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Biomedical subjects

Y K Chan

Publications and source records attributed to Y K Chan.

At least 73 records · Page 4Linked to original sources

Upper and lower bounds for correlations in 2 X 2 tables--revisited.

The correlation coefficient (r) between two dichotomous variables requires a different interpretation from that of the customary correlation between normally distributed continuous variables, since perfect correlation is usually not +1 or -1. The maximum and minimum possible correlations between two dichotomous variables depend on the marginal distributions. An example using data on smoking and lung cancer illustrates that what appears to be a small correlation in the usual sense may in fact be quite large in relation to the maximum possible. Similarly, the interpretation of R2 as the proportion of variance of the dependent variable that is explained by the independent variable(s) is subject to the same consideration. This paper describes the calculation of the upper and lower limits of r for two dichotomous variables. The problem of interpreting R2 in linear regression and the use of R2 for variable selection in stepwise regression applied to dichotomous data are also discussed and illustrated.

Epidemiologic Methods↗

Validation of a risk function to predict mortality in a VA population with coronary artery disease.

A multivariate risk function based on the Cox model was developed in the VA Study of Coronary Artery Bypass Surgery to predict the survival of patients with stable angina pectoris. The methods used in developing and evaluating the performance of the risk function (validation) are described. Performance was evaluated internally by the methods of resubstitution, half-sample replication, and jackknifing, and externally by use of an independent patient population.

Actuarial Analysis↗

Chemical properties of the functional groups of insulin.

The method of competitive binding [Kaplan, Stevenson & Hartley (1971) Biochem. J. 124, 289-299] with 1-fluoro-2,4-dinitrobenzene as the labelling reagent [Duggleby & Kaplan (1975) Biochemistry 14, 5168-5175] was used to determine the chemical properties, namely pK and reactivity, of the amino groups, the histidine residues and the tyrosine residues of the dimeric form of pig zinc-free insulin at 20.0 degrees C. The N-terminal glycine residue of the A-chain has a pK of 7.7 and a slightly higher than normal reactivity. The N-terminal phenylalanine residue of the B-chain has a pK of 6.9 and is approximately an order of magnitude more reactive than a corresponding amino group with the same pK value. The lysine epsilon-amino group has an unusually low pK of 7.0 but has approximately the expected reactivity of such a group. In the case of the two histidine and four tyrosine residues only the average properties of each class were determined. The histidine residues have a pK value of approx. 6.6, but, however, their reactivity is at least an order of magnitude greater than that of a free imidazole group. The tyrosine residues have a pK value of approx. 10, but their average reactivities are substantially less than for a free phenolic group. At alkaline pH values above 8 the reactivity of all the functional groups show sharp discontinuities, indicating that insulin is undergoing a structural change that alters the properties of these groups.

Acetic Anhydrides↗

Protection of patient rights and welfare in the VA cooperative studies program.

Four VA Cooperative Studies Program Coordinating Centers have been established by the Cooperative Studies Program of the Medical Research Service of the Veterans Administration. Affiliated with each Coordinating Center is a Human Rights Committee (HRC). These HRCs function similarly to the Institutional Review Board but differ from it in many significant ways. This paper presents the organizational structures, the responsibilities, and the inherent dynamics of the HRCs. With clear and defined objectives and guidelines, the HRCs monitor the multicenter cooperative studies conducted within the VA health care system. The HRCs strive to balance the need for protecting patients' rights and welfare with the need for research. Its specific role is to ensure that multicenter trials are planned, implemented, and evaluated such that the rights and welfare of study subjects are protected. This is accomplished by reviewing the content and the procedures of the informed consent during the planning stage as well as by the site visits and continuing reviews during the ongoing phase of each cooperative study.

Clinical Trials as Topic↗

Methods for assessing nutritional status of patients with renal failure.

