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Biomedical subjects

M P Lee

Publications and source records attributed to M P Lee.

At least 19 recordsLinked to original sources

Evaluation of NucliSens EasyQ HIV-1 assay for quantification of HIV-1 subtypes prevalent in South-east Asia.

BACKGROUND: Monitoring anti-retroviral therapy requires that viral load assays for human immunodeficiency virus type 1 (HIV-1) be applicable to diverse HIV-1 subtypes. OBJECTIVES: To evaluate NucliSens EasyQ HIV-1 assay for quantitation of common HIV-1 subtypes prevalent in South-east Asia. STUDY DESIGN: One hundred and nineteen plasma samples collected in Hong Kong and Cambodia were used to compare the performance of NucliSens EasyQ HIV-1 and COBAS Amplicor HIV-1 Monitor version 1.5 assays. Viral RNA extracted from the NucliSens MiniMAG was also used for HIV-1 subtyping. RESULTS: Performance of NucliSens EasyQ correlated well with COBAS Amplicor (r=0.777, p<0.001) and the small mean difference (0.0462log(10)IU/mL) obtained in the Bland and Altman model indicated good agreement between two assays. The NucliSens EasyQ assay demonstrated a 95% sensitivity at 500IU/mL and 100% specificity. Reproducibility of this assay was within log(10)2-4IU/mL and had a coefficient of variation between 2.3% and 10.4%. Among the 109 specimens included in the analysis, HIV-1 subtyping identified 64 CRF01_AE, 38 subtype B, 3 subtype C, 3 CRF07_BC and 1 subtype G viruses. CONCLUSIONS: Performance of NucliSens EasyQ was comparable to COBAS Amplicor for HIV-1 viral load monitoring. RNA extracts from NucliSens MiniMAG could be used for HIV-1 viral load monitoring, subtyping and drug resistance mutations detection. Our findings highlight the versatility of both NucliSens EasyQ and COBAS Amplicor in monitoring prevalent subtypes and rare circulating recombinant forms (CRFs) in the South-east Asia region.

Cambodia↗

Illness-related factors, stress and coping strategies in relation to psychological distress in HIV-infected persons in Hong Kong.

This study examined the relationships among illness-related factors, stress, coping strategies and psychological distress in HIV-infected persons in Hong Kong (N=118). Multiple regression analyses were used to examine the models of psychological distress as a function of demographic factors, illness-related factors, psychosocial stressors and coping. Results showed that positive thinking was inversely related to psychological distress and avoidance was associated with higher level of anxiety. However, the use of problem solving was found to be inversely related to anxiety. Results are discussed in the context of Chinese culture and the service in Hong Kong.

Adaptation, Psychological↗

Benign metastasising leiomyoma: a rare but possible cause of bilateral pulmonary nodules in Chinese patients.

We report three cases of benign metastasising leiomyoma, which is a rare cause of multiple lung nodules, in three Hong Kong Chinese females. One patient presented with pleuritic chest pain, another was asymptomatic, while the last presented with haemoptysis. All three patients had previously undergone surgical resection of uterine leiomyomas. Multiple lung nodules mimicking lung metastases were demonstrated on chest radiographs, and all three diagnoses were obtained from lung biopsies. Hormonal therapy was given to two patients with variable responses. To the best of our knowledge, this is the first report of benign metastasising leiomyoma in Hong Kong Chinese population. It highlights the importance of considering this rare and benign disease in premenopausal females presenting with multiple lung nodules.

Adult↗

Corticosteroid therapy in a Chinese patient with nephropathy associated with human immunodeficiency virus infection.

A 52-year-old man with 6 years' history of human immunodeficiency virus infection who was receiving highly active antiretroviral therapy presented with acute renal failure and nephrotic syndrome. Renal biopsy revealed features consistent with nephropathy associated with human immunodeficiency virus infection. Treatment consisted of intravenous methylprednisolone followed by oral prednisolone. The patient's renal function improved, although proteinuria persisted. Human immunodeficiency virus-associated nephropathy is very rare in Asian populations and is more common among blacks. To the best of our knowledge, this is the first documented case of nephropathy associated with human immunodeficiency virus infection occurring in Hong Kong.

AIDS-Associated Nephropathy↗

Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS).

