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Biomedical subjects

M Chan

Publications and source records attributed to M Chan.

At least 37 records · Page 2Linked to original sources

Expression and protective effects of urocortin in cardiac myocytes.

Reverse transcription PCR showed that mRNA encoding the CRH-like molecule, urocortin, is expressed in a rat cardiac myocyte cell line and in primary cultures of cardiac myocytes. Identity of the amplified with the published sequence was established by restriction mapping and direct sequencing. Expression of urocortin mRNA was increased 12-18 h after thermal injury. Urocortin peptide protected cardiac myocytes from cell death induced by hypoxia. The data suggest that urocortin is an endogenous cardiac myocyte peptide which modulates the cellular response to stress.

Animals

De novo lipogenesis predicts short-term body-composition response by bioelectrical impedance analysis to oral nutritional supplements in HIV-associated wasting.

We studied the effects of enteral supplements on protein and energy intakes, body composition, energy expenditure, and gastrointestinal histology in 49 subjects with human immunodeficiency virus-associated weight loss (12.7 +/- 0.9% of body wt). We also determined whether a stable-isotope mass spectrometric measurement at baseline might predict the short-term response of fat-free mass (FFM) measured by bioelectrical impedance analysis. Thirty-nine subjects completed the study after being randomly assigned to receive either a whole-protein-based (n = 22) or a peptide-based (n = 17) formula. A nonsupplemented, nonrandomly assigned group (n = 13) was followed concurrently. Both formulas were well tolerated. Voluntary intakes of energy and protein from nonsupplement sources decreased significantly during supplementation [by 819-1638 kJ (196-382 kcal)/d and 5.6-14.4 g protein/d, respectively; P < 0.01] but to a lesser extent than the intake from the supplement [2300-2510 kJ(550-600 kcal)/d and 19-28 g protein/d, respectively], so that net increases in intakes of protein and energy (P < 0.03), as well as of several vitamins and trace elements were increased. Nevertheless, the mean FFM did not increase for the group as a whole, although there was considerable interindividual heterogeneity. Changes in FFM at 6 wk were significantly inversely correlated (r = 0.65, P < 0.01) with baseline synthesis of fat (de novo hepatic lipogenesis), but not with other potential measures of energy intake (insulin-like growth factor 1 or its binding protein) or inflammation (soluble tumor necrosis factor receptors I or II). The prospective identification of FFM response by measurement of de novo hepatic lipogenesis supported the hypothesis that the subset of wasting patients whose FFM is unresponsive to nutrient supplementation have altered nutrient metabolism.

Adult

Pseudoaneurysm after high tibial osteotomy and limb lengthening.

A case of a young man with anterior tibial artery rupture and pseudoaneurysm formation that occurred during lengthening of a scarred limb is presented. Leg length discrepancy occurred because of previous distal femoral and proximal tibial fractures. Two corrective operations were performed 11 and 2 years earlier at another hospital. As limb deformity persisted, distal femoral and proximal tibial osteotomies combined with limb lengthening were performed. The aim was to achieve 120 mm (70 mm femoral, 50 mm tibial) lengthening. The operative and early postoperative course was uneventful. Twenty-six days after surgery (when femoral and tibial lengthening was 13.5 mm and 5.5 mm, respectively), blood began oozing from the operative scar during limb distraction. At 70 days after surgery (when femoral and tibia lengthening was 41.5 mm and 14 mm, respectively), a rupture and pseudoaneurysm of the anterior tibial artery became apparent. Documentation of a normal pulses in the foot after surgery, the late presentation of pseudoaneurysm, and the initiation of bleeding by limb distraction indicate that limb lengthening either aggravated an unrecognized arterial injury or precipitated de novo rupture of the anterior tibial artery scarred from previous trauma. The pseudoaneurysm was treated successfully by transarterial embolization.

Adult

Heart Retransplantation.

Retransplantation of the heart is not a widely performed procedure, and few centers have large series. The most common indication for heart retransplantation is transplant graft coronary artery disease, followed by acute rejection and primary graft dysfunction. The outcome after heart retransplantation is not as good as with primary transplantation; the one year actuarial survival rate is lower and there are more perioperative complications. The number of episodes of infection and rejection, however, is not increased. The outcome of heart retransplantation for transplant graft coronary artery disease is better than that of retransplantation for rejection or primary graft failure. However, it is still inferior to that of primary heart transplantation. Because of this and the critical shortage of donor hearts, it is suggested that heart retransplantation should be limited to carefully selected patients.

