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Biomedical subjects

W J Simpson

Publications and source records attributed to W J Simpson.

At least 19 recordsLinked to original sources
PubMed1996

Radiotherapy for atypical or malignant intracranial meningioma.

PURPOSE: To study the natural history of intracranial atypical and malignant meningiomas, and the role of radiotherapy in the treatment of these tumors. METHODS AND MATERIALS: The records of the 59 patients who were treated at the Princess Margaret Hospital between 1966 and 1990 with histologically confirmed intracranial atypical or malignant meningiomas were retrospectively reviewed. The median age was 58 years. Twenty-four patients were referred for radiation immediately after diagnosis and the remainder after at least one recurrence. The extent of the most recent surgery prior to radiation was gross total excision in 17, subtotal excision in 35, biopsy in 3, and none or unknown in 4. Seventeen had atypical meningiomas, defined as the presence of mitoses, nuclear atypia, or necrosis. Forty-two had malignant meningiomas on the basis of brain invasion (60%) or a pathologist's designation of malignant or hemangiopericytic meningioma. All patients received megavoltage radiation to a median dose of 50 Gy. RESULTS: Disease progressed in 39 patients (66%) after radiation. Of these, 36 died of meningioma and 3 were alive after further surgery. The 5-year actuarial overall and cause-specific survivals were 28 and 34%, respectively. Age less than 58, treatment after 1975, and a radiation dose of 50 Gy or more were independently associated with higher cause-specific survival by multivariate analysis. CONCLUSIONS: Young age, modern imaging and treatment planning techniques, and a postoperative radiation dose of at least 50 Gy contribute to improved outcome in patients with atypical or malignant meningiomas. We recommend that all patients receive radiotherapy immediately after initial surgery.

Adolescent↗
PubMed1995

Medulloblastoma in adults.

PURPOSE: To assess the outcome and prognostic factors for adult patients with medulloblastoma managed by postoperative radiotherapy between 1958 and 1988 at the Princess Margaret Hospital. METHODS AND MATERIALS: A retrospective review was undertaken of 48 patients age 16 years or older who received radiotherapy for medulloblastoma. The median age at diagnosis was 25 years, with 36 male and 12 female patients. Sixteen tumors were confined to midline structures, and 32 were localized to a cerebellar hemisphere or involved midline and lateral structures. The desmoplastic variant was reported in 12 cases. Complete macroscopic removal was achieved in 22 patients, subtotal removal in 23, and biopsy only in 3. Forty-six patients received craniospinal radiation and 2 patients received local irradiation only. RESULTS: Median overall survival was 7.9 years, and 5- and 10-year overall survival was 62% and 41%, respectively. Significant factors for disease-free survival were M stage (M0 vs. M1-4, p = 0.0005), functional state at the time of radiotherapy (1-2 vs. 3-5, p = 0.005), and the absence or presence of hydrocephalus preoperatively (p = 0.02). Twenty-four patients developed recurrent disease, with 14 relapsing first in the posterior fossa. Subtotal removal of tumor (p = 0.04) was the only factor predictive of posterior fossa relapse. CONCLUSIONS: Patients with disease outside the posterior fossa at diagnosis, symptomatic patients (neurologic functional state 3-5) at the time of radiotherapy, and those who present with hydrocephalus have poorer disease-free survival. Gross total resection improved posterior fossa control.

Adolescent↗
PubMed1994

Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors.