BACKGROUND: Severe acute respiratory syndrome (SARS) was diagnosed in Hong Kong in over 1700 patients between March and early June 2003. METHODS: 115 patients diagnosed with SARS were admitted to Queen Elizabeth Hospital, a large regional hospital in Hong Kong, from March 2003, of whom 100 were either discharged or were dead at 31 May. The patients were prospectively studied after admission to assess their short term outcomes and the risk factors associated with adverse outcomes, defined as death or the need for mechanical ventilation RESULTS: At the time of writing 18 patients had died, with a crude mortality rate of 15.7% and a 21 day mortality of 10% (standard error 3%). Thirty nine patients (34%) were admitted to the intensive care unit, 30 of whom (26%) required mechanical ventilation. Multivariate analysis showed that age above 60 (hazards ratio (HR) 3.5, 95% CI 1.2 to 10.2; p=0.02), presence of diabetes mellitus or heart disease (HR 9.1, 95% CI 2.8 to 29.1; p<0.001), and the presence of other comorbid conditions (HR 5.2, 95% CI 1.4 to 19.7; p=0.01) were independently associated with mortality. However, only the presence of diabetes mellitus and/or cardiac disease (HR 7.3, 95% CI 3.1 to 17.4; p<0.001) was associated with adverse outcomes as a whole. CONCLUSION: SARS is a new disease entity that carries significant morbidity and mortality. Specific clinical and laboratory parameters predicting unfavourable outcomes have been identified.

Adult↗

Clinical profiles of human immunodeficiency virus-associated lymphoma in Hong Kong.

OBJECTIVE: To identify the clinical and prognostic features of human immunodeficiency virus-associated lymphoma in the local population with a view to designing more effective treatment strategies. DESIGN: Retrospective review. SETTING: Referral hospital, Hong Kong. SUBJECTS AND METHODS: All patients (n=10) with human immunodeficiency virus-associated lymphoma managed at Queen Elizabeth Hospital from January 1995 to December 2001. RESULTS: All patients were men with a median age of 39 years. The median CD4 cell count at the time of diagnosis of lymphoma was 0.056 x 10(9)/L. All tumours were diffuse large B-cell lymphomas, with the exception of one systemic Burkittlike lymphoma. Systemic lymphoma was diagnosed in seven patients and three had primary central nervous system lymphoma. Combined antiretroviral therapy was continued or given to five of the six patients who received some form of chemotherapy or radiotherapy treatment. Of the two patients with primary central nervous system lymphoma who received whole brain irradiation therapy, one patient survived 41 months in clinical remission after diagnosis and the other patient died of sepsis while in partial remission 19 months after diagnosis. The four patients with systemic lymphoma who received standard- or reduced-dose chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone had a median survival of 3 months. CONCLUSION: The clinical profiles of these patients were similar to those of patients with human immunodeficiency virus-associated lymphoma in western countries. The overall survival of patients was poor with conventional chemoradiotherapy. Other innovative treatment approaches should be investigated to prolong the survival of this patient group.

Adolescent↗

Clinical and electrophysiological aspects of distal ulnar neuropathy.

OBJECTIVES: To evaluate the use of fixed distance side to side comparison of abductor digiti minimi (ADM) and first dorsal interosseous (FDI) compound muscle action potential (CMAP) studies in the diagnosis of distal ulnar neuropathy. MATERIALS AND METHODS: Thirty normal controls underwent ADM and FDI CMAP studies bilaterally at a fixed ADM recording to stimulating point distance of 6 cm. Side to side mean latency differences to both muscles were calculated. Twenty patients with suspected unilateral distal ulnar neuropathy from routine nerve conduction studies had positive results when compared with controls. RESULTS: The upper limit of normal for side to side mean latency difference at 3 SD above the mean was 0.394 and 0.474 ms for ADM and FDI, respectively. All 20 patients had side to side mean CMAP latency difference above 3 SDs in the ADM, FDI or both muscles. Fifty percent of cases had involvement of the superficial sensory branch. CONCLUSIONS: Fixed distance side to side CMAP latency comparison is a useful electrodiagnostic adjunct for distal ulnar neuropathy. Trauma was the most common aetiology in the 20 reported cases. Correlation was found between aetiological factors and sites of lesions as localized with this method.

