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PubMed1998

CDKN2 (MTS1/p16INK4A) gene alterations in adult T-cell leukemia/lymphoma.

p16INK4A is a cyclin-dependent kinase inhibitor (CDKI), and regulates the cell cycle negatively. Recently, p16INK4A protein was shown to be encoded by the CDKN2 gene, which is identical to multiple tumor suppressor gene 1 (MTS1) on chromosome 9p21, where genetic alterations occur frequently in many malignant tumors. As the loss of p16INK4A function by genetic alterations leads to inappropriate progression of the cell cycle, the CDKN2 gene has been investigated intensively as a new candidate tumor suppressor gene in many malignant tumors. Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy associated with human T-cell lymphotrophic virus type 1 (HTLV-1). As the development to ATL is believed to require not only HTLV-1 infection but also accumulation of genetic alterations, we investigated the relationship between alterations in the CDKN2 gene and ATL. Alterations in the CDKN2 gene were detected in approximately 15 to 20% of ATL patients. Interestingly, most of the patients with CDKN2 gene alterations had the aggressive form of ATL. The CDKN2 gene appears to be the major tumor suppressor gene on chromosome 9p21, and alteration in this gene may play an important role during late stages in the transformation process induced by HTLV-1.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1989

Short-term psychological outcome of anterior temporal lobectomy.

The purpose of this investigation was to determine the short-term behavioral and emotional effects of anterior temporal lobectomy (ATL). Forty-one patients who underwent ATL were administered a standardized measure of emotional adjustment (Mental Health Inventory) on four occasions: preoperatively, and 1, 3, and 6 months postoperatively. Patients who were rendered totally seizure-free by ATL showed significant improvements on multiple indices of psychological distress and psychological well-being, improvement that continued up to 3 months after surgery and remained constant at 6 months postoperatively. Patients who were significantly improved (greater than 75% reduction in seizure frequency) but continued to experience some seizure activity showed no significant improvements in behavioral or emotional adjustment. The clinical and theoretical significance of these findings is discussed, and it is suggested that functional outcome (for instance, mental health) following ATL may be best predicted by a binary seizure outcome classification (seizure-free or not seizure-free).

Epilepsy↗
PubMed1997

A cost-effectiveness analysis of anterior temporal lobectomy for intractable temporal lobe epilepsy.

Patients with medically intractable temporal lobe epilepsy are potential candidates for anterior temporal lobectomy (ATL), in which epileptogenic temporal lobe tissue is localized and surgically removed. This surgical approach can eliminate or drastically reduce seizures in the majority of patients. The authors used a decision-analysis model to examine the cost-effectiveness of a surgical evaluation and treatment protocol for medically intractable temporal lobe epilepsy. This model compared a cohort treated with the new protocol with a continuation of their immediate preoperative medical management and projected these differences over the patient's lifetime. The Markov model incorporated postoperative seizure status, patient quality of life, death from surgical and natural causes, discounting, and the direct medical costs associated with outpatient evaluation, hospitalization, surgery, antiepileptic drugs, and lifetime outpatient treatment. The intent-to-treat analysis included patients who underwent evaluation but were not eligible for ATL. Sensitivity analyses were also performed on the variables in the model. Data from the baseline model indicated that evaluation for ATL provided an average of 1.1 additional quality-adjusted life years (QALYs) compared with continued medical management, at an additional cost of $29,800. Combining the clinical and economic outcomes yielded a cost-effectiveness ratio of $27,200 per QALY. This value is comparable to other accepted medical or surgical interventions, such as total knee arthroplasty ($16,700/QALY) or coronary artery balloon angioplasty ($40,800/QALY). Sensitivity analyses demonstrate that the results are critically dependent on postoperative seizure status and improvement in quality of life. Although further work is necessary to quantify the improvement in quality of life after epilepsy surgery better, the present data indicate that ATL for treatment of intractable temporal lobe epilepsy is a cost-effective use of medical resources.

Adult↗
PubMed2006

Seizure and memory outcome following temporal lobe surgery: selective compared with nonselective approaches for hippocampal sclerosis.

