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Biomedical subjects

K K Ng

Publications and source records attributed to K K Ng.

At least 19 recordsLinked to original sources

Penile colour duplex ultrasonography as a screening tool for venogenic erectile dysfunction.

INTRODUCTION: Vasculogenic impotence is one of the major causes of erectile dysfunction. Cavernosometry and cavernosography is traditionally the gold standard for evaluation of venogenic impotence. However, it is invasive and there are potentially significant complications. Penile colour flow Doppler imaging (PCDI) is non-invasive and can be used to assess venous incompetence. MATERIALS AND METHODS: One hundred and sixty-eight patients were referred for PCDI assessment from March 1998 to February 2001. Forty-three of these also had cavernosogram and cavernosometry done and were included in the study. RESULTS: The sensitivity was 93.9%, the specificity was 90.0%, the accuracy was 93.0% with a negative predictive value of 81.8% and a positive predictive value of 96.9%. Kappa value of 0.81 was obtained, indicating excellent agreement between PCDI and cavernosogram and cavernometry. CONCLUSIONS: Penile colour flow Doppler imaging is accurate in the assessment of venogenic erectile dysfunction. It can replace cavernometry and cavernosogram as a screening tool. Cavernometry and cavernosogram should only be done in cases when PCDI suggests venogenic impotence, and when surgery is contemplated.

Adult↗

Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.

The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water-mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor, and leading to the formation of a cinnamate acyl-enzyme derivative via a tetrahedral transition state. Comparisons with structures of photoreversible cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a productive conformation in contrast to the photoreversible cinnamates. In summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition of chymotrypsin by natural coumarins and provides a structural basis for the design of more potent mechanism-based inhibitors against a wide range of biologically important chymotrypsin-like enzymes.

Animals↗

Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer.

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.

Adult↗

Isolated paraaortic lymph node recurrence after definitive irradiation for cervical carcinoma.

PURPOSE: To evaluate the clinical features of isolated paraaortic lymph node (PALN) recurrence after definitive radiotherapy, and analyze the prognostic factors and effect of salvage treatment. METHODS AND MATERIALS: Of a total 876 patients who received pelvic radiotherapy after the diagnosis of primary cervical carcinoma, 26 were found to have isolated PALN recurrence as the first recurrent site, and these patients enrolled in this study. Only those with primary-site carcinoma controlled and who were free of other distant metastases were eligible. Nineteen of the 26 patients accepted salvage therapy. Fourteen patients accepted concurrent chemoradiation (CCRT), 1 accepted radiation to the paraaortic region, and 4 accepted chemotherapy alone. Clinical parameters evaluated included tumor markers (SCC and CEA) and image studies. RESULTS: Seven of the 26 patients were alive and disease-free. All 7 survivors had salvage treatment with radiation to the paraaortic region and concurrent cisplatin-based chemotherapy. None of the patients receiving chemotherapy or radiation alone enjoyed long-term, disease-free survival. The 5-year survival rate for isolated PALN recurrence of the 14 patients who accepted salvage concurrent chemoradiation (CCRT) was 51.2%. The presence of a clinical symptom at the time of PALN recurrence was analyzed. Seven of the 12 asymptomatic patients and none of the 14 symptomatic patients survived without disease after salvage treatment. The SCC levels at recurrence showed a statistically significant relationship to disease-free survival. CONCLUSIONS: An SCC level of < or = 4 ng/ml and a lack of symptoms at the time of recurrence were good prognostic factors in isolated PALN recurrence after primary radiation therapy. In addition to concurrent CCRT, periodical surveillance with tumor markers and imaging studies allowed early detection and salvage of those patients.

Adult↗

X-ray crystallographic analyses of complexes between bovine beta-trypsin and Schiff base copper(II) or iron(III) chelates.

