Primary hepatic pregnancy.
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Biomedical subjects
Publications and source records attributed to K W Lo.
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Immunoglobulin D multiple myeloma (IgD MM) is a rare subtype that accounts for 1% to 3% of MM and shows higher aggressiveness with distinctive clinical and laboratory features. However, there is little information in the literature on their karyotypes, which are mainly derived from G-banding results. Our current study on 2 Chinese IgD MM thus represents the first description of cytogenetic data on this subtype based on an integrated analysis with G-banding and multicolor spectral karyotyping (SKY). Both of our cases showed some usual features of MM, as well as a few novel translocations including t(3;22), t(6;19), t(X;19) and the 3 whole-arm translocations namely t(1;6)(q10;p10), t(4;9)(q10;p10), and t(16;18)(q10;q10). We also identified recurrent chromosomal rearrangements involving breakpoints 3p21 and 19q13, which may suggest to be unique aberrations that may underline the pathogenesis of this distinctive biological MM subtype.
OBJECTIVE: To investigate the clinical and prognostic significance of human papillomavirus (HPV) in a Chinese population of cervical cancers. METHODS: We studied 121 cervical cancer tissue samples from patients treated at our hospital. Identification and typing of HPV were done by polymerase chain reaction (PCR) using consensus primers MY11 and MY09 followed by direct DNA sequencing. The results were correlated with various clinical and prognostic parameters. RESULTS: We found HPV DNA in 95 (78.5%) cases, including HPV-16 in 59 (48.8%) and HPV-18 in 14 (11.6%) cases. chi(2) analysis revealed no significant correlation between the presence of HPV DNA and age at diagnosis, clinical stage, histologic type, tumor grading, 2-year and 5-year survival rate. Of the factors evaluated, age at diagnosis and histologic type were found to have a statistically significant relationship with HPV type. The mean age of the HPV-18 group was 48.6 years compared to 57.1 years for the HPV-16 group (p = 0.045) and 58.2 years for the HPV-negative group (p = 0.04). HPV-18 was detected more often in adenocarcinomas (AC) than in squamous cell carcinomas (SCC). Conversely HPV-16 was detected significantly more often in SCC (p < 0.0001). The HPV-negative group also had a higher incidence of SCC (p = 0.007). HPV-18-positive patients seemed to have more nodal involvement than both HPV-16-positive patients (45.5 vs. 20.8%) and HPV-negative patients (45.5 vs. 18.2%); however, it did not reach statistical significance. CONCLUSIONS: These observations suggest that the presence of HPV DNA does not bear any clinical or prognostic significance in a Chinese population of cervical cancers. HPV-18 is found more often in younger patients and is associated with AC.
UNLABELLED: Death-associated protein (DAP) kinase is a novel gene regulating apoptosis induced by IFN-gamma. In B-cell malignancies, loss of DAP kinase expression is commonly associated with promoter hypermethylation. These characteristics of DAP kinase may be of particular relevance in multiple myeloma (MM), a B-lineage malignancy in which prolonged survival capacity of the malignant plasma cells may be critical in the induction and maintenance of tumor cells. PURPOSE: The involvement and potential role of DAP kinase in MM pathogenesis was examined. EXPERIMENTAL DESIGN: In this investigation, methylation-specific PCR was conducted on primary MM and MM cell lines. Methylation status findings were correlated with clinical parameters. RESULTS: We first demonstrated frequent DAP kinase hypermethylation in 24 of 36 primary MMs (20 of 26 at diagnosis and 4 of 10 with relapse/residual MM after treatment), 1 of 2 patients with monoclonal gammopathy of undetermined significance, and 1 of 3 MM cell lines studied. The high frequency of DAP kinase hypermethylation was similarly observed in MM of different stages, immunoglobulin isotypes, and histological grades, with or without plasmacytomas. Although not statistically significant, the overall survival of patients with DAP kinase methylation was notably shortened among 23 MM patients followed prospectively (P = 0.38 by Kaplan-Meier method and log-rank test). This preliminary finding suggests prognostic implications of DAP kinase in MM that may deserve further investigation. CONCLUSIONS: Our data suggest an important role for DAP kinase in MM tumorigenesis.
