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Biomedical subjects

K K Ng

Publications and source records attributed to K K Ng.

At least 55 records · Page 3Linked to original sources
PubMed2000

Phase I and pharmacokinetic study of 10-propargyl-10-deazaaminopterin, a new antifolate.

The 10-deazaaminopterins are a new class of rationally designed antifolates demonstrating greater antitumor effects than methotrexate in murine tumor models and human tumor xenografts. Their design was aimed at improving membrane transport and polyglutamylation in tumor cells, resulting in increased intracellular accumulation and enhanced cytotoxicity. Compared with other 4-aminofolate analogues, 10-propargyl-10-deazaaminopterin (PDX) is the most efficient permeant for the RFC-1-mediated internalization and substrate for folylpolyglutamate synthetase. PDX demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate or edatrexate. We undertook a Phase I study with PDX to identify the potential toxicities and define an optimal dose and schedule. Thirty-three patients were enrolled, all of whom had non-small cell lung cancer (NSCLC) and were treated previously with a median of two prior chemotherapy regimens. Initially, PDX was administered weekly for 3 weeks in a 4-week cycle. Mucositis requiring dose reduction and/or delay in the first cycle occurred in four of six patients treated at the initial dose level (30 mg/m2), making this the maximal tolerated dose for PDX given on this schedule. The treatment schedule was then modified to every 2 weeks. Twenty-seven patients were treated twice weekly with a total of 102 four-week cycles (median, 2 cycles/patient). Mucositis was the dose-limiting toxicity, with grade 3 and 4 mucositis occurring in the first two patients treated at the 170 mg/m2 dose level. Other toxicities were mild and reversible. No neutropenia was observed. The recommended Phase II dose is 150 mg/m2 biweekly. At that dose level, the mean area under the curve was 20.6 micromol x h, and the mean terminal half-life was 8 h. Two patients with stage IV NSCLC had major objective responses, and five patients had stable disease for 7 (two patients), 9 (one patient), 10 (one patient), and 13 months (one patient). PDX is a new antifolate with manageable toxicity and evidence of antitumor activity in NSCLC. A Phase II trial in NSCLC and a Phase I trial with paclitaxel are under way. These studies will also quantitate the expression of genes controlling internalization (RFC-1) and polyglutamylation of PDX in tumor cells as correlates of response.

Aminopterin↗
PubMed2000

Clinical manifestations of tuberculosis in HIV-infected patients.

OBJECTIVE: The purpose of the present study was to evaluate the impact of HIV infection on the clinical presentation of tuberculosis. METHODOLOGY: We retrospectively studied the impact of HIV infection on the clinical presentation of tuberculosis. A total of 60 consecutive patients co-infected with HIV and tuberculosis were identified. RESULTS: Majority were male (88.3%) and the most common transmission category was heterosexual contact (80%). Most were in the advanced stage of HIV infection; 93% had CD4 cell count less than 200/mm3. Concerning the site of tuberculosis involvement, 37% had pulmonary involvement alone, 13% had extrapulmonary disease involving one single site, 50% had both pulmonary and extrapulmonary involvement. Fifteen (25%) patients also met the criteria of disseminated tuberculosis, who had a significantly lower mean CD4 cell count than those with pulmonary involvement alone (mean 40 vs 102; P = 0.048). Chest radiographs comprised a wide spectrum of manifestations. A considerable proportion had primary pulmonary tuberculosis pattern (38%) and normal radiographs (8.5%). CONCLUSIONS: Our patients generally had advanced HIV infection; 93% of those had CD4 lymphocyte count < 200/mm3. Extrapulmonary involvement and disseminated disease were common. Radiographic manifestations of pulmonary tuberculosis were often 'atypical' due to the greater proportion of primary tuberculosis among our patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Brain MRI of hippocampal volumetry in patients with refractory temporal lobe epilepsy.

OBJECTIVE: To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy. METHODS: Eighty-four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry. A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0.91. RESULTS: Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient. Other MRI abnormalities were detected in 18 patients with or without coexisting HA. CONCLUSIONS: Hippocampal sclerosis can be detected presurgically in many patients by brain MRI. Additional abnormalities not detected by brain CT can also be demonstrated.

Adult↗
PubMed2000

Practice of breast self-examination among high risk Chinese women in Hong Kong.

