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Biomedical subjects

P A Forsyth

Publications and source records attributed to P A Forsyth.

At least 37 records · Page 2Linked to original sources
PubMed1998

High levels of gelatinase-B and active gelatinase-A in metastatic glioblastoma.

PURPOSE: Extra-neural metastases from glioblastoma multiforme (GBM) are rare. Because gelatinases-A and -B have been implicated in tumor invasion/metastasis in non-neural tumors, we compared the expression of gelatinase-A and -B in 2 patients (both had a prior craniotomy performed) with extraneural metastases from GBM to expression levels in 24 other gliomas; 15 non-metastatic GBMs, 9 other lower grade gliomas, and 7 normal brain tissues. METHODS: The intracerebral tumor from both patients, patient # 1's extraneural metastases, 24 other gliomas, 1 sample of reactive astrocytes and 7 normal brain tissues were studied using gelatin zymography. The active form of gelatinases was confirmed by co-migration after activation with APMA. RESULTS: Expression of the latent form of gelatinase-A correlated with glioma grade (r = 0.486; p = 0.0053). Active gelatinase-A was found only in the 2 GBMs with extraneural metastases and patient # 1's cervical metastases. In contrast, latent gelatinase-B levels correlated more strongly with histologic grade (r = 0.577; p = 0.0009) (higher levels with higher grades). Very high levels of gelatinase-B were seen in both GBMs with extraneural metastases, a cervical extraneural metastases, and 2 GBMs without metastases. CONCLUSIONS: We observed that gelatinases-A and -B are present in most gliomas but we found active gelatinase-A only in the GBMs with extraneural metastases suggesting that the active form of this enzyme may determine the metastatic potential of GBMs. We propose that high levels of gelatinolytic activities are associated with intracerebral invasion and rarely, metastases of GBMs.

Adult↗
PubMed1997

Motor neuron syndromes in cancer patients.

Previous reports indicate that motor neuron disease (MND) may rarely be associated with systemic cancer. We have encountered 14 patients with MND and cancer who formed three distinct groups. Group 1: Three patients developed a rapidly progressive MND, less prominent symptoms of involvement of other areas of the nervous system, and anti-Hu antibodies. Group 2: Five women developed signs of upper motor neuron (UMN) disease, initially resembling primary lateral sclerosis (PLS), and breast cancer. In 4, symptoms of UMN occurred within 3 months of cancer diagnosis or tumor recurrence. They had no metastases or spinal cord compression. Serum anti-neuronal antibodies were negative. Three patients are alive (follow-up of 156, 15, and 12 months), and 2 remain without lower motor neuron signs. Group 3: Six patients developed MND resembling amyotrophic lateral sclerosis between 47 months before and 48 months after their cancer diagnosis. In group 1, the MND associated with the anti-Hu antibody is unequivocally paraneoplastic. In group 2, the proximate onset of MND with the diagnosis of cancer or its recurrence, its pure or long-lasting UMN signs, and its association with breast cancer, suggest that the disorder may be paraneoplastic. Although for most cancer patients who develop MND the occurrence of both disorders is probably coincidental, in some patients with MND a careful search for an underlying cancer is warranted (ie, patients in groups 1 and 2).

Aged↗
PubMed1997

Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing.

BACKGROUND: Paclitaxel-induced peripheral neuropathy (PN) may be severe and dose-limiting at initial doses > or = 275 mg/M2, but its neurotoxicity at doses < or = 250 mg/M2 has been incompletely characterized. The purposes of this study were to characterize and quantify paclitaxel-induced PN and to determine the utility of quantitative sensory testing (QST). METHODS: We prospectively examined clinically and by QST 37 women with metastatic breast cancer, treated with paclitaxel (200-250 mg/m2) (average number of cycles = 7.3 over an average of 20.1 weeks). QST included thermal threshold (TT) and vibration threshold (VT). RESULTS: Paresthesias appeared in 31 (84%) patients after an average of 1.7 cycles and an average cumulative dose of 371.5 mg/M2. Symptoms occurred after the first or second dose in 26 (84%) patients and then stabilized in 10 (32%), improved in 13 (42%) despite continued treatment, resolved completely in 6 (19%), and were progressive in 2 (7%). Paclitaxel was discontinued in only 1 (3%) patient because of neurotoxicity and no patient required dose reduction because of PN. Thirty-six (97%) developed signs of PN. The most sensitive QST was great toe VT but QST did not predict or identify subclinical PN in any patient. Neurologic syndromes other than PN developed in 12 (32%) patients, and 7 were due to metastatic cancer. CONCLUSIONS: 1) Paclitaxel-induced PN is mostly sensory, and begins after the first or second dose. At these doses the neuropathy is mild, and rarely dose-limiting. 2) QST quantified the neuropathy but was less sensitive than the clinical examination. 3) Knowledge of the features of paclitaxel's PN allows it to be differentiated from other neurologic syndromes which may signal tumor progression.