PURPOSE: Radiation therapy is often an integral part of postoperative treatment in patients with nonfunctional pituitary adenomas. The Princess Margaret Hospital (PMH) experience was reviewed and analyzed to establish the role of radiation therapy in local control relative to its complications, and to see if subgroups of patients with a greater or lesser risk of recurrence postsurgery can be defined. METHODS AND MATERIALS: Records of 160 patients with nonfunctional pituitary adenoma treated between 1972 and 1986 were reviewed retrospectively. The review focused on 128 patients treated with surgery and postoperative radiation as initial therapy. The median total dose was 45 Gy. Local tumor control was defined as lack of progression or recurrence of adenoma as assessed clinically and by imaging studies. The following factors were analyzed for prognostic significance in local tumor control: age, sex, direction of tumor extension, radiation dose, and preoperative tumor size as reflected by the radiation field size. Complications including hypopituitarism and second tumors were analyzed. Hypopituitarism was defined as requirement for permanent hormone replacement therapy. RESULTS: With a median follow-up duration of 8.3 years, the 10-year actuarial local control rate was 87% for the entire 160 patients and 91% for the 128 patients given postoperative radiation as initial treatment. For the 29 patients referred for treatment of recurrent tumor, the 10-year local control rate was 78%. Prognostic factors for local control identified in univariate analysis included age (p = 0.005) and radiation field size (p = 0.0001). Older patients and those with larger tumors requiring large radiation portals were less likely to achieve durable local control. These two factors remained significant in a multivariate analysis (p < 0.005). The major complication, hypopituitarism requiring hormonal replacement with thyroxine, glucocorticoid, and sex hormone was observed to date in 65% (100 out of 155), 68% (105 out of 154), and 67% (85 out of 127) of evaluable patients, respectively. Radiation was the contributing cause of the hypopituitarism in only 23%, 16%, and 13%, respectively. There were no cases of brain necrosis or radiation damage to the optic pathways. Two patients developed a fatal in-field glioma of the brain stem at 10 and 15 years following radiation. CONCLUSION: Postoperative external beam radiation therapy is highly effective in preventing recurrence of hormonally inactive pituitary adenomas. Hypopituitarism is commonly observed, but radiation can only be incriminated as the contributing cause in approximately one-fifth of the cases. Treatment of patients at the time of recurrence gave comparable local control rates to those irradiated initially. Favorable patients (age < or = 50, with small tumors removed totally) probably can be safely observed postoperatively with radiation reserved for recurrence.

Adenoma↗
PubMed1994

Nucleotide sequence and analysis of the gene in Borrelia burgdorferi encoding the immunogenic P39 antigen.

The P39 antigen is a specific, highly conserved, and immunogenic protein of Lyme disease spirochetes, Borrelia burgdorferi sensu lato. The nucleotide sequence of the gene encoding this protein was determined and found to be the first of two tandemly arranged open reading frames located on the spirochete's chromosome. These two open reading frames were designated bmpA for the gene encoding P39 and bmpB for the gene encoding the putative protein ORF2 encoded by the second open reading frame. The nucleic acid sequence identity for the two open reading frames was 62% while their deduced amino acid sequences were 52% identical. Comparison to sequence data bases demonstrated that the deduced amino acid sequences of both P39 and ORF2 were homologous to TmpC, a putative outer or cytoplasmic membrane lipoprotein of the syphilis spirochete, Treponema pallidum.

Amino Acid Sequence↗
PubMed1994

Extragonadal germ cell tumors. A 14-year Toronto experience.

BACKGROUND: Extragonadal germ cell tumors (EGCT) represent only 2-5% of adult germ cell malignancies. Because they are rare and biologically distinct from testis cancer, their natural history and optimal management continue to be defined. The clinical characteristics, treatment, and outcome of 40 patients are presented here. METHODS: Patients were identified through the medical records of four University of Toronto teaching hospitals. All patients were treated in specialized oncology units between 1978 and 1993. RESULTS: Thirty-seven males and three females age 16-54 years (median, 24 years) with primary mediastinal (n = 24), retroperitoneal (n = 7), CNS (n = 7), and widespread (n = 2) EGCT were identified. Eight of nine patients (88%) with mediastinal seminoma are alive with no evidence of disease (NED) at 4-132 months (median, 45 months). After combined modality therapy, only 8 of 15 patients (53%) with mediastinal nonseminomas achieved complete remission (CR); 1 experienced relapse and died, resulting in 7 of 15 patients (47%) with NED at 45-86 months (median, 70 months). All three patients with retroperitoneal seminomas achieved CR and all have NED at 77, 103, and 120 months, respectively. Two of four patients with retroperitoneal nonseminomas have died, and the other two are alive at 36 and 54 months. Seven patients with CNS germinomas (seminoma) achieved CR after craniospinal radiation therapy, but one subsequently died after local relapse. The overall survival rate was 87% (median, 74 months). One patient with widespread choriocarcinoma died and the other achieved CR. CONCLUSIONS: Regardless of site of presentation, extragonadal seminomas have a greater than 80% 5-year disease-free survival rate. Mediastinal nonseminomas are biologically distinct, with a poorer prognosis. Treated with cisplatin-based chemotherapy followed by aggressive resection, approximately 50% of patients survive. CNS seminomas have a good prognosis. Nonseminomas of the CNS are extremely rare and were not represented in the current series. These findings concur with other reported series.

Adolescent↗
PubMed1994

Radioiodine ablation of residual tissue in thyroid cancer: relationship between administered activity, neck uptake and outcome.

