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Biomedical subjects

H S Chan

Publications and source records attributed to H S Chan.

At least 91 records · Page 5Linked to original sources
PubMed1992

Therapeutic problems in the management of elderly patients with tuberculosis.

Adverse reactions to antituberculous drugs are more common in the elderly. With the increasing numbers of elderly people and the higher incidence of tuberculosis in this age group, clinicians will encounter more therapeutic problems in the use of antituberculous drugs than in younger patients. Existing studies regarding pharmacological and non-pharmacological factors which may predispose to increased adverse effects in the elderly are reviewed. Reduced clearances of isoniazid and rifampicin at steady state, possible increase in free drug concentration of drugs normally bound to albumin, possible differences in disposition of toxic metabolites such as hydrazine, concomitant administration of both isoniazid and rifampicin, poor nutrition and severity of the disease in the elderly may be contributing factors. Further studies in these areas should provide clearer guidelines on whether dosages or drug combinations should be modified in elderly patients with tuberculosis.

Aged↗
PubMed1991

P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma.

BACKGROUND AND METHODS: Multidrug resistance in chemotherapy for cancer is characterized by increased genetic expression of P-glycoprotein, which acts as an ATP-dependent drug-efflux pump. To determine whether P-glycoprotein levels are of prognostic value in such cases, we measured these levels immunohistochemically in a retrospective study of sequential tumor samples from 67 children with neuroblastoma. RESULTS: P-glycoprotein was not detected in pretreatment samples from either of the 2 patients with Stage I disease, any of the 21 with Stage II disease, or any of the 8 with Stage IVS disease, but it was detected in the samples from 1 of the 17 patients with Stage III disease (6 percent) and 12 of the 19 with Stage IV disease (63 percent). Of the 44 patients with nonlocalized neuroblastoma (Stage III, IVS, or IV), 26 of the 31 who were negative for P-glycoprotein had a complete response to primary treatment, as compared with 6 of the 13 who were positive for P-glycoprotein (84 percent vs. 46 percent, P = 0.0232 by Fisher's exact test). Log-rank analysis of outcome, with simultaneous stratification according to tumor stage and age, showed that the group that was negative for P-glycoprotein had significantly longer relapse-free survival (P = 0.0011) and overall survival (P = 0.0373) than the group that was positive. CONCLUSIONS: Expression of P-glycoprotein before treatment may predict the success or failure of therapy for nonlocalized neuroblastoma. Neuroblastoma may be a promising tumor to treat with anticancer drug therapy combined with a chemosensitizing agent capable of reversing P-glycoprotein-mediated multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Neuroblastoma stage IV-S: a heterogeneous disease.

Eighteen patients were diagnosed and treated for Stage IV-S neuroblastoma at The Hospital for Sick Children, Toronto between January 1971 and December 1988. All patients were 6 months of age or younger at diagnosis. Nine patients (50%) have remained disease free with a mean follow-up of 9.3 years. Of the seven patients under 6 weeks of age at presentation, four presented in the early neonatal period and died, three due to mechanical complications related to progressive disease, and one due to late recurrence. The remaining three patients under 6 weeks of age, two of whom had skin involvement at diagnosis, are alive and disease free. Six of the 11 patients over 6 weeks of age at presentation survived, combined modality therapy (CMT) being more effective than single modality treatment. N-myc was studied from tumor tissue at diagnosis in four patients and was amplified in three (25x, 25x, 100x), all of whom had late disease progression and died. The patient with a single gene copy has no evidence of disease 24 months following diagnosis. Our study confirms the heterogeneity described in this clinically defined group of patients. Because of it, management of Stage IV-S neuroblastoma cannot be uniform and until further development of a subclassification, or a reclassification based on molecular biologic markers is developed, pediatric oncologists will regularly be confronted with a decision whether or not to treat a newly presenting patient that fits into the clinical classification IV-S.

Adrenal Gland Neoplasms↗
PubMed1991

The genetics of retinoblastoma. Relevance to the patient.

