Search PubMed⌕ Search

Biomedical subjects

W J Simpson

Publications and source records attributed to W J Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1987

Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients.

This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.

Adenocarcinoma↗
PubMed1987

Evidence for group A-related M protein genes in human but not animal-associated group G streptococcal pathogens.

Group G streptococci have on their surface antiphagocytic M protein-like antigens. To determine if these organisms have genes similar to the M protein genes of Streptococcus pyogenes (group A), DNA from independent group G isolates of human and animal origin were tested for homology to probes representing sequences encoding the carboxy-terminus and leader peptide of the type 12 M protein (M12) of group A streptococci. All eight human-associated group G strains tested had DNA homologous to the carboxy-terminal probe. Six of these strains also had DNA that hybridized with the leader peptide probe. Using probes representing the group A M12 gene (emm12) and adjacent 5' sequences, we found that one of these strains, known to produce an M12 antigen, had a nearly complete duplication of the group A emm12 gene, differing only in 0.26 kb of sequence at the 5' end. The other human-associated strains did not hybridize with emm12-specific sequences. None of the group G strains had homology to 5' proximal sequences thought to be associated with group A emm12 regulation, but all the human-associated strains had DNA homology to a 1.5 kb DNA segment which mapped 2.5 kb upstream of the emm12 gene in group A streptococci. None of the twelve animal-associated strains tested hybridized with any of the probes used in this study. These results suggest that human but not animal-associated group G isolates have group A-related M protein genes. We propose that expression of these genes are critical for infection of the human host and that group A and G shared upstream sequences could encode additional virulence factors.

Animals↗
PubMed1987

Expression of M type 12 protein by a group A streptococcus exhibits phaselike variation: evidence for coregulation of colony opacity determinants and M protein.

Three major categories of colony opacity were observed for natural variants of the M type 12 (M12) group A streptococcus strain CS24. Colony opacity variants that switched between two alternative categories at significantly high frequencies were identified and are referred to as switching between more opaque (Op+) and less opaque (Op-) phenotypes. Twenty lineages of such variants were derived for analysis and were assessed for resistance to phagocytosis, acid-extractable M12 antigen, and M12 mRNA, criteria which define the M protein-positive phenotype (M+). Transition from the M+ to the M protein-negative phenotype (M-) correlated with a change from Op+ to Op-. Reversion to the Op+ phenotype was accompanied by reversion to the M+ state in all variants except one and occurred at a higher frequency than the forward M+ to M- switch. These data demonstrate the existence of M12 protein phaselike switching in the group A streptococcus strain CS24. The discovery of an Op+ M- revertant confirmed that colony opacity and M protein can be expressed independently and are distinct gene products. We suggest that coregulation of colony opacity and M protein expression accounts for their association among descendents of strain CS24. Southern blot hybridization analyses of digested genomic DNA from 27 M- variants and 15 M+ revertants were performed with DNA probes containing M12 protein and adjacent upstream sequences. DNA deletions were identified only in two stable M- variants, approximately 1.3 and 1.4 kilobases upstream from the M12 gene, respectively, whereas all unstable M- variants lacked detectable rearrangements. This suggests that deletions within or adjacent to the structural gene are unlikely to be responsible for the reversible switch in M protein expression. However, the association with the stable M- phenotype and the location of these deletions, as well as two other deletions, approximately 0.5 kilobase upstream from the M12 promoter in two previously described variants of strain CS24 suggests that a second gene product is required for full expression of M12 protein synthesis in this strain.

Antigens, Bacterial↗
PubMed1987

Streptococcus pyogenes type 12 M protein gene regulation by upstream sequences.

A partial nucleotide sequence that included 1,693 base pairs of the M12 (emm12) gene of group A streptococci (strain CS24) and adjacent upstream DNA was determined. Type 12 M protein-specific mRNA of strain CS24 is transcribed from two promoters (P1 and P3) separated by 30 bases. The transcription start sites of the emm12 gene were located more than 400 bases downstream of a deletion that causes decreased M-protein gene transcription in strain CS64. Deletion analysis of M protein-expressing plasmids indicated that an upstream region greater than 1 kilobase is required for M-protein gene expression. The M-protein gene transcriptional unit appears to be monocistronic. Analysis of the emm12 DNA sequence revealed three major repeat regions. Two copies of each repeat, A and B, existed within the variable 5' end of the gene; repeat C demarcated the 5' end of the constant region shared by emm12 and emm6.

