibitor was as effective as cpt-cyclic AMP or a selective PDE4 inhibitor. However, the PDE5 inhibitor had no effect on basal or isoproterenol-stimulated cyclic AMP levels and did not stimulate mucin secretion. The results showing, for the first time, correction of the CFTR mucin secretion defect by a PDE5 inhibitor, which may involve cyclic GMP, will have a major impact in development of a rational drug treatment for cystic fibrosis.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Age-specific effects of juvenile rheumatoid arthritis-associated HLA alleles.

OBJECTIVE: To define the onset and duration of effect of the HLA alleles that are associated with disease susceptibility and protection in juvenile rheumatoid arthritis (JRA) and 2 of its subtypes. METHODS: We typed 680 patients with JRA and 254 ethnically matched unrelated controls for HLA class I and II genes. The frequency of each allele was calculated for each of the age-at-onset, onset type, and sex categories and plotted against the allele frequency in the control population. Survival analysis (with onset of disease as the terminating event) was used to calculate the age by which 50% (St0.5) and 80% (St0.2) of the children with particular alleles and combinations of alleles develop disease. This allele-specific survival analysis also allowed for the comparison of the overall survival functions for the various JRA subtype and sex categories. RESULTS: Certain alleles are strongly associated with early susceptibility to pauciarticular JRA, including HLA-A2, DR8, DR5, and DPB1*0201. Fifty percent of the children carrying at least 1 of these alleles had disease onset prior to their third birthday. Among children who carried HLA-A2 and any 2 HLA-DR alleles (DR3, DR5, DR6, or DR8), the median age at the onset of pauciarticular disease was 2.7 years. Combinations of A2 and DPB1*0201 and one DR allele narrowed the window further to a median age at onset of 2.4 years. B27 and DR4 were associated with protection early in life but with increased risk later in childhood, with St0.5 values of 7.3 and 6.6 years, respectively, for pauciarticular JRA and St0.5 values of 10.2 and 10.7 years, respectively, for polyarticular JRA. Sex strongly influenced the age at which many of the alleles have their effect. CONCLUSION: These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease.

Age Factors↗
PubMed1999

Analysis of sickness absence among employees of four NHS trusts.

OBJECTIVES: To determine the value of using routinely collected sickness absence data as part of a health needs assessment of healthcare workers. METHOD: Sickness absence records of almost 12900 NHS staff for one calendar year were analysed. Three measures of absence, the absence rate, the absence frequency rate, and the mean duration of absence, were assessed for the population and comparisons made between men and women, full and part time and different occupational groups of staff. Also, the main causes of sickness absence were found. RESULTS: Almost 60% of the study population had no spells of sickness absence in the year of study and almost 20% had only one spell of sickness absence. Female staff were more likely to have experienced sickness absence than male staff. Although absence due to conditions related to pregnancy were included in the analysis, the incidence of these was not sufficient to account for the higher rates of absence among female staff. In general, full time staff had greater rates of sickness absence than part time staff. 71% of all absences were of < 1 week duration. The main known causes of sickness absence were respiratory disorders, digestive disorders, and musculoskeletal disorders. CONCLUSIONS: The transition from units managed directly from the health board to trusts with individual responsibility for personnel issues at the time of data collection resulted in variations in the quality of data available for analysis. This together with the use of "dump" codes has influenced the quality of the analysis. However, such data should be available for analysis to tailor occupational health care to the needs of the population.

Absenteeism↗
PubMed1998

Comparative sequence analysis of the human T cell receptor beta chain in juvenile rheumatoid arthritis and juvenile spondylarthropathies: evidence for antigenic selection of T cells in the synovium.

