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Biomedical subjects

W K Lo

Publications and source records attributed to W K Lo.

At least 19 recordsLinked to original sources

Paradoxical deterioration during anti-tubercular treatment in a dialysis patient on maintenance steroid therapy.

We report a 38-year-old Chinese woman with lupus nephritis on peritoneal dialysis and long-term maintenance steroid therapy. This patient developed paradoxical deterioration during anti-tubercular therapy for tuberculous lymphadenitis. The deterioration resolved spontaneously without change to pharmacotherapy. Paradoxical deterioration that may spontaneously resolve is a potential complication of anti-tubercular treatment in patients on long-term renal replacement therapy.

Adrenal Cortex Hormones↗

Extended experience in the use of laparoscopic ultrasound to detect pelvic nodal metastasis in patients with cervical carcinoma.

OBJECTIVE: To evaluate the use of laparoscopic ultrasound (USG) to detect pelvic nodal metastasis in patients with early stage cervical carcinoma. METHODS: Laparoscopic USG was used to search for pelvic lymph node metastasis in stage Ia2 to IIa cervical carcinoma patients before radical hysterectomy. Suspicious lymph nodes identified by laparoscopic USG were removed laparoscopically for pathological confirmation by frozen section. If nodal metastasis was diagnosed, radical hysterectomy would be cancelled but enlarged lymph nodes were removed preferably by laparoscopic approach before closing the abdomen. These patients were treated with radiotherapy after recovering from the surgery. By comparing the laparoscopic USG and pathological findings of lymph nodes removed with or without radical hysterectomy, diagnostic accuracy of laparoscopic USG was determined. RESULTS: Ninety-three patients were recruited and the final analysis included 90 patients. Laparoscopic USG found suspicious lymph nodes in 17 patients and nodal metastases were confirmed pathologically in 14 of them. Three patients with macroscopic and five patients with microscopic pelvic nodal metastases were missed by laparoscopic USG. The accuracy, sensitivity, specificity, positive and negative predictive value of laparoscopic USG in detecting pelvic lymph node metastasis were 87.8%, 63.6%, 95.6%, 82.4%, and 89%, respectively. Macroscopic metastatic nodes were successfully removed laparoscopically in 11 out of 14 patients and laparotomy was required for the other three patients. CONCLUSIONS: Laparoscopic USG can be performed with no major morbidity. This technique is sensitive in detecting macroscopic but not microscopic metastatic pelvic lymph nodes. Removal of macroscopic metastatic nodes identified via laparoscopic USG via laparoscopic approach could be accomplished in majority of patients.

Adult↗

Expression of apoptotic regulators and their significance in cervical cancer.

Insufficient apoptosis is implicated in many human cancers, including cervical carcinoma. The objectives of this study were to explore changes of apoptosis-regulating gene expression and their clinical significance in cervical cancer. The expression of apoptosis-regulating genes, including five Bcl-2 family and two caspase family members, was evaluated in 43 cervical invasive squamous cell carcinomas, using immunohistochemistry. Specimens in which >or=10% of the neoplastic cells showed cytosolic immunoreactivity were considered to be immunopositive. Results were correlated with clinico-pathologic characteristics of the subjects. All seven apoptotic regulators examined were positive in a proportion of the tumors. The percentage of cases expressing Bax was higher in the patients without evidence of disease after treatment than in the patients alive with disease or who died of disease (P<0.05). A significant difference in disease-free survival was detected between Bax-positive and -negative groups (P<0.05), and in overall survival between Mcl-1-positive and -negative groups (P<0.05). Significant association between the seven markers tested was only found for caspase 3 and Bak immunoreactivity in cervical carcinoma (P<0.05). The results demonstrate expression of multiple apoptosis-modulating proteins in cervical cancer. There appears to be complex regulation of apoptosis protein levels in association with clinical behavior of cervical squamous cell carcinoma.

Apoptosis↗

Analgesic efficacy of continuous delivery of bupivacaine by an elastomeric balloon infusor after abdominal hysterectomy: a prospective randomised controlled trial.

