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Biomedical subjects

C K Chan

Publications and source records attributed to C K Chan.

At least 19 recordsLinked to original sources

Simulations of the temperature dependence of energy transfer in the PSI core antenna.

In order to understand the organization of the PSI core antenna and to interpret results obtained from studies of the temperature and wavelength dependence of energy transfer and trapping in the PSI particles, we have constructed a model for PSI in which spectral heterogeneity is considered via a self-consistent approach based on Forster transport. The temperature dependence of the absorption and emission spectra of the individual Chl molecules in the protein matrix is calculated based on a model Hamiltonian which includes a phonon contribution. Time and wavelength resolved kinetics of PSI at different temperatures are investigated by means of two-dimensional lattice models. We conclude that wavelength-dependent fluorescence decay kinetics result only when two or more bottlenecks exist in the energy transfer and trapping process. A single trap or several pseudo-traps with spectrally identical environments do not lead to wavelength dependent decays. Simple funnel arrangements of the spectral types can be ruled out. At least one pigment with energy lower than the photochemical trap located close to the reaction center is required to produce the trends of the fluorescence lifetimes observed experimentally. The remainder of the core antenna is consistent with a random arrangement of spectral types.

Bacterial Proteins

An improved technique for management of dislocated posterior chamber implants.

Many techniques for repositioning dislocated posterior chamber implants described in the recent literature involve intricate intraocular manipulation of a needle or other sharp instrument. The author describes an improved sulcus fixation technique, which combines the best features of external and internal approaches. Its main features involve temporary externalization of the haptics for easy and secured placement of suture knots, and subsequent reinternalization of the same haptics through horizontal sclerotomies directly external to the ciliary sulcus for precise fixation of the dislocated posterior chamber implant with consistency. Between May 1989 and December 1990, this technique was successfully used for posterior chamber intraocular lens repositioning in 12 cases. The main advantages of this technique include: (1) easy suture placement, (2) less chance of suture slippage with the secured knots, and (3) avoidance of difficult intraocular maneuvers and possible tissue injury. This improved technique expedites the process of posterior chamber implant repositioning.

Adult

Phorbol ester-induced actin assembly in neutrophils: role of protein kinase C.

The shape changes and membrane ruffling that accompany neutrophil activation are dependent on the assembly and reorganization of the actin cytoskeleton, the molecular basis of which remains to be clarified. A role of protein kinase C (PKC) has been postulated because neutrophil activation, with the attendant shape and membrane ruffling changes, can be initiated by phorbol esters, known activators of PKC. It has become apparent, however, that multiple isoforms of PKC with differing substrate specificities exist. To reassess the role of PKC in cytoskeletal reorganization, we compared the effects of diacylglycerol analogs and of PKC antagonists on kinase activity and on actin assembly in human neutrophils. Ruffling of the plasma membrane was assessed by scanning EM, and spatial redistribution of filamentous (F)-actin was assessed by scanning confocal microscopy. Staining with NBD-phallacidin and incorporation of actin into the Triton X-100-insoluble ("cytoskeletal") fraction were used to quantify the formation of (F)-actin. [32P]ATP was used to detect protein phosphorylation in electroporated cells. Exposure of neutrophils to 4 beta-PMA (an activator of PKC) induced protein phosphorylation, membrane ruffling, and assembly and reorganization of the actin cytoskeleton, whereas the 4a-isomer, which is inactive towards PKC, failed to produce any of these changes. Moreover, 1,2-dioctanoylglycerol, mezerein, and 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol, which are nonphorbol activators of PKC, also promoted actin assembly. Although these effects were consistent with a role of PKC, the following observations suggested that stimulation of conventional isoforms of the kinase were not directly responsible for actin assembly: (a) Okadaic acid, an inhibitor of phosphatases 1 and 2A, potentiated PMA-induced protein phosphorylation, but not actin assembly; and (b) PMA-induced actin assembly and membrane ruffling were not prevented by the conventional PKC inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, staurosporine, calphostin C, or sphingosine at concentrations that precluded PMA-induced protein phosphorylation and superoxide production. On the other hand, PMA-induced actin assembly was inhibited by long-chain fatty acid coenzyme A esters, known inhibitors of nuclear PKC (nPKC). We conclude that PMA-induced actin assembly is unlikely to be mediated by the conventional isoforms of PKC, but may be mediated by novel isoforms of the kinase such as nPKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

High incidence of bronchospasm with regular administration of aerosolized pentamidine.