OBJECTIVE: To identify features of the T cell receptors (TCRs) present on clonally expanded T cells in the joints of patients with similar types of childhood rheumatic disease. Vbeta8 and Vbeta20 TCRs were selected as prototypic for polyarticular juvenile rheumatoid arthritis (JRA) and pauciarticular/juvenile spondylarthropathy (SpA), respectively. METHODS: The portion of the TCR beta chain involved in antigen recognition in the synovial tissue, synovial fluid, and peripheral blood from patients with JRA and juvenile SpA was cloned and sequenced. The frequency of expanded clonotypes, size of expansions, the Jbeta region, and sequence motifs were determined for >2,000 sequences. RESULTS: The majority of Vbeta20 and Vbeta8 clonal expansions were found in the joint rather than the peripheral blood. While instances of both Vbeta8 and Vbeta20 clonal expansion were detected in all disease types, the features of these expanded clonotypes were specific for disease type and Vbeta family. For example, Vbeta20 clonal expansion was characterized by many small expanded clonotypes in samples from patients with pauciarticular JRA and juvenile SpA while single large Vbeta8-specific expansions were found only in patients with polyarticular disease. Motifs specific to individual patients were identified, and for Vbeta20 clonotypes, a motif was found in synovial tissue samples. CONCLUSION: Identification of common TCR features in oligoclonal expansions within individual patients and between patients with the same type of JRA suggests the recognition of a common or limited group of antigens in these diseases.

Amino Acid Sequence↗
PubMed1998

Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03.

PURPOSE: To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS: One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS: Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION: Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.

Aged↗
PubMed1998

Contrasting cytokine profiles in the synovium of different forms of juvenile rheumatoid arthritis and juvenile spondyloarthropathy: prominence of interleukin 4 in restricted disease.

OBJECTIVE: To determine the pattern of expression of Type 1 and Type 2 cytokines in synovial tissues and fluids (SF) of patients with different forms of juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), and to contrast these with findings in adult patients with RA. METHODS: Sixty-three SF mononuclear cell preparations and synovial tissue samples from 50 patients with JRA or JSpA and 7 synovial tissues from patients with adult onset RA were analyzed by reverse transcription polymerase chain reaction for the presence or absence of interleukin 2 (IL-2), tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), and IL-10 and IL-4 mRNA. RESULTS: IL-4 mRNA was identified significantly more often in the synovial compartment of patients with pauciarticular onset disease (JRA or JSpA) compared with polyarticular onset JRA (58 vs 14%; p < 0.01) or RA (29%). Similarly, IL-4 mRNA was detected more often in those with a persistently pauciarticular disease course compared to those with a polyarticular course (68 vs 30%; p < 0.01). Furthermore, the combination of IL-4 and IL-10 mRNA was found more frequently in nonerosive compared with erosive disease (38 vs 15%; p < 0.05). IL-2 and TNF-beta mRNA were found in all groups. IFN-gamma mRNA was detected in 33% of those with systemic onset JRA compared with 85% of other types of JRA (p < 0.01). CONCLUSION: This study provides further evidence of immunopathological differences between chronic forms of arthritis with childhood onset, and highlights similarities with and differences from adult RA. Our findings suggest that IL-4, possibly in combination with IL-10, has an antiinflammatory or disease restricting role.

Adolescent↗
PubMed1997

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.

PURPOSE: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. METHODS AND MATERIALS: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. RESULTS: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. CONCLUSION: Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Adult↗
PubMed1997

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.

Antineoplastic Agents, Alkylating↗
PubMed1997

Event-free survival of children with biologically favourable neuroblastoma based on the degree of initial tumour resection: results from the Pediatric Oncology Group.

We analysed the 2-year event-free survival (EFS) of 49 patients 1 year of age and older, with stage 2B or 3 neuroblastoma, treated on Pediatric Oncology Group protocols 8742 and 9244, with respect to the degree of tumour resection at diagnosis. The 2-year EFS rate for 21 children whose tumours were completely resected at diagnosis was 85% (SE = 10%) compared with an EFS rate of 70% (SE = 9%) for the 28 children whose tumours were incompletely resected at diagnosis. Despite the observed trend in favour of complete resection, these EFS curves were not statistically significantly different (P = 0.259). Patients with favourable Shimada histology tumours had an EFS rate of 92% (SE = 7%) compared with a rate of 58% (SE = 15%) for patients with unfavourable histology tumours. EFS curves for the two histologic groups were significantly different (P = 0.009). The impact of aggressive surgery and adjuvant chemotherapy on the outcome of patients with biologically favourable regional neuroblastoma is still unclear.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Long-term results of selective renal shielding in patients undergoing total body irradiation in preparation for bone marrow transplantation.