Journal Article

Mammogram screening of Chinese women in Kwong Wah Hospital, Hong Kong.

The incidence of primary carcinoma of the breast in Hong Kong has been rising. A screening team including radiologists, breast surgeons, cytopathologists, a full-time gynaecologist and mammographers was set up at Kwong Wah Hospital. The screening method includes a clinical breast examination (CBE) and two-view mammography. The target age group is 40-70. A total of 13,033 women were screened from March 1993 to March 1995 and 8504 mammograms were performed. A double reading system was used, with an experienced mammographer as the first reader. The films were then read by radiologists and were reported. All abnormal films and normal films with palpable masses or clinical symptoms were reviewed in a weekly meeting. A total of 113 biopsies were performed including 86 stereotactic-guided fine needle aspirations (FNA) and 27 stereotactic-guided hook-wire biopsies. Four FNA showed malignant cells and another five showed suspicious cells. Eleven hook-wire biopsies showed carcinoma. The benign to malignant ratio of the hook-wire biopsies was 16:11 (< 1.5). The total number of carcinomas disclosed was 42, and 16 of these were not palpable. Four palpable tumours were not detected by mammography. The overall carcinoma of the breast detection rate was 4.94/1000, with a rate of 4.61/1000 for the 40-49-year age group and a rate of 6.46/1000 for the over 50 years of age group. The incidence of ductal carcinoma in situ plus T1 tumours was 2.82/1000.

Adult

Siderophore production by cystic fibrosis isolates of Burkholderia cepacia.

Sixty-one Burkholderia cepacia isolates from patients with cystic fibrosis (CF) and four plant isolates were screened for production of the siderophores salicylic acid (SA), pyochelin, cepabactin, and ornibactins and fingerprinted by a PCR-based randomly amplified polymorphic DNA (RAPD) method. Of the 24 RAPD types determined, 22 (92%) were associated with isolates that produced SA, 21 (87%) were associated with isolates that produced ornibactins, 15 (60%) were associated with isolates that produced pyochelin, and 3 (12%) were associated with isolates that produced cepabactin. Of the 24 RAPD types plus 2 phenotypic variants of types 1 and 9, 3 were associated with isolates that produced all four siderophores, 8 were associated with isolates that produced three siderophores, 12 were associated with isolates that produced two siderophores, and 3 were associated with isolates that produced only one siderophore. These results suggest that the numbers and types of siderophores produced by CF isolates of B. cepacia correlate with RAPD type and that SA and ornibactins are the most prevalent siderophores produced.

Burkholderia cepacia

Multisensor system and artificial intelligence in housing for the elderly.

To improve the safety of a growing proportion of elderly and disabled people in the developed countries, a multisensor system based on Artificial Intelligence (AI), Advanced Telecommunications (AT) and Information Technology (IT) has been devised and fabricated. Thus, the habits and behaviours of these populations will be recorded without disturbing their daily activities. AI will diagnose any abnormal behavior or change and the system will warn the professionals. Gerontology issues are presented together with the multisensor system, the AI-based learning and diagnosis methodology and the main functionalities.

Activities of Daily Living

Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer.

Radiation doses to the tumour and non-tumorous liver compartments from yttrium-90 microspheres in the treatment of hepatic cancer, as estimated by a partition model, have been verified by correlation with the actual doses measured with a beta probe at open surgery. The validity of the doses to the lungs, the tumour and non-tumorous liver compartment as estimated by the partition model was further evaluated in clinical settings. On the basis of the observation that one of three patients who received more than 30 Gy from a single treatment and one of two patients who received more than 50 Gy from multiple treatments developed radiation pneumonitis, it was deduced that an estimated lung dose < 30 Gy from a single treatment and a cumulative lung dose < 50 Gy from multiple treatments were probably the tolerance limits of the lungs. Three of five patients who received lung doses > 30 Gy as estimated by the partition model and were predicted to develop radiation pneumonitis, did so despite the use of partial hepatic embolization to reduce the degree of lung shunting. Furthermore, a higher radiological response rate and prolonged survival were found in the group of patients who received higher tumour doses, as estimated by the partition model, than in the group with lower estimated tumour doses. Thus the radiation doses estimated by the partition model can be used to predict (a) complication rate, (b) response rate and (c) duration of survival in the same manner as the actual radiation doses measured with a beta probe at open surgery. The partition model has made selective internal radiation therapy using 90Y microspheres safe and repeatable without laparotomy.

