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Biomedical subjects

T Siegal

Publications and source records attributed to T Siegal.

At least 55 records · Page 3Linked to original sources
PubMed1989

Intracranial meningiomas after high-dose irradiation.

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with "spontaneous" meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.

Adolescent↗
PubMed1989

Muscle cramps in cancer patients.

We prospectively evaluated 50 cancer patients with new complaints of muscle cramps. Neurologic examination and laboratory evaluation identified disorders related to neural, muscular, or biochemical abnormalities in 41 (82%) patients. Abnormalities were confined mainly to the peripheral nervous system and included peripheral neuropathy in 22 patients, root and plexus pathology in 17 patients (six with leptomeningeal metastases), and polymyositis in two patients. Hypomagnesemia accounted for muscle cramps in only one patient. Identifiable causes of muscle cramps were related mostly either to metastatic or nonmetastatic complications of the underlying malignancy (14 patients) or to complications of its treatment (21 patients). Cramps, or rather complaints of cramps, were the presenting symptom of recognizable and previously unsuspected neurologic dysfunction in 64% (27 of 42) of the identified causes. Therefore, we conclude that muscle cramps in cancer patients may not be a benign complaint and that they usually mark the presence of an identifiable neurologic disorder. The use of simple clinical and laboratory measures is rewarding in the evaluation of these patients and leads to diagnosis in the majority of them.

Adolescent↗
PubMed1989

Current considerations in the management of neoplastic spinal cord compression.

Nearly 20% of patients with neoplastic involvement of the vertebral column develop spinal cord compression, and in 8% this is the initial manifestation of cancer. Important determinants of functional prognosis are: 1) tumor biology, 2) pretreatment neurologic status, and 3) tumor location within the spinal canal and the therapy employed. Future efforts should be invested in manipulation of the last two determinants. Delay in neurologic deterioration may be achieved by pharmacologic manipulation of the deleterious pathophysiologic processes operating in the compressed spinal cord, as recently demonstrated in experimental animal models. Use of modern neuro-imaging techniques (metrizamide myelography combined with computed tomography, and/or magnetic resonance imaging) will accurately define tumor extent and location. Radiotherapy is indicated in highly or moderately radiosensitive tumors. Surgery is reserved for the following situations: diagnosis in doubt, previous radiation exposure, radioresistant tumors, neurologic deterioration during irradiation, and the presence of spinal instability or bone compression of the neural structures. The location of the compressing tumor will dictate the surgical approach--a vertebral body resection in an anterior or anterolateral tumor and a laminectomy in a posterior or posterolateral deposit. Modern instrumentation techniques for spinal column stabilization or vertebral body replacement will allow immediate painless ambulation and a better quality of life for these patients.

Humans↗
PubMed1988

Early and delayed neurotoxicity of mitoxantrone and doxorubicin following subarachnoid injection.

Doxorubicin (DXR) and Mitoxantrone (MXN) were administered into the subarachnoid space of mice or the ventricular system of rats. The maximal non-toxic systemic single dose (zero mortality = LDo) of DXR or MXN was used as reference for planning drug doses for CSF administration. LDo in mice were: 8 mg/kg DXR and 6 mg/kg MXN; in rats: 6 mg/kg DXR and 4.5 mg/kg MXN. Signs of neurotoxicity were remarkably similar in DXR or MXN treatment animals and included: head tremor, atactic-dystonic posture and circling behavior. The toxicity was dose dependent. Doses of greater than or equal to 10% the LDo caused early appearance of clinical signs: a dose of 10% LDo caused neurotoxicity in 90% of DXR treated mice and in only 15% of MXN-treated animals. Treatment with 25% LDo MXN caused neurotoxicity in 30% of treated animals. Doses of less than or equal to 5% the LDo caused a delayed onset of DXR neurotoxicity in one third of treated mice (after 60-90 days). In rats, neurotoxicity was of an early onset and augmented severity following doses of greater than or equal to 5% LDo. Abnormal histopathological findings were detected only in symptomatic animals with early toxicity and were usually restricted to superficial cortical layers in mice or the basal surface of the brainstem in rats. Brains of mice with delayed toxicity were unremarkable. The levels of monoamine neurotransmitters and their metabolites (DA, DOPAC, HVA, NE, 5HT) in the striatum, cortex and cerebellum of mice with early and delayed DXR neurotoxicity did not differ from normal brains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparison of soluble dexamethasone sodium phosphate with free dexamethasone and indomethacin in treatment of experimental neoplastic spinal cord compression.