OBJECTIVE: To investigate the analgesic efficacy and morphine-sparing effect of continuous bupivacaine wound infiltration after abdominal hysterectomy. DESIGN: Prospective, randomised controlled trial. SAMPLE: Fifty-two female ASA I or II patients were enrolled with 26 patients in each of the study and control groups. METHODS: The study group received 0.5% bupivacaine infusion into the incisional (Pfannenstiel) wound via an elastomeric infusor at 2 mL/hr for 48 hours postoperatively plus morphine via a patient controlled analgesia (PCA) pump. The control group had only PCA morphine. RESULTS: There were no significant differences in the visual analogue scores (VAS) for pain nor PCA morphine usage for 48 hours postoperatively CONCLUSION: That continuous infusion of the incisional wound with 0.5% bupivacaine did not confer additional analgesia over PCA morphine after abdominal hysterectomy

Adult↗

Bispectral index in assessment of adequacy of general anaesthesia for lower segment caesarean section.

Awareness among parturients during general anaesthesia for caesarean section, though now uncommon, remains a concern for obstetric anaesthetists. We examined the adequacy of our general anaesthetic technique for avoiding explicit awareness by determining the depth of anaesthesia using Bispectral Index (BIS) monitoring. Twenty ASA1 parturients having general anaesthesia for lower segment caesarean section were studied. The drugs and doses used for each anaesthetic were similar Intraoperative Bispectral Index, haemodynamic parameters, end-tidal isoflurane concentration and inspired nitrous oxide fraction were measured and the postoperative incidence of explicit awareness was assessed. All anaesthetists were blinded to the Bispectral Index value throughout the operation. The depth of anaesthesia at various stages of the operation was evaluated by recording the Bispectral Index. Patients were interviewed for any intraoperative recall or awareness at the end of operation. A median BIS of 70 or below was recorded on most occasions during surgery. The range was 52 to 70, with values reaching 60 and below at intubation, uterine incision and delivery. Haemodynamic stability was satisfactory and there was no case of uterine atony, fetal compromise or postpartum haemorrhage. No patient experienced intraoperative dreams, recall or awareness. Our current general anaesthetic technique appeared inadequate to reliably produce BIS values of less than 60 that are associated with a low risk of awareness. However, no patients experienced explicit awareness.

Adult↗

Reactivation of systemic lupus erythematosus in a dialysis patient after tuberculous peritonitis.

The disease activity of patients suffering from lupus nephritis usually becomes quiescent after the onset of end stage renal failure. Reactivation of lupus activity, especially after a long period of dialysis, is uncommon. Factors that might trigger off lupus reactivation after dialysis have not been well defined. We report a case of a 43-year-old Chinese woman on long-term peritoneal dialysis, who developed lupus reactivation with cerebral involvement 2 weeks after she was diagnosed to have tuberculous peritonitis. The close temporal relationship between the tuberculous peritonitis and the lupus reactivation raise the possibility that the tuberculous infection might have triggered off the lupus reactivation.

Adult↗

Single dose diclofenac suppository reduces post-Cesarean PCEA requirements.

PURPOSE: To assess the analgesic efficacy of administering, immediately after surgery, a single dose of diclofenac (100 mg suppository) to women who had undergone lower segment Cesarean section (LSCS) under combined spinal-epidural anesthesia, and received post-operative patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2% and fentanyl 2 microg x ml(-1). METHODS: Forty-eight ASA physical status I or II term parturients scheduled for elective LSCS under regional anesthesia were enrolled into this randomised double-blind study. The patient-controlled epidural analgesia device was programmed to deliver a bolus of 4 ml of local anesthetic mixture with a lockout period of ten minutes and an hourly limit of 12 ml. There was no baseline infusion. The study commenced upon the patient's first demand for analgesia post-operatively and the patients were assessed at one, six, 12 and 24 hr post-operatively for pain scores on movement, dermatomal level of sensory blockade, degree of motor blockade and volume of local anesthetic used. At conclusion of the study, patients' satisfaction scores were recorded. RESULTS: The two groups of patients were similar demographically. Patients who received a diclofenac suppository used 52.8 +/- 17.8 ml of local anesthetic mixture while those who did not, used 74 +/- 25 ml (P <0.005). Pain scores and satisfaction scores did not differ significantly between the groups. CONCLUSION: A single administration of 100 mg diclofenac suppository is effective in reducing post-Cesarean epidural local anesthetic/opioid requirements by 33% for the first 24 hr post-operatively.

