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K W Chan

Publications and source records attributed to K W Chan.

At least 181 records · Page 10Linked to original sources
PubMed1997

Jaffee v. Redmond: making the courts a tool of injustice?

In July, 1996, the United States Supreme Court held in Jaffee v. Redmond that statements made to a psychotherapist are privileged communications in a federal action. Prior to Jaffee, the federal courts were not in agreement as to whether this privilege existed. The majority found strong public and private interests that were furthered by recognition of the privilege. The minority, however, reasoned that the "occasional injustices" due to the exclusion of evidence made the courts a tool of injustice. Although the privilege is now recognized in federal courts, its contours and exceptions remain to be decided on a case by case basis.

Disclosure↗
PubMed1996

Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.

G protein-gated inwardly rectifying K+ (GIRK) channels, which are important regulators of membrane excitability both in heart and brain, appear to function as heteromultimers. GIRK1 is unique in the GIRK channel family in that although it is by itself inactive, it can associate with the other family members (GIRK2-GIRK5) to enhance their activity and alter their single-channel characteristics. By generating a series of chimeras, we identified a phenylalanine residue, F137, in the pore region of GIRK1 that critically controls channel activity. F137 is found only in GIRK1, while the remaining GIRK channels possess a conserved serine residue in the analogous position. The single-point mutant GIRK4(S143F) behaved as a GIRK1 analog, forming multimers with GIRK2, GIRK4, or GIRK5 channels that exhibited prolonged single-channel open-time duration and enhanced activity compared with that of homomultimers. Expression of the corresponding GIRK1 (F137S) mutant alone resulted in appreciable channel activity with novel characteristics that was further enhanced upon coexpression with other GIRK subunits. Thus, although the F137 residue renders the GIRK1 subunit inactive, when combined with other GIRK heteromeric partners it alters their gating and contributes to their enhanced activity.

Amino Acid Sequence↗
PubMed1996

Design of a novel bicistronic expression vector with demonstration of a p16INK4-induced G(1)-S block(1).

Traditional eukaryotic gene expression systems have many shortcomings that make them unsuitable for the analysis of cytotoxic and growth-arrest genes. An intestinal alkaline phosphatase bicistronic expression vector was specifically designed to facilitate such studies. Intestinal alkaline phosphatase serves as a marker of cells that have been transfected and, therefore, must also be co-expressing the gene under study. Using flow cytometry, a trivariate analysis was performed on p16INK4-transfected U87 glioblastoma cells. An average G1-S block of 77.5% was demonstrated compared to controls despite a 1% transfection efficiency. This vector has universal applications, including: (a) analysis of cytotoxic and growth-inhibitory genes in transient assays; (b) 100% enrichement in gene expression studies, especially in low transfection efficiency experiments; and (c) facilitation of the study of cell cycle kinetics.

Alkaline Phosphatase↗
PubMed1996

Risk factors for recurrence in patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation.

OBJECTIVE: To identify risk factors for cancer recurrence in patients with stage IB, IIA, and IIB cervical carcinoma after abdominal radical hysterectomy with pelvic lymph node dissection and postoperative pelvic irradiation. METHODS: One hundred and eighty-seven patients with cervical carcinoma stage IB (n = 63), IIA (n = 43), and IIB (n = 81) disease who received abdominal radical hysterectomy with pelvic lymph node dissection and postoperative pelvic irradiation were followed-up for 2-10 years. The histologic type, grade, lymphovascular tumor emboli, tumor size, invasion sites, deep cervical stromal invasion, and pelvic lymph node metastases were assessed for correlation with cancer recurrence. RESULTS: Recurrence occurred in 45 cases (24%), of whom 40 had died of the disease at the 5-year follow-up period. Univariate proportional hazards analysis revealed that the significant risk factors were adenocarcinoma, bulky tumor size (4 cm or greater), lymphovascular tumor emboli, deep cervical stromal invasion, and lymph node metastases, especially iliac nodal metastases and bilateral nodal metastases. Multivariate proportional hazards analysis showed that bulky tumor size (hazard ratio 2.34), tumor emboli (hazard ratio 2.74) and iliac nodal metastases (hazard ratio 5.31) remained significant risk factors. In contrast, no deaths occurred in the other 142 cases who did not have recurrence. CONCLUSION: This retrospective study suggests that stage IB, IIA, and IIB cervical carcinoma cases with the above-mentioned pathologic factors are at higher risk of recurrence after abdominal radical hysterectomy with pelvic lymph node dissection and postoperative pelvic irradiation.