Since wasting and malnutrition are common problems in patients with renal failure, it is important to develop techniques for the longitudinal assessment of nutritional status. This paper reviews available methods for assessing the nutritional status; their possible limitations when applied to uremic patients are discussed. If carefully done, dietary intake can be estimated by recall interviews augmented with dietary diaries. Also, in a stable patient with chronic renal failure, the serum urea nitrogen (N)/creatinine ratio and the rate of urea N appearance reflect dietary protein intake. A comparison of N intake and urea N appearance will give an estimate of N balance. Anthropometric parameters such as the relationship between height and weight, thickness of subcutaneous skinfolds, and midarm muscle circumference are simple methods for evaluating body composition. Other methods for assessing body composition, such as densitometry and total body potassium, may not be readily applicable in patients with renal failure. More traditional biochemical estimates of nutritional status such as serum protein, albumin, transferrin, and selected serum complement determinations show that abnormalities are common among uremic patients. Certain anthropometric and biochemical measurements of nutritional status are abnormal in chronically uremic patients who appear to be particularly robust; thus, factors other than altered nutritional intake may lead to abnormal parameters in such patients. Serial monitoring of selected nutritional parameters in the same individual may improve the sensitivity of these measurements to detect changes. Standards for measuring nutritional status are needed for patients with renal failure so that realistic goals can be established optimal body nutriture.

Adipose Tissue↗

Hydrogen metabolism of Azospirillum brasilense in nitrogen-free medium.

Production of H2 by Azospirillum brasilense under N2-fixing conditions was studied in continuous and batch cultures. Net H2 production was consistently observed only when the gas phase contained CO. Nitrogenase activity (C2H2 reduction) and H2 evolution (in the presence of 5% CO) showed a similar response to O2 and were highest at 0.75% dissolved O2. Uptake hydrogenase activity, ranging from 0.3 to 2.5 mumol H2/mg protein per hour was observed in batch cultures under N2. Such rates were more than sufficient to recycle nitrogenase-produced H2. Tritium-exchange assay showed that H2 uptake was higher under Ar than under N2. Uptake hydrogenase was strongly inhibited by CO and C2H2. Cyclic GMP inhibited both nitrogenase and uptake hydrogenase activities.

Acetylene↗

A simple electron cone interlock system for the clinac-18.

A simple electron cone-collimator interlock system has been developed for the Clinac-18. Each cone is assigned a special slot in the storage cabinet and, upon being taken for treatment setup, sends out a binary coded decimal (BCD) signal to the control console. The voltage from the collimator setting must match the BCD signal or a comparator logic will drive the fault matrix to prevent the accelerator from energizing.

Electrons↗

Measurement of denitrification in two freshwater sediments by an in situ acetylene inhibition method.

An acetylene inhibition method was satisfactorily used for the in situ measurement of denitrification in two sediment-water systems incubated for not more than 22 h. In the presence of added nitrate, denitrification acted as a source of nitrous oxide in a drainage pond, but acted as a sink in its absence. The averaged rates of nitrous oxide accumulation with nitrate enrichment in the absence and presence of acetylene were 0.15 and 0.30 mg of N mh, respectively. Acetylene reduction at an average rate of 0.07 mmol of C(2)H(4) formed mh was simultaneously measured in the absence of added nitrate. In a small eutrophic lake where nitrogen was nonlimiting, the in situ rates of sediment denitrification were 0.09 and 0.11 mg of N mh in the presence and absence of macrophytes, respectively, and no acetylene reduction activity was found.

Journal Article↗

An attempt at synchronization of marrow cells in acute leukemia: relationship to therapeutic response.