BACKGROUND: The incidence of breast cancer in Hong Kong is increasing and breast self-examination (BSE) as a screening tool is becoming more popular, especially among first-degree relatives (FDR) of breast cancer victims. BSE may be more applicable to Chinese women as their breast size is smaller. This study explores the BSE practice in this group of women. METHODS: A cross sectional study was conducted by sending questionnaires to 330 FDR of breast cancer patients treated in the Department of Surgery, University of Hong Kong. BSE behavior was studied with respect to its frequency, awareness, completeness and confidence of practice. RESULTS: 110 subjects returned the questionnaires with a response rate of 33%. The mean age of the respondent was 37 years. Only 57 women (52%) were practicers. The practicers have a stronger BSE awareness (P < 0.01) and a lower mean score on thought barriers (P = 0.002) than the non-practicers. 40% of the practicers gain their BSE knowledge through clinicians and their mean period of practice was 3.2 years. 68% of the practicers performed BSE completely. The overall confidence rate was 35%, but the rate was 43% among those who performed complete BSE. Thirteen factors possibly related to the completeness and rate of confidence of BSE examination were studied. The only factor that significantly determined completeness was the time spent for each examination (P = 0.002). The complete practicers required a longer time than the incomplete practicers (6.60 and 2.96 min, respectively). Women with a stronger BSE intention (P = 0.001) and a lower mean score on thought barriers (P = 0.001) performed the examination confidently. CONCLUSIONS: Slightly over half of the FDR practice BSE. The majority perform a complete BSE but they are not confident in finding abnormalities. Women spending more time on BSE are associated with a higher rate of completeness. However, only those with a stronger BSE intention and lesser thought barriers are more confident in their practice.

Adult↗
PubMed1999

Induction chemotherapy employing dose-intense cisplatin with mitomycin and vinblastine (MVP400), followed by thoracic surgery or irradiation, for patients with stage III nonsmall cell lung carcinoma.

BACKGROUND: Cisplatin-based induction chemotherapy before surgery or irradiation has improved the survival of patients with Stage III nonsmall cell lung carcinoma (NSCLC). Encouraged by earlier results with preoperative MVP (cisplatin [120 mg/m(2) or 25 mg/m(2)/week], vinblastine, and mitomycin) for Stage IIIA patients with clinically apparent mediastinal (N2) disease, the authors conducted a Phase II trial of the safety and efficacy of induction MVP400 with the dose intensity of cisplatin doubled from 25 to 50 mg/m(2) per week. METHODS: From October 1992 to March 1996, 37 patients with Stage IIIA (26) or Stage IIIB (11) NSCLC began the MVP400 induction chemotherapy program. Four doses of cisplatin (100 mg/m(2)), 7 doses of vinblastine, and 2 doses of mitomycin were given over 9 weeks. Patients received either surgery or irradiation after induction treatment. RESULTS: Overall, the response rate was 65% (95% confidence interval, 49-81%) with a complete resection rate of 67%. The median survival was 17 months, with 66% of patients alive at 1 year. Complete resection and Stage IIIA involvement were favorable prognostic indicators for survival. No Stage IIIB patients underwent a complete resection. Myelosuppression was the most common side effect. There were no treatment-related deaths. CONCLUSIONS: Although high response and complete resection rates were again demonstrated, results with the MVP400 regimen were not improved over those achieved with MVP regimen tested earlier with Stage IIIA (N2) patients. The authors continue to recommend MVP as an induction chemotherapy regimen for clinical trials.

Adult↗
PubMed1999

Preoperative prognostic variables and the impact of postoperative adjuvant therapy on the outcomes of Stage IB or II cervical carcinoma patients with or without pelvic lymph node metastases: an analysis of 891 cases.