OBJECT: The aim of this study was to compare seizure and memory outcome in patients with medically refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) treated using an anterior temporal lobectomy (ATL) or a selective amygdalohippocampectomy (SA). METHODS: Surgical outcome data were prospectively collected for 2 to 11 years in 161 consecutive patients with MTLE/ HS. Eighty patients underwent an ATL and 81 an SA. Seizure control achieved with each technique was compared using the Engel classification scheme. Postoperative memory testing was performed in 86 patients (53%). At the last follow up, 72% of the patients who had undergone an ATL (mean follow up 6.7 years) and 71% of those who had undergone an SA (mean follow up 4.5 years) were seizure free (Engle Class IA). Estimated survival in patients in Engel Classes I, IA, and I and II combined did not differ between the two surgical techniques. Preoperatively, 58% of the patients had verbal memory scores one standard deviation (SD) below the normal mean. One third of the patients with preoperative scores in the normal range worsened after surgery, although this outcome was not related to the surgical technique. In contrast, one third of those whose preoperative scores were less than -1 SD experienced improvement after surgery. Nine (18%) of the 50 patients whose left side had been surgically treated improved their verbal memory scores by more than one SD. Seven (78%) of these nine underwent an SA (p = 0.05). CONCLUSIONS: Both ATL and SA can lead to similar favorable seizure control in patients with MTLE/HS. Preliminary data suggest that postoperative verbal memory scores may improve in patients who undergo selective resection of a sclerotic hippocampus in the dominant temporal lobe.

Adult↗
PubMed2005

Purification and characterization of a lectin from Arisaema tortuosum Schott having in-vitro anticancer activity against human cancer cell lines.

A lectin with in-vitro anticancer activity against established human cancer cell lines has been purified by affinity chromatography on asialofetuin-linked amino activated silica beads from the tubers of Arisaema tortuosum, popularly known as Himalayan Cobra lily, a monocot plant from the family Araceae. The bound Arisaema tortuosum lectin (ATL) was eluted with glycine-HCl buffer, pH 2.5. ATL was effectively inhibited by asialofetuin, a complex desialylated serum glycoprotein as well as by N-acetyl-D-lactosamine, a disaccharide. It gave a single band corresponding to a subunit molecular weight of 13.5 kDa in SDS-PAGE, pH 8.8 both under reducing and non-reducing conditions. When subjected to gel-filtration on Biogel P-200, it was found to have a molecular weight of 54 kDa, suggesting a homotetramer structure, in which individual polypeptides are not bound to each other with disulfide bonds. ATL is a glycoprotein with 0.9 % carbohydrate content, stable up to 55(o)C and at pH 2 to 10. The lectin had no requirement for divalent metal ions i.e. Ca(2+) and Mn(2+) for its activity. However, as reported for other monocot lectins, ATL gave multiple bands in isoelectric focusing and Native PAGE, pH 8.3. The lectin was found to inhibit in vitro proliferation of human cancer cell lines HT29, SiHa and OVCAR-5.

Animals↗
PubMed1999

[Adult T-cell leukemia with elevated serum hyaluronic acid levels paralleling disease activity].

We report on two adult T-cell leukemia (ATL) patients whose levels of serum hyaluronic acid (HA) moved in parallel with the clinical activity of their disease. A 66-year-old man was admitted to our hospital because of unconsciousness and hypotension. Acute type ATL complicated by hypercalcemia and myelofibrosis was diagnosed. Before therapy, the level of patient's serum HA was 2,045 to 4,010 ng/ml (normal range: 50 >). After he achieved complete remission (CR) through chemotherapy, his serum HA was 36 ng/ml. Several months later, however, his ATL relapsed, and his serum HA increased to 393 ng/ml. The other patient was an 80-year-old man who had been admitted on the suspected diagnosis of ATL. Before chemotherapy, his serum HA was high (3,420 ng/ml). After CHOP therapy, he entered CR and his HA decreased to 122 ng/ml. He remains in CR with slightly elevated levels of HA (127 to 212 ng/ml), and is being followed up on an out-patient basis.

Aged↗
PubMed2000

[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].

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.

Aged↗
PubMed1999

Factors contributing to physicians' success in the advanced trauma life support program in Israel.