A retrospective review was performed to evaluate the effectiveness of radioiodine in the ablation of residual thyroid tissue after surgery for differentiated thyroid cancer. 121 patients were treated at the Princess Margaret Hospital, Toronto, Canada between 1977 and 1989, with the activity of radioiodine determined empirically. Ablation of residual thyroid was determined by 131I nuclear scans, using absent visible uptake (compared with background) as the criterion for successful ablation. 97 patients (80%) had successful ablation of residual thyroid tissue after the first administration of radioiodine. Patients with higher iodine uptake in the neck had a tendency to receive higher activities of 131I. There were no statistically significant differences in age, sex, type of surgery, initial iodine uptake in the neck and administered radioiodine activity between those successfully ablated and those that were not. Patients receiving less than 3.7 GBq (100 mCi) tended to have lower iodine uptake (< 5% at 24 or 48 h), but their rate of thyroid ablation was just as high as those given 3.7 GBq or more. In order to take advantage of this, we have formalized our approach by deriving guidelines to the empiric determination of radioiodine activity based on the iodine uptake in the neck. Among the 11 patients treated with lobectomy only, the ablation rate was 64%. Although this was not significantly lower than for other forms of surgery, we continue to recommend completion thyroidectomy for this group of patients, if the goal of treatment is to ablate all thyroid tissue.

Adult↗
PubMed1993

Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk.

BACKGROUND: Many case reports in the literature associate cranial radiation therapy with the development of brain tumors. Quantitation of the risk of second brain tumors after irradiation in childhood is available, but it is seldom reported for those treated by radiation therapy as adults. METHODS: A retrospective review was made of 367 patient records registered at the Princess Margaret Hospital with a diagnosis of pituitary adenoma from 1972 to 1986. Three hundred five patients treated with megavoltage radiation therapy form the basis of this report. Second brain tumors were identified and the patient case histories described. The risk of second brain tumor after irradiation was estimated by calculating the observed/expected (O/E) ratio, age- and sex-adjusted to the Ontario population. RESULTS: Of the 305 patients in this study, 4 had glioma of the brain. All gliomas arose within the previous radiation field(s), with a latency of 8-15 years after radiation therapy. Additional treatment was compromised by the location of the glioma and the moderately high doses of radiation received previously; all four patients died of their gliomas. Our cohort of patients had a relative risk of malignant brain tumor 16 times greater than that of the general population in Ontario (P < 0.001; 95% confidence interval, 4.4-41). The cumulative actuarial risk of secondary glioma after radiation therapy was 1.7% at 10 years and 2.7% at 15 years. CONCLUSIONS: There was a clinically significant increased risk of malignant brain tumor developing after radiation therapy for pituitary adenoma. Because there is no reported association between pituitary adenomas and gliomas of brain, this excess risk is attributed to irradiation. Before advising radiation therapy for pituitary adenoma, the risk:benefit ratio, including the risk of secondary brain tumors, should be carefully considered.

Adenoma↗
PubMed1993

Spinal cord ependymomas: a retrospective analysis of 59 cases.

PURPOSE: To determine the outcome of patients with primary spinal ependymoma treated with postoperative radiotherapy and to identify clinical and treatment variables predictive of outcome. METHODS AND MATERIALS: A retrospective chart review was undertaken of 59 spinal ependymoma patients referred to the Princess Margaret Hospital between 1958 and 1987. All patients were treated with radiation therapy to either the site of the primary tumor or the craniospinal axis. There were 23 female and 36 male patients with a median age of 37 years (range: 8-66 years). Median follow-up was 130 months (range: 1-371 months). Clinical variables including age, sex, length of symptoms, functional status, tumor location, and grade as well as treatment variables including extent of surgery, radiation dose and treatment volume were analyzed for influence on outcome. RESULTS: Treatment was well-tolerated with no cases of radiation myelopathy identified. Overall actuarial survival at 5 and 10 years was 83% and 75%, respectively. Eleven patients had recurrent tumor with the 9/11 having a component of their recurrence within the treatment field. Median time to recurrence was 2 years with 9 of the 11 recurrences within the first 3 years. Tumor grade was the only independent variable identified as predictive of outcome. Patients with well differentiated tumors had a 5-year cause-specific survival of 97% compared to 71% for those with intermediate or poorly differentiated tumors (p = 0.005). CONCLUSION: We conclude that postoperative irradiation for patients with spinal ependymomas is associated with a favorable outcome and that tumor grade is a major prognostic factor. Based on results of this series and a review of the literature, specific management recommendations are made for this rare tumor.

