Search PubMed⌕ Search

Biomedical subjects

C H Chan

Publications and source records attributed to C H Chan.

At least 73 records · Page 4Linked to original sources
PubMed1996

Reactivity of murine cytokine fusion toxin, diphtheria toxin390-murine interleukin-3 (DT390-mIL-3), with bone marrow progenitor cells.

Myeloid leukemias can express interleukin-3 receptors (IL-3R). Therefore, as an antileukemia drug, a fusion immunotoxin was synthesized consisting of the murine IL-3 (mIL-3) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mIL-3 hybrid gene was cloned into a vector under the control of an inducible promote. The fusion protein was expressed in Escherichia coli and then purified from inclusion bodies. The fusion toxin was potent because it inhibited FDC-P1, an IL-3R-expressing murine myelomonocytic tumor line (IC50 = 0.025 nmol/L or 1.5 ng/mL). Kinetics were rapid and cell-free studies showed that DT390-mIL-3 was as toxic as native DT. DT390-mIL-3 was selective because anti-mIL-3 monoclonal antibody, but not irrelevant antibody, inhibited its ability to kill. Cell lines not expressing IL-3R were not inhibited by the fusion protein. Because the use of DT390-mIL-3 as an antileukemia agent could be restricted by its reactivity with committed and/or primitive progenitor cells, bone marrow (BM) progenitor assays were performed. DT390-mIL-3 selectively inhibited committed BM progenitor cells as measured by in vitro colony-forming unit-granulocyte-macrophage and in vivo colony-forming unit-spleen colony assays. To determine if this fusion protein was reactive against BM progenitor cells required to rescue lethally irradiated recipients, adoptive transfer experiments were performed. Eight million DT390-mIL-3-treated C57BL/6 Ly5.2 BM cells, but not 4 million, were able to rescue lethally irradiated congenic C57BL/6 Ly5.1 recipients, suggesting that progenitor cells might be heterogenous in their expression of IL-3R. This idea was supported in competitive repopulation experiments in which DT390-mIL-3 treated C57BL/6 Ly5.2 BM cells were mixed with nontreated C57BL/6 Ly5.1 BM cells and used to reconstitute C57BL/6 Ly5.1 mice. A significant reduction, but not elimination, of Ly5.2-expressing cells 95 days post-BM transplantation and secondary transfer experiments indicated that IL-3R is not uniformly expressed on all primitive progenitor cells. The fact that some early progenitor cells survived DT390-mIL-3 treatment indicates that this fusion toxin may be useful in the treatment of myeloid leukemias that express the IL-3R.

Animals↗
PubMed1996

All-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL).

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All-trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event-free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p = 0.001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p = 0.001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p = 0.007). In conclusion, ATRA was shown to improve the CR rate, reduce induction mortality and significantly prolong the event-free survival.

Adolescent↗
PubMed1996

Persistence of AML1 rearrangement in peripheral blood cells in t(8;21).

Translocation (8;21)(q22;q22) involves fusion of the AML1 gene with the ETO gene, generating an AML1/ETO fusion transcript that can be detected by the polymerase chain reaction (PCR). Persistence of the AML1/ETO transcript has been demonstrated by PCR in patients with t(8;21) in long-term remission, but the rearranged AML1 gene could not be detected by Southern analysis, showing that the t(8;21) clone existed as minimal residual disease (MRD). In one patient with t(8;21), AML1/ETO could be detected serially in the peripheral blood. However, rearrangement of the AML1 gene was also found to persist. Furthermore, the hybridization intensities of the rearrangement bands showed that some of the mature myeloid cells also possessed the AML1 rearrangement. Thus, the presence of AML1/ETO in this case appeared to be due to persistence of the mutated clone as mature myeloid cells instead of MRD, implying that the t(8;21) had occurred in a preleukemic myeloid progenitor cell capable of differentiation.

Acute Disease↗
PubMed1996

Interleukin-5 messenger RNA expression in peripheral blood CD4+ cells in asthma.

