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Biomedical subjects

T Chen

Publications and source records attributed to T Chen.

At least 397 records · Page 22Linked to original sources

Social status, gonadal state, and the adrenal stress response in the lizard, Anolis carolinensis.

Adult males of the small arboreal iguanid lizard, Anolis carolinensis, form social dominance hierarchies when placed in habitats with limited resources. Skin color changes occur during hierarchy formation, most conspicuously in subordinates, who appear darker (more brown) than dominants (more green). Because skin color in this species is under the control of hormones frequently associated with physiological stress, radioimmunoassay of plasma levels of the principal reptilian adrenal steroid, corticosterone, was performed. To examine the influence of gonadal androgen, known to influence the aggression that attends hierarchy formation, lizard pairs were constituted in which one or both members were castrated. Corticosterone levels of intact subordinates were significantly elevated, whereas those of castrated subordinates or dominants showed levels comparable to those of isolates. No significant differences in spermatogenic stage could be detected between intact dominants or subordinates.

Animals↗

Small cell bronchogenic carcinoma: factors associated with pneumonia during chemotherapy.

Sixty-five patients with small cell bronchogenic carcinoma were treated with intensive induction chemotherapy and supportive treatment. The clinical course of 43 patients who had pretreatment spirometry and arterial blood gases was studied. Thirteen patients developed pneumonia. Moderate hypoxemia, advanced age, and a low forced expiratory flow 25%-75% were associated with the development of pneumonia. Endobronchial obstruction and neutropenia, other factors associated with infection in cancer patients, appeared to be less important in this patient population.

Adult↗

Characterization of insulin-like growth factor I receptors on cultured rat bone cells: regulation of receptor concentration by glucocorticoids.

A specific receptor for insulin-like growth factor I (IGF-I) has been demonstrated in cultured fetal rat osteoblast-like bone cells. Specific binding of [125I]IGF-I to bone cells incubated at 15 C reached a steady state by 5 h. Half-maximal inhibition of [125I]IGF-I binding by unlabeled IGF-I was observed at 7 ng/ml. Multiplication-stimulating activity, insulin, and proinsulin were less effective than unlabeled IGF-I in competing for receptor occupancy. Scatchard analysis showed a curvilinear plot, with a Ka similar to that observed in human fibroblasts. Incubation of cell monolayers with glucocorticoids resulted in a concentration-dependent increase in [125I]IGF-I binding. This increase in [125I]IGF-I binding was dependent on cell density. After a 2-day exposure to dexamethasone, no increase in binding was observed in sparsely plated cells; however, an increase in binding was observed after 3 days in culture (log phase) and was maximal by 5 days (peak log phase). These data indicate that rat bone cells possess a specific receptor for IGF-I with binding characteristics similar to those reported in human fibroblasts, and that IGF-I receptor concentrations are increased by exposure to glucocorticoids. A role for glucocorticoids and IGF-I in rat bone proliferation is suggested by these findings.

Animals↗

Hepatocellular carcinoma in the alcoholic.

The conversion of alcoholic hepatitis into cirrhosis and the eventual development of hepatocellular carcinoma (HCC) has been documented by serial biopsies in patients with uncomplicated alcoholism. Ethanol toxicity, nutritional deficiency and immunological abnormalities in a genetically predisposed individual appear to account for this sequence which can be accelerated by the hepatitis B virus and other noxious agents. Immune deficiency in malnourished alcoholics with liver disease diminishes response to the hepatitis B vaccine and may contribute to the development of HCC. Antigenic moieties in Mallory bodies appear to contribute directly to cytotoxicity and fibrosis in alcoholics, and may act like proto-oncogens. Available Mallory-body-specific monoclonal antibodies will hopefully facilitate diagnosis and treatment. Studies of DNA and collagen synthesis by in vitro perfusion of percutaneous liver biopsies provide information on precursor lesions of HCC. Abstinence, nutrient therapy and drug-induced anabolism lead to repair of liver damage and correction of immunological abnormalities, both of which may contribute to development of HCC in alcoholics with cirrhosis.

Carcinoma, Hepatocellular↗

Synthesis of, and animal experiments with, N-isopropyl-p-123I-iodo-amphetamine (IMP) and 18F-3-deoxy-3-fluoro-D-glucose (3-FDG) as tracers in brain and heart diagnostic studies.

