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)

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.
Leukemia 1998 Jun
PMID:Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991). 963 13

We report a 48-year-old woman with adult T-cell leukemia who had refractory arthralgia, intense headaches, and fever. Leukemic cell infiltration of the cerebrospinal fluid was detected but no other acute signs were observed. Abnormal lymphocytes with lobulated nuclei were found in the synovial fluid, and a histologic examination revealed proliferation into the synovium. Because combination chemotherapy did not elicit a favorable response, the patient was treated with a pentostatin bolus injection. The articular symptoms disappeared and complete remission was obtained. Six months later, she experienced arthralgia again together with a gradual increase of abnormal lymphocytes in peripheral blood. Sixteen months later, the patient was given pentostatin and achieved a complete remission again. She is still free from relapse without further therapy after 36 months, and her articular symptoms have not returned either. There were no adverse effects due to pentostatin. The patient's serum IL-6 level was elevated, suggesting that IL-6 may play a role in arthropathy.
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PMID:[Effective pentostatin-based treatment of adult T cell leukemia in a patient with severe arthritis]. 975 Apr 55

The use of all-trans retinoic acid (RA) for remission induction markedly increases survival of patients with acute promyelocytic leukemia (APL) compared to patients treated solely with cytotoxic chemotherapy. However, clinical resistance to this agent develops rapidly, which has been associated with a progressive decline in plasma drug concentrations. Previous studies suggested that 9-cis RA, a retinoid receptor 'pan agonist' did not induce its own catabolism to the same extent as all-trans RA. Therefore, we conducted a dose-ranging study of this compound in patients with both relapsed and newly diagnosed APL. We treated 18 patients with morphologically diagnosed APL (13 relapsed, five newly diagnosed). The daily dose of 9-cis RA ranged from 30 to 230 mg/m2/day given as a single oral dose. Four of 12 (33%) relapsed patients (three of whom were previously treated with all-trans RA) and four of five (80%) newly diagnosed patients achieved complete remission. The sole failure in the newly diagnosed group died early from an intracranial hemorrhage. One other patient with t(9;12) translocation had substantial hematologic improvement. The drug was generally well tolerated; headache and dry skin were the most common adverse reactions. Three patients were treated with corticosteroids for signs of incipient 'RA syndrome.' These preliminary data suggest that 9-cis RA is an effective agent for remission induction and deserves further investigation in patients with retinoid-sensitive APL.
Leukemia 1998 Oct
PMID:Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. 976 93

It is well known that Down's syndrome is sometimes associated with leukemia. However, there have been only a few case reports of a relationship between Down's syndrome and brain tumors. We report 2 cases with histological diagnoses of germinoma. The 1st case was a 10-year-old boy with Down's syndrome complaining of seizure and left hemiparesis. Computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed a mass lesion in the right basal ganglia and thalamus. Histological examination indicated two cell pattern germinomas. The 2nd case was a 20-year-old man with Down's syndrome complaining of headache and vomiting. CT scan and MRI showed a pineal region tumor with marked hydrocephalus. Surgical specimens showed typical germinoma. Only 13 cases of brain tumors associated with Down's syndrome have been reported. A higher incidence of germ cell tumors seems to be related to chromosomal abnormalities.
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PMID:Intracranial germinoma associated with Down's syndrome. Report of 2 cases. 987 49

The frequency and severity of neurologic symptoms in children with systemic cancer is unknown. The authors reviewed the records of children with systemic cancer for whom a neurologic consultation was requested between 1993 and 1996. The 157 patients had 161 malignancies and 205 consultations. Leukemia (59) and lymphoma (34) were the most common malignancies. The 68 solid tumors included neuroblastoma (13), Ewing's sarcoma, and rhabdomyosarcoma (10 each). In contrast to adults, in whom back pain and altered mental status are the most common reasons for neurologic consultation, headache (33) and seizures (29) were the most common symptoms in children. Structural lesions were present in 84% of patients with headache and focal deficit and in 14% of patients with isolated headache. Structural disease was identified in 37% of children with seizures. Neurologic signs were caused by complications of cancer therapy in 70 instances and to direct tumor invasion of the nervous system in 60. In 71 consultations, neurologic symptoms could not be attributed to cancer or its treatment. The spectrum of neurologic symptoms in children with cancer differs from adults and requires the consulting neurologist to have a thorough knowledge of childhood cancer and its effects on the nervous system.
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PMID:Neurologic consultations in children with systemic cancer. 1008 40