Combined Modality Therapy↗
PubMed1996

Use of minors as bone marrow donors: current attitude and management. A survey of 56 pediatric transplantation centers.

OBJECTIVE: To determine the current attitude about the use of minors as bone marrow donors in pediatric bone marrow transplantation (BMT) centers in North America. STUDY DESIGN: A questionnaire was mailed to 70 North American BMT centers. The questionnaire asked for opinions on a number of ethical and clinical issues pertaining to the use of minors as marrow donors. A case history was included and respondents were asked to check all appropriate answers listed in the survey. RESULTS: Fifty-six (80%) of 70 centers responded. There was general consensus on many issues. Pediatricians endorse the validity of parental consent, even in potentially controversial situations. Most are prepared to extract marrow from young (about 6 months of age) infants and are willing to use the same donor more than once. There is general approval of performing BMT with experimental protocols, and the projected outcome of BMT does not affect the decision to use a minor as a marrow donor. There is less consensus regarding the optimal management of minors donating a large volume of bone marrow. CONCLUSION: This survey shows a fairly consistent attitude among pediatric BMT centers about the use of minors as marrow donors. The actual management of such donors was not evaluated in detail and requires further study.

Adolescent↗
PubMed1996

Crescentic nodular glomerulosclerosis secondary to truncated immunoglobulin alpha heavy chain deposition.

Nodular glomerulosclerosis secondary to deposition of monoclonal immunoglobulin (Ig) light chains with or without heavy chains is a recognized clinicopathological entity. Recent reports have demonstrated that an identical glomerular lesion may also occur as a result of truncated tau Ig heavy chain deposition. We investigated the nature of Ig deposits in a patient who presented with rapidly progressive renal failure secondary to crescentic nodular glomerulosclerosis. This patient had a relapsing clinical course responsive to treatment with steroid and cyclophosphamide therapy. In this case, both the glomeruli and tubular basement membrane contained granular immune deposits that were reactive to polyclonal antibodies against alpha but not tau or mu Ig heavy chains and nonreactive to anti-kappa and anti-lambda light chain reagents. A monoclonal population of plasma cells secreting alpha and kappa chains was present in the patient's marrow despite the finding of a normal percentage of plasma cells. Serum Immunoelectrophoresis was normal, but immunofixation demonstrated the presence of a monoclonal alpha/kappa band. Immunoblot under dissociating and nondissociating conditions showed that both the patient's urine and serum contained Ig fragments that comprised dimer or monomer of an abnormally short alpha Ig heavy chain (approximately 26 kd) with or without associated kappa light chain. The identity of the abnormal serum alpha Ig heavy chain with that of the glomerular Ig deposits was supported by the finding that both were nonreactive against alpha 1 and alpha 2 subclass-specific monoclonal antibodies despite their reactivity to polyclonal antibodies. Because these monoclonal antibodies would react with structural determinants, which differ between alpha 1 and alpha 2 Ig heavy chains but not those common between them, and because the differences in amino acid sequence between the two largely lie in the CH1 and CH2 domains of the alpha Ig heavy chain, it is hypothesized that the abnormally short alpha Ig heavy chain produced by plasma cells in this patient contains deleted CH1 and CH2 domains similar to the findings in patients with tau Ig heavy chain deposition disease.

Biopsy↗
PubMed1996

Clinical toxicity and laboratory effects of granulocyte-colony-stimulating factor (filgrastim) mobilization and blood stem cell apheresis from normal donors, and analysis of charges for the procedures.