Action Potentials↗

The use of remifentanil to facilitate the insertion of the laryngeal mask airway.

UNLABELLED: Propofol is often used as an IV induction drug for anesthesia and the insertion of a laryngeal mask airway (LMA). As a sole anesthetic, it may be associated with undesirable airway responses such as coughing and gagging. We conducted a randomized, double-blinded study to compare the conditions during insertion of the LMA in 120 patients who received normal saline (Group P), remifentanil 0.25 microg/kg (Group R1), or remifentanil 0.5 microg/kg (Group R2) before the induction of anesthesia with IV propofol. The addition of remifentanil significantly improved the conditions of insertion; in Group R1, 82.5% (33 of 40 patients), and in Group R2, 85.0% (34 of 40 patients) had excellent insertion conditions as compared with the Control group P, 32.5% (13 of 40 patients). Patients in Group P were apneic for a mean (SD) time of 85 (38) s, 186 (75) s in group R1, and 284 (130) s in group R2. There was a lesser decrease in mean arterial blood pressure in group R1. We conclude that remifentanil 0.25 microg/kg, when administered after IV propofol 2.5 mg/kg, provides excellent conditions for insertion of the LMA with minimal hemodynamic disturbances. IMPLICATIONS: Small-dose remifentanil can provide excellent conditions for laryngeal mask airway insertion with minimal hemodynamic disturbances.

Adult↗

Segmental mixed nerve conduction studies in ulnar neuropathy at the elbow.

Conventional nerve conduction and electromyography may not be adequate in localizing ulnar neuropathy at the elbow, particularly in longstanding lesions with severe axon loss. Ratios of wrist to elbow and elbow to axilla segmental ulnar mixed nerve amplitudes were determined in 11 patients with ulnar neuropathy at the elbow. In 20 control subjects, the mean ratio was 1.06 +/- 0.25 (standard deviation). All patients had ratios less than two standard deviations of the control mean ratio. This method is a useful adjunct to conventional nerve conduction techniques in the localization of ulnar neuropathy at the elbow.

Adult↗

Hot-stop PCR: a simple and general assay for linear quantitation of allele ratios.

We have developed a simple, quantitative assay for measurement of allele ratios that circumvents the problem of heteroduplex formation skewing the results of restriction endonuclease digestion of PCR products. This assay, 'hot-stop PCR', involves addition of a radiolabelled PCR primer at the final cycle. We applied the assay to analysis of loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) in tumours.

Alleles↗

Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

Animals↗

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↗

Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting.

Genomic imprinting plays a fundamental role in cancer and some hereditary diseases, including Beckwith-Wiedemann syndrome (BWS), a disorder of prenatal overgrowth and predisposition to embryonal malignancies such as Wilms tumor. We have previously shown that the KVLQT1 gene on chromosomal band 11p15 is imprinted, with expression of the maternal allele, and that the maternal allele is disrupted in rare BWS patients with balanced germ-line chromosomal rearrangements. We now show that an antisense orientation transcript within KVLQT1, termed LIT1 (long QT intronic transcript 1) is expressed normally from the paternal allele, from which KVLQT1 transcription is silent, and that in the majority of patients with BWS, LIT1 is abnormally expressed from both the paternal and maternal alleles. Eight of sixteen informative BWS patients (50%) showed biallelic expression, i.e., loss of imprinting (LOI) of LIT1. Similarly, 21 of 36 (58%) BWS patients showed loss of maternal allele-specific methylation of a CpG island upstream of LIT1. Surprisingly, LOI of LIT1 was not linked to LOI of insulin-like growth factor II (IGF2), which was found in 2 of 10 (20%) BWS patients, even though LOI of IGF2 occurs frequently in Wilms and other tumors, and in some patients with BWS. Thus, LOI of LIT1 is the most common genetic alteration in BWS. We propose that 11p15 harbors two imprinted gene domains-a more centromeric domain including KVLQT1 and p57(KIP2), alterations in which are more common in BWS, and a more telomeric domain including IGF2, alterations in which are more common in cancer.

Beckwith-Wiedemann Syndrome↗

Development of a performance assessment capability in the waste management programs of the U.S. Nuclear Regulatory Commission.