BACKGROUND: IL-5 has been implicated in the pathogenesis of asthma through its regulatory role on eosinophil survival, proliferation, and effector function. OBJECTIVE: The study was designed to investigate the relationships between IL-5 messenger RNA expression in circulating CD4+ cells and serum concentrations of eosinophil cationic protein (ECP), a marker of eosinophil activation, and disease activity in asthma. METHODS: IL-5 gene expression was assessed semiquantitatively in ex vivo stimulated CD4+ cells by reverse transcription-polymerase chain reaction and serum ECP concentration measured from venous blood samples collected from patients with acute severe asthma before the commencement of systemic steroid therapy (day 1) and on day 7 and from patients with stable asthma and healthy volunteers. RESULTS: IL-5 gene expression was significantly higher in patients with acute asthma before steroid treatment than in those with stable disease and healthy subjects (p < 0.0001). Similar results were obtained with serum ECP levels: levels in patients with acute asthma were highest (20.30 +/- 5.31 micrograms/L), followed by levels in patients with stable asthma (2.76 +/- 0.65 micrograms/L) and levels in normal control subjects (1.37 +/- 0.06 micrograms/L; p < 0.01 for all comparisons). Significant falls in both IL-5 expression and serum ECP level were seen on day 7 (p < 0.001) and coincided with a significant improvement in peak expiratory flow (p < 0.0001). Significant correlations were observed between IL-5 expression and ECP level (rho = 0.39, p < 0.01), IL-5 expression and peak expiratory flow (rho = -0.55, p < 0.0002), and peak expiratory flow and ECP level (rho = -0.32, p < 0.04). CONCLUSION: Our data therefore support an important regulatory role of IL-5 on eosinophil function in human asthma in vivo.

Acute Disease↗
PubMed1996

Gene expression of interleukin-3 and granulocyte macrophage colony-stimulating factor in circulating CD4+ T cells in acute severe asthma.

BACKGROUND: Interleukin (IL)-3 and granulocyte macrophage colony-stimulating factor (GM-CSF) may influence the inflammatory process in asthma through their regulatory role on eosinophil survival, differentiation and effector function. OBJECTIVE: To examine the relationships between IL-3 and GM-CSF messenger (m) ribonucleic acid (RNA) expression in peripheral blood CD4+ cells and serum levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, and disease activity in asthma. METHODS: Venous blood was drawn from patients with acute severe asthma prior to the commencement of systemic steroid therapy (day 1) and 7 days afterwards (day 7), patients with stable disease and normal healthy volunteers. The capacity for expression of IL-3 and GM-CSF in ex vivo stimulated circulating CD4+ cells was assessed semi-quantitatively by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found that the capacity for expression of IL-3 and GM-CSF was significantly higher in acute asthmatics prior to steroid treatment (n = 24) than those in stable disease (n = 38) and healthy subjects (n = 32, P < 0.001 for IL-3 and < 0.05 for GM-CSF), but no difference was observed between the latter two groups. Further assessment made in 15 of the 24 acute asthmatics 7 days after systemic steroid treatment revealed a significant reduction in GM-CSF expression (P < 0.05) but not for IL-3. At the same time, PEF also improved significantly from 30.4 +/- 3.5% of predicted value to 72.9 +/- 7.2% (P < 0.0001) and serum ECP concentration also fell from 19.9 +/- 5.9 micrograms/L to 4.3 +/- 2.0 micrograms/L (n = 10, P < 0.01). CONCLUSION: Our data suggest both IL-3 and GM-CSF may be important in the pathogenesis of acute severe asthma.

Acute Disease↗
PubMed1996

Effect of renal transplantation on pulmonary function in patients with end-stage renal failure.

Ten patients with end-stage renal failure on maintenance dialysis underwent serial lung function tests before and at monthly intervals after renal transplantation. Mean values of forced expiratory volume within 1 s, forced vital capacity, and total lung capacity were within the normal range before and up to 6, months after transplantation. The mean value of residual volume (RV) was above the normal range during all periods measured (157.8 +/- 21.5% predicted before transplantation and 121.2 +/- 17.0% predicted at 6 months after transplantation). No statistically significant changes in lung volumes were detected over a course of 6 months, but there was a trend for a reduction in RV after transplantation. The single-breath diffusion capacity for carbon monoxide (DLCO) was in the high-normal range before transplantation (115.7 +/- 9.5% predicted). It remained high at 1 month after transplantation (124.5 +/- 12.2% predicted), but it gradually came down to the normal range from the 2nd month onwards. At 6 months after transplantation the mean DLCO was 83.8 +/- 7.3% of predicted which was significantly (p < 0.0001) lower than the value before transplantation. We conclude that raised DLCO and RV values occurred in patients with end-stage renal failure on maintenance dialysis which were most likely the result of pulmonary vascular congestion, and these abnormalities tend to improve after renal transplantation.

