Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.
Cancer 1989 May 15
PMID:Subacute brain atrophy after radiation therapy for malignant brain tumor. 270 69

LY 195448 is a phenethanolamine that has shown anti-tumour activity in a range of murine tumour models, although its mechanism of action is unknown. Pre-clinical studies have indicated the absence of "standard" side effects such as myelosuppression and gastrointestinal toxicity. The present phase I trial was carried out in nine patients at doses ranging up to 133 mg/m2. The major toxicities up to that dose were mild, reversible hypotension, tachycardia and tremor. No haematological or biochemical toxicity was observed. Murine pharmacokinetics were assessed at a dose level that was effective in experimental tumours and compared with human pharmacokinetic parameters derived from this study. The results indicated the clinical possibility of reaching peak drug levels associated with experimental activity. However, no responses were seen at the doses used. This study was terminated prior to its completion due to an unexplained loss of activity against murine tumours since September 1987. No significant loss of the in vitro anti-mitotic activity originally reported by Boder et al. [3] was observed. Possible reasons for the apparent loss of in vivo activity have been intensively investigated, but no cause has been determined. Therefore, clinical trials with LY 195448 have been discontinued.
Cancer Chemother Pharmacol 1989
PMID:Phase I clinical and pharmacokinetic study of LY 195448. 275 4

Interleukin (IL)-2 administration leads to respiratory dysfunction due to increased vascular permeability. This study examines the role of thromboxane (Tx)A2 in IL-2 induced lung injury in sheep with chronic lung lymph fistulae. This preparation enables evaluation of permeability prior to the development of gross edema. IL-2, 10(5) units/kg (n = 6), or its excipient control (n = 5) was given as an i.v. bolus over 2 min. After 2 h of IL-2 administration, plasma TxB2 increased from 168 to 388 pg/ml (P less than 0.05) and lung lymph TxB2 from 235 to 694 pg/ml (P less than 0.05). Mean pulmonary artery pressure (MPAP) rose from 13 to 29 mm of Hg (P less than 0.05) at 30 min and remained elevated for 4 h while the pulmonary artery wedge pressure was unchanged at 4 mm of Hg. Arterial oxygen tension (PaO2) fell from 88 to 77 mm of Hg (P less than 0.05). Lung lymph flow (QL) rose from 2.2 to 3.8 ml/30 min (P less than 0.05) at 1 h and to 6.4 ml/30 min at 3 h. This rise coincided with an increase in the lymph/plasma (L/P) protein ratio from 0.67 to 0.77 (P less than 0.05). In contrast, the non-IL-2-infused sheep (n = 3) recruitment of the lung vasculature by left atrial balloon inflation led to a rise in QL from 2.4 to 8.2 ml/30 min, whereas the L/P ratio declined from 0.62 to 0.25, suggesting that the protein-rich lymph flow after IL-2 administration reflected increased microvascular permeability. In further proof of an increase in permeability, IL-2 administration into sheep (n = 2) with an inflated left atrial balloon led, after a pressure-independent L/P protein ratio had been achieved, to an increase in L/P protein ratio and decrease in protein reflection coefficient. At 2 h after IL-2, the blood leukocyte count fell from 8156 to 4375/mm3 (P less than 0.05) primarily due to a 73% drop in lymphocytes. The platelet count declined from 292 to 184 x 10(3)/mm3 (P less than 0.05). Body temperature rose from 38.9-40.3 degrees C (P less than 0.05), and shaking chills were common. Pretreatment with the Tx synthetase inhibitor OKY 046 (n = 7) lowered baseline plasma and lymph TxB2 levels to 22 and 52 pg/ml (P less than 0.05) and prevented the IL-2-induced increase in plasma and lung lymph TxB2 (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1989 Jul 01
PMID:Role of thromboxane in interleukin 2-induced lung injury in sheep. 278 52

We administered anti-Leu 2a, a murine monoclonal antibody to the human suppressor-cytotoxic T-cell subset, to 20 patients with advanced cancer to determine the toxicity and its ability to deplete circulating Leu 2(+) lymphocytes. Four doses were tested, 1, 5, 25, and 100 mg, and the infusion rate varied from 2 to 24 h. Administration of anti-Leu 2a produced rapid (within 4 h) depletion of circulating Leu 2(+) lymphocytes, the magnitude and duration of which were dose dependent: the 1-mg dose caused a less than 50% fall in circulating Leu 2(+) lymphocytes, while the higher doses caused 75-98% depletion of those cells in 10 of 17 patients so treated. The duration of depletion of Leu 2(+) cells was 1-2 days after 5 mg of anti-Leu 2a, 3-4 days after 25 mg, and 4-30+ days after 100 mg. In seven patients (3-5, 3-25, and 1-100 mg), there was persistence of variable numbers of circulating mouse Ig-coated Leu 2(+) cells, possibly indicating impaired capacity to clear these cells. Modulation of the Leu 2a antigen after antibody treatment was not observed. Peak serum levels of anti-Leu 2a were (medians): 5-mg dose = 350 ng/ml, 25-mg dose = 5500 ng/ml, and 100-mg dose = 48,000 ng/ml; murine antibody was detectable in the serum for 7-14 days after the 100-mg dose. All patients had increased titers of antimouse antibody following treatment with peak titers on day 14. The most common toxicity was shaking chills. This occurred within 1.5 h of beginning the infusion, lasted for no more than 30 min, and did not require cessation of the treatment. Anti-Leu 2a administration caused a clinically unimportant, but statistically significant fall in hematocrit (mean = -7%) and platelet (mean = -23%) count and a transient (less than 1 day duration) fall in the total lymphocyte count. Thus, infusion of murine monoclonal anti-Leu 2a can cause substantial depletion of the suppressor-cytotoxic T-cell subset with modest toxicity.
Cancer Res 1987 May 15
PMID:Depletion of suppressor-cytotoxic T-lymphocytes by administration of a murine monoclonal antibody. 295 61

