Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose provided relatively little clinical benefit for patients with refractory leukemia. The dose-limiting toxicity is CNS toxicity with increasingly severe encephalopathy at doses > or = 640 mg/m2. It would be reasonable to investigate further dose escalation of hepsulfam in a divided dose schedule to minimize the peak concentrations which may be related to the encephalopathy. EEG monitoring is recommended for early detection of slowing of alpha rhythm waves. Hematopoietic stem cell support will probably be required at total doses exceeding 800 mg/m2.
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PMID:Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies. 778 Nov 39

Two patients presented with fever and nodular pulmonary infiltrates 9 and 6 months after marrow transplantation for leukemia. The second patient also had painful subcutaneous nodules that subsequently ulcerated. Both had a history of sinusitis and both had recently been treated with corticosteroids. During treatment with antibacterial and antifungal antibiotics, they developed rapid mental deterioration, coma and/or seizures. CT findings included hydrocephalus with extensive cortical and periventricular hypodensities in the first patient, and hydrocephalus with a cerebellar hemorrhage and edema in the second patient. Cerebrospinal fluid had a low glucose and elevated protein levels with few erythrocytes and little or no pleocytosis. Despite therapy with broad-spectrum antibiotics, including coverage for opportunistic infections, both patients died. Autopsy revealed Acanthamoeba species causing necrotizing meningoencephalitis, pneumonitis and adrenalitis in the first patient and causing necrotizing meningoencephalitis and dermatitis in the second patient. While these are the only reported cases of disseminated Acanthamoeba infection in marrow transplant recipients, a review of the literature suggests that this organism may be a new cause of opportunistic infections.
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PMID:Acanthamoeba meningoencephalitis after bone marrow transplantation. 799 73

In a population based register of stroke (n = 536) compiled in Perth, Western Australia during an 18 month period in 1989-90, 60 cases (11%) of primary intracerebral haemorrhage were identified among 56 persons (52% men). The mean age of these patients was 68 (range 23-93) and 46 (77%) events were first ever strokes. The crude annual incidence was 35 per 100,000, with a peak in the eighth decade, and a male predominance. Deep and lobar haemorrhages each accounted for almost one third of all cases. The clinical presentations included sudden coma (12%), headache (8%), seizures (8%), and pure sensory-motor stroke (3%). Primary intracerebral haemorrhage was the first presentation of leukaemia in two cases (both fatal) and it followed an alcoholic binge in four cases. 55% had a history of hypertension. 16 (27%) patients, half of whom had a history of hypertension, were taking antiplatelet agents, and one patient was taking warfarin. There were only two confirmed cases of amyloid angiopathy. The overall 28 day case fatality was 35%, but this varied from 100% for haemorrhages in the brainstem to 22% for those in the basal ganglionic or thalamic region. Other predictors of early death were intraventricular extension of blood, volume of haematoma, mass effect, and coma and severe paresis at onset. Although based on small numbers, these data confirm the heterogeneous nature of primary intracerebral haemorrhage, but they also suggest a different clinical spectrum of this type of stroke in the community compared with the experience of specialist neurological units.
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PMID:Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome. 805 17

We report a rare case of adult T-cell leukemia (ATL) in which the patient had an acute type of ATL involving the central nervous system (CNS) after remission of adult respiratory distress syndrome (ARDS) due to human T lymphotropic virus type 1 associated bronchopneumopathy. A 62-year-old woman was admitted to the hospital because of ARDS. Pulse therapy with methylprednisolone improved ARDS, but she fell into a coma due to ATL and CNS invasion 5 months after recovery. Although chemotherapy decreased the fraction of abnormal lymphocytes, her consciousness level did not improve and she died.
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PMID:Adult T-cell leukemia involving the central nervous system after remission of adult respiratory distress syndrome. 825 91

Coma, hemiparesis, unilateral optic neuropathy, and anosmia manifested in a patient with leukemia after he received only three courses of intravenous high-dose cytosine arabinoside (ARA-C). The patient's mental status returned to normal after several days, and his hemiparesis resolved. However, the visual loss persisted, and near complete visual loss in the other eye ensued over the following month. Severe bilateral optic atrophy appeared as the visual loss progressed. Anosmia became evident after resolution of the coma and did not improve. The patient had previously had a thoracic myelopathy 2 weeks after receiving low-dose i.v. ARA-C. The neurotoxicity of high-dose i.v. ARA-C may arise at much lower cumulative doses than has been reported. In addition to cerebellar dysfunction and somnolence, high-dose i.v. ARA-C may produce optic neuropathy, anosmia, and hemiparesis.
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PMID:Encephalopathy, myelopathy, optic neuropathy, and anosmia associated with intravenous cytosine arabinoside. 850 43