Adult↗
PubMed1997

Prospective study of postoperative magnetic resonance imaging in patients with malignant gliomas.

PURPOSE: We studied the natural history of postoperative enhancement on magnetic resonance (MR) scans in patients with malignant glioma to determine the following: (1) when a postoperative MR scan most accurately shows residual enhancing tumor; and (2) whether repeated doses of the contrast agent gadopentetate dimeglumine (Gd-DTPA) were well tolerated. PATIENTS AND METHODS: Seventeen patients with malignant glioma underwent tumor resection; four (24%) had nonenhancing tumors preoperatively. Serial MR scans were performed on postoperative days 1, 3, 5, 7, 14, and 21 and were analyzed qualitatively and quantitatively. The evolution of enhancement and subacute hemorrhage were described and measured. A uniform schedule of postoperative dexamethasone administration was used in all but four patients (24%) (each required higher doses to maintain neurologic function). RESULTS: Nontumoral, marginal (i.e., postsurgical) enhancement, potentially mimicking residual tumor, developed in eight patients (53%), including tumors that were nonenhancing preoperatively, and was maximal from days 5 to 14. Tumor enhancement was optimally visualized on postoperative days 3 to 5. Nine of 10 patients (90%) with gross residual enhancing tumor showed an increase of enhancing tumor size during the study. Methemoglobin was detected at some time in all patients (100%) and was usually minor, but in six (35%) it interfered with residual tumor assessment. The 97 doses of Gd-DTPA, administered in 17 patients, were well tolerated. CONCLUSION: When accurate assessment of residual enhancing tumor is needed in patients with malignant glioma, an MR scan performed on postoperative days 3 to 5 should minimize the confounding effects of postsurgical enhancement and methemoglobin. The repeated administration of Gd-DTPA over several weeks is well tolerated.

Adolescent↗
PubMed1996

Biology and management of AIDS-associated primary CNS lymphomas.

Primary central nervous system (CNS) lymphoma is the most common brain tumor in patients with AIDS and occurs in about 10% of this population. CT/MR scan usually demonstrates single or multiple contrast enhancing masses that are radiographically indistinguishable from other CNS processes such as toxoplasmosis. Brain biopsy, positive cerebrospinal fluid (CSF) cytology, or possibly the demonstration of Epstein-Barr viral DNA in the CSF can establish the diagnosis. Cranial radiotherapy (RT) has been the cornerstone of therapy and produces responses in most patients, but their median survival is still only a few months. The addition of chemotherapy to RT may prolong survival in a sub-group of patients.

Brain↗
PubMed1996

Malignant supratentorial glioma in the elderly: is radiotherapy useful?

OBJECTIVES: To determine (1) if radiotherapy (RT) improves survival or neurologic function in elderly patients with malignant supratentorial glioma (MSG) and (2) which prognostic factors predict survival. BACKGROUND: The prevalence of MSG is increasing because both the number of elderly patients and the age-adjusted incidence are increasing. Because age is a powerful negative prognostic factor in MSG, it is not clear if RT is useful in the elderly. DESIGN/METHODS: We retrospectively studied 103 patients from the Southern Alberta Cancer Registry diagnosed January 1, 1978, to December 31, 1993, aged 70 yrs, with MSG in whom sufficient clinical and follow-up information was available. Multiple treatment and patient factors were compared with survival and neurologic function score. Diagnosis was confirmed in 15 (14.6%) by biopsy, in 66 (64.1%) by resection, and in 22 (21.4%) by clinical course and typical radiographic appearance only. RESULTS: All patients died and median survival was 3.9 months. Better neurologic function at diagnosis and administration of RT were independently associated with significantly longer survivals (p = 0.001 and < 0.001; log rank test). However, RT was only associated with longer survival in patients aged less than 80 years. Neurologic status only rarely improved following RT. CONCLUSIONS: The prognosis for elderly patients with MSG is poor. RT is unlikely to benefit patients who are aged 80 years or older. RT has a short-lived benefit for patients who are functionally disabled.