Adult↗
PubMed1996

Paroxetine in the treatment of Chinese patients with depressive episode: a double-blind randomized comparison with imipramine.

BACKGROUND: Paroxetine is a potent inhibitor of serotonin re-uptake. Although it has been widely used as an antidepressant in western countries, its efficacy and side effects in the Chinese are unknown. METHODS: Patients with major depressive episode were recruited from the outpatient clinic and the acute wards of the Department of Psychiatry, Veterans General Hospital-Taipei in 1994. Severity of depression was evaluated with Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression (CGI) and the adverse effects were evaluated with Treatment Emergent Symptom Scale (TESS). Forty Chinese patients with HAM-D scores > or = 18 at the beginning of the first dose were randomized to receive paroxetine (20 to 30 mg/day) or imipramine (100 to 125 mg/day). The dosage was designed as a fixed-adjustable regimen for an active treatment period of six weeks. The patients and the clinical investigators were both blind to the medication until the end of the trial. RESULTS: Five patients violating the trial protocol were excluded from this study, leaving 35 patients for efficacy and adverse effect analyses. Sixty-seven percent (12/18) of paroxetine-treated patients and 65% (11/17) of imipramine-treated patients showed a 50% or more reduction in HAM-D scores. The rate of patients whose mood recovered to normal or near-normal (borderline) was higher in the paroxetine group (66.7%) than in the imipramine group (35.3%), but the difference was not statistically significant (p = 0.13). At the end of this trial, the mean reduction of HAM-D scores was similar between groups (20.2 +/- 9.1 vs 15.3 +/- 8.4, p > 0.1). Three patients in the paroxetine group and two patients in the imipramine group withdrew prematurely due to adverse effects of impatience. Adverse effects of anticholinergic effects were reported more frequently in the imipramine group than in the paroxetine group (p = 0.01). CONCLUSIONS: In comparison with imipramine, paroxetine affords fewer anticholinergic adverse effects without the sacrifice of efficacy in the treatment of depressed Chinese patients.

Adult↗
PubMed1995

A murine cytokine fusion toxin specifically targeting the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor on normal committed bone marrow progenitor cells and GM-CSF-dependent tumor cells.

A fusion protein was synthesized consisting of the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mGM-CSF hybrid gene was cloned into a vector under the control of an inducible promoter and the protein expressed in Escherichia coli. After induction, a protein was purified from inclusion bodies in accord with the deduced molecular weight of DT390 mGM-CSF. Cell-free studies of the adenosine diphosphate-ribosylating activity of DT390 mGM-CSF showed results that were similar to those of native DT. The DT390 mGM-CSF immunotoxin inhibited FDCP2.1d, a murine myelomonocytic tumor line expressing the GM-CSF receptor with an IC50 (concentration inhibiting 50% activity) of 5 x 10(-11) mol/L. The fusion toxin was specifically cytotoxic and directed by the GM-CSF portion of the molecule because addition of a monoclonal antibody directed against GM-CSF inhibited its ability to kill the cell line. Cell lines that do not express GM-CSF receptor were not inhibited by the fusion toxin. DT390 mGM-CSF was also able to specifically inhibit normal committed bone marrow (BM) progenitor cells as measured in clonal colony-forming unit granulocyte-macrophage assays. Together, these findings indicate that DT390 mGM-CSF may be useful as a novel tool for purging BM of contaminating leukemia cells or in vivo for eliminating residual leukemia cells. Also, it can be used to determine whether committed and/or noncommitted BM progenitor cells express the GM-CSF receptor.

Amino Acid Sequence↗
PubMed1995

The effect of age on the presentation of patients with tuberculosis.