For the investigation of brain functions 18F-3-deoxy-3-fluoro-D-glucose (3-FDG) and N-isopropyl-p-123I-iodo-amphetamine (IMP) were synthesized and the course of radioactivity measured in several organs of mice. The results can be summarized as follows: IMP is rapidly extracted from the blood and reaches a value of less than 1% g within the first 15 min; 123I-radioactivity in the lungs shows a maximum of 76%/g as soon as half a minute after injection and decreases with a concomitant increase in the liver and brain; The maximum 123I-uptake in the brain of 11%/g is reached after 30 min and levels off at a constant value of 10%/g; 30 min after injection the brain/blood ratio for IMP is about 14; The time course of 3-FDG in the brain has a maximum of 4.8%/g as soon as 5 min after injection and decreases to a constant value of 3%/g within 1 hr; and Accumulation of 18F- radioactivity in the heart reaches a maximum of 14%/g after 1 hr and is eliminated with a half-life of 300 min. Comparative clinical studies with 3-FDG and 3-0-11C-methyl-D-glucose (CMG) have shown that 3-FDG can be considered as a CMG-analogue and thus can be used for the in-vivo determination of local glucose perfusion and transport rates.

Amphetamines↗

Diminished biparietal diameter and abdominal circumference growth in twins.

Forty-three women with uncomplicated twin pregnancies and reliable menstrual dates had serial ultrasonic measurements of the fetal biparietal diameter (BPD) and abdominal circumference. The 25th, 50th, and 75th fetal BPD and abdominal circumference growth percentiles were generated from this normal twin population and compared with those for singletons. A slowing of both BPD and abdominal circumference growth in twins was noted in the third trimester. However, newborn anthropometric data were collected that suggest that the head circumference of twins is comparable to that of singletons. This discrepancy between ultrasonic BPD and neonatal head circumference in predicting head size may possibly be explained by dolichocephaly attributed to uterine crowding. For the antenatal assessment of growth in twins the authors recommend the use of BPD and abdominal circumference charts derived specifically from such uncomplicated twin pregnancies. When the BPD growth is abnormal, the head circumference and abdominal circumference should be measured to assess whether or not fetal growth is normal.

Abdomen↗

Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group Study.

The value of radiotherapy to the chest (RC) in disseminated small cell lung carcinoma (SCLC) has been questioned. Two protocols for disseminated SCLC from the Southwest Oncology Group (SWOG) have been compared. They were developed four years apart. The first one included radiotherapy (RT), 3000 rad in two weeks, to the primary tumor, mediastinum and supraclavicular areas, while the second one deleted any RC. Multidrug chemotherapy (CT) and brain RT were used in both protocols. Nonresponders to CT were removed from the study. Our main findings are as follows: (1) Initial chest relapses (patients with no initial extrathoracic relapse) have increased from 24-55% when RC is not given (P = 0.0001). Overall chest relapse (adding those patients that relapsed simultaneously in the chest plus other sites) in the second protocol was 73%. (2) Amount of response to CT does not influence the chances for relapse. Even complete responders to CT have a high chance for chest relapse. (3) Sites of relapse without RC are mainly in the primary tumor, ipsilateral hilus and mediastinum. (4) With RC, relapses shift to the chest periphery, mostly to the lung outside the radiotherapy field and to the pleura. (5) The two very different CT regimens have produced similar percentages and duration of response. (6) CT schema with periodic reinductions prolongs duration of response and survival over schema with continuous maintenance. Hence, interruption of CT to allow RC does not seem to adversely influence CT efficacy. From our results and the review of the literature we conclude that: (1) patients with disseminated SCLC that respond to CT should be given RC to decrease chest relapses. (2) A dose of 3000 rad in two weeks seems to be enough to produce a low percentage of chest relapse in disseminated SCLC, as survival of these patients is short and many will die prior to developing chest relapse. However, according to the literature, 4000-4800 rad is probably a more effective dose. (3) More studies and guidelines are needed to outline proper boundaries of radiotherapy fields, to decrease chances of peripheral chest relapses. (4) Median survival might not be a good parameter to evaluate the impact of RC in disseminated SCLC. The study of long-term survivors seems to be more important.

Carcinoma, Small Cell↗

The influence of radiation therapy quality control on survival, response and sites of relapse in oat cell carcinoma of the lung: preliminary report of a Southwest Oncology Group study.

Two hundred and ninety-eight patients with limited (confined to chest and supraclavicular area, encompassable by a single radiation portal) small cell carcinoma of the lung were entered on Southwest Oncology Group Protocol 7628. Patients were treated with multi-agent chemotherapy and radiation therapy with or without BCG. Radiation therapy quality control analysis, including dosimetric reconstruction and port film review was introduced after the protocol was activated and was retrospectively applied. Patients who were considered major protocol variations had statistically worse survival (40 weeks versus 60 weeks; P = .002), a lesser improvement in response rate after induction chemotherapy (27 versus 48%; P = .05) and a higher chest failure rate (77 versus 55%; P = .047) than evaluable patients. Five patients relapsed in the brain, all associated with chest failure. Quality control is essential in cooperative group studies.