BACKGROUND: Since its introduction in Israel, more than 4,000 physicians from various specialties and diverse medical backgrounds have participated in the Advanced Trauma Life Support course. OBJECTIVES: To analyze the factors that influence the success of physicians in the ATLS written tests. METHODS: A retrospective study was conducted of 4,475 physicians participating in the Israeli ATLS training program between 1990 and 1996. Several variables in the records of these physicians were related to their success or failure in the final written examination of the course. RESULTS: Age, the region of medical schooling, and the medical specialty were found to significantly influence the successful completion of the ATLS course. CONCLUSIONS: Physicians younger than 45 years of age or with a surgical specialty are more likely to graduate the ATLS course. The success rate could be improved if the program's text and questionnaires were translated into Hebrew.

Adult↗
PubMed2000

All-trans-retinoic acid treatment for chemotherapy-resistant acute adult T-cell leukemia.

We report a case in which treatment with all-trans-retinoic acid (ATRA) improved the clinical features of a 47-year-old female patient with acute adult T-cell leukemia (ATL). The patient was first treated several times with combination chemotherapy. but the number of ATL cells increased and other clinical manifestations progressed. ATRA 60 mg was then administered daily. ATRA treatment dramatically improved the patient's clinical features. In vitro examination revealed that ATRA inhibited the growth of ATL cells from the patient. These findings suggest that ATRA may be a useful treatment for patients with chemotherapy-resistant acute ATL.

Acute Disease↗
PubMed2001

Differences between nouns and verbs after anterior temporal lobectomy.

To test the claim that lesions of left anterior and middle temporal cortical structures specifically impair processing of nouns but not verbs, 56 left-hemisphere-language-dominant patients who had undergone anterior temporal lobectomy (ATL) completed tasks assessing confrontation naming of pictured objects and actions, generation of synonyms for nouns and verbs, and semantic lexical judgments about nouns and verbs. Compared with right ATL patients, left ATL patients were impaired across different tasks that assessed naming and comprehension of high-imageability as well as low-imageability nouns. These groups did not differ, however, in verb naming or comprehension on most tasks. Results are consistent with the hypothesized specialization of left temporal lobe structures for processing nouns and suggest that naming problems commonly seen after left ATL extend beyond difficulties with retrieving object names and may be related to subtle disturbances in comprehension of the meanings underlying nominal word forms.

Adult↗
PubMed2001

Case report: acute tumour lysis syndrome.

INTRODUCTION: Acute tumour lysis syndrome (ATLS) is a potentially lethal but preventable complication of oncological treatment. CLINICAL PICTURE: We report a case of a patient with Burkitt's leukaemia who developed ATLS after treatment with chemotherapy. TREATMENT: Standard preventive measures using aggressive hydration, urine alkalinisation and uricosuric agents were instituted before chemotherapy. OUTCOME: However in spite of adequate measures, the patient succumbed to the sequelae of ATLS. CONCLUSIONS: It is therefore important to identify patients who are at a high risk of developing ATLS so that additional measures can be taken to prevent it from occurring.

Acute Disease↗
PubMedDate not supplied

[Serological and epidemiological features of canine American tegumentary Leishmaniasis from Maricá, Rio de Janeiro, Brazil].

A sample of 261 dogs from 134 households located in a periurban area of Maricá, Rio de Janeiro, Brazil, was studied to evaluate serologic reactions and active infection of american tegumentary leishmaniasis (ATL). Eight dogs presented lesions suggestive of ATL, but this was isolated in only three. Using ELISA, 24.5% (64/261) of the dogs studied were positive (sensitivity = 66% and specificity = 76%), associated with isolation in 2 animals and 0.4% (1/261) by indirect immunofluorescence assay (IIF) with no association with isolation. In order to reduce the unspecific reactions to ELISA, a second criterion was used to obtain the cutoff (sensitivity = 33% and specificity = 93%), resulting in a reactivity of 6.9 % (18/261) associated to isolation in a single animal. As observed in this study, serologic results by IIF were not associated with active infection and ELISA showed high unspecific reactions, indicating that the serologic reactions alone are not recommended for ATL diagnosis. ATL scars were been observed in 7 persons in the region and active lesion, under treatment, was observed in one patient. The finding of active lesions, either in dogs or humans, confirmed the existence of active tegumentary leishmaniasis in Maricá, indicating the need for further studies to evaluate the importance of this infection in the municipality.