OBJECTIVE: To study the differences in presentation of young and elderly patients with tuberculosis (TB). DESIGN: Between January 1991 and December 1992 all patients with TB diagnosed at the Department of Medicine, Prince of Wales Hospital, were recruited into the study. The following data were collected: body weight, coexisting medical problems, presenting symptoms, radiographic appearance, sputum results for acid-fast bacilli and peripheral blood biochemistry. The patients were divided into young ( < 65 years) and elderly ( > or = 65 years) age groups and differences in presentation of the 2 groups were analysed. RESULTS: There were 78 young and 94 elderly patients with TB. The elderly patients had lower body weight, less haemoptysis but more non-specific complaints (25% vs 1%, P = 0.001). The chest radiographs in the elderly patients were less likely to have upper lobe infiltration (9% vs 37%, P = 0.0002) but more commonly had extensive infiltration of both lungs (17% vs 2%, P = 0.014). The only biochemical abnormality that was more common in the elderly was a low serum albumin level (64% vs 45%, P < 0.05). CONCLUSION: Elderly patients with TB are more likely to present with non-specific complaints and atypical radiographic appearance. A high index of suspicion and prompt investigations in elderly patients may allow for earlier diagnosis and treatment of TB.

Adolescent↗
PubMed1995

Hepatosplenic gamma delta T-cell lymphoma. A distinctive aggressive lymphoma type.

The T-cell receptor (TCR) expressed on the surface of most T-lymphocytes is of alpha beta type, and only a minority bear the gamma delta-TCR. Similarly, postthymic T-cell lymphomas rarely express gamma delta-TCR. Hepatosplenic gamma delta T-cell lymphoma is an uncommon entity that has so far not been widely recognized. We report one such case that has been comprehensively studied by multiple modalities and showed the unique occurrence of leukemic picture at presentation. The 39-year-old man presented with fever, marked weight loss, and massive splenomegaly. Peripheral blood showed thrombocytopenia and a white cell count of 5.8 x 10(9)/l, with 66% medium-sized lymphoid cells that had a round or folded nucleus, condensed chromatin and a moderate amount of pale blue cytoplasm. Splenectomy was performed and histologic examination of the spleen, bone marrow, liver, and abdominal lymph nodes demonstrated lymphoma infiltration with a predominantly sinusoidal pattern. Immunohistochemical studies of the lymphoma cells showed a T-cell phenotype: CD2+ CD3+ CD5+ CD7+ gamma delta-TCR+ alpha beta-TCR- CD56+ CD4- CD8- CD16- CD57-. Cytogenetic studies showed complex clonal chromosomal abnormalities of 44,X, -Y, -11, -22, + mar in 3/16 cells. Rearrangement of the TCR gamma chain gene was demonstrated by polymerase chain reaction; the TCR beta chain gene was partially chain reaction; the TCR beta chain gene was partially rearranged. The patient did not respond to single agent chemotherapy, but achieved clinical remission with combination chemotherapy. Based on the available data in the literature, hepatosplenic gamma delta T-cell lymphoma exhibits distinctive clinicopathologic features, and probably represents the neoplastic counterpart of splenic gamma delta T-lymphocytes. This disease is associated with a poor prognosis and usually relapses despite initial response to chemotherapy.

Adult↗
PubMed1995

Intensive consolidation chemotherapy for newly diagnosed acute myeloid leukemia using a regime containing moderate dose cytosine arabinoside and mitoxantrone.

Fifty patients with previously untreated acute myeloid leukemia were treated with an induction regimen consisting of cytosine arabinoside 100 mg/m2 per day by 18 h i.v. infusion for 7 days, daunorubicin 50 mg/m2 per day by i.v. bolus injection for 3 days and etoposide 75 mg/m2 per day by 1 h i.v. infusion for 7 days. Thirty seven of them (74%) went into complete remission (CR) and they all then received two consecutive courses of consolidation chemotherapy consisting of cytosine arabinoside 500 mg/m2 per day by 1 h i.v. infusion every 12 h for 4 days (total eight doses) and mitoxantrone 12 mg/m2 daily by 30 min i.v. infusion for 3 days. They were followed by maintenance chemotherapy with cytosine arabinoside and thioguanine 2 monthly. With a median follow up time of 24 months, 20 of the 37 complete responders had relapsed (54%). The disease-free survival (DFS) of 37 CR patients and the overall survival of all patients at 24 months were 37 and 44%, respectively. Age of patients and number of courses of induction chemotherapy to achieve CR were significant factors predicting DFS. Myelosuppression was the major toxic side effects. Ten patients had prolonged marrow suppression following consolidation chemotherapy. In conclusion, despite the significant myelosuppression observed, overall improvement in treatment outcome was not demonstrable with the use of this intensive consolidation therapy.