A systematic evaluation of changes in pulmonary status by objective spirometric assessment and subjective rating using visual analog scale was performed in a cohort of 134 patients receiving aerosolized pentamidine (AP) for the prevention of Pneumocystis carinii pneumonia. Significant bronchospasm defined as greater than or equal to 15 percent reduction in the forced expiratory volume in 1 s was noted in 26 of 100 (26 percent) of patients receiving AP alone. Despite the use of salbutamol (albuterol) as concurrent aerosolized treatment in 34 subjects, bronchospasm developed in 9 of 34 (26 percent) of the patients. The subjective respiratory status rating scale was found to be unreliable in correctly predicting the development of bronchospasm. We conclude that a high incidence of bronchospasm is present in patients receiving regular AP administration using an ultrasonic nebulizer as studied, and concurrent administration of salbutamol is not fully protective of this acute adverse pulmonary reaction.

Aerosols

Bleomycin-induced pulmonary function abnormalities.

The usefulness of serial PFTs in identifying patients who are developing BIP was assessed in 59 men with non-seminomatous testicular carcinoma. The mean age was 27.7 years and all the patients received a standard three-course chemotherapy regimen consisting of vinblastine, bleomycin, and cis-diamminedichloroplatinum. The average dose of bleomycin was 555.5 units. Serial PFTs, chest roentgenograms, and medical assessments were done prior to each course of bleomycin. Nine (15.3 percent) patients developed pulmonary symptoms due to bleomycin and 23 (39 percent) had significant changes on chest x-ray films. The Dsb dropped significantly with bleomycin treatment; therefore, it is the most sensitive indicator of pulmonary response to bleomycin. However, the Dsb failed to differentiate patients with BIP from those without. The TLC was found to be a much more specific indicator of BIP because reduction in TLC correlated with the development of pulmonary symptoms and roentgenologic changes.

Adolescent

Long-term sequelae after recovery from cytomegalovirus pneumonia in allogeneic bone marrow transplant recipients.

The clinical course of cytomegalovirus (CMV) pneumonia in seven consecutive bone marrow transplant (BMT) recipients during a 24-month period was studied. Retrospective analysis of clinical data on the recipients with CMV pneumonia during the illness and prospective follow-up of those who recovered from the pneumonia was performed. Those who had CMV as the sole pathogen and with lymphocytosis in the BAL or the peripheral blood during the illness recovered from the pneumonia. On the contrary, those who had mixed bacterial or fungal infection with peripheral lymphopenia died. Persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, was observed in the survivors. Two subsequently developed restrictive lung disease and two had relapse of their primary malignancy. These data suggest that CMV pneumonia in BMT patients is associated with significant long-term sequelae. The phenomenon of persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, supports Grundy's hypothesis that CMV pneumonia in BMT recipients is an immunopathologic condition.