Aged↗
PubMed1995

The movement disorder of adult opsoclonus.

We present three cases of the adult opsoclonus-myoclonus syndrome in patients with systemic carcinoma. In addition to opsoclonus and myoclonus, other clinical components of the syndrome can include ataxia, tremor, gait and stance dysfunction, altered mental status, and head and face dyskinesias. The most common etiologies are idiopathic, paraneoplastic, and infectious encephalitis. Radiographic and pathological studies suggest brain-stem dysfunction with associated cerebellar and/or cerebellar pathway dysfunction. In many cases, there is evidence for the involvement of immunologic and/or inflammatory processes in the pathogenesis of this syndrome. The timely recognition of this syndrome is important because of its implications for the underlying etiology and prognosis. The appearance of this syndrome should prompt the search for an occult malignancy.

Adult↗
PubMed1995

Treatment of malignant glioma in adults.

Most patients with malignant glioma fare no better in 1995 than they did 30 years ago. However, high quality precision stereotactic biopsy is available in most centres, tumour resection is safer and more thorough than ever, focused radiation methods are achieving similar rates of tumour control while exposing normal tissues to lower doses of radiation, novel systems for regional drug delivery are being developed, and the chemosensitive nature of oligodendrogliomas has been firmly established. Clinical investigators are now willing to look more critically at methodological issues and address shortcomings in the design and conduct of future phase II and III trials. These advances, although modest, set the stage for a careful and critical evaluation of the first generation of molecular therapies for malignant glioma in adults.

Antineoplastic Agents↗
PubMed1995

Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful?

Fifty-one patients with supratentorial glioma treated with external beam radiotherapy (median dose 59.5 Gy) who then demonstrated clinical or radiographic evidence of disease progression underwent stereotactic biopsy to differentiate tumor recurrence from radiation necrosis. The original tumor histological type was diffuse or fibrillary astrocytoma in 21 patients (41%), oligodendroglioma in 13 (26%), and oligoastrocytoma in 17 (33%); 40 tumors (78%) were low-grade (Kernohan Grade 1 or 2). The median time to suspected disease progression was 28 months. Stereotactic biopsy showed tumor recurrence in 30 patients (59%), radiation necrosis in three (6%), and a mixture of both in 17 (33%); one patient (2%) had a parenchymal radiation-induced chondroblastic osteosarcoma. The tumor type at stereotactic biopsy was similar to the original tumor type and was astrocytoma in 24 patients (47%), oligodendroglioma in eight (16%), oligoastrocytoma in 16 (31%), unclassifiable in two (4%), and chondroblastic osteosarcoma in one patient (2%). At biopsy, however, only 19 tumors (37%) were low grade (Kernohan Grade 1 or 2). Subsequent surgery confirmed the stereotactic biopsy histological findings in eight patients. Follow-up examination showed 14 patients alive with a median survival of 1 year for the entire group. Median survival times after biopsy were 0.83 year for patients with tumor recurrence and 1.86 years for patients with both tumor recurrence and radionecrosis; these findings were significantly different (p = 0.008, log-rank test). No patient with radiation necrosis alone died. Other factors associated with reduced survival were a high proportion of residual tumor (p = 0.024), a low proportion of radionecrosis (p < 0.001), and a Kernohan Grade of 3 or 4 (p = 0.005). In conclusion, in patients with previously irradiated supratentorial gliomas in whom radionecrosis or tumor recurrence was clinically or radiographically suspected, results of stereotactic biopsy could be used to differentiate tumor recurrence, radiation necrosis, a mixture of both lesions, or radiation-induced neoplasm. In addition, biopsy results could predict survival rates.

Adult↗
PubMed1994

Paraneoplastic sensorimotor neuropathy associated with breast cancer.