We have examined the presence of loss of heterozygosity (LOH) on chromosome 3p in histologically normal nasopharyngeal epithelia (NP), dysplastic lesions, and carcinoma of the nasopharynx from different ethnic and geographic regions. Microdissected normal NP from noncancerous individuals and nasopharyngeal carcinoma (NPC) samples from both the high-risk group (southern Chinese in Hong Kong) and two low-risk groups for NPC (central/northern Chinese in Anhui/Beijing and Caucasians in Toronto) were included. All NPC samples showed high incidence of 3p deletion (81-100%). High frequencies of LOH on 3p were also detected in normal NP (73.9%) and dysplastic lesions (75%) from the southern Chinese. Significant lower frequency of LOH on 3p was noted in normal NP from the low-risk groups (20%) than those from high-risk groups (P = 0.0003). The presence of such genetic alterations in the histologically normal NP and dysplastic lesions suggests that it is an early event in tumor development. The higher frequency of 3p LOH found in normal NP from southern Chinese compared with those from low-risk groups may be related to the distinct cancer incidence among these populations.
Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in other parts of the world. To better understand the molecular basis of this cancer, we performed high-resolution allelotyping on 27 microdissected primary tumors using 382 microsatellite markers. We have detected high frequencies of allelic imbalance on 3p (96.3%), 9p (85.2%), 9q (88.9%), 11q (74.1%), 12q (70.4%), 13q (55.6%), 14q (85.2%), and 16q (55.6%). Nonrandom allelic changes of 12q and 16q were revealed for the first time. In addition, loss of heterozygosity on chromosomal arms 1p (37.0%), 5q (44.4%), and 12p (44.4%) were also common in NPC. Multiple minimally deleted regions, 7-40 cM, were identified at 3p14-24.2, 11q21-23, 13q12-14, 13q31-32, 14q24-32, and 16q22-23. Frequent deletions of these minimally deleted regions implied the presence of tumor suppressor genes that may be involved in the development of NPC. Consistent loss of heterozygosity on 3p, 9p, and 14q in almost all tumors suggested that such changes are critical events in NPC tumorigenesis.
We studied the kinetics of circulating EBV DNA in the plasma of nasopharyngeal carcinoma (NPC) patients. Serial weekly sampling of 10 NPC patients revealed a rapid decline in plasma EBV DNA concentration after treatment. In two subjects, an initial rise in the circulating EBV DNA level was observed immediately after treatment initiation. Plasma EBV DNA levels were monitored daily during the first treatment week in a second cohort of five patients, and the results indicated that an initial rise in plasma EBV DNA concentration could be observed in all subjects during the first treatment week. This observation is consistent with the liberation of EBV DNA after therapy-induced cancer cell death. After this initial rise, plasma EBV DNA concentration was found to decay with a median half-life of 3.8 days (interquartile range, 2.4-4.4 days). Kinetic analysis of circulating tumor-derived DNA during treatment may be a powerful tool for evaluating the in vivo response of NPC and other tumors to antineoplastic treatment and may improve our understanding of the biology of plasma nucleic acids.
OBJECTIVE: To compare the potency, side effects, and duration of action of triptorelin and leuprorelin acetate after i.m. injections. DESIGN: Prospective, double-blind crossover clinical study. SETTING: A teaching hospital. PATIENT(S): Fifty-four patients with pelvic endometriosis. INTERVENTION(S): Twenty-seven patients had three doses of i.m. triptorelin (3.75 mg) followed by three doses of i.m. leuprorelin acetate at 4-week intervals. Twenty-one patients had three doses of i.m. leuprorelin acetate (3.75 mg) followed by three doses of i.m. triptorelin, also at 4-week intervals. MAIN OUTCOME MEASURE(S): Menopausal symptoms, time taken for menstruation to return, serum E(2), FSH, LH levels, lipid profiles, and liver function tests. RESULT(S): The potencies of triptorelin and leuprorelin acetate in lowering the serum E(2), FSH, and LH levels were comparable. The severity of menopausal symptoms, changes in the lipid profile and liver function parameters were similar after triptorelin and leuprorelin acetate. The resurgence of ovarian activities and the spontaneous return of menstruation occurred significantly earlier after leuprorelin acetate than triptorelin. CONCLUSION(S): Both drugs are equally potent in down-regulating the pituitary-ovarian function, and their side effects are similar. Triptorelin has a longer duration of drug action and can be administered over a longer interval period.