To establish the structural basis underlying the activity of a novel series of metal-chelate trypsin inhibitors, the structures of p-amidinosalicylidene-l-alaninato(aqua)copper(II) (1a), m-amidinosalicylidene-l-alaninato(aqua)copper(II) (1b), bis(p-amidinosalicylidene-l-alaninato)iron(III) (2a), and bis(m-amidinosalicylidene-l-alaninato)iron(III) (2b) bound to bovine beta-trypsin were studied by X-ray crystallography. The amidinium group of the inhibitor donates hydrogen bonds to Asp189, Gly219 and Ser190, as seen before in trypsin-benzamidine complexes. The copper(II) ion of 1a is situated away from trypsin's catalytic triad residues, and is octahedrally coordinated by a Schiff base and three water molecules. In contrast, the copper(II) ion of 1b is situated close to the catalytic triad and adopts a square pyramidal coordination geometry. The iron(III) ion of 2a is octahedrally coordinated by two Schiff base ligands and, like the copper(II) ion of 1a, is situated away from the catalytic triad. The p-amidinophenyl ring of a second Schiff base ligand of 2a is directed toward a hydrophobic groove formed by Trp215 and Leu99. Finally, the iron(III) ion of 2b appears to be replaced by magnesium(II), which is octahedrally coordinated by a Schiff base, Gln192 and two water molecules. One of the Schiff base ligands seen in the trypsin-2a complex or in the unbound form of 2b is replaced by water molecules and Gln192. His57 and Ser195 form water-mediated interactions with the magnesium(II) ion of 2b, and Ser195 also forms a hydrogen bond with the phenolic oxygen atom of the Schiff base ligand. These structures reveal a novel mode of interaction between metal-chelate inhibitors and serine proteases, thus providing a structural basis for the development of more potent inhibitors against a variety of trypsin-like enzymes.

Animals↗

Air enema for diagnosis and reduction of intussusception in children: clinical experience and fluoroscopy time correlation.

PURPOSE: The objective of this study was to correlate the fluoroscopy time with radiologic outcome in the pneumoreduction of intussusception in children. METHODS: From September 1995 to December 1997, a prospective analysis of 181 cases of pediatric intussusception with pneumoreduction without sedation was done. A receiver operating characteristic curve of fluoroscopy time was drawn for correlation with radiologic outcome. RESULTS: The overall success and failure rates of pneumoreduction were 84% and 16%, respectively. Three patients (1.6%) experienced colon perforation. The mean fluoroscopy time was 2.8 +/- 1.7 minutes in successful procedure and 4.9 +/- 2.8 minutes in failed procedures (P < 0.001). Analysis of the receiver operating characteristic curve of fluoroscopy time indicates that 4 minutes fluoroscopy time was a good critical point in differentiating successful and failed cases. In those 18 patients who had successful reduction with fluoroscopy times of more than 4 minutes, 4 patients had clinical symptoms for more than 1 day and 14 patients less than 1 day. One of those 4 patients required operation 1 day later because of peritonitis caused by necrosis of terminal ileum. Two patients had high fever in the next 2 days and recovered after antibiotic treatment. CONCLUSIONS: Pneumoreduction is a good method in treatment of intussusception with high successful rate. Four minutes is the critical point of procedure. Reduction with greater than 4 minutes in those patients having illness more than 1 day might not benefit and have more complications.

Air↗

Ultrasound guided puncture of the brachial artery for haemodialysis fistula angiography.

BACKGROUND: Arterio-venous (a-v) fistulae of haemodialysis patients frequently require function assessment by angiography. The purpose of the present study was to determine the efficacy and safety of ultrasound-guided transbrachial catheterization when a-v fistulae were evaluated. METHODS: Between July 1996 and December 1997, 208 dialysis patients, whose a-v fistulae (arterial inflow < 50 ml/min or venous pressure > 150 mm Hg in three consecutive HD sessions) were at the wrist or elbow, underwent transbrachial angiography using an ultrasound-guided 20-gauge IA needle to evaluate fistula function. Procedure-related symptoms or complications were noted in 28 patients and these were analysed. RESULTS: No apparent cases of vessel spasm or thrombosis were noted. Reported symptoms in 28 patients (13.5%) included local arm pain (3.3%), transient paresthesia (0.9%), mild ecchymosis (10.6%) and haematoma (0.9%). All complications were minor and none required surgical intervention. CONCLUSION: Ultrasound-guided puncture of the brachial artery is a safe, reliable and effective procedure in skilled hands and should be the preferred means of catheterization whenever haemodialysis angiography is performed.