Paraneoplastic sensorimotor neuropathy occurs in association with many different types of cancer. The clinical findings are heterogeneous, and the pathogenesis is unknown. We have encountered 9 women with breast cancer and shared neurological features that suggest a distinct paraneoplastic syndrome. The syndrome is characterized by upper and lower extremity paresthesias and numbness, itching, muscle weakness and cramps, and in some, radicular symptoms and signs. Serum and CSF inflammatory changes suggested an immune pathogenesis but none had detectable antibodies directed at nervous system elements. Six patients presented with neuropathy 2 months to 8 years before the discovery of the breast cancer. In 7 the neoplastic disease was localized to the breast and axillary lymph nodes. The neurologic course was chronic in all, and while symptoms were annoying, disability was minimal until late. One improved transiently with plasmapheresis, and three had mild transient improvement with treatment of the cancer. Recognition of this paraneoplastic syndrome may forewarn the physician of an underlying breast malignancy.

Adenocarcinoma↗
PubMed1994

Combined-modality therapy in the treatment of primary central nervous system lymphoma in AIDS.

PURPOSE: Conventional therapy--ie, treatment with corticosteroids and cranial radiotherapy (RT)--is inadequate to treat AIDS-related primary central nervous system lymphoma (PCNSL), as it achieves a median survival of only 2 to 5 months. Chemotherapy added to RT in non-AIDS PCNSL improves disease control and prolongs survival. We studied the efficacy of this approach with RT in AIDS-related PCNSL. METHODS: Ten AIDS patients with PCNSL were treated with chemotherapy--nine at diagnosis and one at recurrence. None had evidence of systemic lymphoma. All patients treated at diagnosis received pre-RT methotrexate--eight also received thiotepa and procarbazine--followed by whole-brain RT. The patient treated at recurrence (who had been previously irradiated) received chemotherapy alone, including methotrexate, thiotepa, and procarbazine. RESULTS: All had enhancing lesions on MRI and five (50%) had a single lesion (seven [70%] had a ring-enhancing mass). No patient had a response to corticosteroids. Four of seven (57%) assessable patients had a partial or complete response to chemotherapy prior to RT. Six of seven (86%) assessable patients had a complete response at the end of treatment. Median survival was 3.5 months for all 10 patients and 7 months for the eight patients who completed therapy. Two patients survived for 1 year or longer. Eight patients died--six from infection (two treatment-related), one from progressive dementia, and one from a gastrointestinal hemorrhage. CONCLUSION: AIDS-related PCNSL responds to chemotherapy and RT, but only a few patients benefit with prolonged survival.

Adult↗
PubMed1993

Supratentorial pilocytic astrocytomas. A clinicopathologic, prognostic, and flow cytometric study of 51 patients.

BACKGROUND: Supratentorial pilocytic astrocytomas are uncommon tumors, the prognosis and management of which have been controversial. METHODS: The authors retrospectively studied the clinical and pathologic aspects of 51 patients with supratentorial pilocytic astrocytomas, with particular reference to their response to treatment. RESULTS: The study group consisted of 25 male and 26 female patients (median age, 15 years). The extent of surgical removal was gross total or radical subtotal in 16 patients and subtotal removal or biopsy in 35. At a median follow-up of 14.9 years, 41 patients were alive. Overall survival was 82% at 10 and 20 years; 89% of surviving patients were fully active. Survival at 10 years was 100% for the 16 patients who underwent gross total or radical subtotal removal and 74% for the 35 who had subtotal tumor removal or biopsy. No association was found between pathologic features such as histologic grade or flow cytometric characteristics and patient survival. CONCLUSIONS: Supratentorial pilocytic astrocytomas behave differently from low-grade astrocytomas of the diffuse or fibrillary type in that they have a favorable prognosis. Radiation therapy appears not to be needed for patients undergoing gross total removal. In patients undergoing subtotal resection, close follow-up with additional surgery or radiation therapy at the time of tumor progression is recommended. Patients who have biopsy only should receive radiation therapy. Histologic grading and flow cytometric analysis add little to clinical decision making with regard to patients with pilocytic astrocytoma.

Adolescent↗
PubMed1993

Headaches in patients with brain tumors: a study of 111 patients.

We examined 111 consecutive patients with primary or metastatic brain tumors identified by CT or MRI to characterize brain tumor headache. The median age was 44 years; 34% had primary and 66% metastatic tumors. Headaches were present in 48%, equally for primary and metastatic brain tumors. Headaches were similar to tension-type in 77%, migraine-type in 9%, and other types in 14%. The typical headache was bifrontal but worse ipsilaterally, and was the worst symptom in only 45% of patients. Unlike true tension-type headaches, brain tumor headaches were worse with bending over in 32%, and nausea or vomiting was present in 40% of patients. The "classic" early morning brain tumor headache is uncommon. Nausea, vomiting, an abnormal neurologic examination, or a significant, change in prior headache pattern suggest that the headache may be caused by a tumor.