Adolescent↗
PubMed1995

Lack of association between HLA-DQ and -DR genotypes and asthma in southern Chinese patients.

Asthma is an inflammatory disease with a strong genetic predisposition. We have studied a group of unrelated asthmatic patients of southern Chinese origin on their HLA-DR and -DQ regions using molecular techniques and compared them with 104 healthy controls of the same ethnic origin. Restriction fragment length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha and DQ beta loci of the subjects. Polymerase chain reaction (PCR) using sequence specific primer (SSP) for DQ beta genes was also performed. No significant difference was found in the HLA-DQ and -DR loci between the patients and the controls. All patients had their serum IgE antibody levels measured, bronchial reactivity assessed by histamine broncho-provocation and cutaneous reactivity to common allergens determined by skin-prick tests to Dermatophagoides pteronyssinus, Dermatophagoides farinae, mixed grass pollens, Aspergillus fumigatus, cat fur and dog dander and they were classified respectively. The HLA-DR and -DQ genotypes of these subgroups of patients were compared. There was no significant difference among these subgroups of patients according to their serum IgE levels, the degree of bronchial reactivity and whether they were positive for the skin tests for the various allergens respectively. The results suggest that HLA-DQ and -DR genotypes are not associated with asthma in southern Chinese people.

Adolescent↗
PubMed1995

Euthyroid sick syndrome in pulmonary tuberculosis before and after treatment.

Alterations of circulating thyroid hormones are frequently present in chronic nonthyroidal illnesses and may predict prognosis. Pulmonary tuberculosis, a common treatable debilitating disease, may provide a useful model for detailed evaluation of changes of thyroid hormones in relation to subsequent recovery or mortality. Over a period of 12 months, we performed a prospective study of 40 consecutive Chinese patients aged over 50 years and admitted with newly diagnosed pulmonary tuberculosis. Blood samples were drawn for serial thyroid function tests [free thyroxine (T4), free triiodothyronine (T3) and thyroid-stimulating hormone] before treatment and at 1, 2 and 4 months afterwards. Mortality was determined up to 12 months of follow-up. The euthyroid sick syndrome occurred in 63% of patients at presentation. Twelve of 25 euthyroid sick patients died as compared to one of 15 patients with normal baseline thyroid function tests (P < 0.02). Among euthyroid sick patients, those who died had significantly lower free T3 concentration at presentation than those who survived (P < 0.05). An undetectable free T3 concentration at presentation was associated with a subsequent mortality of 75% (9 of 12). Of the survivors, all patients demonstrated a significant rise in serum free T4 concentrations following treatment, which was apparent by 1 month. These data suggest that an undetectable free T3 concentration at presentation reflects severity of illness and predicts a subsequent high mortality.

Aged↗
PubMed1995

Elevated interleukin-2 receptor level in patients with active pulmonary tuberculosis and the changes following anti-tuberculosis chemotherapy.

Soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. We have undertaken a study to examine the serum sIL-2R levels in patients with pulmonary tuberculosis (TB) and the changes following anti-TB chemotherapy. Forty four patients with pulmonary TB or tuberculous pleural effusion were recruited. Serum was collected from the patients before and at 1, 2, 4 and 6 months after initiation of anti-TB chemotherapy. Serum sIL-2R level was measured by an enzyme immunoassay. The mean sIL-2R level before treatment was 1,452 +/- 103 (SEM) U.ml-1, which was significantly higher than that of healthy control subjects (374 +/- 30 U.ml-1). There was no significant change in the sIL-2R level at 1 month, but there was a gradual reduction from the second month onwards. At the sixth month the mean sIL-2R level was 1080 +/- 81 U.ml-1, which was significantly lower than that before treatment. However, despite clinical improvement, the sIL-2R levels at the sixth month were still significantly higher than those of control subjects. We conclude that sIL-2R levels were elevated in patients with pulmonary TB and there was a gradual reduction following anti-TB chemotherapy. However, the sIL-2R levels were still higher than control subjects at completion of treatment, suggesting a delayed resolution of the inflammation in patients with pulmonary TB.

Adolescent↗
PubMed1995

Respiratory symptoms in elderly Chinese living in Hong Kong.