Antineoplastic Agents↗

Combination chemotherapy, radiotherapy, and BCG immunotherapy in limited small-cell carcinoma of the lung: a Southwest Oncology Group Study.

From November 1976 to March 1979 the Southwest Oncology Group treated 298 patients with limited (disease confined to the chest and encompassed by one radiotherapy port) small-cell carcinoma of the lung with combination chemotherapy and radiotherapy with or without BCG immunotherapy. Two induction chemotherapy programs were utilized: (1) cyclophosphamide, vincristine, methotrexate, fluorouracil; or (2) cyclophosphamide, doxorubicin, and vincristine. Patients received 4500 rads of radiation therapy to the bulk primary tumor and 3000 rads to whole brain followed by maintenance chemotherapy. One-half of all the patients were randomized to receive one vial (5 x 10(8)) of high viability Pasteur BCG by scarification technique given on days 8 and 15 of each 21--28 day treatment cycle. Increased granulocytopenia accompanied the addition of BCG immunotherapy. Patients receiving BCG achieved a response rate of 49% vs. those patients not receiving BCG of 44% (P = 0.579). Median response duration was 40 weeks for the BCG arms and 38 weeks for the arms without BCG; survival was no different, 42 weeks for the BCG arms vs. 50 weeks for the arms without BCG. In patients who responded to therapy and survived longer than one year, those who continued to receive BCG therapy demonstrated a slight, yet significant, survival benefit over those patients not receiving BCG (93 weeks vs. 81 weeks, P = 0.03). It appears that BCG immunotherapy has no beneficial effect on response rate, duration of response, or survival in programs using chemotherapy and radiotherapy for control of limited small-cell carcinoma of the lung except in this small group of long-term survivors.

Antineoplastic Agents↗

Correction of perfusate concentration for sample removal.

Repeated sampling of a drug solution that is recirculated through a perfused body increases the rate of drug disappearance from the perfusate. When the volume of the drug solution (VT) is maintained constant by addition of drug-free perfusate after sampling, the measured drug concentration (Ci) can be corrected for drug removed in previous samples by using the equation C'i = CiVTC'i-1/(VT - VS)Ci-1, where C'i is the corrected drug concentration in the ith sample, VS is the volume of the sample, and C'1 = C1. An error in an particular Ci is not transmitted to a subsequent C'i value. The method can be used when the time interval between samples and when VS vary from sample to sample, but return of the drug from the perfused body to the perfusate after sampling may cause C'i to be overestimated.

Perfusion↗

Vitamin D resistant rickets with alopecia: cultured skin fibroblasts exhibit defective cytoplasmic receptors and unresponsiveness to 1,25(OH)2D3.

A new case of vitamin D dependent rickets (Type II) with alopecia in a 5 yr old child is reported. Skin fibroblasts were propagated in culture and analyzed for cytoplasmic 1,25(OH)2D3 receptors. The rachitic cells failed to exhibit specific, high-affinity binding sites by either Scatchard analysis or sucrose density gradient. Furthermore, a rise in 24-hydroxylase activity could not be elicited following incubation of the rachitig cells with 1,25(OH)2D3. Fibroblasts from a non-rachitic child examined in parallel experiments demonstrated high affinity binding sites (Kd = 0.1 nM, Nmax = 33 fmol/100 micrograms DNA) and the induction of 24-hydroxylase activity. The molecular basis of the unresponsiveness of the cells from the rachitic child appears to be due to defective or absent 1,25(OH)2D3 receptors.

Alopecia↗

Isolated pleural effusion in small cell lung carcinoma: favorable prognosis. A review of the Southwest Oncology Group experience.

The currently accepted staging system for small cell lung cancer considers patients who present with a pleural effusion as having extensive disease, but no series of such patients has been reported. Between 1974 and 1980, 56 patients with ipsilateral pleural effusion as the only evidence of metastatic spread beyond the primary tumor and regional nodes were place on three consecutive Southwest Oncology Group studies of chemotherapy and radiation therapy for small cell lung cancer. Effusions were cytology-positive in 24: response rates and survival were not different whether cytology was positive or negative. The overall response rate was 77 percent, with 36 percent who achieved complete response, a result comparable to that for patients with limited disease. The survival of effusion "only" patients did not differ significantly among the studies. Median survival of 54 weeks and survival curve for the effusion "only" group as a whole was identical to that of all patients classed as having limited disease by the usual criteria. Long-term disease-free survival was observed just as commonly: 2/17 patients from the first study have disease-free survival at greater than five years, and overall disease-free survival at greater than two years is 22 percent. Performance status does not explain the favorable survival in this subgroup, since only 55 percent of effusion patients were fully ambulatory (comparable to extensive disease patients as a group) and even fully ambulatory patients with extensive disease rarely had disease-free survival greater than two years. Patients with ipsilateral pleural effusion as their only evidence of metastasis should be staged as having limited disease.