BACKGROUND: The purpose of this study was to investigate pretreatment variables that could predict prognosis and to evaluate the impact of postoperative adjuvant therapy on the outcomes of patients with Stage IB or II cervical carcinoma with or without pelvic lymph node metastases. METHODS: Eight hundred ninety-one patients with Stage IB or II cervical carcinoma who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment at a single institution were analyzed. Potential prognostic variables were studied. RESULTS: Among the variables that could be assessed before treatment, depth of cervical stromal invasion (determined by magnetic resonance imaging), clinical stage, tumor size, grade of differentiation, and DNA index (determined by flow cytometry) were independent predictors of outcome in multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) were defined using these variables. Five-year recurrence free survival (RFS) rates for the low, intermediate, and high risk groups were 94.6%, 82.7%, and 62.3%, respectively (P = 0.0001), and overall survival (OS) rates were 98.4%, 84.5%, and 68.7%, respectively (P = 0.0001). Among patients with pelvic lymph node metastases who were free of parametrial extension, those who received postoperative chemotherapy or chemoradiotherapy had significantly better RFS (P = 0.017) and OS (P = 0.043) than those who received no adjuvant therapy. Among patients without pelvic lymph node metastases but at high risk of recurrence, those who received adjuvant radiotherapy had significantly better RFS (P = 0.015) and marginally improved OS (P = 0.087) compared with those who received no adjuvant therapy. CONCLUSIONS: A model containing assessable pretreatment variables for predicting the prognoses of patients with early stage cervical carcinoma was formulated. Subsets of patients for whom postoperative chemotherapy or radiotherapy might be beneficial were identified. The data from this retrospective review may be useful when future prospective trials of the treatment of early stage cervical carcinoma are designed.

Adult↗
PubMed1999

Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Antibodies, Monoclonal↗
PubMed1999

Radical resection and intraoperative radiotherapy for a recurrent endometrial cancer after prolonged remission following aggressive salvage therapy: case report.

The prognosis of recurrent endometrial carcinomas is generally poor, except for isolated vaginal relapse. We report a case of recurrent endometrial cancer in a 58-year-old woman who initially received a type I extended hysterectomy with bilateral salpin-go-oophorectomy and bilateral para-aortic and pelvic lymph node dissection. The first recurrence occurred in the left parametrium 7 months after the primary surgery. The salvage therapy consisted of radiotherapy combined with hormonal therapy (tamoxifen and Megace). Complete remission was achieved initially. Subsequently, the patient accepted six courses of chemotherapy (cisplatin and Adriamycin) for progressive elevation of cancer antigen 125 (CA-125). The CA-125 levels remained elevated with titers fluctuating around 100 U/ml until a second recurrence at the left iliac 75 months following salvage therapy. The second salvage treatment consisted of maximal debulking of the pelvic mass and intraoperative radiotherapy (IORT) followed by four courses of chemotherapy with paclitaxel and carboplatin. Complete remission was again accomplished, with clinical investigations and molecular markers returning to normal. The patient has been clinically free of disease for more than 2 years since the second relapse of cancer. In this particular case, we found that repeated recurrence could occur after a long complete remission following salvage therapy; however, the disease could be recontrolled with further aggressive salvage efforts. A multimodality approach with combinations of radical resection, IORT, and paclitaxel-based chemotherapy can be offered to patients with localized recurrent or repeatedly recurrent endometrial carcinoma after previous cisplatin-based chemotherapy and pelvic radiation.

CA-125 Antigen↗
PubMed1998

Ca2+-dependent structural changes in C-type mannose-binding proteins.

C-type animal lectins are a diverse family of proteins which mediate cell-surface carbohydrate-recognition events through a conserved carbohydrate-recognition domain (CRD). Most members of this family possess a carbohydrate-binding activity that depends strictly on the binding of Ca2+ at two sites, designated 1 and 2, in the CRD. The structural transitions associated with Ca2+ binding in C-type lectins have been investigated by determining high-resolution crystal structures of rat serum mannose-binding protein (MBP) bound to one Ho3+ in place of Ca2+, and the apo form of rat liver MBP. The removal of Ca2+ does not affect the core structure of the CRD, but dramatic conformational changes occur in the loops. The most significant structural change in the absence of Ca2+ is the isomerization of a cis-peptide bond preceding a conserved proline residue in Ca2+ site 2. This bond adopts the cis conformation in all Ca2+-bound structures, whereas both cis and trans conformations are observed in the absence of Ca2+. The pattern of structural changes in the three loops that interact with Ca2+ is dictated in large part by the conformation of the prolyl peptide bond. The highly conserved nature of Ca2+ site 2 suggests that the transitions observed in MBPs are general features of Ca2+ binding in C-type lectins.

Amino Acid Sequence↗
PubMed1998

Coupling of prolyl peptide bond isomerization and Ca2+ binding in a C-type mannose-binding protein.