In an experimental rat model of neoplastic spinal cord compression, the in vivo effect of steroidal and nonsteroidal anti-inflammatory agents on the water content, prostaglandin E2 (PGE2) production, and specific gravity of the compressed cord segments were assessed, as well as the effect on the course of the disease. Paraplegic animals presented a consistent increase in the water content, PGE2 synthesis, and specific gravity in the compressed cord segments. The effect of treatment given on onset of paraplegia with either dexamethasone sodium phosphate (Dex-p; 10 mg/kg twice daily), or free dexamethasone (F-dex; 8.25 mg/kg twice daily) or indomethacin (10 mg/kg twice daily), was evaluated after 30 hours of therapy. Both F-dex and indomethacin eliminated spinal cord edema but varied in the rate of inhibitory effect on PGE2 production (dexamethasone less than indomethacin). Dexamethasone sodium phosphate failed to reduce spinal cord edema and PGE2 synthesis, but specific gravity changes were corrected by each of the administered agents. Evaluation of the effect of treatment on the course of the disease required dose reduction by 50% for Dex-p and F-dex, and to 25% for indomethacin, to avoid lethal toxicity. Treatment was started on appearance of the first sign of neurologic dysfunction (Grade 1) and continued to paraplegia (Grade 5). In the saline-treated rats, the mean time interval between Grades 1 and 5 was 2.7 +/- 0.3 days. Free dexamethasone, Dex-p, and indomethacin significantly prolonged this interval by 57%, 54%, and 48% respectively (P less than 0.005). The three agents differed in their ability to control the increases in water content and in PGE2 production, but proved almost equally effective in the prompt control of the specific gravity changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Antibiotic therapy for infected Ommaya reservoir systems.

The major complication of prolonged use of a permanently implanted Ommaya reservoir system is bacterial infection, encountered in 3 to 15% of patients. The best therapeutic approach to ventriculitis and meningitis occurring in the presence of this device is still a subject of debate. We reviewed our experience in 66 consecutive patients receiving intraventricular therapy via the Ommaya reservoir for leptomeningeal metastases or for subacute sclerosing panencephalitis. Eight episodes of infection occurred during the period of treatment, and all of them responded to systemic antibiotics with or without intraventricular treatment. Removal of the Ommaya reservoir was avoided, and therapy via the device for the underlying disease was resumed as soon as the infection was controlled. No relapse of infection occurred during a minimal follow-up of 40 days. On the basis of our experience and review of the literature, we challenge the concept that the Ommaya device, as a foreign body, must be removed to treat such infections successfully.

Adolescent↗
PubMed1988

Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 1. Effect on water content and specific gravity.

Water content and specific gravity were measured in the cervical, high thoracic, thoracic, and lumbar segments in an experimental model of neoplastic epidural spinal cord compression in rats harboring a thoracolumbar tumor. Increased content of water was observed only in the compressed lumbar cord segments of paralyzed rats (P less than 0.04). A progressive increase in specific gravity values of the compressed segments accompanied the increasing severity of neurological dysfunction (P less than 0.003 in paraplegic rats). Electron microscopy of the compressed cord revealed enlarged interstitial spaces, myelin breakdown, and extravasated blood cellular elements. Treatment with dexamethasone (10 mg/kg q 12 hr x 3) failed to reduce the increased content of water, but corrected specific gravity changes. Treatment with indomethacin (10 mg/kg q 12 hr x 3) reduced both elevated water content and specific gravity values back to normal levels. In untreated animals, the interval between the first neurological sign (limp tail) and paraplegia was 2.8 +/- 0.34 days (mean +/- SE). Treatment with dexamethasone lengthened this period by 28.6% (P less than 0.05); treatment with indomethacin lengthened it by 66.4% (P less than 0.005). We conclude that, because the specific gravity measurements in this model reflect complex pathophysiological processes, their translation into water content values is not advisable. Pharmacological intervention with indomethacin compares favorably with dexamethasone in reduction of spinal cord edema and in delaying the onset of paraplegia.