Animals↗
PubMedDate not supplied

[Defects in the visual field in resective surgery for temporal lobe epilepsy].

INTRODUCTION: Temporal lobe resection is the most used procedure in epilepsy surgery. Visual field defects after resection are frequent. AIM. We try to detect the frequency and severity of visual field defect after anterior temporal lobectomy (ATL) and to study the functional consequences. PATIENTS AND METHODS: We studied 30 patients with refractory temporal lobe epilepsy (15 men, 12 51 years, m= 32.9), in which ATL was performed (11 right, 19 left). The neocortical and hippocampal resection was variable. Visual field was studied with computerized campimetry type Humphrey. Our survey was filled to study the campimetric consequence, seizures incidence, quality of life and surgery satisfaction. RESULTS: Some campimetric disturb was found in 27 patients (90 %), superior or minor homonimus quadantapnosia in 18 (60 %), major one 8 and homonimus hemianopsia in one. Incongruent defects appeared in 19. The bigger neocortical and hippocampal resection was, the bigger defect, with exceptions. Only patient with a hemianopsia was conscious the deficit. 20 patients (66.6 %) were seizures free in the last year. 28 had better quality of life and 29 (96.6 %) would have chosen surgery again. CONCLUSION: Visual field defects after ATL, although frequent, have little functional consequences and in quality of life. The quality of life is better when seizures stopped. After ATL patients are very glad with their decision.

Adolescent↗
PubMed2001

[Adult T-cell leukemia/lymphoma. Clinical aspects].

BACKGROUND DATA: Adult T-cell leukemia/lymphoma (ATL) is a malignant proliferation of activated CD4+ T lymphocytes. The disease is almost exclusively found in patients living in retrovirus HTLV-1 endemic areas. VIROLOGY: In ATL, monoclonal HTLV-1 provirus is integrated into atypical lymphocytes, called clover-leaf lymphocytes. The pathogenic mechanism leading to HTLV-1-induced leukemogenesis remains obscure. The disease generally occurs after a long latency period. FOUR CLINICAL SUBTYPES: The diversity of the clinical presentation has led to the classification of ATL into four subtypes: acute or prototype, lymphoma, chronic, and painless. In the acute form of ATL there is a tumor syndrome associated with paraneoplastic hypercalcemia and a high rate of opportunistic infections due to the immunodepression predominated by cellular immunity. CLINICAL COURSE: Prognosis is poor for the acute and lymphomatous forms with a median survival of 6 and 10 months respectively. Infectious episodes are frequent, often caused by Pneumocystis carinii, and require systematic prophylaxis. Screening for anguilulosis and prophylaxis is also necessary.

Adult↗
PubMed2003

Activation of HTLV-I long terminal repeat by apoptosis inducing agents: mechanism and implications for HTLV-I pathogenicity (review).

HTLV-I is the etiological agent of adult T-cell leukemia (ATL), tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) and certain other clinical disorders. After infection in human the virus enters into a latent state, in which very low viral gene expression can be detected. On the other hand several major characteristics of ATL and TSP/HAM indicate that their genesis requires activation of the dormant virus. TSP/HAM is characterized by high virus expression, which accounts for most of its immunopathological manifestations, whereas the process leading to ATL is believed to be initiated by the viral Tax protein, implying that it requires, at least, a temporary activation of the latent virus. Data from our and other laboratories suggest that this activation may likely be induced by environmental or/and intrinsic apoptosis-inducing factors. Moreover, we have demonstrated a mechanistic linkage between the activation of the viral promoter and the early stage of the apoptotic cascade. However, we have also shown that Tax rescues virus-expressing T-cells from apoptotic death. This suggests that Tax protein, emerging after activation of the latent virus, can rescue the host cells of the activated virus from the ultimate apoptotic death. Since the development of both TSP/HAM and ATL seems to depend on the viral Tax protein, we describe a possible system for anti Tax gene-therapy approach based on a negative transdominant mutant Tax gene.

