Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For over 30 years, oral 6-mercaptopurine (6-MP) has been a mainstay of systemic maintenance therapy for acute lymphoblastic leukemia. Despite its efficacy as an antileukemic agent, 6-MP has not been previously administered by the intrathecal (IT) route. In anticipation of a clinical trial of IT 6-MP, preclinical cytotoxicity and pharmacology studies were performed to define a safe, effective dose. The optimal concentration (greater than 1 microM) and duration of exposure (greater than 12 h) to 6-MP required for cytotoxicity were determined in vitro using human leukemia cell lines. The dose required to achieve the desired cerebrospinal fluid concentrations in humans was derived from pharmacokinetic parameters determined in rhesus monkeys. A phase I/II study was then performed in pediatric patients with refractory meningeal leukemia. Nine patients (aged 3.5 to 16 years) with chronic meningeal leukemia (2 to 6 central nervous system relapses) were entered onto the study. All had previously failed, at a minimum, IT methotrexate, IT cytarabine, and cranial (+/- spinal) radiation. A 10-mg IT dose of 6-MP (calculated to produce cytotoxic cerebrospinal fluid levels for 12 h) was administered twice weekly for 4 weeks. There were four complete responses and three partial responses. The duration of complete responses ranged from 7 to 22 weeks. Observed toxicities were not dose limiting and included mild headache (three patients) and minimal nausea (two patients). Pharmacokinetic studies performed in patients confirmed that cerebrospinal fluid concentrations of 6-MP were greater than 1 microM for 12 h. These results indicate that the IT administration of 6-MP is feasible, is not associated with significant toxicity, and has definite activity in patients with refractory meningeal leukemia.
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PMID:Intrathecal 6-mercaptopurine: preclinical pharmacology, phase I/II trial, and pharmacokinetic study. 193 71

We describe a patient with acute myelomonocytic leukemia who demonstrated leukemic cell infiltration to scratched wounds and scars from trauma. A 65-year-old Japanese woman developed low grade fever, headache and exanthema. Hematology testing disclosed leukocytosis of 95,600/mm3 with 65% monocytes and 9% blast cells. Infiltrated erythema and nodules were disseminated over most of her body. Moreover, linear scratched wounds and traumatic scars were indurated. Skin biopsy showed dense atypical mononuclear cell infiltration with monocytic characteristics. We discuss the possible reasons for the infiltration of leukemia cells into the wounds and scars from trauma.
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PMID:Leukemia cutis in acute myelomonocytic leukemia: infiltration to minor traumas and scars. 193 54

Immature hematopoietic elements have been identified in eight Wright-stained cytocentrifuge preparations of lumbar puncture-derived cerebrospinal fluid (CSF) from infants and children. These immature hematopoietic elements probably represent contamination from vertebral bone marrow. Recognition that the nucleated cells in the CSF are a contaminant and not indicative of infection or leukemia is important to the immediate care of the child. The only adverse clinical sequela of this contamination identified has been a transient headache. Bone marrow contaminants are one of several abnormalities of CSF found in childhood diseases and may or may not elevate the CSF white blood cell count. This supports the need for pathologist review of all CSF cytocentrifuge preparations from children.
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PMID:Hematopoietic elements in cerebrospinal fluid in children. 201 79

A pilot study was performed to investigate the toxicity, pharmacokinetics and therapeutic effect of intrathecally administered radiolabelled monoclonal antibody (MAb) in patients with meningeal acute lymphoblastic leukaemia (ALL). Six children aged 3-16, in second or subsequent central nervous system (CNS) relapse of ALL, received between 629 and 1480 MBq of 131Iodine conjugated to either MAb HD37 (CD19, n = 2) or WCMH15.14 (CD10, n = 4). Conjugate was administered as a single injection either via an Ommaya reservoir (n = 4) or by lumbar puncture (n = 2). Acute toxicity was manifest by headache (n = 4), nausea and vomiting (n = 4) and pyrexia (n = 2). All acute symptoms resolved within 72 h. Transient myelosuppression occurred in three patients. Pharmacokinetic studies included investigation of whole body, blood and CSF clearance of isotope. 131I was seen to clear from the CSF by biexponential kinetics. Five patients responded to therapy. In four, the CSF became clear of blast cells at both 2 and 4 weeks following antibody injection, but evidence of relapse was seen at 6 weeks. The fifth patient, with blast cells present on a cytospin preparation, responded to therapy over an 8-week period but relapsed at 12 weeks. This study demonstrates the potential of targeted radiotherapy in CNS ALL, but further studies are necessary to increase the length of remission.
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PMID:A pilot study of monoclonal antibody targeted radiotherapy in the treatment of central nervous system leukaemia in children. 202 71

We reviewed 63 cases of cytologically confirmed leptomeningeal metastases (LM). 31 (49%) had solid tumors 17 (27%) had leukemia and 15 (24%) had lymphoma. The most common presenting symptom was pain (76%) with radicular discomfort (58%), headache (32%), neck or back pain (17%). The predominant neurological signs were mental status abnormalities (49%), weakness (47%), seizures (14%). The mode of presentation varied with tumor type. Patients with leukemia (18%) and lymphoma (13%) tended to present frequently with LM without systemic involvement, or during periods of apparent remission (leukemia 35%, lymphoma 27%), while patients with solid tumors had established systemic metastases (90%) at time of presentation. Laboratory studies did not vary among the groups. 71% had positive cytology on the first lumbar puncture (LP) and only 8% required more than 2 LPs. The cell count was a poor predictor of positive cytology as 29% of LP's with positive cytology and 36% of all LP's had less than 4 cells/mm. We conclude that 1) LM presents with pain and seizures more frequently than has been previously recognized; 2) LM is frequently the mode of presentation in patients with leukemia and lymphoma and; 3) cytology is positive frequently in CSF specimens with normal cell counts and chemistries.
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PMID:Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. 208 37

Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23-36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity (greater than or equal to grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 microM) and prolonged exposure to plasma levels exceeding 50 microM may result in a higher incidence of serious non-hematologic toxicity.
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PMID:Clinical toxicity associated with tiazofurin. 220 Jul 59

Rhinocerebral mucormycosis is a rare and fatal deep fungus infection occurring in debilitated patients. Its reports have been recently increased because of the increase of such conditions as uncontrolled diabetics, leukemia, and cancer. A 60-year-old male suffering from continuous headache and fever was diagnosed as meningitis, and repeated culture of cerebrospinal fluid was negative. Antibiotic therapy was ineffective. CT scan revealed brain abscess in the right frontal lobe and bone defect over the right posterior ethmoidal sinuses. Both maxillary and ethmoidal sinuses were operated on 38 years ago. The patient was suspected to have rhinologic brain abscess. We intended to remove the source of infection in the right posterior ethmoidal sinuses beneath the base of the skull and to repair the defect of dura mater. The operation was tried on the 6th hospital day. There was a cyst in the posterior ethmoidal sinuses and an intact denuded dura mater over the cyst. The causative organism was not detected by smear test, bacteriological and fungal culture. He relapsed into lethargy, and died on the 21st hospital day due to the vast cerebral infarction. Autopsy revealed rhinocerebral mucormycosis. The literature on this disease was also reviewed and discussed.
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PMID:[Phinocerebral mucormycosis--report of a case]. 229 52

A 13-year-old girl with a ten-year history of lymphoblastic leukemia and several central nervous system (CNS) relapses developed a bone marrow relapse and accelerated CNS leukemia. Following treatment with CNS radiation and intravenous chemotherapy, she developed fever, pancytopenia, headache, and vomiting. Her neurological function deteriorated and she died on the 20th hospital day. Multiple CSF examinations failed to disclose either leukemic cells or organisms. Blood cultures obtained from a Broviac catheter yielded Micrococcus species. Postmortem examination showed meningoependymitis with intracellular coccal organisms. The pathology of this infection resembles intracranial Whipple's disease. Intracranial intracellular bacterial infection should be excluded in the infectious complications in the immunocompromised host.
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PMID:An unusual central nervous system infection in a young immunocompromised host. 242 54

A 66-year-old woman was admitted to the Medical College Hospital of Oita on February 23, 1988, because of headache and fever. Chest X-P and chest CT findings showed a coin lesion in r-S4. Cryptococcus neoformans was isolated from the CSF. Abnormal lymphocytes with lobulated nuclei were found in 0-5% of peripheral leukocytes. The ATLA-antibody was positive and bone marrow smear showed normal myelogram. According to these data, we diagnosed the patient as smouldering adult T-cell leukemia accompanied with pulmonary cryptococcosis and cryptococcal meningitis. C. neoformans disappeared from the CSF and cryptococcal antigen was not detectable after Amphotericin B and Flucytosine treatment. On April 1, the patient complained of a dry cough, high fever and dyspnea. A chest X-ray showed bilateral patchy infiltrations. By the methenamine silver staining, cysts of Pneumocystis carinii were found in the specimens of transbronchial lung biopsy and bronchoalveolar lavage fluid. The abnormal shadow on chest X-ray disappeared after TMP-SMX and aerosolised pentamidine treatment.
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PMID:[A case of adult T-cell leukemia with pulmonary cryptococcosis, cryptococcal meningitis and Pneumocystis carinii pneumonia]. 250 95

A case of malignant astrocytoma following radiotherapy for pituitary adenoma is presented in detail with a review of the literature. A 38 year-old housewife had developed a growth-hormone secreting pituitary adenoma, and received a total of 50 Gy at the pituitary region. Four years and six months later, she began suffering headache and vomiting. Computed tomography showed an extensive low density with ring enhancement in the right temporal region, corresponding to the previously irradiated field. A right frontotemporoparietal craniotomy was carried out, and a soft and reddish tumor was partially removed. The histological diagnosis was that of malignant astrocytoma. The patient was submitted to postoperative radiochemotherapy, receiving a total of 60 Gy, nimustine hydrochloride (ACNU), and tegafur (FT). Subsequently, after three months of clinical relief, she developed tumor regrowth, and died four months later. The present case fulfills the criteria for radiation-induced tumor established by Cahan et al.: A tumor location within irradiated area, no evidence of tumor prior to radiotherapy, a long latency period between radiation and tumor occurrence, and histological verification of the tumor. Thirty-nine cases of radiation-induced gliomas including the present case have been reported in the literature. It is noteworthy that the majority occur in the younger age bracket. Male preponderance is noted as it is in primary cerebral gliomas. The primary lesions for radiation frequently include leukemia and lymphoma. Craniopharyngioma, pituitary adenoma, and medulloblastoma etc are also included.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Malignant astrocytoma following radiotherapy in pituitary adenoma: case report]. 268 39


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