The U.S. Nuclear Regulatory Commission (NRC) staff has developed a performance assessment capability to address three programmatic areas in nuclear waste management: high-level waste, low-level waste, and decommissioning of licensed facilities (license termination). The NRC capability consists of: (1) methodologies for performance assessment; (2) models and computer codes for estimating system performance; (3) regulatory guidance in various forms, such as regulations, Branch Technical Positions, and Standard Review Plans; and (4) a technical staff experienced in executing and evaluating performance assessments for a variety of waste systems. Although the tools and techniques are refined for each programmatic area, general approaches and similar issues are encountered in all areas.

Government Agencies↗

Identification and characterization of genes required for hyphal morphogenesis in the filamentous fungus Aspergillus nidulans.

In the filamentous fungus Aspergillus nidulans, germination of an asexual conidiospore results in the formation of a hyphal cell. A key feature of spore germination is the switch from isotropic spore expansion to polarized apical growth. Here, temperature-sensitive mutations are used to characterize the roles of five genes (sepA, hypA, podB-podD) in the establishment and maintenance of hyphal polarity. Evidence that suggests that the hypA, podB, and sepA genes are required for multiple aspects of hyphal morphogenesis is presented. Notably, podB and sepA are needed for organization of the cytoskeleton at sites of polarized growth. In contrast, podC and podD encode proteins that appear to be specifically required for the establishment of hyphal polarity during spore germination. The role of sepA and the pod genes in controlling the spatial pattern of polarized morphogenesis in germinating spores is also described. Results obtained from these experiments indicate that the normal pattern of germ-tube emergence is dependent upon the integrity of the actin cytoskeleton.

Aspergillus↗

Two novel genes in the center of the 11p15 imprinted domain escape genomic imprinting.

We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal transferable fragment (STF) from human chromosome 11p15 and the identification of nine known genes and four novel genes within this STF. We now report the isolation of two novel cDNAs, designated here as TSSC4 and TSSC6 (tumor-suppressing STF cDNA 4 and 6), located within the STF. TSSC4 and TSSC6 encode predicted proteins of 329 and 290 amino acids, respectively, with no close similarity to previously reported proteins. TSSC4 and TSSC6 are both located in the center of a 1 Mb imprinted domain, which contains the imprinted genes TSSC3, TSSC5, p57(KIP2), KVLQT1, ASCL2, IGF2 and H19. However, we found that neither TSSC4 nor TSSC6 was significantly imprinted in any of the fetal or extra-embryonic tissues examined. Based on this result, the imprinted gene domain of 11p15 appears to contain at least two imprinted subdomains, between which TSSC4 and TSSC6 substantially escape imprinting, due either to lack of initial silencing or to an early developmental relaxation of imprinting.

Alleles↗

LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids.

Mammalian imprinted genes are frequently arranged in clusters on particular chromosomes. The imprinting cluster on human chromosome 11p15 is associated with Beckwith-Wiedemann syndrome (BWS) and a variety of human cancers. To clarify the genomic organization of the imprinted cluster, an extensive screen for differentially expressed transcripts in the 11p15 region was performed using monochromosomal hybrids with a paternal or maternal human chromosome 11. Here we describe an imprinted antisense transcript identified within the KvLQT1 locus, which is associated with multiple balanced chromosomal rearrangements in BWS and an additional breakpoint in embryonal rhabdoid tumors. The transcript, called LIT1 (long QT intronic transcript 1), was expressed preferentially from the paternal allele and produced in most human tissues. Methylation analysis revealed that an intronic CpG island was specifically methylated on the silent maternal allele and that four of 13 BWS patients showed complete loss of maternal methylation at the CpG island, suggesting that antisense regulation is involved in the development of human disease. In addition, we found that eight of eight Wilms' tumors exhibited normal imprinting of LIT1 and five of five tumors displayed normal differential methylation at the intronic CpG island. This contrasts with five of six tumors showing loss of imprinting of IGF2. We conclude that the imprinted gene domain at the KvLQT1 locus is discordantly regulated in cancer from the imprinted domain at the IGF2 locus. Thus, this positional approach using human monochromosomal hybrids could contribute to the efficient identification of imprinted loci in humans.

Animals↗