The relationship between changes in the bone marrow labeling index and the patient's subsequent response to cycle-specific agents was studied by the South-eastern Cancer Study Group in adults with acute leukemia. Ninety-eight patients were randomized to one of two treatment regimens. Schedule 1 consisted of a single intravenous (i.v.) push of cytosine arabinoside followed in 48 hours by a large dose of oral methotrexate distributed over 24 hours and i.v. vincristine. Leucovorin rescue was employed to control the toxic effects of the high dose methotrexate and the cycle was repeated every 7 days. Schedule 2 differed only in that there were three daily injections of cytosine arabinoside preceding vincristine and methotrexate injections and each cycle was given every 10 days. Cell kinetic studies were performed in 30 patients and revealed that the majority of patients who had a response to therapy had some increase in the marrow labeling index 48 hours after cytosine arabinoside injection. In general, those patients who had no response to therapy had little change. There was no significant difference between schedules in the ability to induce an increase in labeling index 48 hours after cytosine arabinoside or in the increment achieved by the responders. However, there was a significant difference in the response rate seen with these schedules. Schedule 1 achieved only a 24% remission rate in acute nonlymphocytic leukemia (ANLL) while schedule 2 was associated with a 52% remission rate. In acute lymphoblastic leukemia (ALL) both schedules induced a 60% remission rate while none of the four patients with blast crisis of chronic granulocytic leukemia (CGL) responded. Analysis of the characteristics associated with remission revealed that more females achieved a remission than males and that the presence of pretreatment infection was the greatest contributing cause of early death and thus severely limited the ability to achieve a remission. As opposed to the current regimens used in ANLL, schedule 2 did not require significant bone marrow hypoplasia (as judged by the degree of hematological toxicity) to achieve a remission and there was no decrease in response seen with increasing age. The data suggest that increased efficiency of cycle-specific, antitumor agents may occur by increasing the proportion of human leukemic cells in DNA synthesis.

Adult↗

A comparison of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) vs. nitrogen mustard in advanced Hodgkin's disease.

A randomized study of patients with advanced Hodgkin's disease was designed to determine whether the improved therapeutic effectiveness of combination chemotherapy was due to the use of a combination of drugs or might be achieved with a single agent if given as intensively and for as long a period. A combination of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) was compared with nitrogen mustard (HN2) alone. Treatment with both regimens was given to tolerance on cylic basis and was continued for six cycles of treatment. Sixty-one evaluable patients were treated with MOPP and 47 with HN2. The complete remission rate of 47.5% with MOPP was significantly better than the 12.8% with HN2 (p less than .05). Complete remission lasted a median of 15 months after MOPP and 12 months after HN2. The survival of patients initially treated with MOPP was significantly better than that of those initially treated with HN2.

Drug Evaluation↗

1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU), cyclophosphamide, vincristine- and prednisone-(BCOP). A new therapeutic regimen for diffuse histiocytic lymphoma.

Sixty-seven evaluable patients with mixed cellular and histiocytic lymphomas, both nodular and diffuse, were treated with a combined drug regimen of BCNU, cyclophosphamide, vincristine, and prednisone administered for six monthly courses. Of 28 previously untreated patients with diffuse histiocytic lymphoma, 14 (50%) achieved a complete remission, and an additional 7 (25%) had a good partial response for an overall remission rate of 75%. Complete remissions were also obtained among the small number of mixed and nodular histiocytic lymphomas which were treated. The median survival for previously untreated patients with diffuse histiocytic lymphoma who achieved a complete remission is nearly two years and 42% (8/19) of these patients remain in their initial unmaintained remission (range 2-119 weeks). Hematologic toxicity, although acceptable, was the limiting factor. Granulocytes were more often and more severely depressed than platelets.

Carmustine↗

Determination of endotoxicity in bacterial vaccines.

Endotoxicity of bacterial vaccines was quantitated in mice by using actinomycin D as potentiating agent. The results were compared with those obtained by the mouse weight gain test. The lethality of Escherichia coli lipopolysaccharide was increased 2,140 times when 12.5 mug of actinomycin D was used. The mean lethal dose values of heated and unheated pertussis vaccines were similar in the actinomycin D enhancement assay, but the unheated vaccine was significantly more toxic in the mouse weight gain test. Acetone-inactivated typhoid vaccine was slightly less toxic than the heat-phenol-inactivated vaccine in both the actinomycin D enhancement assay and mouse weight gain test. Endotoxicity of experimental vaccines prepared by extraction of Pseudomonas aeruginosa strains was high as compared with E. coli lipopolysaccharide. The BALB/c mice were about four times more susceptible than the random bred NIH strain mice. The results indicate that the actinomycin D enhancement assay had the advantages of being more sensitive and probably more specific.

Acetone↗