Adolescent↗
PubMed1993

Oligodendroglioma. The Princess Margaret Hospital experience (1958-1984).

BACKGROUND: Oligodendrogliomas are rare central nervous system (CNS) tumors. Although surgery remains the primary treatment, the role of postoperative radiation treatment remains a matter of controversy. This study assesses whether postoperative radiation improves survival and local tumor control when compared with surgical treatment alone. METHODS: The medical records of 72 patients with the diagnosis of oligodendroglioma, registered at the Princess Margaret Hospital (PMH) between 1958 and 1984, were reviewed retrospectively. The data of 68 patients were evaluated, but 4 patients were excluded from the analysis because of inadequate follow-up. The median follow-up period at the time of analysis was 7.5 years. Tumors were classified as oligodendrogliomas, malignant oligodendrogliomas, or mixed oligoastrocytomas. Fifty-eight (85%) patients received postoperative irradiation at initial diagnosis, and 10 (15%) patients were treated with surgery alone. In most patients (76%), the radiation dose was 5000 cGy in 25 fractions given during a period of 5 weeks. RESULTS: Five- and 10-year overall survival was 66% and 30%, respectively. Forty-two (62.0%) patients experienced disease relapse during the follow-up period. The median time to relapse from initial diagnosis was 2.6 years. Most tumor recurrences were at the primary site. Two patients developed distant metastasis within the CNS axis. Histologic subtype was the only significant prognostic factor for survival. The patients with oligodendroglioma and malignant oligodendroglioma had 5-year survival rates of 73% and 32%, respectively (P = 0.033). CONCLUSIONS: The authors drew three conclusions. (1) Most patients eventually died with this tumor from local recurrence without distant metastasis. Local tumor control remains the major problem. (2) Tumor histologic subtype is a significant prognostic factor. (3) No statistically significant benefit can be attributed to postoperative irradiation; however, the number of patients not receiving radiation therapy was small (10). Thus, the role of radiation therapy remains a matter of controversy.

Adult↗
PubMed1992

Factors affecting antibacterial activity of hop compounds and their derivatives.

The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone.

Anti-Bacterial Agents↗
PubMed1992

Evidence consistent with horizontal transfer of the gene (emm12) encoding serotype M12 protein between group A and group G pathogenic streptococci.

Human isolates of Lancefield group G streptococci harbor sequences homologous with the structural gene (emm) encoding M protein, a major virulence factor in Streptococcus pyogenes (a group A Streptococcus species). We used DNA-DNA hybridization, restriction endonuclease chromosomal profiling, and multilocus enzyme electrophoresis to examine genetic relationships between group A and group G streptococcal strains expressing homologous serologic type 12 M (M12) protein. All M12 group A strains studied had very similar restriction endonuclease genomic profiles and multilocus enzyme genotypes. In contrast, the restriction enzyme genomic profile and multilocus enzyme genotype of the M12 group G strain CS140 were strikingly different from those characterizing the M12 group A organisms. DNA-DNA hybridization studies revealed, on average, 57% genomic similarity between the M12 group A and group G strains. Taken together, our data demonstrate that a gene encoding M12 protein occurs in two highly divergent chromosomal backgrounds, a result suggesting that an episode of horizontal gene transfer and recombination has occurred between two streptococcal lineages.

Antigens, Bacterial↗
PubMed1992

Failure of intragastrically administered Yersinia pestis capsular antigen to protect mice against challenge with virulent plague: suppression of fraction 1-specific antibody response.

We evaluated the Yersinia pestis capsular (fraction 1 [F1]) antigen as a potential oral immunogen in mice. We found that single doses of as much as 0.4 mg of F1, administered by intragastric (ig) intubation, were unprotective and did not stimulate production of detectable levels of specific antibody. Three weekly ig doses resulted in low serum antibody levels that also did not provide protection against challenge with virulent Y. pestis. Assays of type-specific antibody following intubation and subsequent challenge with a subcutaneous inoculation of F1 revealed that the quantity of antigen intubated and the secondary IgG2a antibody levels were inversely related, suggesting the induction of tolerance to intragastrically administered F1 antigen. Transfer of spleen cells from intubated mice to F1 immune recipients failed to demonstrate suppression of specific antibody, indicating that the immune tolerance observed in intubated mice was not due to a T suppressor cell-mediated effect. The results of this study indicate that Y. pestis F1 antigen is not likely to be an efficacious immunogen for oral vaccination of mice against plague.