The purpose of this study was to evaluate the effect of partial renal shielding used in conjunction with total body irradiation (TBI) on the incidence of bone marrow transplantation nephropathy (BMT Np) seen as a late sequelae after transplantation. Of 402 patients who have undergone bone marrow transplantation (BMT) at the Medical College of Wisconsin (MCW) 157 were greater than 18 years of age, received 14 Gy TBI and survived at least 100 days post-transplant. The incidence of BMT nephropathy was evaluated in these patients by dose to the kidneys. In the 72 patients who received 14 Gy TBI with no renal shielding, the actuarial risk of developing BMT Np at 2 1/2 years (30 months) post-BMT was 29 +/- 7%. Sixty-eight patients received 14 Gy TBI with partial renal shielding of 15% (renal dose = 11.9 Gy), the actuarial risk of developing BMT Np was 14 +/- 5% at 2 1/2 years. Seventeen patients received 14 Gy TBI with renal shielding of 30% (renal dose = 9.8 Gy); none of this group have developed BMT Np despite a median follow-up of over 2 1/2 years (985 days). The trend of decreasing BMT Np with increasing shielding is statistically significant (P = 0.012). Prognostic factors such as age, type of transplant and good-risk vs poor-risk disease status were evaluated and were similar in each cohort of patients described above. We conclude that given the statistically significant benefit seen here in the reduced incidence of BMT Np by the use of selective renal shielding, this should be seriously considered for all patients who receive TBI, but especially for patients whose renal doses exceed 10 Gy.

Actuarial Analysis↗
PubMed1997

Antibodies to the 45 kDa DEK nuclear antigen in pauciarticular onset juvenile rheumatoid arthritis and iridocyclitis: selective association with MHC gene.

OBJECTIVE: To study the frequency of autoantibodies to the 45 kDa DEK nuclear antigen, a putative oncoprotein, in a sample of patients with juvenile rheumatoid arthritis (JRA), and to make correlations with disease subtype and complications such as iridocyclitis. Class I and Class II HLA associations with reactivity to the antigen were also sought. METHODS: Sera from 146 HLA typed patients with JRA representing all subtypes were analyzed for reactivity with the 45 kDa DEK protein by immunoblotting. The antigen was purified to near homogeneity from nuclei of HeLa cells. RESULTS: Antibodies to DEK were found in 57% of all patients with JRA compared to 3% of controls (p < 0.0001). Antibodies were detected more frequently in pauciarticular onset (78%) than in polyarticular onset patients (29%; p < 0.01) and controls (3%; p < 0.0001). 97% of patients with JRA (regardless of onset subtype) and iridocyclitis had anti-DEK antibodies compared to 47% of patients without eye disease (p < 0.0001). Anti-DEK antibodies were found more frequently in females compared to males in the pauciarticular onset disease group (84 vs 42%; p < 0.01). The occurrence of anti-DEK antibodies was closely associated with positive antinuclear antibody serology, and a strong association with the Class I gene HLA-A2 was also observed. CONCLUSION: Antibodies to the 45 kDa DEK protein are characteristic of the pauciarticular onset subtype of JRA, particularly in patients with a history of iridocyclitis. The occurrence of anti-DEK antibodies is significantly but paradoxically associated with the presence of the HLA-A2 allele in such patients.

Adolescent↗
PubMed1996

Final report of a phase I/II trial of hyperfractionated and accelerated hyperfractionated radiation therapy with carmustine for adults with supratentorial malignant gliomas. Radiation Therapy Oncology Group Study 83-02.