Adult↗

Tuberculosis infection in Chinese patients undergoing continuous ambulatory peritoneal dialysis.

A retrospective study of the prevalence and pattern of tuberculosis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was performed. Thirty-eight cases of tuberculosis were diagnosed among 790 patients (18 men, 20 women; mean age, 58 +/- 12.6 years) between July 1994 and June 2000. The interval between the initiation of CAPD and onset of tuberculosis ranged from 1 to 168 months (median, 22 months). There were 18 cases of pulmonary tuberculosis, 14 cases of tuberculous peritonitis, 5 cases of tuberculous lymphadenitis, and 1 case of tuberculous synovitis. Patients with pulmonary tuberculosis usually presented with fever, constitutional symptoms, and pleural effusion or pulmonary infiltrates on chest radiograph. Abdominal pain and turbid dialysate were the main presenting symptoms in patients with tuberculous peritonitis. Diagnosis was established by positive culture in 20 patients, typical histological characteristics on a tissue biopsy specimen in 10 patients, and response to empirical antituberculous treatment in 8 patients. The duration of symptoms before the diagnosis of tuberculosis and initiation of antituberculous treatment ranged from 7 to 57 days (median, 30 days). Antituberculous treatment consisted of isoniazid, rifampicin, pyrazinamide, and ofloxacin for 9 to 15 months. Antituberculous treatment generally was well tolerated. Twenty-seven patients (71%) completed antituberculous treatment. No recurrence of tuberculosis was observed after a mean follow-up of 19.8 months. Eleven patients (29%) died while on antituberculous treatment; none of the deaths appeared to be directly caused by tuberculosis. We conclude that: (1) tuberculosis is prevalent among CAPD patients in our locality; (2) extrapulmonary tuberculosis, particularly tuberculous peritonitis, is common; and (3) a high index of suspicion for tuberculosis among CAPD patients is warranted to ensure early diagnosis and prompt initiation of treatment.

Aged↗

Progressive demyelinating neuropathy after initiation of continuous ambulatory peritoneal dialysis--report of two cases.

We report on two patients who developed rapidly progressive demyelinating neuropathy within 6 to 10 weeks after the initiation of continuous ambulatory peritoneal dialysis. The neuropathy in one patient resolved after kidney transplantation while that of the other patient improved with immunosuppressive therapy. The close temporal relationship between the initiation of peritoneal dialysis and the onset of neuropathy suggests that these two events may be causally related.

Adult↗

A retrospective survey of attitudes toward acceptance of peritoneal dialysis in Chinese end-stage renal failure patients in Hong Kong--from a cultural point of view.

OBJECTIVE: We undertook to study the attitudes toward dialysis of patients approaching end-stage renal failure and to analyze those attitudes from a cultural perspective. SETTING: The study was performed in the pre-dialysis clinic of a tertiary referral renal center. PATIENTS: All patients of Chinese ethnic origin seen in the pre-dialysis clinic from 1995 to 2000 for assessment of dialysis therapy were included. METHOD: We performed a retrospective analysis of patient records with regard to attitudes of the patients toward dialysis, reasons for those attitudes, and factors that could lead to a subsequent change in attitude. RESULTS: We assessed 462 patients over the 6-year period. Their mean age was 65.5 +/- 13.3 years, and 43.9% of the patients had diabetes. Peritoneal dialysis (PD) was offered to 74% of the patients, and hemodialysis (HD) to 3.9%. Among the patients offered PD, only 44% accepted dialysis. After counselling, 54% of the patients who originally declined PD ultimately accepted it. The major reasons for refusing PD were the ideas of "having lived long enough" and "lack of family support." Most other reasons could be overcome by counselling. Only a minority of patients demanded hemodialysis. CONCLUSIONS: Declining an offer of dialysis was common. Counselling helped patients to accept PD. Certain cultural elements that hindered acceptance of dialysis were involved in the ideas of "having lived long enough" and "lack of family support." Those cultural elements should be tackled more specifically during counselling.

Adult↗

Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia.