Carcinoma, Small Cell↗

Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphatic leukemia: a pediatric oncology group study.

The efficacy of intrathecal (i.t.) chemoprophylaxis was compared with cranial radiotherapy plus i.t. methotrexate (MTX) in a Southwest Oncology Group (SWOG) study accessing 408 patients from September 10, 1974, to October 29, 1976. Randomization was stratified by prognostic groups (PGs) based on age and white blood cell count at diagnosis. All received induction therapy with vincristine and prednisone (Pred); maintenance therapy consisted of daily 6-mercaptopurine and weekly MTX. Consolidation for arm 1 employed cyclophosphamide and L-asparaginase followed by biweekly 5-day courses of parenteral MTX. The first dose of each course of MTX was given i.t. in triple chemoprophylaxis (MTX, hydrocortisone, and cytosine arabinoside). During maintenance, i.t. chemoprophylaxis was bimonthly and 28-day Pred "pulses" were given every 3 mo. Arm 2 i.t. chemoprophylaxis was initiated on achievement of remission, and arm 3 i.t. on treatment day 1; both continued 1 yr. Arm 4 induction included two doses of L-asparaginase. On achievement of remission, CNS prophylaxis (radiotherapy, 2400 rad plus i.t. MTX) was given. For all, therapy was discontinued after 3 yr of continuous complete remission. Survival and the incidence of extramedullary relapse were similar for the treatments employing either i.t. chemoprophylaxis or radiotherapy plus i.t. MTX upon achievement of remission. Among poor prognosis patients, the duration of complete remission was significantly better with the regimen using i.t. chemoprophylaxis as a component of consolidation therapy than with the regimen employing i.t. chemoprophylaxis early in induction or with the treatment using radiotherapy plus i.t. MTX for CNS prophylaxis. In poor prognosis patients, the initiation of i.t. chemoprophylaxis during consolidation was also associated with hematologic remissions that were significantly better than those achieved with the treatment employing early CNS chemoprophylaxis or with the regimen using radiotherapy plus i.t. MTX. Among average prognosis patients, therapy with CNS chemoprophylaxis during consolidation, as well as the regimen employing radiotherapy and i.t. MTX for CNS prophylaxis, produced hematologic remissions that were significantly longer than those obtained with the regimen using early CNS chemoprophylaxis. Hematologic remissions of good prognosis patients who received treatment with the regimen employing i.t. chemoprophylaxis during consolidation were statistically superior when compared to the regimen employing CNS radiotherapy plus i.t. MTX. This study indicates that i.t. chemoprophylaxis may be substituted for cranial radiotherapy when utilizing effective systemic regimens. Additionally, chemoprophylaxis may be reduced from 3 to 1 yr in patients with good prognostic factors.

Adolescent↗

Intergroup Hodgkin's disease in children study of stages I and II: a preliminary report.

The intergroup study of involved-field (IF) radiotherapy, IF radiotherapy plus MOPP chemotherapy, and extended-field (EF) radiotherapy for treatment of Hodgkin's disease in children has assessed 305 patients. Of these, 279 were "not ineligible" (no mediate cause for disqualification). Among 223 randomized patients, 144 were evaluable, 131 had documentation of complete or partial remission, 20 of the remitters relapsed, and two died. Among 62 nonrandomized patients with favorable presentations (unilateral upper neck, unilateral inguinal, or massive mediastinal disease), 29 had documented remission, two relapsed, and none died. Length of initial disease control (LIDC) was used to measure duration of response. LIDC was best in patients given IF plus MOPP, and 95% are disease free. EF was better than IF radiotherapy (P = 0.004). Of the disease characteristics prognostic for response (stage, histologic subtype, and presence of symptoms), only the last factor had a statistically significant effect on LIDC (P = 0.004). Ninety-six percent of the patients survive. Using criteria developed by the committee, 23% of the staging procedures reviewed were nonevaluable and 28% of the radiotherapy treatments were nonevaluable. The necessity for criteria for evaluation of staging and treatment is certain. Length of followup is too short for correlations of treatment with significant late effects and for relevant therapeutic recommendations.

Antineoplastic Agents↗