Antigens, Bacterial↗
PubMed1985

Canadian survey of thyroid cancer.

We report the results of a multicentre retrospective chart review of 2214 patients with thyroid cancer registered at 13 radiotherapy centres between 1958 and 1978. The data analysed included sex, age at the time of diagnosis, pathological diagnosis, extent of disease before treatment, types of treatment and their complications, and the rates of recurrence and survival up to 24 years after diagnosis. Although papillary cancers were most common, anaplastic and miscellaneous tumours were more frequent than expected, which reflects the type of patients referred by endocrinologists and surgeons to radiotherapy centres. There were marked differences in patterns of referral to the centres. Some patients with papillary and follicular thyroid cancers died of these cancers up to 20 years after diagnosis. The clinical manifestations, treatment and outcome of the rarer types of thyroid malignant tumours were of particular interest. The influence of age at the time of diagnosis on survival rates for patients with papillary or follicular thyroid cancer was highly significant, indicating much more aggressive behaviour of these cancers in older patients, particularly those beyond the age of 60 years. A more detailed analysis of tumour subtypes should provide new information on their natural history and lead to better management.

Adenocarcinoma↗
PubMed1984

Radiation-induced cerebellar chondrosarcoma. Case report.

The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation.

Adult↗
PubMed1983

Ependymomas: results of radiation treatment.

Between 1958 and 1980, 102 patients with the diagnosis of ependymoma were seen at the Princess Margaret Hospital. Eleven patients had recurrent disease or were treated elsewhere and 91 patients received radiation therapy following their primary surgical procedure. Fifty patients had cranial tumors and 41 had spinal tumors. The overall survival at five years was 60% and at 10 years was 54%. Those patients with spinal tumours did significantly better with a five year survival of 83% versus 43% for the group with cranial tumors. The other prognostic factors included tumor grade, functional status, age of the patient and interval from surgery to radiation. The most common site of relapse was at the original tumor location, but five patients did show spread through the craniospinal axis. An analysis of dose and the volume treated is made and recommendations for therapy given.

Adolescent↗
PubMed1983

The stability of ergocalciferol in rodenticidal baits.

Concentrations of the rodenticide ergocalciferol (vitamin D2) in samples of rodent baits laid in foodstores and in the laboratory were monitored over several months. Bait samples were solvent extracted and ergocalciferol concentration determined by high pressure liquid chromatography (HPLC). Ergocalciferol levels were constant for more than 21 days in dry samples and did not fall by more than 30% in 100 days. When water (10% w/w) was added to the baits in the laboratory the ergocalciferol concentration fell by approximately 30% in 30 days. In these wet laboratory samples there was a rapid visible growth of fungus and in normal rodent control use baits should have been replaced when such deterioration became evident.

Drug Stability↗
PubMed1983

M-type 57 group A streptococcus bacteriocin.

All 40 tested isolates of M-type 57 group A streptococci gave the same, highly characteristic inhibitory pattern (P-type 614) when tested by deferred antagonism using a set of nine indicator strains. One component of this inhibitory activity was attributed to the production of a bacteriocinlike substance, streptococcin A-M57 (SA-M57). Production of SA-M57 was enhanced by the presence of blood and also by growth at an alkaline pH. Partially purified SA-M57 was obtained from culture supernatants by a combination of ammonium sulphate fractionation and column chromatography. On Sephadex G-100 two different molecular weight forms (SA-M57 alpha, greater than 100 000; SA-M57 beta, 33 000) were demonstrated. Both SA-M57 forms were protease and heat sensitive and had identical inhibitory activity against a collection of indicator bacteria. The adsorption to and rate of kill of sensitive cells by SA-M57 was enhanced in the presence of human plasma. Partially purified SA-M57 preparations were devoid of M-type 57 protein and curing studies showed that loss of SA-M57 did not correlate with loss of M protein production.