BACKGROUND: Apheresis of granulocyte-colony-stimulating factor (filgrastim)-mobilized blood stem cells from normal donors is now being used in place of a marrow harvest in transplantation. How the adverse effects of and charges for this procedure compare with those of the standard marrow harvest is not known. STUDY DESIGN AND METHODS: Forty consecutive normal subjects who received filgrastim 96 micrograms/kg) subcutaneously twice daily for 4 to 6 days in preparation for apheresis were monitored prospectively by clinical and laboratory evaluation. RESULTS: Sixty-two percent of the subjects required oral analgesics. None discontinued filgrastim prematurely. Bone pain (82%), headache (70%), fatigue (20%), and nausea (10%) were reported. Filgrastim caused a mean eightfold increase in neutrophil counts, a mean twofold increase in lymphocyte counts, a mean twofold rise in alkaline phosphatase and lactate dehydrogenase levels, and minor changes in serum potassium, magnesium, and uric acid. Adverse events and laboratory effects resolved within 7 days after apheresis. No apheresis stem cell donor required transfusion or hospitalization, and only one required an additional clinic visit after completion of apheresis. By comparison, a retrospective analysis of 33 normal marrow donors demonstrated that all received transfusion(s), 3 were hospitalized, 3 required additional clinic visits after the marrow harvest. The median total charges related to the two procedures were comparable (p = 0.43), although the charges were significantly lower for donors requiring only one apheresis procedure (p = 0.002). CONCLUSION: Filgrastim mobilization and apheresis of blood stem cells constitute a safe, well-tolerated, and comparable or less expensive alternative to the traditional marrow harvest.

Adolescent↗
PubMed1996

Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C.

BACKGROUND & AIMS: Sustained response to interferon treatment for chronic hepatitis C is unsatisfactory. This study examined whether combining interferon alfa with ribavirin induces a better sustained efficacy than interferon alone in the treatment of chronic hepatitis C. METHODS: Sixty noncirrhotic patients with chronic hepatitis C were randomly assigned to three groups. Group 1 received 1200 mg oral ribavirin daily plus 3 million units of recombinant interferon alfa 2a thrice weekly for 24 weeks, group 2 received the same dose of interferon alfa 2a alone for 24 weeks, and group 3 received no treatment. The patients were then followed up for an additional 96 weeks. RESULTS: At the end of treatment, a complete response (normal serum alanine aminotransferase level and undetectable serum hepatitis C virus RNA) was achieved in 16 of the 21 patients in group 1 (76%), as compared with 6 of 19 in group 2 (32%) and none in group 3. At 96 weeks after the end of treatment, patients in group 1 sustained a higher complete response rate than patients in group 2 (43% vs. 6%). CONCLUSIONS: Combined treatment with ribavirin and interferon alfa 2a for 24 weeks is more effective than interferon alfa 2a alone for the treatment of chronic hepatitis C. The biochemical and virological responses were sustained in about one half of the treated patients for at least 2 years after cessation of the therapy.

Adult↗
PubMed1996

A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins.

GTP-binding (G) proteins have been shown to mediate activation of inwardly rectifying potassium (K+) channels in cardiac, neuronal and neuroendocrine cells. Here, we report functional expression of a recombinant inwardly rectifying channel which we call KGP (or hpKir3.4), to signify that it is K+ selective, G-protein-gated and isolated from human pancreas. KGP expression in Xenopus oocytes resulted in sizeable basal (or agonist-independent) currents while coexpression with a G-protein-linked receptor, yielded additional agonist-induced currents. Coexpression of KGP and hGIRK1 (a human brain homolog of GIRK1/Kir3.1) produced much larger basal currents than those observed with KGP or hGIRK1 alone, and upon coexpression with receptor, similarly large agonist-induced currents could be obtained. Pertussis toxin treatment significantly diminished agonist-dependent currents due to either KGP or KGP/hGIRK1 expression. Interestingly, PTX also significantly reduced basal KGP or KGP/hGIRK1 currents, suggesting that basal activity is largely the result of G-protein gating as well. When the two channels were coexpressed with receptor, the relative increase in current elicited by agonist was similar whether KGP and hGIRK1 were expressed alone or together. When in vitro translated or when expressed in Xenopus oocytes or CHO mammalian cells, KGP gave rise to a nonglycosylated 45-kD protein. Antibodies directed against either KGP or hGIRK1 coprecipitated both proteins coexpressed in oocytes, providing evidence for the heteromeric assembly of the two channels and suggesting that the current potentiation seen with coexpression of the two channel subunits is due to specific interactions between them. An endogenous oocyte protein similar in size to KGP was also coprecipitated with hGIRK1.

Acetylcholine↗
PubMed1996

Na+ activation of the muscarinic K+ channel by a G-protein-independent mechanism.