Mast cells (MC) are multipotent hemopoietic effector cells producing diverse mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase+ MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plasmin-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD117/c-kit+, CD123/IL-3R alpha-, CD11b/C3biR-), biochemical analysis (cellular ratio [ng:ng] of tryptase to histamine >1), and electron microscopy. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 30% diffusely scattered MC, and a complex karyotype. No dense, compact MC infiltrates (mastocytosis) were detectable in bm sections. Despite hyperfibrinolysis and mediator syndrome (flushing, headache), the patient received remission induction polychemotherapy (DAV) followed by two cycles of consolidation with intermediate dose ARA-C (2 x 1 g/m2/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without evidence of recurring MDS. Moreover, in response to chemotherapy, the hyperfibrinolysis and mediator syndrome resolved, and the circulating c-kit+ MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement.
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PMID:Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells. 1033 14

A 7-y-old boy with acute lymphoblastic leukaemia (ALL) received 600 mg of i.v. methotrexate (MTX) over 2 h, followed by triple intrathecal therapy (TIT) with cytosine arabinoside 30 mg, methylprednisolone 10 mg and MTX 300 mg (instead of the prescribed 12 mg). Ninety minutes later the patient developed headache, loss of consciousness and generalized hypertonia. He was transferred to the Intensive Care Unit, intubated and treated with phenobarbital. Three hours after the TIT, the levogyrus form of folinic acid (equivalent to double doses of the racemic product) was started i.v. at a dose of 100 mg every 3 h for 24 h, and every 6 h in the following 24 h. Cerebrospinal fluid was examined and was found normal. The patient subsequently remained in normal neurological status. The favourable outcome in our case suggests that folinic acid rescue may be adequate to prevent sequelae in patients who undergo intrathecal MTX overdoses up to 300 mg.
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PMID:Successful treatment of intrathecal methotrexate overdose with folinic acid rescue: a case report. 1044 41

Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.
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PMID:Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation. 1051 80

A 73-year-old man with acute adult T-cell leukemia (ATL) in remission was re-admitted to our hospital due to drowsiness, headache, and bilateral knee joint pain on May 17, 1998. On admission, examinations revealed decreased serum sodium concentration (112 mEq/l), low plasma osmotic pressure (259 mOsm/l), and elevated antidiuretic hormone(5.6 pg/ml). Cerebrospinal fluid examination showed an increased number of abnormal flower-like lymphocyte (951/microliter). Brain computed tomography and magnetic resonance imaging found no abnormality in the hypothalamus or pituitary gland. These findings yielded a diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Though ATL patients typically exhibit a variety of clinical symptoms, SIADH is rarely one of the complications. Further investigation showed that IL-1 beta and IL-6 concentrations were increased in spinal fluid but not in serum. Recently, it has been reported that exogeneous IL-6 is an inducer of ADH secretion, and that primary ATL cells and HTLV-I infected cell lines can produce IL-6. In this case, we speculated that IL-6 produced by ATL cells that infiltrated a cerebral lesion may have played an important role in the development of SIADH.
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PMID:[Syndrome of inappropriate antidiuretic hormone secretion associated with meningeal infiltration of tumor cells and elevated interleukin-1 beta and interleukin-6 in cerebrospinal fluid of a patient with adult T-cell leukemia]. 1072 44

Allogeneic bone marrow transplantation is frequently associated with neurological complications, particularly intracerebral bleeds and infections. Cerebral venous sinus thrombosis has only rarely been reported following allogeneic transplants. We report three cases of cortical venous thrombosis following allografting for acute lymphoblastic leukaemia. Two patients received marrow from HLA-identical siblings and one from an unrelated donor. Two of the patients presented with grand mal seizures and one presented with a headache. No neurological abnormalities were found upon clinical examination and lumbar puncture was normal in all three cases. In two of the patients computed tomography (CT) of the brain was normal and in the third showed non-specific abnormalities. Magnetic resonance imaging (MRI) with MR angiography (MRA) demonstrated cerebral venous sinus thrombosis in all three patients. In conclusion, cerebral venous sinus thrombosis should be considered in the differential diagnosis when neurological symptoms occur following allogeneic bone marrow transplantation. We therefore advocate the use of MRA for unexplained neurological symptoms post-allograft since without it cerebral venous sinus thrombosis may easily be missed.
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PMID:MR angiographic diagnosis of cerebral venous sinus thrombosis following allogeneic bone marrow transplantation. 1074 67


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