The understanding of the molecular biology of human cancer has advanced rapidly in the last decade, in part due to discoveries in the rare, pediatric ocular tumor, retinoblastoma. RB studies have led to recognition of a class of human genes, the tumor suppressor genes, that are critical in the initiation and progression of the malignant process. Mutations in the RB1 gene initiate RB and other specific tumors. They may also contribute to progressive stages of many other malignancies. The protein product of RB1 (p110RB1) is a basic regulator of the cell cycle. In the absence of normal protein, the cell proceeds to the next cell division without the potential to become quiescent. Understanding the genetics of RB has benefited the patients, as the precise identification of the RB1 mutations in families has led to accurate prediction of individuals at risk for RB tumors. It seems unlikely, in the foreseeable future, that direct genetic manipulation of mutant RB1 genes will play a role in therapy, but complete understanding of the function of p110RB1 may eventually allow exploitation of its powerful antiproliferative effect. Other molecular genetic events in addition to RB1 mutations are documented in RB tumors, and may play a critical role in the full malignant phenotype. The oncogene, N-myc, is amplified in some RB tumors and is expressed in normal fetal retina. The cytogenetic abnormality, i(6p), is almost unique to RB tumors. The molecular and tissue-specific roles of these abnormalities are not yet known. Many RB tumors also acquire excessive expression of the cell surface membrane glycoprotein, p170, linked to multidrug resistance, whether or not the RB tumor has been exposed to chemotherapy. We anticipate that ways to avoid or counteract the drug resistance of excessive p170 expression will be developed for other pediatric tumors and eventually will be applied to chemotherapy for RB patients.

Child↗
PubMed1991

Multidrug-resistant phenotype in retinoblastoma correlates with P-glycoprotein expression.

Chemotherapy plays an important role in therapy for patients with extraocular and metastatic retinoblastoma. The authors used chemotherapy for management of selected patients with uncontrolled intraocular tumors or tumors larger and more posteriorly located than those conventionally treated with local cryotherapy or photocoagulation. Rapid regrowth of some tumors after an initial excellent chemotherapy response led us to investigate the hypothesis that failure of treatment is caused by P-glycoprotein-related multidrug resistance. By using a sensitive immunoperoxidase method, increased P-glycoprotein was detected in five multidrug-resistant and two selectively plant alkaloid-resistant retinoblastoma cell lines and in the intraocular and metastatic tumors from which they were derived. In four chemotherapy-treated cases, increased P-glycoprotein in the tumor samples correlated with clinically relevant drug resistance. None of the four chemosensitive tumor cell lines had increased P-glycoprotein expression. Continuous surveillance of P-glycoprotein levels in metastatic retinoblastoma may be a useful guide to drug therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Obstructive sleep apnea presenting with nocturnal angina, heart failure, and near-miss sudden death.

An obese woman with a one-year history of episodic nocturnal chest pain was admitted because of shock and pulmonary edema. A clinical diagnosis of acute myocardial infarction and cardiogenic shock was made. She was ventilated and successfully resuscitated. Subsequent investigations showed no evidence of cardiac dysfunction or coronary disease, but sleep study confirmed the diagnosis of obstructive sleep apnea syndrome (OSAS). We suggest that the nocturnal angina and heart failure in this patient might have resulted from extreme hypoxemia produced by OSAS. This case raised the possibility that the high cardiovascular mortality rate reported in OSAS might not necessarily relate to underlying coronary artery disease. Further investigations are required to delineate the true incidence of coronary disease in patients with OSAS.

Aged↗
PubMed1991

The disposition of antituberculous drugs in plasma of elderly patients. I. Isoniazid and hydrazine metabolite.

The plasma profiles of isoniazid (INH) and hydrazine (HYD) metabolite were compared in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month after treatment for tuberculosis with INH, rifampicin (RIF) and pyrazinamide (PZA). There was no difference in the pharmacokinetics of INH between the two age groups. The clearance for INH at steady-state was significantly lower than after the first dose. After the first dose the maximum concentration (Cmax) for HYD was significantly higher (p less than 0.05) in the elderly (0.4 +/- 0.07 microgram/ml) than in the young (0.24 +/- 0.08 microgram/ml). HYD is produced in significant amounts during INH metabolism and this should not be neglected when evaluating INH related toxicity.

Acetylation↗
PubMed1991

The disposition of antituberculous drugs in plasma of elderly patients. II. Isoniazid, rifampicin and pyrazinamide.

The pharmacokinetics of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) were studied in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month of treatment for pulmonary tuberculosis. Elderly patients exhibited more side effects but there were no age-related changes in the pharmacokinetics of any of the three drugs when used in this combination. The clearance for INH and RIF at steady-state were significantly lower than after first-dose, while that of PZA remained unchanged. At steady-state the clearances for INH and RIF were not characteristic of polymorphic metabolism and auto-enzyme induction, respectively. Elderly patients are more sensitive to antituberculous (anti-TB) drugs; therefore, a modification in the dosage for this patient group should be considered.

Adult↗
PubMed1990

Bronchoscopic aspiration and bronchoalveolar lavage in the diagnosis of sputum smear-negative pulmonary tuberculosis.