Nasopharyngeal carcinoma (NPC) is a commonly occurring tumor in southern China. Although several causative factors have now been recognized, the genetic basis underlying its tumorigenesis is still unclear. To identify potential chromosomal aberrations for further investigations, comparative genomic hybridization (CGH) analysis was applied to the study of genomic imbalances in 10 NPC biopsy specimens. Before CGH analysis, the tumor cell content within the biopsy specimens was enriched by tissue microdissection, and universal genome amplification was performed on the recovered DNA. Recurrent chromosomal gains were detected on 1q (6 of 10 cases), 2q (5 of 10 cases), 3q (7 of 10 cases), 6p (8 of 10 cases), 6q (5 of 10 cases), 7q11.2 (4 of 10 cases), 8q (6 of 10 cases), 11q13, 12, and 15q (8 of 10 cases each), 17q (6 of 10 cases), and 20q (5 of 10 cases). Common losses were identified on 3p (5 of 10 cases), 9p (5 of 10 cases), 11q14-qter (8 of 10 cases), and 14q (5 of 10 cases). Among these aberrations, 7, 8, and 11 gains were further investigated on a series of NPC tissue samples, by interphase fluorescent in situ hybridization (FISH), for the incidence of alpha-satellites: 7, 8, and 11 c-myc and Int-2. Low-level increases of alpha-satellite 7 (9 of 34 cases; 26.5%), alpha-satellite 8 (15 of 34 cases; 44%), and alpha-satellite 11 (8 of 32 cases; 25%) were detected, whereas high-level copy gains of c-myc (21 of 34 cases; 62%) and Int-2 (26 of 34 cases; 76.5%) were more frequently found. Our series is the first to identify genomic overrepresentations of c-myc and Int-2 in NPC. The high incidence of Int-2 amplifications strongly suggests a role of this proto-oncogene in the pathogenesis of NPC.
STUDY OBJECTIVE: To evaluate the role of outpatient diagnostic hysteroscopy. DESIGN: Retrospective review (Canadian Task Force classification II-2). SETTING: University teaching hospital-based outpatient clinic. PATIENTS: One thousand six hundred women, 67.3% premenopausal and 32.7% postmenopausal. INTERVENTION: Diagnostic hysteroscopy without premedication or anesthesia; endometrial sampling or hysteroscopy-guided biopsy was performed when appropriate. MEASUREMENTS AND MAIN RESULTS: Outpatient hysteroscopy was successfully performed in 1468 women (91.8%). Eleven women (0. 7%) developed vasovagal response during the procedure, 18 required hospital admission because of pain or hemorrhage, and 2 were suspected of having uterine perforation. All recovered spontaneously without intervention. Intrauterine anatomic pathology was diagnosed in 17.0%; the overall frequency of myomas and endometrial polyps was 12.3% and 7.1%, respectively. The sensitivity and positive predictive value of hysteroscopy without biopsy in diagnosing endometrial carcinoma were only 58.8% and 20.8%, respectively. Of 1112 women with hysteroscopic impression of normal or atrophic endometrium, 10 (0.9%) had endometrial hyperplasia on biopsy. CONCLUSION: Hysteroscopy without biopsy carries low sensitivity and positive predictive value in the diagnosis of endometrial carcinoma and hyperplasia. In our opinion the predictive value of a negative hysteroscopy is inadequate, and endometrial biopsy should be performed during hysteroscopy for accurate diagnosis of endometrial histopathology.
