Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Frequent allelic losses on chromosome 22q in small cell lung carcinomas (SCLCs) and advanced non-small cell lung carcinomas indicate the presence of tumor suppressor gene(s) on this chromosome arm. We detected a homozygous deletion at 22q12.1 in a SCLC cell line, Lu24. Cloning of the breakpoints of the Lu24 deletion revealed that the deletion was interstitial and 428, 131 bp in size. The deleted region contained the SEZ6L (Seizure 6-like) gene, whose structure had been partially determined by the chromosome 22 sequencing project. We determined the full length cDNA sequence for the SEZ6L gene based on the genomic sequence for the SEZ6L locus using the GENSCAN program and the RT - PCR method. The deduced SEZ6L protein was a transmembrane protein of 1024 amino acids with multiple domains involved in protein - protein interaction and signal transduction. SEZ6L expression was detected in a variety of human tissues, including lung, while its expression was detected in 14 (30%) of 46 lung cancer cell lines examined. Missense mutations were detected in three (7%) of the 46 cell lines, and a 1 bp deletion in the polypyrimidine tract preceding exon 4 was detected in one (2%) of 46 primary lung cancers. Therefore, it is possible that genetic and/or epigenetic SEZ6L alterations are involved in the development and/or progression in a subset of lung cancer, although functional analysis of the SEZ6L gene as well as molecular analysis of other genes in the homozygously deleted region is necessary to understand the pathogenetic significance of 22q deletions in human lung carcinogenesis.
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PMID:Identification of a 428-kb homozygously deleted region disrupting the SEZ6L gene at 22q12.1 in a lung cancer cell line. 1117 39

Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. Twelve subunits have been identified in vertebrates, and mutations of one are recognized in a rare form of human epilepsy. Mice with genetically manipulated neuronal nAChR subunits exhibit behavioral or autonomic phenotypes. Here, we report the first model of an acquired neuronal nAChR disorder and evidence for its pertinence to paraneoplastic neurological autoimmunity. Rabbits immunized once with recombinant alpha3 subunit (residues 1-205) develop profound gastrointestinal hypomotility, dilated pupils with impaired light response, and grossly distended bladders. As in patients with idiopathic and paraneoplastic autoimmune autonomic neuropathy, the severity parallels serum levels of ganglionic nAChR autoantibody. Failure of neurotransmission through abdominal sympathetic ganglia, with retention of neuronal viability, confirms that the disorder is a postsynaptic channelopathy. In addition, we found ganglionic nAChR protein in small-cell carcinoma lines, identifying this cancer as a potential initiator of ganglionic nAChR autoimmunity. The data support our hypothesis that immune responses driven by distinct neuronal nAChR subtypes expressed in small-cell carcinomas account for several lung cancer-related paraneoplastic disorders affecting cholinergic systems, including autoimmune autonomic neuropathy, seizures, dementia, and movement disorders.
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PMID:Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease. 1263 83

Paraneoplastic limbic encephalitis (PLE) is a disorder characterized by severe cognitive dysfunction and seizures. It is usually associated with small cell lung carcinoma. Diagnosis is difficult because clinical markers are often lacking, and symptoms usually precede the diagnosis of cancer. Serological detection of antineuronal antibodies can be useful. We describe a patient with symptoms of limbic encephalitis, negative for paraneoplastic antibodies, in whom lung cancer was detected.
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PMID:[Paraneoplastic limbic encephalitis and lung cancer]. 1504 93

Limbic encephalitis was identified as a clinicopathological entity in 1968. Up to a few years ago, 200 cases were described, most associated with lung cancer and more infrequently with other tumors. The recent identification of patients with this syndrome, idiopathic limbic encephalitis, who never develop cancer and have high titers of antibodies to voltage-gated potassium channels (VGKC) and an excellent response to immunosuppressive therapy, has extended the etiological spectrum and suggests that the syndrome may be under-recognized. The disorder, which develops in a few days or weeks, is characterized by the development of short-term memory loss, seizures, confusion and psychiatric features. The presence of symptoms beyond the limbic system is highly suggestive of a paraneoplastic origin. When limbic encephalitis is suspected, the following tests should be performed in order to demonstrate: a) involvement of the temporal lobes (EEG and brain MRI); b) presence of inflammatory abnormalities in the CSF, and c) the presence of onconeural antibodies or anti-VGKC. Once the diagnosis is confirmed by the clinical picture and MRI findings, treatment must be initiated without waiting for the antibody results because its negativity does not exclude the diagnosis. Detection of an onconeural antibody will confirm that the limbic syndrome is paraneoplastic and will help us to search for an underlying tumor and to predict possible response to the treatment. The recommended treatment is cycles of methylprednisolone (1 g/day for 3 to 5 days). Therapeutic response in the idiopathic limbic encephalitis is excellent and may be good in limbic encephalitis with anti-Ma2 or without onconeural antibodies. On the contrary, immunosuppressant treatment is not usually effective in limbic encephalitis associated to anti-Hu antibodies.
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PMID:[Limbic encephalitis: a probably under-recognized syndrome]. 1570 18