Muscarinic potassium channels (KACh) are composed of two subunits, GIRK1 and GIRK4 (or CIR), and are directly gated by G proteins. We have identified a novel gating mechanism of KACh, independent of G-protein activation. This mechanism involved functional modification of KACh which required hydrolysis of physiological levels of intracellular ATP and was manifested by an increase in the channel mean open time. The ATP-modified channels could in turn be gated by intracellular Na+, starting at approximately 3 mM with an EC50 of approximately 40 mM. The Na(+)-gating of KACh was operative both in native atrial cells and in a heterologous system expressing recombinant channel subunits. Block of the Na+/K+ pump (e.g., by cardiac glycosides) caused significant activation of KACh in atrial cells, with a time course similar to that of Na+ accumulation and in a manner indistinguishable from that of Na(+)-mediated activation of the channel, suggesting that cardiac glycosides activated KACh by increasing intracellular Na+ levels. These results demonstrate for the first time a direct effect of cardiac glycosides on atrial myocytes involving ion channels which are critical in the regulation of cardiac rhythm.

Adenosine Triphosphate↗
PubMed1996

Fractionated high-dose cyclophosphamide for advanced pediatric solid tumors.

PURPOSE: The objective of this study was to determine the tolerance and toxicities of high-dose cyclophosphamide (CPA) at 7 g/m2 given in four fractions over 8 h in children with advanced solid tumors. PATIENTS AND METHODS: Twenty children aged 1 1/2-19 years (median, 12 years) received 24 courses of high-dose CPA at 7 g/m2 for the treatment of advanced malignant solid tumor. CPA was given in four 1-h infusions of 1.75 g/m2 each, with 1 h of rest between each dose. MESNA was used as a uroprotective agent and was continued for 24 h after the final dose of CPA. With only one exception, all patients were discharged at the end of MESNA infusion and received granulocyte colony-stimulating factor, prophylactic ciprofloxacin, and co-trimoxazole. RESULTS: Severe but transient myelosuppression was observed. The median time to neutrophil and platelet recovery was 17 and 19 days, respectively. Fever developed after 13 of the 24 courses, and hospitalization was required. Extramedullary toxicities were mild. No patient showed cardiomyopathy or hemorrhagic cystitis. Forty-six percent of the courses were managed entirely on an outpatient basis. Objective tumor response was seen in five patients. CONCLUSIONS: CPA at 7 g/m2 is well tolerated by children with advanced malignancies and should be considered in earlier phases of antineoplastic therapy.

Adolescent↗
PubMed1996

Accumulation of p53 protein in inverted transitional cell papilloma of the urinary bladder.

Aims-To study the possible accumulation of p53 protein in inverted papilloma of the urinary bladder.Methods-Formalin fixed, paraffin wax embedded sections from 14 cases of inverted papilloma of the urinary bladder were studied retrospectively. Accumulation of p53 was detected by immunohistochemistry using a mouse monoclonal antibody directed against p53. p53 protein reactivity was scored as follows: 0 = 10%; 1 = 10% to <30%; 2 = 30% to <50%; and 3 = >50% of cells p53 positive.Results-The 14 sections were scored as follows: 3 in four cases; 2 in four cases; 1 in one case; and 0 in five cases. Overall, nine (64%) of the 14 cases were positive for p53 protein.Conclusions-The accumulation of p53 protein in inverted papilloma of the urinary bladder suggests that p53 may have has an important role in the neoplastic process of this tumour. However, the benign nature of inverted papillomas suggests that p53 protein accumulation is not related to tumour invasiveness and metastasis. p53 reactivity cannot be used as a marker of malignancy for urothelial neoplasia. Further studies are required to determine the role of p53 protein in the oncogenesis of urothelial neoplasms.

Journal Article↗
PubMed1996

Bone SPECT to assess mandibular invasion by intraoral squamous-cell carcinomas.