Animals↗
PubMed1988

Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 2. Effect on edema and prostaglandin synthesis.

Edema formation and prostanoid production (prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in a model of neoplastic epidural cord compression (NSCC) in rats harboring a thoracolumbar tumor. Tumor-free and tumor-bearing animals were randomized for three treatments at 12-hour intervals with saline, dexamethasone (10 mg/kg i.p.), or indomethacin (10 mg/kg i.p.). Increase in water content was observed only in the compressed lumbar cord segments of paralyzed rats; the cervical and thoracic segments did not differ from controls. The rate of release of prostaglandins was evenly distributed along the spinal segments in tumor-free rats. In tumor-bearing rats, a consistent significant increase in PGE2 production was found in the compressed lumbar segment in the presence of neurological dysfunction: early (limp tail), P less than 0.05; paraplegia, P less than 0.001. A significantly elevated PGE2 synthesis preceded the increase in water content by 2 to 3 days. A 2-fold increase in TXB2 was detected in only one of three experiments, and synthesis of 6-keto-PGF1 alpha was elevated to 4 times the normal value (P less than 0.005) in two of three experiments. Dexamethasone failed to inhibit prostaglandin synthesis in the spinal cord of normal controls or paralyzed rats, whereas in nonneural tissues (liver, uterus) it reduced synthesis of the three metabolites by at least 50%, thus demonstrating a differential effect on central nervous system (CNS) vs. non-CNS tissues. Dexamethasone also failed to reduce the increased water content of the compressed segments.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Alteration of blood-brain-CSF barrier in experimental meningeal carcinomatosis. A morphologic and adriamycin-penetration study.

An experimental model of meningeal carcinomatosis has been produced by subarachnoid inoculation of B16 melanoma cells into C57BL mice. Injection of 10(3) viable cells was sufficient to cause 100% tumor incidence and death within a median survival time of 17 days. The tumor infiltrated diffusely the meninges of the brain and spinal cord and filled the ventricular system. Electron microscopic study of the leptomeningeal tumor revealed newly formed microvessels with fenestrated endothelium. The integrity of the blood-brain barrier was studied by the extravasation of the Evans blue and the Horseradish peroxidase tracers. Barrier disruption became evident from the seventh day on, using Evans blue. Electron microscopy study showed peroxidase activity in the luminal and abluminal sides of the meningeal microvessels, and within the tight junctions. Similar findings were noted in cortical capillaries adjacent to the meningeal tumor. Brain concentrations of Adriamycin (ADR) following administration of an intravenous dose of either 10 mg/kg or 50 mg/kg were measured on days 0 to 14 after tumor inoculation. A significant increase in mean +/- SEM content of whole brain ADR was observed only with the 50 mg/kg dose in days 7 to 14 (0.69 +/- 0.02 micrograms/g wet tissue weight) as compared to tumor-free controls (0.43 +/- 0.01, p less than 0.05). Our study suggests that barrier alteration in meningeal carcinomatosis allows extravasation of tracer solutes. Still, in order to achieve a significant increase in a water soluble drug penetration through the disrupted barrier, a high-dose drug regimen is required.

Animals↗
PubMed1987

CSF myelin basic protein levels in leptomeningeal metastases. Relationship to disease activity.

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Adolescent↗
PubMed1987

Experimental neoplastic spinal cord compression: evoked potentials, edema, prostaglandins, and light and electron microscopy.