OBJECTIVE: We sought to investigate the subclinical effect of external cephalic version on fetal circulation. STUDY DESIGN: A prospective observational study was conducted on 136 subjects who had external cephalic version at or beyond 36 weeks of gestation without clinical complication. Doppler ultrasonographic studies of the umbilical and middle cerebral circulations were performed before and after the external cephalic version. The following Doppler indexes were measured: (1) the pulsatility index of the umbilical artery, which represents disturbance of placental circulation, and (2) the pulsatility index of the fetal middle cerebral artery, which represents fetal response. The Wilcoxon signed rank test was used for all statistical analyses. RESULTS: There was no significant difference in pulsatility index of the umbilical artery before and after external cephalic version (P =.674). There was a statistically significant reduction in the pulsatility index of the middle cerebral artery after external cephalic version (P =.043), and this difference existed only among multiparous women (P =.029), among those in whom the external cephalic version was considered to be difficult (P =.038), and when the placenta was posteriorly located (P =.028). The reduction in pulsatility index was not related to whether the external cephalic version was successful. In all cases the Doppler indexes remained within the normal ranges, and there were no associated fetal complications. CONCLUSION: External cephalic version was not associated with any significant disturbance of placental resistance to blood flow. Conversely, external cephalic version was associated with a significant reduction in the pulsatility index of the middle cerebral circulation, especially among the multiparous women, after a difficult procedure or in those with a posterior placenta. This probably represents a normal fetal physiologic response to manipulation of the fetal head.
OBJECTIVE: Our aim was to investigate whether external cephalic version performed near term increases the concentration of cell-free fetal deoxyribonucleic acid in maternal plasma. STUDY DESIGN: Forty-five patients who had singleton male fetuses and were undergoing external cephalic version at or beyond 36 weeks of gestation were recruited during a 20-month period. Maternal venous blood samples were taken before and within 10 minutes after external cephalic version. Deoxyribonucleic acid was extracted from the plasma samples. The amount of fetal deoxyribonucleic acid was quantified by means of the SRY gene on the Y chromosome as a fetal marker. The change in SRY gene concentration before and after external cephalic version was compared by paired sample t test. RESULTS: There was a significant increase in the concentration of fetal deoxyribonucleic acid in maternal serum after external cephalic version (before, 296 +/- 209 copies per milliliter; after, 369 +/- 228 copies per milliliter; P =.014). This increase in the concentration of deoxyribonucleic acid was most profound among the nulliparous patients after a successful version and in the presence of a posterior placenta. The location of the placenta was found to be the most significant factor accounting for the change in the deoxyribonucleic acid concentration. CONCLUSIONS: External cephalic version near term imposed a significant disturbance to the maternalplacental interface. Fetal deoxyribonucleic acid is a sensitive marker that is useful in the assessment of subclinical fetal-maternal hemorrhage.
OBJECTIVES: To investigate factors associated with the occurrence of transient fetal bradycardia after external cephalic version, and labour outcome after isolated transient fetal bradycardia. DESIGN: Cohort study. SETTING: Teaching hospital with a policy of offering external cephalic version for breech presentation at or beyond 36 weeks of gestation. POPULATION: Four hundred and twenty-nine external cephalic versions performed over a 5-year period. METHODS: Between group differences were compared with the unpaired t test or the chi2 test. Logistic regression analysis was performed to exclude confounding effects. MAIN OUTCOME MEASURES: Incidence of caesarean section for fetal distress. RESULTS: Transient fetal bradycardia occurred in 8.4% of external cephalic versions, and was associated with a successful version (OR 16.45, P < 0.001), a difficult procedure (OR 3.70, P = 0.001), and nulliparity (OR 2.83, P = 0.007). The incidence of intrapartum caesarean section for fetal distress was 16.7% in pregnancies with transient fetal bradycardia, compared with 7.9% in those without (OR 2.34, 95% CI 0.81, 6.71). CONCLUSIONS: Transient fetal bradycardia after external cephalic version may be associated with a higher risk of intrapartum caesarean section for fetal distress.