Neurological manifestations are reported in 5 to 10% of cases of lung cancer. We present a series of 216 consecutive patients of lung cancer of which 8 patients presented first with neurological manifestations without overt respiratory symptoms. The present study aimed to identify the number of patients of lung cancer presenting with primary neurological symptoms, the nature of the presentations, and the outcome of these patients among 216 patients who presented over a 2 year period in the Institute of Postgraduate Medical Education and Research, Kolkata. Out of 8 patients, 3 patients presented with seizures, 3 patients with hemiparesis and 2 patients with paraparesis. Thus, 3.7% (8/216) of patients in our series presented with a neurological manifestation. We concluded that primary neurological manifestations are rare in lung cancer. The lungs should be the first site of evaluation in a case of a cerebral metastasis with an unknown primary.
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PMID:Primary neurological manifestations of lung cancer--a retrospective analysis of 8 patients. 1592 6

Brain metastases are an important sequelae of many types of cancer, most commonly lung cancer. Current treatment options include whole-brain radiation therapy (WBRT), surgical resection, stereotactic radiosurgery, and chemotherapy. Corticosteroids and antiepileptic medications are commonly used for palliation of mass effect and seizures, respectively. The overall median survival is only 4 months after WBRT. Combined-modality strategies of WBRT with either chemotherapy or novel anticancer agents are under clinical investigation. Promising results have been obtained with several experimental agents and confirmatory phase III trials are underway. Although improvement in overall survival has not been seen universally, reduction in death due to progression of brain metastases and prolongation of the time to neurologic and neurocognitive progression have been reported in selected series. On the basis of these findings, it might be possible to identify new agents that may enhance the efficacy of WBRT.
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PMID:Current management of brain metastases, with a focus on systemic options. 1613 88

Epidemiological studies suggest that environment plays an important role in the aetiology of cancer. Thus, if a cancer (e.g. prostate cancer (CaP)) arises in males, one could hypothesize that risk in co-habiting partners might be elevated. We conducted an observational-questionnaire study in NorthWest England evaluating the medical histories of CaP males and their female partners. Details regarding previous partners (>10y) were also sought. Self-filled questionnaires were obtained from 548 males, 81 of whom provided information on previous female partners (PFPs) and 448 current female partners (CFPs). Observed rates over a 30-y period (1971-2001) of common cancers (breast, colorectal or lung) in female partners and colorectal cancer in males were compared to the cumulative expected probability (estimated using crude incidence rates for England provided by the Office of National Statistics, UK) using a Chi-Square Goodness-of-Fit test. Colorectal cancers in males were similar to national estimates. Rates for breast, colorectal or lung cancer among CFPs and the total female cohort (CFPs plus PFPs) were also similar to estimates. However, observed rates for breast or lung cancers among PFPs were significantly (P< or =0.001) elevated. Our results suggest no evidence of elevated risk among female partners of CaP males.
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PMID:An observational study of cancers among female partners of UK-resident prostate cancer patients. 1633 69

A 47-year-old female patient suffering from advanced lung cancer with metastatic bone and brain disease participated in a passive exercise program, consisting of neuromuscular electrical stimulation (NMES) five times a week, carried out for 4 weeks. After the training period, the results of the 6-min walk (420 m before and 603 m after the training period) have improved by 44%, which demonstrates the increase of physical performance (mobility, endurance capacity). The results of the "Timed up and go" indicate an improvement of mobility and functional health of skeletal muscles. Furthermore, the quality of life (QOL)-scales (assessed by using the SF-36 health survey) "Physical functioning", "Role-physical", "Mental health", "Role-emotional", "Vitality", "Bodily pain", and "General health" showed improvements after the intervention period. Feasibility, safety, and beneficial effects of the NMES program were proven for the patient in this case study. These findings indicate that NMES, initiated and executed with appropriate care, may serve as a useful supportive means of palliative treatment in some patients with advanced cancer and metastatic disease, especially in cases of metastatic involvement of the brain and of the skeletal system with the risk of seizures and pathological fractures where volitional training is not allowed.
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PMID:Neuromuscular electrical stimulation for a patient with metastatic lung cancer--a case report. 1683 45

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance. Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.
Lung Cancer 2006 Aug
PMID:Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with limited stage small cell lung cancer. 1678 84

Survival rates from childhood cancer have dramatically improved over the past three decades; average overall 5-yr survival rates are now > 75%. However, this has been achieved by treatments associated with significant morbidity that may present many years later. This review seeks to delineate the basic information necessary to evaluate flight-training candidates with a history of childhood cancer. We performed a literature review using the Medline database with appropriate search terms related to delayed morbidity and mortality associated with childhood cancer; we did not attempt to evaluate the risk of recurrent cancer. The neurological, cardiovascular, and pulmonary systems were identified areas of aeromedical concern. Central nervous disease and treatment-related effects may increase the risk of seizures or other neurocognitive sequelae. The cardiac toxicity of chemotherapeutic agents such as anthracyclines and radiation may cause late-occurring arrhythmia, cardiac failure, and sudden death, while available screening modalities are of limited value. Pulmonary disease and related treatment effects may cause a 9-fold increase of late-occurring pulmonary fibrosis and lung cancer, with increasing prevalence as long as 25 yr following the cancer diagnosis. Additionally, second malignancies may occur in up to 12.5% of cancer survivors at 25 yr after cancer diagnosis, affecting medical clearance for flight training. In summary, this review discusses the relevant aeromedical issues, including disabilities with specific relevance to the flying environment, risk estimation of late-occurring treatment complications, and possible interactions with occupational exposures in aircrew.
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PMID:Long-term survivors of childhood malignancies--aeromedical dilemmas and implications. 1718 23


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