Adult↗
PubMed1992

[Pulmonary complications in patients with adult T-cell leukemia].

In order to investigate the character of pulmonary complications in patients with adult T-cell leukemia (ATL), a pathological and bacteriological study was performed in 92 autopsy cases with hematologic malignancies including 17 cases of ATL and 103 autopsy cases with solid malignancies from 1981 to 1990. Among 17 cases with ATL, pulmonary complications were seen in 16 cases (94.1%); pulmonary infection in 14 (82.3%), leukemic cell pulmonary infiltration in 9 (52.9%), pulmonary hemorrhage in 5 (29.4%), pulmonary alveolar calcinosis in 2 (11.8%), and idiopathic interstitial pneumonia in 2 (11.8%). The causative microorganisms were virus in 10; 9 of which were cytomegalovirus, followed by bacteria infection in 4 cases, mainly pseudomonas aeruginosa, and fungal infection in 3, mainly cryptococcus. pneumocystic carinii and mycobacterium tuberculosis were not detected. It is suggested that patients with ATL are severely compromised with chiefly cellular immunodeficiency, and administration of sulfamethoxazole-trimethoprim and isoniazid is very effective in prevention of pneumocystis carinii pneumonia and pulmonary tuberculosis.

Cytomegalovirus Infections↗
PubMed1992

[Adult T-cell leukemia with various pulmonary complications].

A 59-year-old male, born in Wakayama prefecture, was admitted to our hospital because of cervical lymph node swelling, huge mass lesions in both liver and head of the pancreas, and multiple nodular shadows in the left lung. Lymph node biopsy revealed a necrotic lesion containing tuberculous bacilli with no epithelioid cells or giant cells. Adult T-cell leukemia (ATL) was diagnosed by the presence of atypical lymphocytes with a convoluted nucleus and positive anti-ATL antibody. During successful treatment of Mycobacterium tuberculosis with ethambutol, isoniazid and rifampicin, ATL transformed to the blastic phase. The new pulmonary infiltrates improved after treatment with both combination chemotherapy for ATL and antibiotics. However, new infiltrative shadows appeared in both lungs, and were resistant to treatment and the patient died of acute respiratory failure. Histological examination of the lung at autopsy showed interstitial fibrosis with infiltration of leukemic cells and cytomegalovirus infection.

Cytomegalovirus Infections↗
PubMed1992

Phase I study of YK-176 (2'-deoxycoformycin) in patients with adult T-cell leukemia-lymphoma. The DCF Study Group.

YK-176 is a newly isolated 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, produced by Aspergillus nidulans. In a cooperative phase I study, YK-176 was administered to 22 patients, comprising 18 with adult T-cell leukemia-lymphoma (ATL), two with cutaneous T-cell lymphoma (CTCL), one with lymphoblastic lymphoma of T-cell type and one with carcinoma of the uterine cervix. Doses of YK-176 ranged from 3.0 to 9.0 mg/m2 and were given intravenously for three consecutive days. General malaise, anorexia, nausea, vomiting and low grade fever were frequently encountered, but were transient and not dose-related. At all dose levels hematological toxicities were mild. Two of seven patients receiving 7.0 mg/m2 for three consecutive days developed hepatocellular enzyme elevations (grade 2) and one patient, proteinuria (grade 2). One of two patients given 9.0 mg/m2 for three consecutive days manifested a life-threatening (grade 4) disturbance of consciousness and dyspnea, presumably ascribable to the drug-related toxicity of YK-176. The results suggest that 7.0 mg/m2 i.v. for three consecutive days is the maximum acceptable dose of YK-176. Central nervous system, pulmonary and possibly renal toxicities appeared to be dose-limiting. Out of the 20 patients evaluable for therapeutic response, partial remissions were observed in four, three with ATL and one with CTCL, who received less than 7.0 mg/m2 for three consecutive days. We conclude that YK-176 is an active agent against ATL at doses that may not be associated with prohibitive toxicity. A starting dose of 5.0 mg/m2 for three consecutive days is recommended for further phase II studies on ATL.

Adult↗