A proline residue flanked by two polar residues is a highly conserved sequence motif in the Ca2+- and carbohydrate-binding site of C-type animal lectins. Crystal structures of several C-type lectins have shown that the two flanking residues are only observed to act as Ca2+ ligands when the peptide bond preceding the proline residue is in the cis conformation. In contrast, structures of the apo- and one-ion forms of mannose-binding proteins (MBPs) reveal that, when the Ca2+-binding site is empty, the peptide bond preceding the proline can adopt either the cis or trans conformation, and distinct structures in adjacent regions are associated with the two proline isomers. In this work, measurements of Ca2+-induced changes in intrinsic tryptophan fluorescence, and fluorescence energy transfer from tryptophan to Tb3+, reveal a slow conformational change in rat liver MBP (MBP-C) accompanying the binding of either Ca2+ or Tb3+. The Ca2+-induced increase in intrinsic tryptophan fluorescence shows biphasic kinetics: a burst phase with a rate constant greater than 1 s(-1) is followed by a slow phase with a single-exponential rate constant ranging from 0.01 to 0.05 s(-1) (36 degrees C) that depends on the concentration of Ca2+. Likewise, addition of EGTA to Ca2+-bound or Tb3+-bound MBP-C causes a decrease in intrinsic tryptophan fluorescence with biphasic kinetics consisting of a burst phase with a rate constant greater than 1 s(-1), followed by a slow phase with a single-exponential rate constant of 0.065 s(-1). In contrast, Tb3+ fluorescence produced by resonant energy transfer from MBP-C decreases in a single kinetic phase with a rate constant greater than 1 s(-1), implying that the slow change in tryptophan fluorescence monitors a conformational change that is not limited in rate by ion dissociation. The rate constants of the slow phases accompanying Ca2+ binding and release are strongly affected by temperature and are weakly accelerated by the prolyl isomerase cyclophilin. These data strongly suggest that the binding of either Ca2+ or Tb3+ to MBP-C is coupled to a conformational change that involves the cis-trans isomerization of a peptide bond. Fitting of the data to kinetic models indicates that, in the absence of Ca2+, the proline in approximately 80% of the molecules is in the trans conformation. The slow kinetics associated with cis-trans proline isomerization may be exploited by endocytic receptors to facilitate sorting of carbohydrate-bearing ligands from the receptor in the endosome.

Animals↗
PubMed1998

Ultrasound and CT findings of a cecal lymphangioma presenting with intussusception.

A rare case of cecal lymphangioma which presented as intussusception was reported. The patient was a 28-year-old female who suffered from vomiting, abdominal pain and mass for 6 days. Ultrasonography revealed a multilocular cyst that measured 7 cm in maximal diameter, and an adjacent target-like mass with concentric layering in the right abdomen. Computed tomography confirmed the sonographic findings with fatty component in the target-like mass. Intussusception in adults is a diagnostic challenge to a physician due to its vague and nonspecific presentations. Laparatomy is indicated because of underlying pathology in a vast majority of cases. Diagnosis can be established by the characteristic findings mentioned above.

Adult↗
PubMed1997

Structure of a selectin-like mutant of mannose-binding protein complexed with sialylated and sulfated Lewis(x) oligosaccharides.

Rat serum mannose-binding protein in which residues 211-213 have been changed to the Lys-Lys-Lys sequence found in E-selectin binds HL-60 cells and the oligosaccharide 3'-NeuAc-Le(x). To understand how this mutant, designated K3, mimics the carbohydrate-binding properties of E-selectin, structures of K3 alone and in complexes with 3'-NeuAc-Le(x), 3'-sulfo-Le(x) and 4'-sulfo-Le(x) have been determined at 1.95-2.1 A resolution by X-ray crystallography. The region of K3 that interacts with bound oligosaccharides superimposes closely with the corresponding region of unliganded E-selectin. In each of the oligosaccharide-protein complexes, the 2- and 3-OH of Fuc coordinate Ca2+ and form a network of cooperative hydrogen bonds with amino acid side chains that also coordinate the Ca2+. Lys211 of the K3 mutant, which corresponds to Lys111 of E-selectin, interacts with each of the three bound ligands: the N zeta atom donates a hydrogen bond to the 4-OH of Gal in 3'-NeuAc-Le(x), forms a water-mediated hydrogen bond with the 4-OH of Gal in 3'-sulfo-Le(x), and forms a salt bridge with the sulfate group of 4'-sulfo-Le(x). Lys213 packs against an otherwise exposed aromatic residue and forms a water-mediated hydrogen bond with Lys211 which may help to position that residue for interactions with bound oligosaccharides. These structures are consistent with previous mutagenesis and chemical modification studies which demonstrate the importance of the Ca2+ ligands as well as Lys111 and Lys113 for carbohydrate binding in the selectins, and they provide a structural basis for understanding the selective recognition of negatively charged Le(x) derivatives by the selectins.