A structured interview survey was carried out in 150 women who came for their first antenatal visit in a university hospital in Hong Kong between June and July 1998. Their opinions and perceptions of fetal and maternal safeties on different modes of delivery for both cephalic and breech presentation, and external cephalic version (ECV) were surveyed. Their decisions on the management of term breech-presenting pregnancy were examined. Most women (92%) preferred vaginal delivery to Caesarean delivery (CS) in case of cephalic presentation, mainly because it was a natural way of parturition. They perceived that vaginal delivery was safer than CS for both mothers and babies, but the reverse was true for breech presentation. About 82% chose ECV as the first choice of managing breech presentation, mainly because a successful version allowed a natural way of delivery. Only 2% of women considered ECV ineffective, and 13.3% and 18.7% considered it not safe for mothers and fetuses respectively. Therefore, ECV should be an available option in all obstetric units. Adequate counselling and explanation would improve the acceptance of ECV.
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Flight parameter estimation methods for an airborne acoustic source can be divided into two categories, depending on whether the narrow-band lines or the broadband component of the received signal spectrum is processed to estimate the flight parameters. This paper provides a common framework for the formulation and test of two flight parameter estimation methods: one narrow band, the other broadband. The performances of the two methods are evaluated by applying them to the same acoustic data set, which is recorded by a planar array of passive acoustic sensors during multiple transits of a turboprop fixed-wing aircraft and two types of rotary-wing aircraft. The narrow-band method, which is based on a kinematic model that assumes the source travels in a straight line at constant speed and altitude, requires time-frequency analysis of the acoustic signal received by a single sensor during each aircraft transit. The broadband method is based on the same kinematic model, but requires observing the temporal variation of the differential time of arrival of the acoustic signal at each pair of sensors that comprises the planar array. Generalized cross correlation of each pair of sensor outputs using a cross-spectral phase transform prefilter provides instantaneous estimates of the differential times of arrival of the signal as the acoustic wavefront traverses the array.
Recently, cell-free EBV DNA has been detected in the plasma and serum of patients with nasopharyngeal carcinoma (NPC). We studied the relationship between plasma/serum EBV DNA and tumor recurrence. Using real-time quantitative PCR, the median plasma EBV DNA concentration in 10 patients with tumor recurrence was determined to be 32,350 copies/ml, whereas that in 15 patients in continuous remission for a mean period of 2 years was 0 copy/ml. Longitudinal follow-up of 17 NPC patients revealed 6 individuals with tumor recurrence and 11 patients who remained in remission. Significant elevations in serum EBV DNA, sometimes up to 6 months before detectable clinical deterioration, were observed in the patients who subsequently developed tumor recurrence. Continuously low or undetectable levels of serum EBV DNA were observed in the patients who remained in remission. These results suggest that plasma/serum cell-free EBV DNA may be a valuable tool for the monitoring of NPC patients for the early detection of tumor recurrence.
Nasopharyngeal carcinoma (NPC) is rare in most parts of the world, but prevalent in Southern China. Although this disease poses a serious health problem in our population, the genetic alterations that lead to the development of NPC have yet to be defined. In a comparative genomic hybridization (CGH) study on NPC by our group, loss of the long arm of chromosome 13 has been identified as a frequent event. To investigate further the involvement of this genetic alteration in NPC tumorigenesis, we examined 31 primary NPC tumours by LOH analysis with a panel of 13 microsatellite polymorphic markers distributed along the long arm of chromosome 13. It was found that 19/31 tumours (60%) showed LOH for markers on chromosome 13q. The highest frequency of LOH was found at loci D13S133 (53.6%) on 13q14.3 and D13S796 (38.5%) on 13q32-34. Two distinct smallest deletion regions were delineated: the first region between D13S133 and D13S119 at 13q14.3-22, and the second region between D13S317 and D13S285 at 13q31-34. Our findings show that LOH of 13q is a common event in NPC and that at least 2 putative tumour-suppressor loci may be present on 13q. Mapping of the critical regions of these loci suggests that some candidate tumour-suppressor genes on 13q, other than Rb and BRCA2, may be involved in the development of NPC.