Spinal cord compression was induced in Fischer rats by percutaneous inoculation of 10(6) cells of malignant fibrous histiocytoma anterior to the T13 vertebral body. Paraplegia and incontinence occurred in all animals after 14-27 days (median, 23 +/- 3.0 days). Autonomic dysfunction and a measurable increase in tumor volume were documented with the use of computer tomography. The tumor penetrated the vertebral bone, invaded the epidural space, and gradually compressed the lumbar spinal segments. Electron-microscopic examination revealed dilated intermyelin spaces containing exuded homogenous material and extravasated leukocytes and erythrocytes. Myelin breakdown was accompanied by the presence of lipid-laden macrophages. Sequential recording of somatosensory evoked potentials (SEP) revealed a progressive increase in the latency of the cervical responses, which preceded the onset of clinical signs. In the presence of paraplegia, spinal cord conductivity was abolished. The levels of the prostaglandins TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in the compressed and remote spinal cord segments during the presymptomatic and symptomatic periods. Only PGE2 was significantly elevated (P less than 0.001) in the paraplegic rats, all along the spinal cord segments. A significant increase in water content was measured in the compressed lumbar segments in the presymptomatic period, and when paralysis set in it was increased in the adjacent low thoracic area as well. Tissue specific gravity was significantly increased only in paraplegic rats in the compressed (P less than 0.01) and the adjacent low thoracic areas (P less than 0.05) but no significant change occurred during the presymptomatic period. Multiple mechanisms play a role in the pathogenesis of neurologic symptoms in neoplastic spinal cord compression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Selective route of doxorubicin administration improves outcome in experimental malignant epidural cord compression.

Epidural spinal cord compression was produced in adult Fischer rats by injection of 10(6) viable cells of malignant fibrous histiocytoma anterior to the T-13 vertebral body. Using a tracer dye, it was demonstrated that a portion of the inoculum was always present in the anterior epidural space at the time of inoculation. Paraplegia and incontinence occurred consistently on Days 14 to 27 (median, 23 +/- 3.0). By sequential computed tomographic scans, the growth of the paravertebral tumor was documented and its volume was calculated. A single dose of cisplatin (i.p., 6 mg/kg) or doxorubicin (DXR, i.v. jugular, 6 mg/kg) was administered on Day 1. On Day 18, tumor volume was significantly reduced by DXR (P less than 0.001) and cisplatin (P less than 0.01), but paraplegia continued to occur as in the untreated rats. Comparison of treatment outcome with DXR administered via the jugular vs. the tail vein revealed that both were equally effective in retarding the growth of the paravertebral tumor, and both caused a similar transient leukopenia. However, only the tail DXR brought about a significant delay in the onset of paraplegia (P less than 0.004) and significantly increased the survival (P less than 0.001). It is suggested that the lack of efficacy of systemic chemotherapy for tumors located in the epidural space is probably related to inadequate drug exposure. The improved outcome with tail DXR infusion may be explained by the regional spinal venous perfusion, which allows an increase in the local drug concentration during its first passage through the epidural venous plexus.

Animals↗
PubMed1985

Leptomeningeal metastases: reduction in regional cerebral blood flow and cognitive impairment.

Twenty-six patients with recently diagnosed leptomeningeal metastases underwent multiple diagnostic procedures in order to assess possible cerebral parenchymal involvement. Pretreatment studies included detailed neurological examination, computed tomographic scan, electroencephalogram, neuropsychological assessment, psychiatric evaluation, and measurement of regional cerebral blood flow (rCBF) using the xenon 133 inhalation technique. At diagnosis 50% of the patients had symptoms and signs of cerebral dysfunction. Computed tomographic scanning and electroencephalography detected abnormalities in 42% and 58%, respectively. Scoring was abnormally low on at least three neuropsychological tests in 93% of the patients. The mean rCBF was reduced in 88% of patients by 16.1 +/- 2.5% (mean +/- SEM; range, 8 to 45%) compared with age-matched controls (p less than 0.001). rCBF was reduced and cognition was impaired in patients with or without overt cerebral manifestations. Neuropsychological testing and rCBF measurement may be helpful in early detection of cerebral dysfunction in patients with leptomeningeal metastases.

Adolescent↗
PubMed1985

Leptomeningeal metastases: peripheral nerve and root involvement--clinical and electrophysiological study.

Twenty-five patients with recently diagnosed leptomeningeal metastases underwent a prospective clinical and electro-physiological study to assess the mode and extent of peripheral nerve and spinal root involvement. Motor conduction velocities and F wave latencies in the legs were found frequently to be disturbed compared with normal subjects and a control group of cancer patients. F wave changes were the most sensitive indicator of root involvement. Electrophysiological abnormalities were detected in 20 patients, compared with 15 who had abnormal clinical signs suggesting peripheral nerve dysfunction. Electrophysiological studies can be useful in the evaluation of patients with suspected leptomeningeal metastases, and repeated recording of F wave latencies may serve to indicate root recovery in a clinically stable patient.

