Omental fibromatosis presenting as an incarcerated inguinal hernia.
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Biomedical subjects
Publications and source records attributed to K W Chan.
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The differentiation of male specific sensory rays in the nematode Caenorhabditis elegans is a complex process regulated by multiple genetic components. A novel approach with heat shock treatment was employed to show that multistep regulation is involved in this process. Intervention in this stepwise regulation resulted in phenocopy of specific gene mutations. The results suggest that differential gene function acting at a precise time frame is necessary to guide the normal differentiation of sensory rays.
BACKGROUND: Information on the safety and efficacy of allogeneic peripheral blood progenitor cell (PBPC) collection in filgrastim-mobilized normal donors is still limited. STUDY DESIGN AND METHODS: The PBPC donor database from a 42-month period (12/94-5/98) was reviewed for apheresis and clinical data related to PBPC donation. Normal PBPC donors received filgrastim (6 microg/kg subcutaneously every 12 hours) for 3 to 4 days and subsequently underwent daily leukapheresis. The target collection was > or =4 x 10(6)CD34+ cells per kg of recipient's body weight. RESULTS: A total of 350 donors were found to be evaluable. Their median age was 41 years (range, 4-79). Their median preapheresis white cell count was 42.8 x 10(9) per L (range, 18.3-91.6). Of these donors, 17 (5%) had inadequate peripheral venous access. Leukapheresis could not be completed because of apheresis-related adverse events in 2 donors (0.5%). Of the 324 donors evaluable for apheresis yield data, 221 (68%) reached the collection target with one leukapheresis. The median CD34+ cell dose collected (first leukapheresis) was 462 x 10(6) (range, 29-1463). The main adverse events related to filgrastim administration in donors evaluable for toxicity (n = 341) were bone pain (84%), headache (54%), fatigue (31%), and nausea (13%). These events were rated as moderate to severe (grade 2-3) by 171 (50%) of the donors. In 2 donors (0.5%), they prompted the discontinuation of filgrastim administration. CONCLUSION: PBPC apheresis for allogeneic transplantation is safe and well tolerated. It allows the collection of an "acceptable" PBPC dose in most normal donors with one leukapheresis, with minimal need for invasive procedures.
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Melanocytic proliferation in young people may sometimes pose a diagnostic dilemma. This is particularly so when a desmoplastic component is present. Because the two main differential diagnoses, desmoplastic malignant melanoma and desmoplastic Spitz nevus, share some morphologic features, the diagnosis of desmoplastic malignant melanoma may be overlooked. Distinction between the two is important because they show completely different biological behavior. The age of patient, site of lesion, histologic findings of melanocytic atypia, neurotropism, mitosis, and maturation help to distinguish the two entities. We report a case of desmoplastic malignant melanoma occurring in the buttock of an 18-year-old Chinese girl. Histologically, it had typical features of desmoplastic malignant melanoma with junctional melanocytic atypia and prominent neurotropism. Clinical and histologic differences between desmoplastic malignant melanoma and desmoplastic Spitz nevus are reviewed. We conclude that although desmoplastic Spitz nevus occurs much more commonly in adolescents, desmoplastic malignant melanoma can occur in this age group and even in non-sunexposed skin. Microscopic findings remain the mainstay that guides the final diagnosis.
Mucocelelike tumors of the breast encompass a spectrum of pathologic lesions, including benign tumor, atypical ductal hyperplasia, carcinoma in situ, and colloid carcinoma. Because the fine-needle aspiration (FNA) cytology of mucocelelike tumors covering this pathologic spectrum is not well defined, a study of 21 cases of mucocelelike tumors was conducted. Benign lesions are likely to be poorly cellular and to contain cohesive clusters of cytologically bland cells arranged in two dimensional sheets in the background of abundant mucoid material. Colloid carcinomas are usually highly cellular and contain loosely cohesive clusters and dissociated cells with nuclei showing minimal to mild atypia. The most discriminating feature between benign and malignant lesions appears to be the presence of many dissociated cells with intact cytoplasm. Cases with atypical ductal hyperplasia, with some bordering on carcinoma in situ as seen in 7 of the 12 benign cases, may be difficult to identify on FNA cytology, possibly because of sampling. As expected, some of the atypical cases have intermediate features of benign and malignant tumors. Because of overlapping features in borderline cases, we recommend excisional biopsy for all mucocelelike lesions. Myxoid fibroadenoma is more cellular than benign mucocelelike lesions and can be distinguished from carcinoma by the absence of dissociation and presence of numerous bare nuclei of bland morphology in the background. The mucoid material of myxoid fibroadenoma stained brightly pink rather than magenta as in mucocelelike tumors using the Diff Quik stain.
