Cell-mediated immunity in human acute leukemia.

The general cell-mediated immunological reactivity of patients with acute leukemia has been found to be intact, although it may be depressed by extensive disease or by chemotherapy. Patients with acute leukemia also have cellular immune reactivity against tumor associated antigens, as measured by skin tests for delayed hypersensitivity, lymphocyte stimulation, and 51Cr release cytotoxicity. Skin reactions to autologous and allogeneic crude membrane extracts of blast cells correlated with disease state, positive in many patients in remission and negative in most patients in relapse. Extracts of human lymphoid tissue culture cell lines derived from lymphomas or leukemia also gave positive reactions in patients with acute leukemia, and also in patients with lymphoma and nasopharyngeal carcinoma. The antigens detected in the skin tests with the lymphoid cell lines appear to be different from those associated with Epstein-Barr virus (EBV) and from those detected in the 51Cr release assay. Evidence is presented which suggests a complex variety of antigens on blast cells and on the cell lines. Although leukemia associated antigens were also detected by lymphocyte stimulation and by cytotoxicity assays, the results did not correlate with the skin tests nor with each other. The possible use of these assays for monitoring the chemotherapy and immunotherapy of acute leukemia patients is discussed.     

Thyrotropin-secreting pituitary adenoma presenting as hypokalemic periodic paralysis

Thyrotropin (TSH)-secreting pituitary adenoma presenting with hypokalemic periodic paralysis is extraordinarily rare and may be misdiagnosed. We describe a 44-year-old man who suffered from acute muscle weakness and inability to ambulate upon awakening in the morning. Physical examination showed hypertension, tachycardia, and symmetrical flaccid paralysis of all extremities. The major biochemical abnormality was hypokalemia (K+, 2.0 mmol/L) with low urine K+ excretion. A thyroid function study revealed elevated thyroid hormone levels and inappropriately high TSH concentrations (2.10 microU/mL). Brain magnetic resonance imaging delineated a pituitary tumor with suprasellar extension. After trans-sphenoidal removal of tumor, he became clinically and biochemically euthyroid without any further attack of paralysis. Pathological findings confirmed a TSH-secreting adenoma with exclusive TSH immunostaining. TSH-secreting pituitary adenoma must be kept in the differential diagnosis in any thyrotoxic periodic paralysis patients with detectable TSH levels to avoid delaying diagnosis and management.     

Population-based chest X-ray screening for pulmonary tuberculosis in people living with HIV/AIDS, An Giang, Vietnam.

SETTING: Human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) program, An Giang Province, Vietnam. OBJECTIVE: To evaluate the coverage and yield of a chest radiography (CXR) screening program for tuberculosis (TB) among people living with HIV/AIDS (PLHA), risk factors for a TB CXR, inter-rater reliability of CXR readings and direct costs. DESIGN: Retrospective review of routine public health program records and CXRs. RESULTS: An increasing proportion of PLHAs received a screening CXR each year of the program (range 21% in 2001 to 61% in 2004, P<0.001). Of 876 screening CXRs performed, 191 (22%) were classified as suspicious for active TB ('TB CXR'). Compared to PLHAs with a CXR not suspicious for active TB, PLHAs with a TB CXR were more likely to be aged between 24 and 64 years, male and previously treated for TB (P<0.01 for each comparison). Agreement between the expert and local program CXR readings was 81% (kappa 0.50). Direct costs were approximately US$40 per TB suspect identified. Among TB suspects, <10% were followed up with sputum smear examination and enrolled for treatment. CONCLUSION: In An Giang Province, a large proportion of PLHAs are screened for TB annually, and one in five persons screened is classified as a TB suspect based on CXR. Annual CXRs may be a high-yield, inexpensive method for TB screening in PLHAs, but the follow-up of TB suspects to confirm diagnosis and initiate treatment is crucial.     