Animals↗
PubMed1991

Myelopathy following hyperfractionated accelerated radiotherapy for anaplastic thyroid carcinoma.

From 1975 to 1982, 32 patients with a diagnosis of anaplastic carcinoma of the thyroid were entered into a protocol of hyperfractionated accelerated radiotherapy. The tumor dose was 30-45 Gy at 1 Gy per fraction given 4 times a day at 3-h intervals. The results were disappointing with a median survival of less than 6 months. Two patients developed radiation myelopathy at 8 and 13 months, total spinal cord dose being 39.9 and 48.3 Gy, respectively. The risk of spinal cord damage was much higher than expected. The possible radiobiological causes and clinical implications are discussed.

Carcinoma↗
PubMed1991

Antibody to a 39-kilodalton Borrelia burgdorferi antigen (P39) as a marker for infection in experimentally and naturally inoculated animals.

Borrelia burgdorferi expresses a conserved, species-specific 39-kDa protein (P39) that can stimulate antibodies during human infection. To confirm that anti-P39 antibodies are produced consistently in animals exposed to infectious spirochetes, white-footed mice, Peromyscus leucopus, and laboratory white mice, Mus musculus (strain BALB/c), were experimentally inoculated with either infectious or noninfectious B. burgdorferi and the antibody response to P39 was determined by immunoblot at 21 days postinoculation. All mice inoculated with approximately 10(7) infectious B. burgdorferi produced anti-P39 antibodies and were cultured positive for this spirochete. Mice inoculated with similar numbers of inactivated or viable noninfectious B. burgdorferi still producing P39 did not induce anti-P39 antibodies. By contrast, putative antiflagellin antibodies were detected in less than 18% of the infected animals, which supports the notion that antibody reactive with flagellin may not be reliable as a marker for B. burgdorferi exposure as was originally thought. Mice infected with B. burgdorferi following exposure to ticks (Ixodes dammini) produced anti-P39 antibodies no later than 7 days postinfection, indicating that P39 is an effective immunogen in natural infections. Notably, anti-P39 antibodies were the predominant B. burgdorferi reactive antibodies detected early in the infection. Our results indicate that anti-P39 antibodies are produced in response to an active infection and are therefore reliable markers for infection in experimentally and naturally inoculated animals.

Animals↗
PubMed1991

Molecular and immunological analysis of a polymorphic periplasmic protein of Borrelia burgdorferi.

Borrelia burgdorferi is the causative agent of Lyme disease, a tick-borne spirochetosis with a worldwide prevalence. To assist the categorization and typing of fresh isolates from global foci, we have identified a unique species-specific periplasmic protein (P22-A) conserved among all North American and European isolates examined. The gene encoding this antigen was cloned, and the recombinant was used to screen serum collected from experimentally infected animals. Although antibodies were detected in all infected animals at 21 days after inoculation with live, low-passage spirochetes, the response was stronger in other animals that were inoculated with inactivated and lysed bacteria. This result, along with the immune electron microscopy data, suggests P22-A is concentrated in the periplasmic space. The P22-A antigens exhibited size heterogeneity among different isolates, ranging between 20 and 23 kDa, but as a group the P22-A antigens appeared to retain antigenic homogeneity. Thus, P22-A can serve as a structural marker for characterizing new isolates of B. burgdorferi and may prove useful in future serological assays with a mixture of B. burgdorferi-specific antigens.

Animals↗
PubMed1991

Changes in antigenic reactivity of Borrelia burgdorferi, the Lyme disease spirochete, during persistent infection in mice.

Adult laboratory mice, Mus musculus, were shown to be suitable experimental animals for studying infectivity, persistent infection, and in vivo antigenic changes of Borrelia burgdorferi. Sixteen mice were inoculated intraperitoneally with a low-passage culture of an uncloned strain of B. burgdorferi and 16 months later spirochetes were reisolated from the urinary bladder of 15 (94%) of the mice. Spirochetes recovered from the urinary bladder of one persistently infected mouse were tested for infectivity and found to be infectious when passaged into four laboratory mice. Western blot analysis of immune serum from each of the persistently infected mice demonstrated that spirochetes used to infect the mice reacted differently when compared with the spirochetes subsequently reisolated from the mice, demonstrating for the first time that changes in antigenic reactivity had occurred in the spirochete populations during persistent infection.

Animals↗