A patient with acute lymphoblastic leukaemia was mistakenly given vincristine intraventricularly, as part of an intensified course of chemotherapy. Despite a CNS washout and supportive treatment, the patient developed progressive ascending paralysis, gradually lapsed into coma and died some 10 days later. Autopsy and post-mortem histological examination showed evidence of brain death caused by florid encephalomyelitis, apparently induced by the intraventricular administration of vincristine.
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PMID:Accidental intraventricular vincristine administration: an avoidable iatrogenic death. 891 96

Chondronecrosis of the cricoid cartilage is a rare complication of intubation. The records of two children were reviewed. An 8-month-old girl with myelomonocytic leukaemia developed chondronecrosis 10 days after a 2-day period of ventilation. A 4-year-old girl comatose after poisoning by the histamine antagonist, alimemazine, developed chondronecrosis after a 2-day period of intubation. The complication was suspected when extubation led to dyspnoea owing to laryngeal stridor and was confirmed by direct laryngoscopy. We review the development of the condition, the causative factors, treatment and prevention.
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PMID:Chondronecrosis of the cricoid cartilage after intubation. Two case reports. 925 78

Acute myopathy occurs in critically ill patients, receiving neuromuscular blocking agents or corticosteroids during intensive care hospitalisation. We report three patients with acute quadriplegic myopathy, two of whom were not exposed to corticosteroids or neuromuscular blocking agents. The first of these latter two patients had a history of generalised anoxia with coma related to surgery, complicated by multiple organ failure and sepsis. The second patient, suffering from acute leukaemia, developed sepsis and acute respiratory distress syndrome with the need for mechanical ventilation in the intensive care unit. Electrophysiological studies and muscle biopsy findings were consistent with the diagnosis of critical illness myopathy with loss of myosin filaments. Selective loss of myosin was confirmed by biochemical analysis of muscle. These findings demonstrate that acute myopathy with loss of myosin filaments may occur in patients with severe systemic illness without exposure to corticosteroids or neuromuscular blocking agents.
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PMID:Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking agents. 963

This study investigated whether two widely publicized cases of deaths facilitated by physicians were followed by significant peaks in mortality. In March, 1991, Timothy Quill, MD, published a controversial editorial describing the physician-assisted suicide (PAS) of his 45-year-old, female leukemia patient. In a landmark decision in December 1990, the Missouri Supreme Court allowed removal of life support for Nancy Cruzan, a comatose accident victim. Correcting for trends and seasonal fluctuations, the authors examined: (1) U.S. leukemia mortality in the period centered on Quill's editorial, and (2) mortality from accident/coma combinations in the period centered on the Missouri Supreme Court's decision on Cruzan. Female leukemia deaths rose 11.3% above the expected rate (p < .01) just after Quill's article was published. The more closely the decedent matched Quill's patient, the greater the peak, with the largest peak (33.9%) evident for female leukemia patients in their 40s, who were long-term residents of smaller communities (p < .05). Five possible explanations for the findings were assessed, leading to the conclusion that Quill's editorial elicited an increase in mortality. The involvement of physicians in this increase is supported by analysis of the Cruzan case. This showed a mortality peak of 57% for accident/coma patients following the court decision.
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PMID:The influence of medical and legal authorities on deaths facilitated by physicians. 1032 20

Three patients with acute leukaemia, who were severely neutropenic and iatrogenically immunosuppressed post-chemotherapy, developed rapidly fatal septicaemic shock and coma caused by Bacillus cereus (B. cereus). The illness was marked by two phases: a mild febrile illness lasting 6-14 h and accompanied by subtle symptoms of autonomic sympathetic nervous system overactivity, and a second short fulminant one, marked by high fever of 40-41 degrees C accompanied by major central nervous system disturbances, and ending with deep coma and brain stem dysfunction. One patient developed the sepsis in spite of 4 days of coverage with amikacin. In the other two patients, amikacin was commenced at the earliest phase of the infection, but failed to influence the outcome. This form of B. cereus sepsis in neutropenic patients seems to be caused by strains capable of causing bacteraemia and meningitis and has the ability to produce a substance that causes leptomeningeal and neuronal necrosis. Lack of early clinical and laboratory markers inevitably leads to death. Use of antibiotics effective against B. cereus and capable of achieving high concentrations in the cerebrospinal fluid. and identification and neutralization of the necrotizing substance may hopefully help to reverse this fatal illness.
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PMID:Fulminant septicaemic syndrome of Bacillus cereus: three case reports. 1060 35


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