The ability to make a definitive diagnosis in sputum smear-negative pulmonary tuberculosis by bronchoscopic aspiration, bronchoalveolar lavage (BAL), and examination of postbronchoscopy sputum were compared. Thirty-four patients with lesions on chest x-rays suspected of being pulmonary tuberculosis were entered into the study. The diagnosis of pulmonary tuberculosis was subsequently confirmed in 28 patients and the method of arriving at the final diagnosis was analyzed. A positive acid-fast bacilli (AFB) smear result was obtained in 4/28 (14%) of cases by a combination of bronchoscopic techniques and postbronchoscopy sputum examination. Prebronchoscopy sputum culture was positive in 12/28 (43%). Combined with bronchoscopy specimens, a positive AFB culture result was obtained in 26/28 (93%). Sputum examination, bronchoscopic aspiration, and BAL are complementary techniques and together they give a high yield of definitive diagnosis of pulmonary tuberculosis.

Adolescent↗
PubMed1990

Origins of structure in globular proteins.

The principal forces of protein folding--hydrophobicity and conformational entropy--are nonspecific. A long-standing puzzle has, therefore, been: What forces drive the formation of the specific internal architectures in globular proteins? We find that any self-avoiding flexible polymer molecule will develop large amounts of secondary structure, helices and parallel and antiparallel sheets, as it is driven to increasing compactness by any force of attraction among the chain monomers. Thus structure formation arises from the severity of steric constraints in compact polymers. This steric principle of organization can account for why short helices are stable in globular proteins, why there are parallel and anti-parallel sheets in proteins, and why weakly unfolded proteins have some secondary structure. On this basis, it should be possible to construct copolymers, not necessarily using amino acids, that can collapse to maximum compactness in incompatible solvents and that should then have structural organization resembling that of proteins.

Binding Sites↗
PubMed1990

Endobronchial tuberculosis--is corticosteroid treatment useful? A report of 8 cases and review of the literature.

Eight patients with endobronchial tuberculosis diagnosed on bronchoscopy were treated with antituberculosis drugs and a course of prednisone. The progress of the endobronchial lesions was assessed on repeated examinations. The course of the disease was variable and the endobronchial narrowing improved in two patients only. Hypersensitivity reactions associated with initiation of antituberculosis treatment may constitute a special group where corticosteroid is indicated. In other situations, the usefulness of corticosteroid for treatment of endobronchial tuberculosis is not well documented.

Adolescent↗
PubMed1990

Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood.

Increased expression of P-glycoprotein is associated with multidrug resistance (MDR) in many cell lines. Significant levels of P-glycoprotein have been detected in a number of human tumors. The purpose of this study was to determine whether P-glycoprotein expression correlates with both response to chemotherapy and prognosis in soft tissue sarcoma of childhood. In a retrospective study, biopsy samples from 30 cases of rhabdomyosarcoma (RMS) and undifferentiated sarcoma (US) treated at The Hospital for Sick Children in Toronto were analyzed using a semiquantitative immunohistochemical procedure. P-glycoprotein was detected in nine patients, four at diagnosis, and five at subsequent biopsy. All nine patients relapsed after a clinical response (complete [CR] 55%, partial [PR] 45%) to chemotherapy. Twenty of 21 patients with consistently P-glycoprotein-negative tumors received chemotherapy and they all responded clinically (CR 80%, PR 20%). Only one of these 20 patients has relapsed. The probability of relapse-free survival was significantly different (P less than .000000012) in chemotherapy-treated patients whose tumors contained detectable levels of P-glycoprotein (n = 9), compared with those whose tumors contained no detectable P-glycoprotein (n = 20). The overall probability of survival was also significantly different in these two groups (P less than .0000267). Both relapse-free and overall survivals remained statistically different in the two groups of patients when analyzed by the log-rank method, after adjustment for differences in stages and sites. The incidence of other adverse prognostic factors in the two groups, for example, younger and older ages, low pretreatment lymphocyte counts, large tumors, and unfavorable histology were not significantly different. Thus, detectable P-glycoprotein appears to be an important adverse prognostic factor in children with soft tissue sarcoma, and consistent absence of the protein is associated with a favorable prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Solitary fibrous tumor of pleura: expression of cytokeratins.

A case of solitary fibrous tumor of the pleura (SFT) is presented. The histogenesis of this uncommon tumor is debated with most investigators favouring origin in submesothelial fibroblasts. Part of the evidence supporting this has been the persistent negativity of the tumor cells for cytokeratin--a feature militating against origin in mesothelial-lining cells. Our case shows unequivocal focal cytokeratin positivity in tumor cells; we feel that although this indicates mesothelial differentiation it does not militate against origin in submesothelial fibroblasts since, in reactive conditions, these are capable of mesothelial differentiation including expression of cytokeratin. Indeed, it reinforces the hypothesis that SFT is of submesothelial origin. Solitary fibrous tumors can be cellular and atypical. The reactivity of the tumor with cytokeratin, albeit rarely, should be considered in differentiating SFT from sarcomatoid mesothelioma.

Aged↗