The optimal therapy for pure membranous lupus nephritis (MLN) with nephrotic syndrome remains controversial. While the risk of progressive renal deterioration may be small, persistent heavy proteinuria leads to the complications of oedema, hypoalbuminaemia, hyperlipidaemia, hypercoagulability, and venous thrombosis. We examined prospectively the efficacy and tolerability of a sequential immunosuppressive regimen in a cohort of 20 patients with nephrotic syndrome due to pure MLN (WHO Class Va and Vb). Initial therapy comprised prednisolone (0.8 mg/kg/d p.o.) and cyclophosphamide (2-2. 5 mg/kg/d p.o.). Prednisolone dosage was gradually tapered to 10 mg/d at 6 months, when cyclophosphamide was replaced by azathioprine (2 mg/kg/d p.o.) as maintenance therapy. Within 12 months of therapy 11(55%) patients had complete remission (CR), 7(35%) patients achieved partial remission (PR) (proteinuria reduced from 6.2+/-4.0 to 2.0+/-1.7 g/24 h, P<0.01), and 2 patients failed to respond. Improvements in proteinuria and serum albumin level were observed after 3-6 months of treatment. Non-responders had lower baseline serum albumin compared to complete responders. Renal function remained stable during follow-up for 73.5+/-48.9 months. 8 patients had disease relapse at 47+/-15 months. Early complications (</=12 months) included herpes zoster (40%), minor respiratory or urinary tract infections (25%), mild leukopenia (15%), and transient amenorrhea (14.3%). 4 of the 20 patients developed pulmonary tuberculosis during follow-up, at 35+/-24 months after the diagnosis of MLN. 8 patients had hyperlipidaemia. Haemorrhagic cystitis, permanent amenorrhea, vascular complications, and mortality were not observed. We conclude that this sequential immunosuppressive regimen is effective in 90% of patients with MLN and heavy proteinuria. Prudent consideration of the benefits and potential side-effects is required to determine the optimal management for individual patients.
We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin time was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8+/-0.5; ginseng 7.3+/-2.5 microg mL(-1)), time to peak (control 2.6+/-1.0; ginseng 3.1+/-1.1 h), elimination half-life (control 14.3+/-5.8; ginseng 10.6+/-3.1 h), and oral clearance (control 17.5+/-3.3; ginseng 20.2+/-5.5 mL h(-1)) were not significantly different (P>0.05). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776+/-619, ginseng 3830+/-362 sh) and maximum prothrombin time (control 57.2+/-11.8, ginseng 63.3+/-9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.
OBJECTIVES: To examine the histologic features of p21 in penile tumors and to determine the role of p21 and p53 in the pathogenesis of this group of tumors. METHODS: The clinicopathologic features of 87 patients with penile tumors were studied. The expression of p53 and p21 proteins in 49 cases was investigated by immunohistochemistry. RESULTS: Of the 87 tumors studied, 84 represented primary penile tumors (72 malignant and 12 benign) and 3 represented secondary tumors (2 from bladder, 1 from nasopharynx). The primary malignant penile tumors included 66 surface carcinomas with squamous differentiation (92%), 3 cases of Paget disease (4%), 1 case of Bowen disease (1%), and 2 penile urethral squamous cell carcinomas (3%). The former group was subdivided into squamous cell carcinoma (n = 50), verrucous carcinoma (n = 8), basaloid squamous cell carcinoma (n = 3), adenoid squamous cell carcinoma (n = 3), spindle cell carcinoma (n = 1), and adenosquamous carcinoma (n = 1). The benign tumors were squamous cell papillomas (n = 10) and fibromatoses (n = 2). Expression of p21 and p53 was noted in 40% and 89%, respectively, of the 47 patients with primary surface penile carcinoma with squamous differentiation. Positive p21 and p53 expression was also seen in 2 cases of Paget disease. Staining for p21 was often weak and was found in the suprabasal region of carcinomas with squamous differentiation, while p53 expression was seen in the basal region of squamous cell carcinomas. Preinvasive lesions also showed p21 and p53 expression. An inverse correlation between p53 and p21 expression (p53(+)/p21(-) or p53(-)/p21(+)) was noted in half of the squamous cell carcinomas, 4 of 5 verrucous carcinomas, 2 of 3 basaloid squamous cell carcinomas, and in 1 spindle cell carcinoma. The other cases did not show this correlation. CONCLUSIONS: Penile tumors had different histologic variants and p21/p53 expression patterns. Expression of p21 did play a role in some tumors and could be dependent or independent of p53 expression.