Forty-six postmenopausal women with estrogen receptor positive advanced breast cancer were treated with the novel antiestrogen toremifene in this phase II study. The patients had no prior or concurrent hormonal or cytostatic treatment. Sixty milligrams of toremifene was given as a single daily dose for a minimum treatment period of 6 weeks. Eight patients (17%) achieved complete response, 17 (37%) partial response and 12 (26%) showed no change. The median durations of responses were 93, 66 and 24 weeks, respectively. Three patients still continue the treatment in complete response, four patients in partial response. No significant differences in response rates could be seen when related to different estrogen receptor concentrations. The treatment was well tolerated, only two patients had remarkable side-effects; one of the patients interrupted the treatment mainly because of tremor. Our conclusion is that toremifene is an effective, safe and in clinical practice easily applied choice of treatment in estrogen receptor positive advanced breast cancer.
Eur J Cancer Clin Oncol 1988 Apr
PMID:Toremifene, a new antiestrogenic compound, for treatment of advanced breast cancer. Phase II study. 296 65

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.
Cancer Treat Rep 1987 Feb
PMID:Phase II trial of ifosfamide in children with malignant solid tumors. 310 34

The experience that the supplementation of depleted dopamine in the nigro-striatal system of parkinsonian patients with L-dopa improves the clinical triad, akinesia, rigidity and tremor, mainly applies to long-term treatment in the early phase of Parkinson's disease. Complications in motor performance, like on-off response, wearing-off phenomena, peak-dose dyskinesia, biphasic dyskinesia, off-period dystonia and others, after more than 3 to 5 years following the onset of treatment indicate fluctuations in the dopaminergic feedback control system. It is suggested that these complications are due to progressive presynaptic degeneration and late changes in postsynaptic receptor amplification. However, as fluctuations are not imperative in all patients, an important additional aspect seems to be the topography of denervation, which involves different portions of the striatum to varying degrees. Location and extent of denervation are criteria which appear to have predictive value for the malignancy of the disease, the therapeutic response of drugs and complications in long-term treatment.
 ...
PMID:Factors contributing to fluctuations of the dopaminergic nigro-striatal feedback system in Parkinson's disease. 316 34

A phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050) given by intravenous infusion over 30 min or by intratumoral administration was performed in 53 patients with various types of malignant tumors. The dose of rHu-TNF was started with 0.1 x 10(6) U/body for both intravenous infusion and intratumoral administration and increased to 5 x 10(6) U/body for intravenous infusion and 2 x 10(6) U/body for intratumoral administration. The side effects of rHu-TNF given by intravenous infusion included fever, shaking chills, hypotension, general malaise, nausea, and vomiting, and clinical laboratory tests showed elevations of GOT, GPT, and ALP, etc. Among these, only hypotension was dose-related and was considered to be a dose-limiting factor. The maximum tolerable dose estimated was 1 x 10(6) U/body. The plasma concentration of rHu-TNF after completion of a 30-min infusion was dose-dependent, and the elimination half-life was 0.5-2.4 hr. When the rHu-TNF was administered intratumorally, the frequency of side effects was low compared with intravenous infusion.
Cancer Detect Prev 1988
PMID:Phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050). 318 Jan 46

Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side-effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group.
 ...
PMID:A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. 333 19

Twenty-three evaluable patients with advanced breast cancer were treated with MPA, 1,400 mg/m2 daily PO for the first 6 months, and 500 mg/m2 daily PO thereafter. The median total dose was 191,400 mg in 88 days, with the maximum dose given to date 522,600 mg in 282 days. Most patients tolerated high-dose MPA well. Side-effects were minimal and reversible. The commonest side-effects were tremor or edema. The CR plus PR rate was five of 23 (22%). All responding patients were over 50 years of age and had a good performance status. Hormone receptor status was known in four patients only, so that no correlation between receptor status and response could be drawn. MPA appears to be a useful hormone for use in the management of breast cancer. Optimal dosage remains to be determined.
Cancer Chemother Pharmacol 1983
PMID:A phase II study of high-dose medroxyprogesterone acetate in advanced breast cancer. 622 3


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