Loss of heterozygosity (LOH) is a common genetic finding in many human neoplasms, including cervical cancer. The detection of LOH at specific loci in the precursor of cervical cancer, cervical intraepithelial neoplasia (CIN) may help in elucidating the evolution of this cancer, which has a clearly defined histological premalignant phase. However, molecular genetic investigation of CIN is difficult because many of the lesions are very small and sometimes ill defined topographically. In this study we analyzed eighteen polymorphic microsatellite repeats on chromosome 3p in CINs using a method of primer extension pre-amplification (PEP) for whole genome amplification combined with microdissection. These markers encompass chromosome region 3pter-3p12. LOH at one or more loci was detected in five (33%) out of the 15 informative cases with low grade CIN (CIN 1), while 22 (92%) out of 24 cases with high grade CIN (CIN 2 and 3) (P<0.01). The highest incidence (41%) of LOH was detected at locus D3S1038 (3p26.1-3p25.2). Frequent LOH (more than 20%) was also found at other loci including D3S1110 (3p25.3-3p25.1) (31%), D3S656 (3p25.1) (24%), D3S1076 (3p21.2-3p21.1) (29%), D3S1300 (3p21.1-3p14.2) (24%), D3S1600 (3p14.2-3p14.1) (24%), and D3S1079 (3p13) (25%). The results from this study taken together with others indicate that the genetic alterations on chromosome 3p are common in high grade of CIN and are probably early events in cervical carcinogenesis. Tumor suppressor gene(s) that play a role in cervical neoplasm may be located on the short arm of chromosome 3, likely at or near 3p26.1-25.1, 3p21.2-21.1, and 3p14.2-13.

Alleles↗

Lim2(To3) transgenic mice establish a causative relationship between the mutation identified in the lim2 gene and cataractogenesis in the To3 mouse mutant.

PURPOSE: Lim2 is the gene encoding the ocular lens-specific intrinsic membrane protein MP19. We previously reported finding a single nonconservative G->T transversion in exon two of the Lim2 gene. This mutation was linked to the cataract in the To3 (Total opacity number 3) mouse mutant, confirming Lim2 as an ideal candidate gene for the To3 cataract. The aim of the present study was to substantiate a causative relationship between the mutation in the Lim2 gene and cataractogenesis in the To3 mouse mutant. To this end a Lim2To3 transgene cassette was engineered and introduced into fertilized normal mouse embryos to test its ability to induce cataractogenic lens development. METHODS: A Lim2 genomic clone was isolated and purified from a murine 129/SvJ genomic library. A restriction endonuclease map of the gene was generated using classical Southern techniques. The murine Lim2 promoter was characterized by transfecting primary chicken lens epithelial cells with Lim2 promoter-CAT reporter constructs and assaying promoter activity and specificity. This genomic clone was then used in conjunction with PCR to generate a Lim2To3 transgene cassette. After sequencing of the PCR engineered portion, the Lim2To3 transgene was then used to generate Lim2To3 transgenic mice via pronuclear injection. Founder mice and their offspring from outcrosses and intercrosses were characterized by ophthalmic examination, PCR and Southern DNA analysis, RT-PCR mRNA analysis, and histology of lens sections. RESULTS: Two mice, from independent microinjections, were identified as positive for presence of the Lim2To3 transgene cassette as well as presence of bilateral congenital cataracts and reduced eye size and mass. One of these founders was incapable of germline transmission of the transgene to offspring and was not characterized further. The other was capable of germline transmission and was characterized as described above. PCR DNA analysis revealed a perfect concordance between presence of the Lim2To3 transgene cassette and congenital cataract in offspring of this founder. Transgenic hemizygotes exhibited cataract and a reduction in eye and lens size and mass, while transgenic "homozygotes" presented with a more severe cataract and microphthalmic reduction in eye and lens size and mass. Southern analysis revealed approximately 2 copies of the transgene cassette integrated into a single chromosomal site in the founder and all hemizygous offspring. RT-PCR analysis revealed a very low ratio of Lim2To3 transgenic mRNA compared to endogenous normal Lim2. Finally, histology revealed that lens development was abnormal in mutant transgenic animals by embryonic day E15. By E19, just prior to birth, gross disorganization of secondary fibers was observed in mutants. CONCLUSIONS: These transgenic experiments firmly establish a causative relationship between the previously identified mutation in the Lim2 gene and cataractogenesis in the To3 mouse mutant. The low levels of mutant mRNA produced by the transgene cassette as compared to endogenous levels of normal Lim2 mRNA provides evidence that this dominant mutation results in a mutant MP19 protein with altered function rather than simply loss of function.