UNLABELLED: It is important for head and neck surgeons planning their operative approach to assess tumor infiltration to the mandible by intraoral squamous-cell carcinomas. Two- to 3-hr planar bone scintigraphy is sensitive but not specific in detecting mandibular invasion by tumor. We evaluated 3-hr SPECT bone scintigraphy, which provides better anatomical detail, to determine if it more accurately assesses tumor invasion. METHODS: Thirty consecutive patients with proven intraoral squamous-cell carcinomas were studied. Semiquantitative assessment of the mandible was performed with a three-level graded scoring system, based on comparisons of tracer uptake in the mandible to that in the upper cervical vertebrae and in an unaffected part of mandible. Lesion-to-cervical spine (L/S) count ratios and lesion-to-nonlesion (L/N) count ratios in the mandible on the 3-hr SPECT images were calculated. RESULTS: All patients with proven tumor invasion showed higher tracer uptake than those with normal mandible or other dental diseases. The L/S and L/N count ratios on the SPECT images were significantly higher in patients with tumor invasion than in those without (L/S, p < 0.001; L/N, p < 0.01). L/S ratios provided better differentiation than L/N ratios. CONCLUSIONS: Bone SPECT provides a reliable means of assessing tumor invasion to the mandible by intraoral squamous-cell carcinomas.

Adult↗
PubMed1996

Ganciclovir prophylaxis for cytomegalovirus infection in pediatric allogeneic bone marrow transplant recipients.

Twenty-nine pediatric allogeneic bone marrow transplant (BMT) recipients, ages 2-17 years, were followed prospectively for cytomegalovirus (CMV) infection. Patients at risk received ganciclovir (GCV) prophylactically at a dose of 5 mg/kg/day i.v., 3 to 5 days per week, until day 100. Surveillance blood and urines were obtained weekly. Twelve patients developed DMV infection: one patient died with CMV interstitial pneumonitis on day 19 post-transplant prior to initiating GCV prophylaxis; 10 patients developed CMV viremia (n = 9) or viruria (n = 1) between day 30 and day 95 (median day 50) while receiving GCV prophylaxis; and one patient developed asymptomatic CMV viruria on day 130, 1 month after completing GCV prophylaxis. Patients with breakthrough infections on prophylaxis were treated with intensified GCV and i.v. immunoglobulin. No patient developed visceral involvement, although five patients had recurrent viremia. Six of the seven long-term survivors continued to excrete CMV in the urine intermittently for 6 to 28 months post-transplant. GCV was well tolerated with transient, mild neutropenia in five patients and thrombocytopenia in four patients. No extramedullary toxicity was encountered. GCV prophylaxis at a dose of 15-25 mg/kg/week is not adequate to prevent CMV reactivation in children receiving marrow transplants from unrelated donors and/or T cell-depleted grafts.

Adolescent↗
PubMed1996

Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors.

Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.

Adult↗
PubMed1996

Clinics in diagnostic imaging (18). Multilocular cystic nephroma.

A male Chinese infant presented with the incidental finding of a left loin mass. Plain abdominal radiograph showed a large left-sided soft tissue shadow. Ultrasound and computed tomography scans demonstrated a multiloculated cystic lesion arising from the upper pole of the left kidney. Histological examination of the nephrectomy specimen confirmed the diagnosis of multilocular cystic nephroma. The differential diagnoses of infantile renal masses, the role of imaging in assessment of these masses and the surgical management of multilocular cystic nephroma are discussed.

Child, Preschool↗
PubMed1995

Absence of Epstein-Barr virus in penile carcinoma. A study of 42 cases using in situ hybridization.

BACKGROUND: The relationship between Epstein-Barr virus (EBV) and carcinomas of the lower female genital tract has been the focus of some studies in recent years. However, the association between EBV and penile carcinoma never has been investigated. The aim of this study was to identify the possible role of EBV in penile carcinoma of Chinese patients. METHODS: Formalin fixed, paraffin embedded tissue of 42 cases of penile carcinoma (including 7 verrucous, 14 well differentiated, 15 moderately differentiated, and 6 poorly differentiated squamous cell carcinomas), 6 penile warts, and 9 normal penile samples were analyzed for EBV using in situ hybridization for EBV-encoded RNA (EBER). RESULTS: Epstein-Barr virus was only found in a few lymphocytes adjacent to the tumor epithelium in 12% (5 cases) of penile carcinoma. Conversely, the tumor cells, penile warts, and normal penile tissue were negative for EBV. CONCLUSIONS: The results suggest that EBV does not play a major role in the etiology of penile carcinoma.

Adult↗