Bone Marrow Transplantation

Changes in hospital admissions pattern in patients with human immunodeficiency virus infection in the era of Pneumocystis carinii prophylaxis.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) was the leading cause of hospital admissions in patients with human immunodeficiency virus (HIV) infection before the widespread use of PCP prophylaxis. We studied retrospectively the changes in annual hospital admission patterns after the start of a population-based PCP prophylaxis program in Toronto. The purpose of the study was to identify the cogent diseases requiring hospitalization of HIV patients in the current era of PCP prophylaxis. This information is important for the allocation of health care resources in the future as well as for targeting research in the prevention of specific HIV-related diseases. METHODS: The annual HIV-related hospital admissions before and after the start of the Toronto aerosol pentamidine program (May 1989) were studied. All admission records due to AIDS-defining illnesses or occurring in patients with known HIV status in three major referral centers were reviewed. The two periods for comparison were May 1988 through April 1989 and May 1989 through April 1990. The data obtained were stratified according to the following: (1) cause of the illness prompting hospital admission; (2) PCP admissions; and (3) admissions according to the major organ system involved. These categoric data were compared by nonparametric chi 2 tests. RESULTS AND CONCLUSIONS: Population-based prophylaxis of PCP with aerosol pentamidine resulted in a significant reduction in the total number of PCP hospital admissions. Infection remains the principal cause of hospital admission in HIV patients after the start of the PCP prophylaxis program. However, there was an increase in the proportion of hospital admissions due to nonrespiratory-related infections. There was also a modest increase in admissions due to neurologic and gastrointestinal diseases. Central nervous system lymphoma and cytomegalovirus retinitis accounted for the majority of the rise in the nervous system. These data suggest there is a changing pattern of the diseases leading to the hospitalization of patients with HIV infection in the era of PCP prophylaxis.

AIDS-Related Opportunistic Infections

The long-term effects of aerosol pentamidine on pulmonary function. The Toronto Aerosolized Pentamidine Study (TAPS) Group.

Aerosolized pentamidine (AP) has been widely used for prophylaxis of pneumocystis carinii pneumonia (PCP) since 1988. The objective of this study was to evaluate the long-term effects of AP on pulmonary function. Of 36 patients with AIDS who were receiving AP for secondary prophylaxis of PCP, 13 patients had been using AP continuously for more than 52 weeks. AP was given using a Fisoneb ultrasonic nebulizer with five loading doses of 60 mg over two weeks, followed by one dose of 60 mg every two weeks. Baseline PFT were TLC 92 +/- 14% pred, FVC 90 +/- 11% pred, FEV1 91 +/- 11% pred, FEF25-75 95 +/- 17% pred, and DLCO (corrected for hemoglobin) 70 +/- 22% pred. No significant change in TLC, FVC, FEV1, or DLCO was seen after 56 weeks of AP. There was a 20% fall in FEF25-75 seen after 56 weeks, which was statistically significant. However, the clinical significance of a fall of this magnitude in the FEF25-75 is uncertain. Similar results were seen in a smaller subset of patients who received AP for at least 76 weeks. Although the small sample size must be considered, this data suggests that there is no clinically significant change in pulmonary function associated with the use of AP for up to 76 weeks.

Acquired Immunodeficiency Syndrome

Mechanism of the initial charge separation in bacterial photosynthetic reaction centers.

The initial electron transfer in reaction centers from Rhodobacter sphaeroides R26 was studied by a subpicosecond transient pump-probe technique. The measured kinetics at various wavelengths were analyzed and compared with several mechanisms for electron transfer. An unambiguous determination of the initial electron transfer mechanism in reaction centers cannot be made by studying the anion absorption region (640-690 nm), due to the spectral congestion in this region. However, correlations between the stimulated emission decay of the excited state of the special pair, P*, at 926 nm and bleaching of the bacteriopheophytin Qx absorption at 545 nm suggest that the electron transfer at 283 K is dominated by a two-step sequential mechanism, whereas one-step superexchange and the two-step sequential mechanism have about equal contributions at 22 K.

Electron Transport

Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. A randomized, placebo-controlled study.

OBJECTIVE: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). PARTICIPANTS: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. INTERVENTION: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of 5 doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. RESULTS: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and 5 occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P less than 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. CONCLUSION: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia.