AIM OF STUDY: To study the clinical features of dengue illness in hospitalised patients in Singapore. METHODS: One-hundred and thirty hospitalised patients with serologically confirmed dengue illness, from 1 April 1992 to 31 October 1992, were analysed retrospectively. RESULTS: Teenagers and young adults between 15 to 30 years of age were most commonly affected. The male to female ratio was 1.3:1. The mean duration of fever and rash prior to admission were 5.2 +/- 1.5 (mean +/- SD) days and 1.7 +/- 1.7 days respectively. Petechiae were present in 52.3% of the patients. Three-quarters of the patients with petechiae had platelet counts (PCs) of 100 x 10(3) ul-1 or less. Thrombocytopenia (PCs of 100 x 10(3) ul-1 or less) was first documented 5.8 +/- 1.4 days after the onset of illness. The nadir of thrombocytopenia occurred on the 6.4 +/- 1.6 day of illness. The mean duration of thrombocytopenia was 3.6 +/- 1.6 days. Nineteen patients (14.6%) had non life-threatening clinical bleeding or coagulopathy, namely bleeding gums (9 patients), epistaxis (5), vaginal spotting/menorrhagia (4) and prolonged PTT (3). Six patients (4.6%) required platelet transfusion because of severe thrombocytopenia (PCs less than 30 x 10(3) ul-1) and clinical bleeding. There was no secondary fall in the PCs over 2 or more consecutive days when the PCs were in the recovery phase. It took 1 more day to reach PCs of 100 x 10(3) ul-1, the "safe" level commonly used in Singapore to decide discharge of patients, as compared to 80 x 10(3) ul-1. At PCs of 80 x 10(3) ul-1 or more, 2 patients had bleeding gums, 1 each had epistaxis and vaginal spotting. No transfusion was required for these 4 patients. The mean hospital stay was 4.2 +/- 1.5 days. There was no mortality in this study. CONCLUSION: Dengue illness is a relatively benign self-limiting illness. When the PCs are on the rising trend and in the absence of clinical bleeding, it is reasonably safe to discharge patients when the PCs reach 80 x 10(3) ul-1, instead of 100 x 10(3) ul-1. This will shorten each patient's stay by 1 day, resulting in cost saving and more efficient use of hospital beds.
OBJECTIVE: To audit the diagnostic accuracy and value of fine-needle aspiration cytology in the assessment of thyroid nodules over a 5-year period. DESIGN: Retrospective study. SETTING: Private practice, Hong Kong. PATEINTS: The computerised records from cytological and histological examinations of all thyroid specimens submitted from 1993 through 1997 were studied; the 1236 aspirates came from 1033 women and 175 men (gender was not specified in 28 cases). MAIN OUTCOME MEASURES: Cytological reports were classified diagnostically, and histological and cytological correlations were determined. RESULTS: Of the 1236 aspirates, 113 (9.1%) were unsatisfactory; 1013 (82.0%), including cysts, were benign; and 110 (9.0%) were neoplastic or malignant. Histological follow-up was available for 149 cases; 13 were unsatisfactory for cytological diagnosis. Statistical analysis of the remaining 136 cases yielded the following results: sensitivity of fine-needle aspiration cytology, 56%; specificity, 90%; positive predictive value, 74%; negative predictive value, 80%; accuracy, 79%. These results were within the range of previously published values. The sensitivity was improved by combining clinical information: if nodules larger than 3-cm diameter were excised (despite a non-neoplastic aspiration cytology report), the sensitivity increased to 71% and the accuracy to 84%. CONCLUSION: Fine-needle aspiration cytology is an effective screening test to help evaluate whether surgery is required in the management of thyroid nodules. False-positive and false-negative rates can be minimised by taking clinical and imaging data into consideration.