Brain Neoplasms↗
PubMed1993

Intracranial chordomas: a clinicopathological and prognostic study of 51 cases.

Fifty-one patients with intracranial chordomas who were surgically treated between 1960 and 1984 were studied. Median patient age was 46 years, and 73% presented with diplopia or headache. Nineteen tumors were classified as the "chondroid" type. The extent of surgical removal was a biopsy in 11 patients and subtotal removal or greater in 40. Thirty-nine patients received postoperative radiation therapy. At the time of analysis, 17 patients were alive, and the estimated 5- and 10-year survival rates were 51% and 35%, respectively, for the group of 51 patients. Univariate analysis showed that: 1) patients undergoing resection lived longer (the 5-year survival rate was 36% for the 11 biopsy patients compared with 55% for the 40 patients who had resection; 2) patients who underwent postoperative radiotherapy tended to have longer disease-free survival times; and 3) overall and disease-free survival data were the same for patients with chondroid tumors and those with typical chordomas. Multivariate analysis showed that: 1) age was the factor most strongly associated with longer overall and disease-free survival; 2) diplopia was associated with longer survival; and 3) tumoral mitotic activity tended to be associated with shorter disease-free survival. One tumor metastasized to the cervical cord, and two tumors underwent anaplastic transformation. These data suggest that the prognosis in patients with chordomas is unfavorable, young age is the single factor most strongly associated with longer survival, surgical resection is beneficial, and postoperative radiotherapy may prolong disease-free survival.

Adult↗
PubMed1992

Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole.

A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.

Adenocarcinoma↗
PubMed1985

Role of oropharyngeal stimulation in cholecystokinin-induced satiety in the sham feeding rat.

The belief that oropharyngeal stimulation potentiates the satiety produced by cholecystokinin (CCK) is based on the demonstration that the ability of 20% pure CCK to suppress feeding is enhanced the closer it is injected to a meal. The increase efficacy of CCK with closer temporal proximity to a meal might simply reflect increased peptide levels at the time of feeding. Further, since oropharyngeal synergy has never been demonstrated with pure CCK, studies were performed to evaluate the role of oropharyngeal stimulation in CCK-induced satiety. Rats equipped with gastric fistulae were injected IP with CCK-8 15 min before a test sham feed. In one condition, rats sham fed for 15 min prior to CCK injection; in the other, they did not. CCK-8 suppressed eating in only those cases when its administration was accompanied by oropharyngeal stimulation. Thus, oropharyngeal cues enhance the satiety action of exogenous CCK. A second experiment examined whether oropharyngeal synergy requires oropharyngeal stimulation prior to peptide delivery. CCK-8 was injected into rats coincident with the initation of a test sham feed. Rats had either sham fed, or not sham fed, for 15 min prior to CCK administration. Both conditions produced similar and significant suppressions of eating during the test sham feed. Thus, oropharyngeal cues enhance the action of CCK and oropharyngeal amplification needs only contiguous pairings of oropharyngeal stimulation and feeding.

Animals↗
PubMed1985

Endogenous cholecystokinin and intestinal satiety.

The role of endogenous cholecystokinin (CCK) as a mediator of intestinal satiety is examined. We used rats equipped with a chronic gastric fistula and an indwelling duodenal catheter to assess the effects of direct duodenal stimulation on sham feeding. To evaluate the contribution of endogenous CCK to intestinal satiety we used a specific competitive antagonist of the satiety action of CCK, proglumide. Intraduodenal infusion of 11 or 5 ml liquid diet suppressed sham feeding. Administration of proglumide caused a partial reversal of the suppression of feeding produced by the 11-ml, but not the 5-ml, intraduodenal infusion. Administration of proglumide alone did not influence sham feeding but completely abolished the suppression of sham feeding induced by a maximal dose of exogenous CCK. These results indicate that CCK contributes to intestinal satiety under specific test conditions only. Moreover, since that component of suppression reversed by proglumide was small in comparison with the overall inhibition of eating, these results indicate that factors other than CCK are important in intestinal satiety.

Analysis of Variance↗