Acquired Immunodeficiency Syndrome

Epstein-Barr virus antibody patterns preceding the diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) patients have elevated IgG and IgA antibody titers against the Epstein-Barr viral capsid antigen (VCA) and the diffuse component of the early antigen complex (EA-D) at diagnosis. Several studies have implied that the presence of anti-VCA-IgA can be used as a screening marker for early NPC. To evaluate this further, we undertook a serologic case-control study based on four serum banks which together had specimens from over 240,000 persons. Seven cases of undifferentiated or poorly differentiated NPC were diagnosed in the period after serum collection ranging from 26 months to 154 months. Two controls per case matched on serum bank, age, sex, race, and date of serum collection were selected by a predetermined random process. For anti-VCA-IgG, the geometric mean titer for cases (88.3) was significantly higher than that for controls (75.5, P less than 0.05). The difference was greatest among the Asian patients. No significant differences were found for anti-VCA-IgA, anti-EA-D, and anti-EA-R or anti-EBNA. No time effects were evident when titers were plotted against time of blood collection preceding diagnosis. Our results do not suggest EBV activation in the period preceding NPC diagnosis, nor that detectable IgA antibody against VCA is a marker for early disease.

Adult

Sleep apnea and systemic hypertension: a causal association review.

OBJECTIVE: To critically examine the causal association between sleep apnea syndrome and hypertension. METHODS: A retrospective systematic critique of five epidemiologic studies published in the English literature during 1978 to 1989 identified on Medline and manual literature searches. The evidence was evaluated using the standard observational criteria for causation: strength of association, consistency, dose-response relationship, temporal sequence, specificity, and biologic plausibility. RESULTS: We found evidence to support a causal association between sleep apnea syndrome and hypertension in consistency and specificity and some evidence to suggest a dose-response relationship. Review of the data dealing with the mechanisms important in the pathogenesis of sleep apnea and hypertension allowed us to advance several theories to provide support for biologic plausibility. CONCLUSION: We concluded that there is a positive association--relative risk estimate between 1.3 and 40--for sleep apnea syndrome and hypertension, but the risk association is unstable. Thus, we believe that there is insufficient data to justify doing polysomnography as part of the routine diagnostic work-up for patients with hypertension.

Causality

Measurement of 4 urinary C-18 oxygenated corticosteroids by stable isotope dilution mass fragmentography.

The cortisol C-18 oxidation pathway leading to the production of 18-hydroxy- and 18-oxocortisol is expressed in adenomatous primary aldosteronism and glucocorticoid remediable aldosteronism. In order to better define the significance of the pathway and its usefulness in differential diagnosis, we have developed a stable isotope dilution mass fragmentographic method for the determination of the tetrahydro metabolites of aldosterone, 18-hydroxycorticosterone and 18-oxocortisol and of unmetabolized 18-hydroxycortisol in urine. Stereochemically correct tetrahydro steroids containing 3 deuterium atoms were synthesized from the available 3-keto-4-pregnenes in 2 steps and 1,2-deuterium-labeled 18-hydroxycortisol was prepared by selective deuteration of the 1,2-double bond of a dienone precursor. Simultaneous measurement of the 4 steroids permitted a comparison of the abnormal products of the C-18 oxidation of cortisol with the normal C-18 oxidation products of corticosterone, 18-hydroxycorticosterone and aldosterone. Application of the method to the definition of the normal range is described.

Adrenal Cortex Hormones

Pneumocystis carinii pneumonia associated with methotrexate therapy in rheumatoid arthritis.

Opportunistic infections occur in patients with rheumatic diseases treated with low dose methotrexate (MTX) with or without other immunosuppressants. Our case report illustrates a fatal case of Pneumocystis carinii pneumonia in a patient with rheumatoid arthritis treated with low dose MTX and glucocorticoid. A review of the literature reveals other opportunistic infections such as Cryptococcus, Nocardia, and herpes zoster presenting in such patients. These occurrences suggest that MTX should be used cautiously in patients with rheumatic disease receiving concomitant medical therapy.

Adolescent

Classifying clinical severity to help solve problems of stage migration in nonconcurrent comparisons of lung cancer therapy.