Bacterial Proteins↗
PubMed1982

Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial.

A prospective randomized trial of 157 patients with malignant astrocytoma (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m2) six weekly and hydroxyurea (HU, 3.5 gm/m2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks) Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P less than 0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimens had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease.

Adult↗
PubMed1982

Management of medullary carcinoma of the thyroid.

Total thyroidectomy is universally advised for the familial variety of MCT. Although total thyroidectomy is also recommended for sporadic cases, partial thyroidectomy may be adequate. Cervical and upper mediastinal nodes should be sampled for microscopic study, even when they are small and appear to be normal. Appropriate neck or mediastinal nodes should be sampled for microscopic study, even when they are small and appear to be normal. Appropriate neck or mediastinal dissection is done if metastasis is present. External radiation is a valuable adjuvant to surgical excision following the apparent complete resection of the tumor, and is beneficial in the management of unresectable disease. Despite local control, patients continue to die from disseminated disease; therefore, there must be a continued search for an effective chemotherapeutic program. Much remains to be learned from calcitonin monitoring of MCT patients.

Adult↗
PubMed1982

Analysis of disagreement in the evaluation of clinical products.

This paper reports an analysis of factors that reduce agreement in clinical evaluation. Four instructors representing different restorative departments met regularly over a four-month period to study the evaluation process. Each participant selected a task from his discipline, identified critical errors made in performing the task, produced these errors in models and extracted teeth, and developed criteria and checklists to aid in categorizing and counting the errors. In weekly sessions the models were evaluated, and judgments were compared. Factors that reduced agreement were identified, discussed, and listed. In some sessions ongoing evaluation was reported orally, tape-recorded, and analyzed to elucidate the underlying mental processes. Analysis indicated that agreement was reduced by 16 factors, including unclear rules, the faculty member's memory, unstandardized aids to judgment, inconsistent observational methods, differences in ability, and differing tendencies to leniency.

Clinical Competence↗
PubMed1981

Radiation treatment for medulloblastoma. A 21-year review.

One hundred and twenty-two patients with medulloblastoma received postoperative irradiation at the Princess Margaret Hospital, Toronto, from 1958 to 1978, inclusive. The surgical procedure in these patients was total resection (44 patients), subtotal resection (66 patients), or biopsy alone (12 patients). Twenty-five patients received adjuvant chemotherapy. Overall 5- and 10-year survival rates were 56% and 43%, respectively. Improved survival rates were associated with an increased degree of resection and with posterior fossa radiation doses of 5200 rads or more. The posterior fossa was the common site of first relapse (in 56 patients, 46%). Systemic metastases at first relapse occurred in 18 of 52 patients (35%), and were associated with the use of ventriculosystemic shunts. Millipore filters did not prevent systemic relapse in shunted patients. A subset of 15 patients who received a posterior fossa dose of 5200 rads or more after a total resection had a 5-year survival rate of 77%, which remained constant to 10 years. This result is considered to be the upper limit that can be achieved by current treatment methods.

Adolescent↗
PubMed1980

Combination chemotherapy in invasive thymoma role of COPP.

Combination chemotherapy consisting of cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) was administered to 5 patients with invasive lymphoepithelial thymoma. Objective evidence of tumor regression was seen in 4 patients. Given prior to preoperative radiation therapy, COPP produced partial remissions in 2 patients, making possible smaller radiation treatment fields. Two patients with pleural involvement when first seen, achieved tumor regression when COPP was given prior to radical radiation therapy. One of these patients remains disease-free at 34 months; the other succumbed to pneumonitis. One patient, presenting with pleural metastasis three years after undergoing incomplete resection of thymoma, failed to respond to treatment. Combination chemotherapy with COPP can produce objective regression of invasive lymphoepithelial thymomas which may be useful in the preoperative management of selected cases, as well as in the management of unresectable or metastatic disease.

Adult↗