Adult↗
PubMed1985

Spontaneous intracranial hemorrhage in a patient with ovarian carcinoma.

A patient with an advanced adenocarcinoma of the ovary developed spontaneous central nervous system (CNS) bleeding as initial evidence of brain involvement by a tumor. The rarity of this phenomenon in patients with ovarian tumors is emphasized and the incidence and course of brain metastases in ovarian cancer are reviewed. Similar to previous reports, our patient had extra abdominal systemic disease at the time CNS involvement was diagnosed. Although good short-term results were achieved with whole-brain irradiation, the prognosis for these patients remains dismal. The incidence of brain metastases may increase in patients with advanced ovarian malignancies given the possibility of achieving long-term survival in a significant percentage of women with widespread disease being currently treated with intensive systemic chemotherapy.

Brain Neoplasms↗
PubMed1985

Surgical decompression of anterior and posterior malignant epidural tumors compressing the spinal cord: a prospective study.

Of 167 episodes of spinal epidural neoplastic compression, 86 were treated by operation. The surgical approach was prospectively selected according to the location of the tumor in the spinal canal. Decompression was achieved by 61 vertebral body resections (VBRs) and by 25 laminectomies. The indications for operation were: neurological relapse after previous radiotherapy, the need to make a tissue diagnosis, a radioresistant tumor, and neurological deterioration during radiotherapy. Before VBR, 28% (17 of 61) were still able to walk, 51% (31 of 61) were parAparetic, and 21% (13 of 61) were paraplegic. Bowel and bladder dysfunction was present in 49% (30 of 61). After VBR, the outcome of only 57 procedures was available for evaluation because of the postoperative death of 4 patients. Eighty per cent (46 of 57) were able to walk, 18% (10 of 57) were paraparetic, and 2% (1 of 57) were paraplegic. Ninety-three per cent had normal sphincter control. Before laminectomy, 8% (2 of 25) were ambulatory, 84% (21 of 25) were paraparetic, and 8% (2 of 25) were paraplegic. Bowel and bladder dysfunction was present in 76% (19 of 25). After laminectomy, only 23 procedures were evaluated because of the postoperative death of 2 patients. Thirty-nine per cent (9 of 23) were ambulatory, 35% (8 of 23) were paraparetic, and 26% (6 of 23) were paraplegic. Fifty-seven per cent regained normal sphincter control. The operative mortality was 7% (4 of 61) in VBR and 8% (2 of 25) in laminectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Vertebral body resection for epidural compression by malignant tumors. Results of forty-seven consecutive operative procedures.

We are presenting our experience with vertebral body resection in forty-seven operative procedures in forty patients with a malignant epidural tumor. The indication for surgery was neural relapse after previous radiotherapy in eighteen procedures, the need for a tissue diagnosis in sixteen, a radioresistant tumor in seven, neural deterioration while receiving radiotherapy in five, and a pathological fracture-dislocation in one. In thirty-three procedures (70 per cent) the level of compression was in the thoracic spine. Replacement of the resected vertebral bodies was achieved by anterior instrumentation and the use of methylmethacrylate in twenty-one procedures (45 per cent), while bone-grafting, cement, and instrumentation in various combinations were used in the remainder. Before surgery all of the patients had some neural deficit. The patient was still able to walk prior to twelve (26 per cent) of the procedures, was paraparetic prior to twenty-three (49 per cent), and was paraplegic prior to twelve (26 per cent). Bowel and bladder dysfunction was present before twenty-five (53 per cent). The outcome of only forty-four procedures could be evaluated because three patients died postoperatively. The patient was able to walk following thirty-five (80 per cent) of the procedures, was paraparetic after eight (18 per cent), and was still paraplegic after one. The patient regained normal sphincter control after forty-one (93 per cent) of the procedures. Three (6 per cent) of the procedures were followed by the death of the patient, and complications occurred after five (11 per cent) of the procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Transplantation↗