OBJECTIVE: To evaluate the liquid-based ThinPrep Papanicolaou test. DESIGN: Prospective comparison of the ThinPrep test with the conventional Papanicolaou test. SETTING: Cervical smear specimens sent to a private practice, Hong Kong. PATIENTS: A total of 16,541 ThinPrep test specimens and 7258 conventional Papanicolaou smears from Hong Kong women who had been screened for cervical cancer between mid-July 1998 and mid-January 1999. MAIN OUTCOME MEASURES: Specimen adequacy, endocervical cell content, epithelial cell abnormalities, and micro-organisms present in both types of cervical smears; histological diagnosis of cervical biopsy specimens of women who had the ThinPrep test. RESULTS: Compared with the conventional Papanicolaou smear test, the ThinPrep test showed a reduction in the frequency of 'unsatisfactory' (0.56% versus 1.36%; P<0.01), 'satisfactory but limited' (1.67% versus 15.87%; P<0.01), and 'atypical squamous cells of undetermined significance' reports (1.72% versus 3.64%; P<0.01). The ThinPrep test was also more effective at detecting squamous intraepithelial lesions, showing a 58% increase for low-grade lesions (2.66% versus 1.68%; P<0.01) and 28% increase for high-grade lesions (1.71% versus 1.34%; P<0.01). The sensitivity and positive predictive value of the ThinPrep system were 97.5% and 94.2%, respectively. The liquid-based method yielded a higher percentage of samples that contained endocervical cells compared with conventional smear specimens (70.57% versus 51.23%; P<0.001). CONCLUSIONS: The ThinPrep test has a high sensitivity and positive predictive value. The ThinPrep test gives higher-quality specimens and has a higher detection rate of squamous intraepithelial lesions than the conventional Papanicolaou smear test. The drawbacks of the liquid-based system, however, pertain to cost and the additional procedures and training needed.
OBJECTIVE: To examine the prevalence of glomerular disease in Hong Kong. DESIGN: Prospective review. SETTING: University teaching hospital, Hong Kong. PATIENTS: All patients who presented with suspected glomerular disease from 1993 through 1997. MAIN OUTCOME MEASURES: Histopathological diagnosis from biopsy examination and clinical features of presentation. RESULTS: A total of 1629 consecutive percutaneous renal biopsies of native kidneys showed glomerular disease in 1413 cases. The most common clinical indication for renal biopsy was persistent proteinuria (n=735; 52.0%), while the most frequently found glomerular lesion was immunoglobulin A nephropathy (n=338; 23.9%). Minimal-change nephrotic syndrome (n=125; 8.8%) and immunoglobulin M nephropathy (n=11; 0.8%), were the most common glomerular diseases that presented with nephrotic syndrome. The male to female ratio for lupus nephritis was 1:14 (n=290), whereas for minimal-change nephrotic syndrome, the ratio was 1.8:1 (n=125). Immunoglobulin A nephropathy and membranous glomerulonephritis (n=117) affected approximately equal numbers of male and female patients. Familial fibrillary glomerulonephritis, a disease hitherto unknown in Hong Kong, was diagnosed in two siblings. CONCLUSION: Immunoglobulin A nephropathy was the most common glomerular disease in this survey and represents an important cause of end-stage renal failure in the Hong Kong population.
BACKGROUND: Microvascular free jejunal transfer was employed for reconstruction of pharyngeal defect resulting from circumferential resection of the hypopharynx. Postoperative radiotherapy to the neck might affect the graft, but this information was lacking. The mucosal changes of the jejunum in response to radiation were identified in this prospective study. METHODS: Normal jejunal mucosa was obtained at operation, and endoscopic jejunal mucosal biopsies were taken during and at completion of radiotherapy. Endoscopic biopsies were repeated at 1, 3, 6, 12, and 24 months afterwards. All jejunal biopsies were subjected to histologic and scanning electron microscopic (SEM) examinations. Nine patients had a complete set of biopsy while 5 other patients who received no radiotherapy also went through a similar sequence of biopsies as controls. RESULTS: Histologic examination showed mucosal edema and extensive blunting of jejunal villi at the completion of radiotherapy. Increased fibrosis with focal loss of glands was noticed at 3 months after radiotherapy, and this remained throughout the 2-year period. SEM revealed patchy loss of microvilli at completion and at 1 month after radiotherapy, but this feature was not apparent in biopsies taken at 3 months onwards, showing that it was only a transient event. CONCLUSIONS: Transient responses and persistent changes of jejunal mucosa to radiotherapy were identified and characterized. The presence of these mucosal lesions was not associated with any clinically significant adverse effect in the graft up to 2 years postradiotherapy.