Amino Acid Sequence↗
PubMed1997

Phase II study of the combination of the novel bioreductive agent, tirapazamine, with cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: Tirapazamine is a bioreductive compound synergistic with cisplatin in preclinical testing. This phase II study was conducted to evaluate the efficacy and toxicity of tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS: Twenty patients with unresectable stage III-B and IV non-small-cell lung cancer who had not received prior chemotherapy were given tirapazamine (390 mg/m2) intravenously (i.v.) over two hours followed one hour later by cisplatin (75 mg/m2) i.v. over one hour every 21 days. RESULTS: Five of 20 patients (25%) had major objective responses (95% confidence interval, 11%-50%). Median duration of response was eight months with a one-year survival of 40%. Toxicities included temporary hearing loss (25%), muscle cramping, diarrhea, skin rash and nausea/vomiting. No grade 3 or 4 hematologic or renal toxicity was observed. CONCLUSIONS: The combination of tirapazamine plus cisplatin appears to be safe and active in the treatment of advanced non-small lung cancer without a substantial increase in toxicity compared to cisplatin alone. A phase III randomized study compared the combination to cisplatin alone has completed accrual. Further evaluation of tirapazamine with other active agents and in multi-modality therapy is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Acute fulminant neuropathy in a patient with Churg-Strauss syndrome.

We report a patient with an acute neuropathy initially mimicking Guillain-Barré syndrome, both clinically and electrophysiologically. Persistent eosinophilia, positive antineutrophil cytoplasmic antibody and eosinophilic vasculitis in sural nerve biopsy later confirmed Churg-Strauss syndrome. Since vasculitic neuropathy can present in an acute and fulminant form, the role of early antibody testing and sural nerve biopsy in atypical cases of acute neuropathy is emphasized.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Enteric intussusception due to metastatic intestinal tumors.

Enteroenteric intussusception caused by metastatic tumors is a very rare condition. Because of its rarity and rather mild abdominal physical presentation, preoperative diagnosis is not easily made. Two cases of enteric intussusception due to metastatic intestinal tumors, with the main symptom of melena, are reported. Intussusception was caused by metastatic liposarcoma in one patient and metastatic melanoma in the other. Both patients had long histories of malignant disease, for 15 and 8 years, respectively. They had undergone repeated surgical treatment for metastatic lesions. The diagnosis of enteric intussusception was initially made by computed tomographic scans and small bowel series and was confirmed by laparotomy and pathologic findings. We suggest that tumor metastasis to the small intestine with intussusception should be considered in patients with recurrent tumors and tarry stools.

Adult↗
PubMed1997

Three-dimensional magnetic resonance cholangiopancreatography for evaluation of obstructive jaundice.

The purpose of this study was to assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) in studying the anatomy, sites, and causes of obstructive jaundice. From September 1994 to May 1996 three-dimensional MRCP was performed on 31 patients with abdominal pain and obstructive jaundice with a fast spin-echo T2-weighted pulse sequence. The images were reconstructed using maximal intensity projection, AVERAGE and SURFACE algorithm processing techniques at a graphics workstation. All the reconstructed images were compared with those obtained using conventional cholangiographic techniques, such as endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography and drainage, and intraoperative cholangiography. The patients' diagnoses included choledochal cyst (13), cholangiocarcinoma (five), choledocholithiasis (four), pancreatic head carcinoma (three), rhabdomyosarcoma (one), papillary Vater carcinoma (one), recurrent gastric carcinoma (one), ascaris (one), and biliary atresia (two). Extrahepatic biliary dilatation was present in all 13 patients with choledochal cyst; the pancreatic ducts and their entrance level to the common bile duct were observed in eight of these patients. The level of obstruction in patients with cholangiocarcinoma was well documented but the biliary tract of one patient with biliary atresia was not identified by MRCP. In one patient with biliary rhabdomyosarcoma, MRCP clearly delineated the extrabiliary extension of the tumor. In a patient with ascaris in the common bile duct an increase in signal intensity inside the digestive tract of the worm denoted fluid in its gut. Lithiasis was shown in all of the four patients with choledocholithiasis. Thus, MRCP is a useful tool in the assessment of biliary tract obstruction and its causes, and is a valuable addition to ultrasonography.

Adolescent↗