Respiratory diseases can cause considerable disability in the elderly because of their limited respiratory reserve as a result of ageing. We have investigated the prevalence of respiratory symptoms and diseases in elderly Chinese in Hong Kong and compared these data with those in elderly Caucasian populations. Two thousand and thirty two (999 male and 1,033 female) subjects, selected by age-stratified random sampling from a register of Hong Kong residents aged 70 yrs and over were interviewed to complete a respiratory questionnaire. Total serum immunoglobulin E (IgE) was measured in 195 subjects. At least one respiratory symptom was reported by 56% of subjects. The most frequently reported symptoms were morning phlegm (26%), chronic cough with phlegm (10%) and wheeze in the past 12 months (8%). Of the self-reported diseases, the commonest was chronic bronchitis (7%), followed by asthma (5%), pulmonary tuberculosis (3%) and emphysema (2%). Of the 218 subjects with obstructive airway diseases, 128 (59%) had sought medical advice in the past 12 months. The most important determinants for respiratory symptoms and diseases were smoking and social class. Total serum IgE was significantly higher in current smokers than nonsmokers and also in those with chronic cough and phlegm than those without these complaints. Our study shows that respiratory ailments in Hong Kong elderly are as common as those reported in Sweden and the USA but less than those in England.

Aged↗
PubMed1995

Inhaled salmeterol and albuterol in asthmatic patients receiving high-dose inhaled corticosteroids.

Salmeterol may be useful in the treatment of asthmatic patients requiring high-dose inhaled steroids, and there have been debates about its anti-inflammatory action. We have compared the efficacy and effects on serum inflammatory markers, including soluble interleukin 2R (sIL-2R), eosinophil cationic protein (ECP), and tryptase of salmeterol and albuterol in 20 patients with moderate to severe asthma who were all receiving high-dose inhaled corticosteroids and inhaled beta 2-agonist on demand. After a 2-week run-in period, they received, in a randomized, crossover, double-blind and placebo-controlled manner, either salmeterol, 50 micrograms twice a day, or albuterol 400 micrograms, four times a day, from a powder inhaler during two 2-week treatment periods, separated by a 2-week washout. Compared with albuterol, salmeterol treatment was associated with better morning and mean peak expiratory flow (p = 0.013 and 0.016, respectively), less daytime and nocturnal symptoms (p = 0.008 and 0.01, respectively), reduced requirement of rescue albuterol (p = 0.04), and better efficacy rating by patients (p = 0.04). However, serum concentration of sIL-2R was significantly higher during regular albuterol treatment (p = 0.014) but no differences were seen in the concentrations of ECP and tryptase between the two treatment periods. We conclude that inhaled salmeterol, 50 micrograms twice daily, confers a better control of asthma than albuterol, 400 micrograms four times daily, in patients with moderate to severe disease, and the latter treatment may be associated with increased T-lymphocyte activation.

Administration, Inhalation↗
PubMed1995

Adverse drug reactions and outcome of elderly patients on antituberculosis chemotherapy with and without rifampicin.

Antituberculosis (anti-TB) chemotherapy with concomitant administration of rifampicin and isoniazid may cause a higher incidence of hepatotoxicity than isoniazid alone. We carried out a prospective study of the adverse reactions to anti-TB drugs and the clinical outcome in elderly patients on anti-TB chemotherapy, to find out whether the omission of rifampicin from standard anti-TB regime would result in a reduction of adverse reactions and/or mortality during anti-TB treatment. Eighty elderly patients (age > 65 years) with TB were recruited into the study. They were randomised to receive anti-TB chemotherapy consisting of isoniazid, pyrazinamide and ethambutol with or without rifampicin for six months. Adverse reactions and mortality occurring during treatment were noted. A significantly higher number of patients on rifampicin had elevated liver enzymes compared with those not receiving rifampicin. All of these reactions responded favorably to adjustment of anti-TB drugs. There was no significant difference between the two groups in the incidence of symptomatic adverse reactions or mortality during treatment. However, five patients not given rifampicin had unsatisfactory resolution radiographically and required additional therapy. We conclude that the inclusion of rifampicin in the anti-TB regime offers a better therapeutic response but without significantly affecting the incidence of adverse reactions or mortality during treatment in elderly patients with TB.

Aged↗