Adolescent↗

The management of non-small-cell lung cancer with oligometastases.

The standard care for patients with non-small-cell lung cancer is chemotherapy of supportive care, with surgery being reserved for palliation of symptoms; however, there is a small group of patients with a finite number of extrathoracic metastases (oligometastases) who may experience improved survival by resection of their metastases and the primary site, with or without systemic treatment. This article summarizes the theoretic basis for resection of metastatic lung cancer, reviews the available data addressing management of disease metastatic to the lung, brain, and adrenal glands, and outlines a model for a future clinical trial to investigate the area further.

Carcinoma, Non-Small-Cell Lung↗

Pyeloureteritis cystica: case report.

Pyeloureteritis cystica, characterized by multiple bubbly filling defects on urography and caused by inflammatory stimuli, is a rare disorder of the ureter. It commonly affects older people. Diagnosis is established by radiological studies. Antibiotics should be given if urinary tract infection is present. Up to now, no other specific treatment can be used to cure this disorder. We report a case of pyeloureteritis cystica associated with urinary tract infection and a ureteral stone in a young woman who presented with hematuria and bilateral flank pain. The pyeloureteritis cystica had a bead-like appearance on intravenous pyelogram and retrograde pyelogram as well as in magnetic resonance urography. The diagnosis and treatment of this disorder are discussed. Magnetic resonance urography can provide high-resolution of coronal images of the entire urinary tract without the use of contrast agents or ionizing radiation. However, the cost of the procedure is a major concern.

Adult↗

Cerebellar metastasis from papillary serous adenocarcinoma of the ovary mimicking Ménière's disease. A case report.

BACKGROUND: In rare cases, cerebellar metastasis originating in serous papillary adenocarcinoma of the ovary can mimick Ménière's disease. CASE: A 51-year-old woman, with complete remission after optimal maximal debulking and chemotherapy for an International Federation of Gynecology and Obstetrics IIIc primary ovarian carcinoma, presented with nausea, vomiting, vertigo and headache 18 months after surgery. Investigations revealed a solitary cerebellar cystic mass, 4.6 x 4.0 x 3.2 cm. Gross total excision of the cerebellar lesion followed by brain irradiation resulted in complete resolution of her symptoms. Histology showed a metastatic tumor consistent with the primary ovarian carcinoma. CONCLUSION: In an atypical presentation in patients with metastatic ovarian carcinoma, thorough investigations should be done to rule out or confirm brain metastasis, which can be aggressively managed to prevent serious consequences and improve outcome.

Adenocarcinoma, Papillary↗

Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry.

OBJECTIVE: To study the clinical characteristics of 2952 patients with epilepsy who had received drug treatment from the neurology outpatient clinics of eight major hospitals in Hong Kong. METHODS: Retrospective review of outpatient records. RESULTS: 1601 (54.3%) males and 1351 (45.7%) females with a median age of 35.8 years (range, 10-94.8) were studied. Seizure types included generalized tonic-clonic in 80.7% of patients, complex partial in 28.3%, simple partial in 14.4%, atypical absence in 2.6% and myoclonic in 1.4%, and 30.4% of patients had more than one seizure type. EEG, CT brain, MRI brain and neuropsychological evaluation were obtained in 81.2%, 61.7%, 17.0% and 2.2% of patients, respectively. The etiology of epilepsy was cryptogenic in 59.9%, symptomatic in 35.1% and idiopathic in 3.9%; the commonest were intracranial infection, cerebral vascular disease, cranial trauma and perinatal insult. Phenytoin, carbamazepine and valproate were the most frequently used drugs and 25.9% of patients were taking more than two drugs. 48.3% of patients had active seizures in the past six months and 26.4% were considered to have unsatisfactory control of their epilepsy. Medical refractoriness of epilepsy was associated with a history of perinatal insult, intracranial infection, congenital brain malformation, intracranial neoplasm, cerebral vascular disease, hippocampal sclerosis, mental retardation and a history of status epilepticus (P < 0.05). CONCLUSION: In this local cohort of adult patients with epilepsy under specialist care, there were a considerable number of patients falling into the category of cryptogenic epilepsy. Risk factors associated with medical refractoriness are similar to previous studies.