To compare the effects of stage migration in the "traditional" 3-stage TNM (tumor, node, metastasis) system with those in a new "expanded" 5-stage system, which has two additional stages for the poor prognostic groups, we used both systems to classify a cohort of 178 patients with primary lung cancer. To check for migrations, the stages in both systems were first assigned using only "old" technological information and were then reassigned using all the available "new" as well as old technological data. Although the 5-stage system had more migrations than the 3-stage system, survival rates were relatively unaffected for patients in the two new stages with poor prognosis. In both TNM staging patterns, the effects of stage migration on survival statistics were most impressive in the prognostically better (TNM I and II) stages. A solution to the migration problem is offered by the "clinical severity" (CS) staging system. Like the expanded TNM system, the CS system has 5 stages and a sharp prognostic gradient among stages. The CS system, however, had fewer technology-induced stage migrations than either TNM system, and the migrations had no substantial impact on stage-specific survival results. The excellent prognostic discrimination and secular stability of the CS system make it superior to the TNM system for comparing treatment results from different eras, especially for patients with stage I and II disease.

Humans

Diagnostic criteria and technology as sources for changing incidences of pulmonary diseases.

PURPOSE: To investigate the impact of changes in diagnostic criteria and technology on the rates of occurrence of pulmonary diseases during each of four different calendar years: 1921, 1941, 1961, and 1982. PATIENTS AND METHODS: The medical records were obtained for all patients discharged from Yale-New Haven Hospital during 1921, 1941, 1961, and 1982 with a diagnosis of either pulmonary tuberculosis or primary lung cancer. Each patient's entire clinical course was then thoroughly reviewed, including all available data obtained in the six-month intervals before and after the patient's hospitalization. Critical diagnostic information obtained during life at any time during this one-year period was acceptable as evidence for the diagnosis. RESULTS: According to modern diagnostic criteria, the existing evidence of pulmonary tuberculosis or primary lung cancer often did not justify those diagnoses in patients hospitalized during each of the four survey years. The proportions of justified diagnoses showed a consistent increase over time: 16%, 42%, 53%, and 86%, respectively, for tuberculosis, and 0%, 54%, 93%, and 93%, respectively, for lung cancer. CONCLUSION: The results suggest that some of the statistical changes in occurrence rates for these two pulmonary diseases may be due to temporal improvements in diagnostic precision, not just to environmental changes or therapeutic advances.

Diagnosis, Differential

Comparative values of the precordial and transesophageal approaches in the echocardiographic evaluation of atrial baffle function after an atrial correction procedure.

Previous methods used to assess atrial baffle function after correction of transposition of the great arteries have included precordial echocardiography and cardiac catheterization. To evaluate whether single plane transesophageal echocardiography might provide additional information, its findings were correlated with information derived from both precordial echocardiography and cardiac catheterization in 15 patients (14 Mustard procedures, 1 Senning procedure) aged 4.2 to 33 years (mean 16.3). Precordial ultrasound with combined imaging, color flow mapping and pulsed Doppler ultrasound visualized the supramitral portion of the common systemic venous atrium in every case but could identify only superior limb obstruction in three of six patients, mid-baffle obstruction in zero of two and inferior limb obstruction in zero of two patients. Transesophageal studies with use of the same range of ultrasound methods demonstrated superior limb obstruction (severe in four, mild in two) in six of six patients, mid-baffle obstruction in two of two and inferior limb obstruction in two of two patients. The entire pulmonary venous atrium was equally well interrogated by either ultrasound approach, with both identifying three cases (two mild, one moderate) of mid-pulmonary venous atrium obstruction. However, individual pulmonary vein velocity profiles could only be recorded by transesophageal pulsed Doppler ultrasound. Precordial studies identified baffle leaks (1 large, 2 small) in only three patients, whereas transesophageal studies identified 11 such baffle leaks (1 large, 10 small), which were multiple in two patients. It is concluded that transesophageal echocardiography provides a more detailed and accurate assessment of atrial baffle morphology and function than is provided by either precordial ultrasound or cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent