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S Saris

Publications and source records attributed to S Saris.

14 recordsLinked to original sources
PubMed1998

Unexpected in vitro chemosensitivity of malignant gliomas to 4-hydroxyperoxycyclophosphamide (4-HC).

To individually tailor chemotherapy for patients with malignant gliomas according to tumor chemosensitivity, a rapid assay system which can be performed with a high success rate is needed. The fluorescent cytoprint assay (FCA) can assess multiple chemotherapeutic agents using small (approximately 500 cells) tumor aggregates very quickly (approximately 1 wk). Tissue samples from 51 patients with malignant gliomas obtained either at time of initial diagnosis (n = 34) or at recurrence were assayed using this method. The assay success rate approached 90% in those culture samples which were histologically verified as tumor. A meaningful number of agents could be tested both on samples obtained by stereotactic biopsy (median, 5) and on specimens from more extensive resections (median, 6). One hundred ninety-three FCAs were performed on a samples obtained from 36 patients. In only twenty six assays (14%) was an agent deemed sensitive (> 90% cell kill) to a chemotherapeutic agent. Sixty-two percent of sensitive FCAs were observed in tumors tested against the activated analog of cyclophosphamide, 4-hydroxyperoxycyclophosphamide (4-HC), where a sensitivity rate (# samples sensitive/total tested against agent) of 64% (95 % CI, 36.6-77.9%) was noted. This rate was significantly higher than with any other agent tested (p = 0.012, two sided McNemar's test) and was not affected by age, histology or disease status. We conclude that: (1) the FCA represents a feasible method for quickly assaying tumors for sensitivity to multiple chemotherapeutic agents; and (ii) malignant gliomas may be particularly sensitive to 4-HC.

Antineoplastic Agents↗
PubMed1998

High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?

PURPOSE: Standard treatments for neoplastic meningitis are only modestly effective and are associated with significant morbidity. Isolated reports suggest that concurrent systemic and intrathecal (i.t.) therapy may be more effective than i.t. therapy alone. We present our experience, which includes CSF and serum pharmacokinetic data, on the use of high-dose (HD) intravenous (i.v.) methotrexate (MTX) as the sole treatment for neoplastic meningitis. PATIENTS AND METHODS: Sixteen patients with solid-tumor neoplastic meningitis received one to four courses (mean, 2.3 courses) of HD (8 g/m2 over 4 hours) i.v. MTX and leucovorin rescue. Serum and CSF MTX concentrations were measured daily. Toxicity, response, and survival were retrospectively compared with a reference group of 15 patients treated with standard i.t. MTX during the same time interval. RESULTS: Peak methotrexate concentrations ranged from 3.7 to 55 micromol/L (mean, 17.1 micromol/L) in CSF and 178 to 1,700 micromol/L (mean, 779 micromol/L) in serum. Cytotoxic CSF and serum MTX concentrations were maintained much longer than with i.t. dosing. Toxicity was minimal. Cytologic clearing was seen in 81% of patients compared with 60% of patients treated intrathecally (P = .3). Median survival in the HD i.v. MTX group was 13.8 months versus 2.3 months in the i.t. MTX group (P = .003). CONCLUSION: HD i.v. MTX is easily administered and well tolerated. This regimen achieves prolonged cytotoxic serum MTX concentrations and CSF concentrations at least comparable to those achieved with standard i.t. therapy. Cytologic clearing and survival may be superior in patients treated with HD i.v. MTX. Prospective studies and a reconsideration of the use of i.t. chemotherapy for patients with neoplastic meningitis are warranted.

Adult↗
PubMed1997

A technique for accurate planning of stereotactic brain implants prior to head ring fixation.

PURPOSE: A two-step procedure is described for accurate planning of stereotactic brain implants prior to head-ring fixation. METHODS AND MATERIALS: Approximately 2 weeks prior to implant a CT scan without the head ring is performed for treatment-planning purposes. An entry point and a reference point, both marked with barium and later tattooed, facilitate planning and permit correlation of the images with a later CT scan. A plan is generated using a conventional treatment-planning system to determine the number and activity of I-125 seeds required and the position of each catheter. I-125 seed anisotropy is taken into account by means of a modification to the treatment planning program. On the day of the implant a second CT scan is performed with the head ring affixed to the skull and with the same points marked as in the previous scan. The planned catheter coordinates are then mapped into the coordinate system of the second CT scan by means of a manual translational correction and a computer-calculated rotational correction derived from the reference point coordinates in the two scans. RESULTS: The rotational correction algorithm was verified experimentally in a Rando phantom before it was used clinically. For analysis of the results with individual patients a third CT scan is performed 1 day following the implant and is used for calculating the final dosimetry. CONCLUSION: The technique that is described has two important advantages: 1) the number and activity of seeds required can be accurately determined in advance; and 2) sufficient time is allowed to derive the best possible plan.

Brachytherapy↗
PubMed1996

Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas.

PURPOSE: Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. PATIENTS AND METHODS: Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) > or = 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3-hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients. RESULTS: Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose-limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors. CONCLUSION: The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.

Adult↗
PubMed1996

Multidisciplinary approach to malignant gliomas.

Primary malignant brain tumors are among the most difficult human malignancies to manage. Other common tumors such as in the lung or breast generally can be cured if caught at an early stage. A 2 cm adenocarcinoma in the peripheral lung field without mediastinal or systemic metastasis can be cured. A small breast carcinoma which has not invaded into the regional lymph nodes can generally be removed with the expectation of permanent control. However, a 1 cm glioblastoma in the anterior right frontal lobe, even with gross total resection and maximum adjunctive radiation, will recur and cause death within a year or two. There is no realistic possibility of cure or even long-term survival. These patients pose unusual management problems. They require different medications such as anticonvulsants and steroids. There are neurocognitive problems and the quality of life is usually worse than for the other common malignancies. They require a multidisciplinary approach with health care providers skilled in a variety of disciplines. Malignant gliomas have two components. There is the main bulk of the tumor (the ring enhancing portion seen on the MRI) and the infiltrating portion than cannot be seen by any imaging method. Local control has improved over the past ten years, but control of the infiltrating portion is still lacking. It is likely that some form of biologic approach will be needed to seek out and kill these infiltrating cells that travel with such ease within the white matter tracts of the brain. Perhaps selective delivery of self-destruct genes to these cells will be possible. Perhaps the search and destroy potential of the immune system can be harnessed. If so, this incurable cancer may some day be brought under control. The effort involved will be extensive both in the laboratory and in the clinic.

Brain Neoplasms↗
PubMed1993

Long-term survival after central nervous system relapse in a patient with osteosarcoma.

BACKGROUND: Since the advent of multiagent adjuvant chemotherapy, survival among patients with localized osteosarcoma has improved to 60% or more. Pulmonary relapse, the most common cause of treatment failure, is associated with less than 25% long-term survival; central nervous system (CNS) metastasis, when it occurs, often presents as a catastrophic clinical event in preterminal patients. METHODS: The authors report a patient with osteosarcoma who had an isolated pulmonary relapse and a subsequent isolated CNS relapse. Complete surgical resection was accomplished on both occasions and followed in the initial instance by adjuvant chemotherapy and in the latter instance by adjuvant whole-brain irradiation. RESULTS: An isolated CNS metastasis was resected and adjuvant whole brain irradiation was administered; the patient is alive and relapse free more than 5 years later. CONCLUSIONS: Patients with osteosarcoma in whom isolated, resectable metastases develop can derive benefit from gross total resection followed by adjuvant chemotherapy or radiation therapy for microscopic residual disease.

Brain Neoplasms↗
PubMed1993

Hydromyelia associated with a posterior fossa cyst.

There are rare reports of children with hydromyelia in association with arachnoid cysts at the foramen of Magendie, and these cases have uniformly been associated with hydrocephalus. We report a case of a 45-year-old woman with a posterior fossa cyst associated with hydromyelia and normal ventricles. This was successfully treated with a cystoperitoneal shunt. We believe this unusual condition is of interest in elucidating potential mechanisms of hydromyelia.

Cerebellar Diseases↗
PubMed1986

Efficacy of clonidine as transdermal therapeutic system: the international clinical trial experience.

Worldwide clinical trial data concerning the pharmacokinetic and pharmacodynamic characteristics of the clonidine transdermal therapeutic system (TTS) are reviewed with reference to its antihypertensive efficacy. The amount of clonidine delivered to the systemic circulation is a direct function of TTS size. After initial patch application, there is a delay of 2 to 3 days before the onset of action, but after removal of the patch, plasma clonidine levels decline slowly, at an elimination half-life of about 20 hours. Evaluation in approximately 2000 patients with mild to moderate hypertension has shown that the bioavailability of transdermal clonidine is comparable to that of oral clonidine and that equivalent blood pressure reductions are achieved. The rate at which dose increases were found necessary to maintain adequate blood pressure control over extended periods reflects a low incidence of tolerance to this new once-a-week dosage form of clonidine, and there has been little evidence of rebound hypertension after discontinuation of TTS treatment.

Administration, Cutaneous↗
PubMed1985

The effect of renal function on enalapril kinetics.