BACKGROUND: Efforts to improve local control and survival by increasing the dose of once-daily radiation therapy beyond 70 Gray (Gy) for patients with malignant gliomas has yet been unsuccessful. Hyperfractionated radiation therapy (HF) should allow for delivery of a higher total dose without increasing normal tissue late effects, whereas accelerated hyperfractionated radiation therapy (AHF) may minimize tumor repopulation by shortening overall treatment time. The Radiation Therapy Oncology Group (RTOG) conducted a randomized Phase I/II study of escalating doses of HF and AHF either carmustine (bis-chlorethyl nitrosourea [BCNU]) fro adults with supratentorial glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). Primary study endpoints were overall survival and acute and chronic treatment-related toxicity. METHODS: From 1983 to 1989, 786 patients with supratentorial gliomas (81% with GBM and 19% with AA) were stratified by histology, age, and performance status and randomized to receive partial brain irradiation, utilizing either HF (1.2 Gy twice daily to doses of 64.8, 72, 76.8, or 81.6 Gy) of AHF (1.6 Gy twice daily to doses of 48 or 54.4 Gy). All patients received carmustine. The distinction of pronistic factors was similar on all arms. RESULTS: There were 747 eligible and analyzable patients among 786 enrolled patients (95%). Two patients had a Grade 5 and 65 patients had a Grade 4 chemotherapy toxicity. Two patients in the 81.6 Gy arm experienced late Grade 4 radiation toxicity and there was 1 late radiation-associated death in the 54.4 Gy arm. The rate of Grade 3 of worse radiation toxicity at 5 years, calculated by the delivered does level, was 3% in the lowest total dose arms (48 and 54.4 Gy), 4% in the intermediate dose arms (64.8 and 72 Gy), and 5% in the highest dose arms (76.8 and 81.6 Gy) (p = 0.54). Survival rates at 2 and 5 years were: 21% and 11%, and 4%, respectively, for GBM patients. There were no significant differences between the treatment arms with regard to median survival time (MST), when analyzed by the originally assigned dose. The MST for all patients varied between 10.8 months and 12.7 months (P = 0.59); between 9.6 months and 11 months for patients with GBM (P = 0.43); and between 30.4 months and 85.8 months for patients with AA (P = 0.78). Analysis of the survival rates for all patients by dose received rather than by dose assigned revealed a 14% 5-year survival rate for the lower HF doses (64.8 and 73 Gy), 11% for the higher doses (76.8 and 81.6 Gy), and 10% for the AHF doses (48 and 54.4 Gy) (P = 0.1). The subgroup a AA patients had a better MST (49.9 months) in the lower received HF doses than in the higher HF doses (34.6 months) (P = 0.35). In contrast, GM patients who received the higher HF doses had survival superior to the patients in the AHF arms (MST of 11.6 months and 10.2 months, respectively, P = 0.04). CONCLUSIONS: The use of HF with BCNU and dose escalation up to 81.6 Gy is both feasible and tolerable, although late toxicity increases slightly with increasing dose. The best MST with the least toxicity were observed for AA in the lower received HF doses (72 and 64.8 Gy). Accordingly, 72 Gy in two 1.2 Gy fractions was used as the investigational arm of a completed Phase III trial (RTOG 90-06). In contrast, for GBM patients, longer survival times were noted in the higher received HF doses (78.6 and 81.6 Gy), suggesting the role for further dose escalation. The low toxicity rate with AHF arms suggest that further dose escalation is possible and is currently occurring in RTOG 94-11.

Adolescent↗
PubMed1996

Patterns of expression of tumor necrosis factor alpha, tumor necrosis factor beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy.

OBJECTIVE: To assess the expression of tumor necrosis factor alpha (TNF alpha), TNF beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis (JRA) and juvenile spondylarthropathy (JSpA), and to determine similarities with and differences from adult RA. METHODS: Twenty-eight synovial tissue samples from patients with JRA, 6 from patients with JSpA, and 6 from patients with RA, selected for the presence of inflammatory infiltrates, were analyzed for the expression of TNF alpha, TNF beta, and their receptors (p55 and p75 TNFR), utilizing the dual approach of reverse transcriptase-polymerase chain reaction and immunohistochemistry analysis. RESULTS: The presence of both TNF alpha and TNF beta expression was demonstrated in most JRA and JSpA tissues, although samples from patients with pauciarticular JRA had somewhat lesser amounts of these cytokines. TNF beta expression correlated significantly with the occurrence of lymphocytic aggregates in tissues. Staining with monoclonal antibodies specific for the p55 and p75 receptors revealed that a diverse range of cell types expressed the receptors, with the most intense p55 staining on vascular endothelial cells. In the vast majority of synovial tissues, far greater numbers of cells expressed the p55 form of the receptor than the p75 form. CONCLUSION: JRA and JSpA synovia are characterized by the presence of TNF alpha, TNF beta, and cells expressing TNFR. These findings provide further evidence that TNF, through autocrine/paracrine mechanisms, may amplify local inflammation, leading to joint destruction. The prominence of TNF beta in the synovium in particular subgroups of JRA patients and in JSpA patients may be a distinguishing feature of these diseases.

Adult↗
PubMed1996

T-cell receptor BV6S1 null alleles and HLA-DR1 haplotypes in polyarticular outcome juvenile rheumatoid arthritis.

JRA is a complex of disease subtypes which are normally identified by clinical features such as age of onset and extent of joint involvement both at onset and during the course of the disease. We previously identified an association between TCR BV6S1 null allele and one subgroup of early-onset pauciarticular patients positive for HLA-DQA1*0101, an HLA haplotype predisposing to a polyarticular course of the disease. In this report we extend this observation by identifying an increased prevalence of this nonfunctional or null allele in the patients with a polyarticular disease course regardless of the mode of onset. This increase was most prominent in clinical subsets that have early onset of the disease and a polyarticular outcome. In one clinical group, stratification of patients by the HLA allele DQA1*0101 strengthened the association considerably. This implies that there is an increased genetic load defined by specific alleles of both MHC and TCR genes.

Alleles↗
PubMed1996

Stage I and II Hodgkin's disease in the pediatric population. Long-term follow-up of patients staged predominantly clinically.

Between January 1, 1970, and December 31, 1990, 42 consecutive pediatric patients were treated at the Medical College of Wisconsin Affiliated Hospitals for early-stage Hodgkin's disease. Thirty patients were clinically staged. Twelve underwent staging laparotomy as a part of staging work-up. Thirty-one patients were treated with radiation therapy (RT) alone. Eleven were treated with combined chemotherapy and RT. For the entire group, overall survival at 5, 10, and 15 years was 98, 98, and 92%, respectively. Disease-free survival was 86, 86, and 79, respectively. There was no significant difference in overall survival or disease-free survival comparing clinically versus pathologically staged patients. There was a trend toward improved disease-free survival favoring pathologically staged patients; however, this difference did not reach statistical significance (p = 0.07). The long-term results of this series fail to show statistically significant superior disease-free or overall survival with surgical staging.

Adolescent↗
PubMed1996

Polymorphism in the LMP2 gene influences disease susceptibility and severity in HLA-B27 associated juvenile rheumatoid arthritis.

OBJECTIVE: To determine the potential contribution of the MHC class II region proteasome subunit gene, LMP2, to disease susceptibility, severity, and phenotype in patients with juvenile rheumatoid arthritis (JRA). METHODS: A CfoI restriction site polymorphism in the coding region of the LMP2 gene was evaluated in 279 patients with JRA and 107 healthy controls of similar ethnicity. Patients were divided into 5 groups on the basis of clinical presentation; 46% had early onset pauciarticular disease, 10% early onset polyarticular, 10% late onset pauciarticular, 20% late onset polyarticular, and 11% systemic onset arthritis. The influence of this LMP2 polymorphism on susceptibility to disease, clinical subtype of disease at onset (age and number of joints involved), progression and severity of joint disease (pauci to polyarticular course and radiographic changes), and occurrence of inflammatory eye disease was evaluated. RESULTS: Comparison of genotypes revealed a significantly increased prevalence of homozygosity for the LMP2 B allele (LMP2 BB genotype) in patients who were older (> or = 6 years) at onset of disease (65%, p < 0.05), particularly in those with pauciarticular (71%) involvement at presentation (p < 0.05), compared to controls (51%). The BB genotype was also more prevalent in patients with a polyarticular course, either from onset (63%) or those who progressed from pauciarticular disease (69%), compared with controls, (p = 0.05 and < 0.05, respectively). Stratification for HLA-B27 and DR4, the HLA alleles most frequently associated with late onset pauciarticular and late onset polyarticular JRA, respectively, revealed a persistent effect of LMP2 BB homozygosity on disease susceptibility and phenotype that remained statistically significant in HLA-B27 positive children, and was not due to linkage disequilibrium. CONCLUSION: We show that homozygosity of the B allele of the proteasome subunit LMP2 increases susceptibility to certain subgroups of JRA, and influences the phenotype of disease, predisposing to more progressive and severe articular disease.

Alleles↗