Adolescent↗

Phase I trial of docetaxel and vinorelbine in patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: With preclinical evidence of synergy, this dose-finding trial examining the combination of docetaxel and vinorelbine given with prophylactic filgrastim for the treatment of patients with nonsmall cell lung carcinoma was undertaken. METHODS: Twenty-seven patients with advanced nonsmall cell lung carcinoma received vinorelbine as an intravenous push immediately followed by docetaxel as a 1-hour intravenous infusion once every 2 weeks at 1 of 7 different dose levels. Vinorelbine was escalated from 15 mg/m(2) (Level I) to 45 mg/m(2) (Level VII) and docetaxel was increased from 50 mg/m(2) (Level I) to 60 mg/m(2) (Level VII). Prophylactic corticosteroids and filgrastim were employed prospectively. RESULTS: After completion of dose Level VII, accrual was terminated because Phase II dose intensity of both agents had been reached and further escalation was believed to be unsafe. At dose Level VII, one episode of first-cycle febrile neutropenia and a death after three treatment cycles due to Haemophilus influenzae sepsis (Grade 5 toxicity according to the Common Toxicity Criteria of the National Cancer Institute) without neutropenia were noted. In all, 209 treatment cycles were administered and febrile neutropenia was observed in only 4 of these treatments (1.9%). Bacteremia occurred in three patients (four episodes) in the absence of neutropenia. Symptomatic onycholysis was observed in three patients. Clinically significant peripheral neuropathy and fluid retention were rare. Confirmed partial responses were noted in 10 patients for a response rate of 37% (95% confidence interval, 20-57%). CONCLUSIONS: Docetaxel at a dose of 60 mg/m(2) and vinorelbine at a dose of 45 mg/m(2), both given every 2 weeks, can be combined safely to achieve Phase II dose intensity of both agents. An ongoing Phase II trial will define the activity of this treatment combination.

Adult↗

Antral web--a rare cause of vomiting in children.

Antral web is a rare cause of gastric-outlet obstruction. We report a case of gastric antral web with intermittent vomiting in a 10-year-old girl who received medical treatment for 6 months. The literature on this anomaly is reviewed with respect to differential diagnosis on the basis of upper gastrointestinal radiographic series, gastroscopy, and treatment planning.

Abdominal Pain↗

Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3.

The three-dimensional structures of pepsin inhibitor-3 (PI-3) from Ascaris suum and of the complex between PI-3 and porcine pepsin at 1. 75 A and 2.45 A resolution, respectively, have revealed the mechanism of aspartic protease inhibition by this unique inhibitor. PI-3 has a new fold consisting of two domains, each comprising an antiparallel beta-sheet flanked by an alpha-helix. In the enzyme-inhibitor complex, the N-terminal beta-strand of PI-3 pairs with one strand of the 'active site flap' (residues 70-82) of pepsin, thus forming an eight-stranded beta-sheet that spans the two proteins. PI-3 has a novel mode of inhibition, using its N-terminal residues to occupy and therefore block the first three binding pockets in pepsin for substrate residues C-terminal to the scissile bond (S1'-S3'). The molecular structure of the pepsin-PI-3 complex suggests new avenues for the rational design of proteinaceous aspartic proteinase inhibitors.

Amino Acid Sequence↗