Transcatheter closure of persistent arterial ducts with different types of coils

BACKGROUND: Different types of coils have been designed for transcatheter closure of persistent arterial ducts. We compared the efficacy and safety of three types of coils: Gianturco coils (Cook), Cook detachable coils (Cook), and Duct Occlud devices (pfm). METHODS: Sixty-three patients underwent coil occlusion of arterial ducts between April 1995 and July 2000. The mean age and weight were 4.8+/-3.4 years and 16.5+/-7.6 kg, respectively. The results and complications of ductal occlusion among the three types of coils were compared. Kaplan-Meier analysis was used to assess reduction in the prevalence of residual shunt with time, and multiple regression analysis was performed to identify predictors of complete occlusion. RESULTS: Coil occlusion of persistent arterial ducts that measured 2. 2 +/- 0.8 mm was feasible in 90% (57/63) of patients. Gianturco coils were used in 29, Duct Occlud devices in 16, and Cook detachable coils in 12 patients. The prevalence of residual shunt at 24 hours, 6 months, 12 months, and 24 months was 42%, 20%, 18%, and 14%, respectively. The reduction in prevalence of residual shunt with time tended to be greater when Gianturco coils were used (P =. 067). Logistic regression identified the use of Gianturco coils to be a significant predictor of complete ductal occlusion on follow-up (P =.04). Pull-through of coils occurred in 4.8% (3/63) and coil embolization in 6.3% (4/63). There was no association between the type of coil and the risk of embolization (P = 1.00). CONCLUSIONS: Transcatheter occlusion of small persistent arterial ducts with coils is safe and effective. There is no advantage of detachable coils (Cook detachable coils and Duct Occlud devices) over nondetachable Gianturco coils in reducing the risk of embolization. Our findings are in favor of the inexpensive, but more effective, Gianturco coils for occluding small arterial ducts of 3 mm or less.     

Di-lysine motif-like sequences formed by deleting the C-terminal domain of aquaporin-4 prevent its trafficking to the plasma membrane

Aquaporin-4 is a transmembrane water channel protein, the C-terminal domain of which is facing the cytosol. In the process of investigating the role of the C-terminal domain of aquaporin-4 with regard to intracellular trafficking, we observed that a derivative of aquaporin-4, in which the C-terminal 53 amino acids had been removed (Δ271-323), was localized to intracellular compartments, including the endoplasmic reticulum, but was not expressed on the plasma membranes. This was determined by immunofluorescence staining and labeling of the cells with monoclonal antibody specifically recognizing the extracellular domain of aquaporin-4, followed by confocal microscopy and flow cytometry. Deletion of additional amino acids in the C-terminal domain of aquaporin-4 led to its redistribution to the plasma membrane. This suggests that the effect of the 53-amino acid deletion on the subcellular localization of aquaporin-4 could be attributed to the formation of a signal at the C terminus that retained aquaporin-4 in intracellular compartments, rather than the loss of a signal required for plasma membrane targeting. Substitution of the lysine at position 268 with alanine could rescue the Δ271-323-associated retention in the cytosol, suggesting that the C-terminal sequence of the mutant served as a signal similar to a di-lysine motif.     

Factors for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma. The surgeon's role in the managed care era

BACKGROUND/AIMS: Length of stay is an important marker of medical resource consumption. In the modern managed care era physicians are driven to deliver the highest quality of care while using fewest resources. Hepatectomy represents a technically challenging and resource-intensive procedure, particularly in the setting of hepatic malignancy and liver cirrhosis. For improving quality of surgical management in such cases, we aimed to identify the factors affecting length of stay after hepatectomy for patients with hepatocellular carcinoma. METHODOLOGY: A total of 375 consecutive surgical hepatocellular carcinoma patients at a tertiary referral center during a 7-year period were reviewed. Length of stay after hepatectomy longer than 14 days was defined as prolonged length of stay. Patients were divided into two groups according to their length of stay. Patients with length of stay less than or equal to 14 days were in Group A and those with length of stay longer than 14 days were in Group B. Data for comparative analysis between both groups were categorized according to preoperative patients' clinical demographic factors, operation-related factors, and pathological factors. The significant univariate factors were used for subsequent multivariate analysis. RESULTS: The significant independent factors were patients' preoperative prothrombin activity, intraoperative blood transfusion, surgical complication, and the time to abdominal drain removal. Among these independent factors, surgical complication (p < 0.001, relative risk 7.01, and 95% confidence interval 3.46 to 14.18) was the most powerful factor for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma. CONCLUSIONS: Most of the independent factors for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma patients are operation-related and surgeon-dependent. The surgeon plays a key role in determining length of stay. By minimizing blood transfusion, surgical complication, and the time to abdominal drain removal, length of stay can be significantly decreased in hepatocellular carcinoma patients undergoing hepatectomy.     

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction

Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1^–/– embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1^–/– mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life.