Animals↗

Spatiotemporal distribution of zonulae adherens and associated actin bundles in both epithelium and fiber cells during chicken lens development.

Zonulae adherens and associated actin bundles (ZA/AB) are believed to play a major role in epithelial folding and invagination during morphogenesis of neural tube and other vesicular structures. The lens morphogenesis is associated with the formation of the lens vesicle in which ZA/AB would be needed during the formation process. However, the existence of ZA/AB in the lens has never been established. In this study we report for the first time the existence of ZA/AB in both lens epithelium and fiber cells during embryonic development of chicken lens from E4 to E20. Light microscopy revealed contacts between the lens epithelium and primary fiber cells, and between the lens epithelium and secondary fiber cells at E4 and E11, respectively. Thin-section electron microscopy consistently revealed ZA/AB near both the apical ends of lens epithelial cells and primary fiber cells at E4. This arrangement manifests as a parallel pair of belt-like ZA/AB along the epithelium-fiber interface. In semi-tangential sections, a continuous belt-like ZA/AB was also evidenced in individual epithelial cells and fiber cells. Furthermore, the same ZA/AB arrangement was observed near both the apical ends of epithelial cells and secondary fiber cells at E11. Besides ZA/AB, macular-type fasciae adherens were distributed regularly between epithelial cells, between primary fibers, between secondary fibers, and between epithelium and both primary and secondary fibers. Immunofluorescence strongly and preferentially labeled N-cadherin at both the apical ends of lens epithelium and primary or secondary fibers at the corresponding ages, suggesting a direct association with the zonulae adherens. Also punctate N-cadherin labeling was commonly seen along various regions of primary and secondary fiber cells at different ages, and to a larger extent in the mature fibers of older lenses. This study suggests that: (1) ZA/AB located at the apices of lens epithelial cells may play a crucial role in the early stages of lens morphogenesis (e.g. lens vesicle formation); (2) ZA/AB of primary and secondary fiber cells originate from the epithelial cells during their elongation and differentiation; (3) owing to the restricted distribution of ZA/AB, abundant fasciae adherens are needed to maintain the structural stability of the epithelium and fiber cells during development and maturation; and (4) N-cadherin is the principle adhesion protein for both the zonulae adherens and fasciae adherens in the lens.

Actins↗

Lenses of SPARC-null mice exhibit an abnormal cell surface-basement membrane interface.

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein involved in cell-matrix interactions. We have shown previously that mice deficient in SPARC develop posterior cortical cataract early in life that progresses to a mature opacity and capsule rupture. To evaluate the primary effects of SPARC deficiency in the lens, we examined the lenses of SPARC-null and wild-type mice by electron microscopy and immunohistochemistry to investigate whether ultrastructural abnormalities occur at the basement membrane (capsule)-lens cell interface in SPARC-null mice. The most notable feature in the lenses of SPARC-null mice, relative to wild-type animals, was the modification of the basal surface of the lens epithelial and fiber cells at the basement membrane (capsule) interface. Electron microscopy revealed numerous filopodial projections of the basal surface of the lens epithelial and fiber cells into the extracellular matrix of the anterior, posterior, and equatorial regions of the lens capsule. In 1 week old precataractous lenses, basal invasive filopodia projecting into the capsule were small and infrequent. Both the size and frequency of these filopodia increased in precataractous 3-4 week old lenses and were prominent in the cataractous 5-6 week old lenses. By rhodamine-phalloidin labeling, we confirmed the presence of basal invasive filopodia projecting into the lens capsule and demonstrated that the projections contained actin filaments. In contrast to the obvious abnormal projections at the interface between the basal surface of the lens epithelial and fiber cells and the lens capsule, the apical and lateral plasma membranes of lens epithelial cells and lens fibers in SPARC-null mice were as smooth as those of wild-type mice. We conclude that the absence of SPARC in the murine lens is associated with a filopodial protrusion of the basal surface of the lens epithelium and differentiating fiber cells into the lens capsule. The altered structures appear prior to the opacification of the lens in the SPARC-null model. These observations are consistent with one or more functions previously proposed for SPARC as a modulator of cell shape and cell-matrix interactions.

Animals↗