Enalapril maleate (MK-421), a nonmercapto-containing angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to enalaprilat (MK-422), the active diacid. We evaluated serum profiles and urinary excretion of oral enalapril maleate in patients with renal disease (group I, creatinine clearance less than 3 ml/min, patients undergoing dialysis, n = 10; group II, creatinine clearance 10 to 79 ml/min, n = 9) compared with healthy subjects (group III, creatinine clearance greater than 80 ml/min, n = 10). Group I received a 10 mg dose during a day while not receiving dialysis and a 10 mg dose 1 hour before dialysis 2 weeks later. Groups II and III received a single 10 mg dose. Blood samples and urine were collected for 48 hours. Impaired renal function resulted in elevated serum and plasma concentrations of enalapril maleate and decreased excretion rates and urinary recovery of enalapril maleate and enalaprilat. The data suggest an apparent increase in the extent of metabolism of enalapril maleate to enalaprilat or an increase in nonrenal elimination of unchanged enalapril maleate in renal disease compared with normal health. Enalaprilat was dialyzable.

Administration, Oral↗
PubMed1983

Chorea caused by caudate infarction.

An ischemic infarct in the caudate nucleus was associated with a contralateral chorea in a 47-year-old, hypertensive, diabetic man. To my knowledge, this is only the second report of isolated caudate infarction associated with chorea. Computed tomography demonstrated the basal ganglion lesion.

Caudate Nucleus↗
PubMed1983

Fibrosarcoma of the heart metastatic to the brain.

A right parietal lobe metastasis of a fibrosarcoma originating in the left atrium of the heart was resected twice in a 33-year-old man. Light microscopy showed lightly packed, pleomorphic spindle cells with abundant collagen production and an alcian blue-positive matrix. Electron microscopy confirmed the fibroblastic character of these cells. Review of the literature reveals one other cardiac fibrosarcoma metastatic to the brain. The case presented is the first reported example of successful surgical resection of this unusual metastatic sarcoma. Although he succumbed to metastatic disease, the patient remained neurologically intact until the time of death.

Adult↗
PubMed1982

Biochemical and dynamic responses to single and repeated doses of methyldopa and propranolol during dynamic physical activity.

Our purpose was to describe changes in potassium disposition with antirenin antihypertensives during dynamic physical activity in normal subjects receiving methyldopa and propranolol. Before the study, 2 hr after dosing and coincident with immediate preexercise on treadmill (at graded increases of exercise), and 2 hr after exercise, blood was sampled for determination of potassium, renin, aldosterone, and catecholamine levels. Blood pressure and heart rate were measured. The results demonstrate no greater increase in potassium after single or multiple doses of methyldopa than after placebo. After the first dose of propranolol there was a greater rise in potassium over that with placebo, but it was not observed after multiple doses, which may be related to the low doses. There were minor, but significant, changes in norepinephrine, renin, and systolic pressure with multiple-dose methyldopa and in renin, heart rate, and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses to exercise win methyldopa and propranolol were biochemically altered rather than functionally impaired. The latter is related to dose and the underlying age and state of health of our subjects. Methyldopa (or clonidine) may be useful in patients with hypertension who exercise and are predisposed to pertubations in potassium disposition.

Adult↗
PubMed1982

Potassium disposition and neuroendocrine effects of propranolol, methyldopa and clonidine during dynamic exercise.

In order to determine the changes in potassium disposition with antirenin, antihypertensives during dynamic physical activity, a double-blind placebo controlled study was undertaken using normal volunteers receiving placebo or single and multiple dose clonidine, methyldopa and propranolol 0.2 mg. followed by 0.1 mg. bid x 7 days, 500 mg. followed by 250 mg. bid x 7 days or 80 mg. followed by 40 mg. bid x 7 days, respectively. Prior to study, 2 hours post dosing and coincident with immediate pre-exercise on treadmill, at graded increases of exercise and 2 hours post exercise (approximately 4 hours post dosing), blood was sampled for potassium, renin concentration, aldosterone and catecholamines. Blood pressure (BP) and heart rate (HR) were measured. The results demonstrate no greater increase in potassium over placebo with single or multiple dose clonidine or methyldopa. Following the initial dose of propranolol, 80 mg., there was a statistically greater rise in potassium over that seen with placebo but not observed with multiple dose. This may be related to the low multiple dose regimen. There were minor but significant changes in norepinephrine, renin and systolic pressure with multiple dose clonidine and methyldopa and in renin, heart rate and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses, to exercise with methyldopa and propranolol are more biochemically altered than functionally impaired, yet the latter is related to dose and the underlying age and state of health of the group being studied.

Aldosterone↗