PURPOSE: Small bowel transplantation (SBT) is the ultimate treatment for intestinal failure. It remains unclear as to which intestinal segment is more suitable for use in segmental SBT. The current study aims to assess the susceptibility of various parts of small intestine to ischemia and reperfusion injury and their capacity for regeneration. METHODS: Thirty-two segments of pig jejunum and ileum were isolated with intact vascular pedicles that were clamped for periods varying from 1/2 to 8 hours. Biopsy specimens were taken immediately before clamp release and 20 minutes afterwards. All segments were anastomosed together before abdominal closure. Laparotomy was performed 24 hours later, and biopsy specimens were taken at all segments. All specimens were examined histologically by a pathologist. RESULTS: Evidence of injury was detected after 1.5 hours of ischemia at jejunum, but only after 5 hours at ileum. More severe injury was noted at the initial period on reperfusion, but there was no further deterioration at the later period. Complete reepithelialization occurred after 24 hours even where there had been total villous sloughing at reperfusion, but regeneration was impossible when the crypts had been damaged completely. CONCLUSIONS: Ileum, because it is more resistant to ischemia and reperfusion injury, may be preferred for segmental SBT. Regeneration of the bowel epithelium is fast, provided that the crypts are not damaged completely.
Adult polycystic kidney disease (APKD) is a common genetic disease with a frequency of 1:1000. Evidence suggests that transforming growth factor alpha (TGF alpha) signaling may contribute to the hyperproliferation of the cystic epithelia in APKD. TGF alpha and epidermal growth factor (EGF) are well known mitogens expressed in the kidney and both exert their biological activities through binding to the same EGF receptor. A transgenic mouse that over-expressed TGF alpha developed renal cysts; raised levels of TGF alpha and EGF receptor mRNA were found in kidneys from two autosomal dominant APKD patients. To study the role of TGF alpha in cyst formation, we analyzed nine anatomically diagnosed adult polycystic kidneys and four normal kidneys using immunohistochemistry. We also traced the possible origins of the cysts by staining with the proximal convoluted tubule (PCT) marker, gp330, and the distal convoluted tubule (DCT) and collecting tubule (CT) marker, peanut agglutinin (PNA). In normal kidneys, TGF alpha protein was concentrated in the DCT and CT and EGF receptor protein in all three tubule types. In the early cysts of APKD, the cystic epithelia showed strong positive staining with TGF alpha, EGF receptor and gp330 but negative with PNA. Strong TGF alpha and EGF receptor staining was also found in the mixture of advanced cysts in the end-stage cystic kidneys although the cysts are likely to be derived from different segment of the renal tubules. This increased TGF alpha and EGF receptor expression in all cases and all types of cysts suggests that autocrine/paracrine stimulation by TGF alpha may be a common mechanism in cyst development in APKD.
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Fibrillary/immunotactoid glomerulopathy is characterized by organized glomerular deposition of extracellular, nonbranching, immunoglobulin-derived microfibrils, which is not associated with systemic diseases such as amyloidosis, cryoglobulinemia, or monoclonal gammopathy. This is an uncommon condition with an obscure etiology and accounts for approximately 1% of primary glomerular diseases in white populations. We report the first case of familial fibrillary/immunotactoid glomerulopathy affecting a brother and a sister in a Chinese family. Both patients presented with heavy proteinuria, which improved transiently on treatment with prednisolone and cyclophosphamide. Human lymphocyte antigen typing for the siblings showed no haplotype association. Despite the generally poor renal prognosis reported in the literature, with 50% of patients reaching end-stage renal failure within 2 to 4 years, both patients had relative preservation of renal function (creatinine clearance from 79 to 76 mL/min/1.73 m2 after 2 years in one patient and from 111 to 99 mL/min/1.73 m2 after 3 years in the other). Our observations show that fibrillary/immunotactoid glomerulopathy can present as a familial condition. Compared with sporadic cases, patients with familial fibrillary/immunotactoid glomerulopathy may have a more favorable renal prognosis.