Adult

Semiquantification of circulating hepatocellular carcinoma cells by reverse transcriptase polymerase chain reaction.

Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies worldwide. Treatment options are severely limited by the frequent presence of metastases. If hepatocyte-specific mRNAs are detected in the circulation, it is possible to infer the presence of circulating, presumably malignant, liver cells. If these can be quantified, it is possible to predict the likelihood of haematogenous metastasis. In this investigation, we have attempted to gain an index of the mass of circulating HCC cells (with reference to the number of hepatoblastoma cells) by measuring the amounts of PCR products for albumin (alb) mRNA and alpha-fetoprotein (afp) mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis. For calibration, total RNA from 1-10(6) HepG2 cells was mixed with total RNA from 10(6) normal peripheral mononuclear cells. A linear relationship was demonstrated between the amount of alb- or afp PCR product and the level of HepG2 total RNA spiked. The assay is sensitive down to a detection level of one HepG2 cell. Alb mRNA was detected in 50% of 18 normal subjects and afp mRNA in only two normal subjects. The alb mRNA cut-off level for the normal was exceeded by seven normal subjects and 34 out of 64 HCC patients, and that for afp mRNA was exceeded by six HCC patients but none of the normal subjects. The level of alb mRNA detected was not linearly proportional to the amount of afp mRNA detected in peripheral blood of the same patients, suggesting heterogeneous expression of alb and afp genes in different circulating tumour cells. In addition, no significant linear association between the levels of afp mRNA and serum AFP was observed. Semiquantification of both mRNA markers for HCC cell detection may prove useful in prediction of metastases.

Biomarkers, Tumor

Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin.

The selective delivery of a high dose of radiation to malignant hepatic tumours by infusion of non-biodegradable yttrium-90 (90Y) microspheres via the hepatic artery while sparing the non-tumorous liver parenchyma depends on the tumour-to-normal uptake ratio (T/N) of the therapeutic radiopharmaceutical. Using intrahepatic arterial technetium-99m macroaggregated albumin (99Tcm-MAA), the effect of tumour type, tumour vascularity assessed by hepatic angiography (HAG), tumour size and the degree of extrahepatic shunting on the T/N was investigated in 377 patients with hepatocellular carcinoma (HCC) and 25 patients with colorectal liver metastases. HCC was shown to have a wider range of T/N (0.2-26.5) compared with liver metastases (2.3-7.2). HCC with vascularity grade 1 on HAG had significantly lower T/N but there was no significant difference in HCC with higher vascularity grades. This confirmed that vascularity on HAG does not predict T/N. Overall there was no correlation between T/N and tumour size. Large tumours (> 20 cm) had a significantly lower T/N, probably due to necrosis in the tumour centres. A decrease in mean T/N with increasing percentages of lung shunting was observed in HCC. Determination of T/N by simulation with 99Tcm-MAA is recommended before internal radiation therapy with 90Y microspheres.

Carcinoma, Hepatocellular

Arteriovenous shunts in patients with hepatic tumors.

UNLABELLED: The study aimed to investigate the influence of tumor type, tumor size, tumor vascularity and treatment on arteriovenous shunts between the liver and lungs in patients with hepatic cancer. METHODS: Our previous assessment of the degrees of lung shunting using intra-arterial 99mTc-macroaggregated albumin in 125 patients with hepatocellular carcinoma (HCC) was extended to include 377 patients with HCC and 25 patients with colorectal liver metastases. Patients were given 111 MBq (3 mCi) of 99mTc-macroaggregated albumin during hepatic angiography. The lungs and the liver were localized as regions of interest on the digitized gamma scintigraphic image. The total counts taken over the lungs divided by the total counts taken over both the lungs and the liver gave the percentage of lung shunting. Tumor size was measured by computerized tomography or ultrasound scan. Tumor vascularity was assessed based on the degree of neovascularization. Linear regression and Wilcoxon rank test were used for statistical analysis. RESULTS: Patients with HCC had a higher median (7.6%) and a wider range (< 1-75.4%) of percentages of lung shunting when compared with those with colorectal liver metastases (median, 4.7%; range, < 1-23.9%). The lung shunting correlated with the tumor size in the 377 patients with HCC (r = 0.359; p < 0.0001). Excluding one outlier, we found a similar correlation in 24 patients with colorectal metastases (r = 0.686; p < 0.0001). In HCC, the mean lung shunting increased with increasing tumor size, up to 15 cm, and then remained almost unchanged, up to a size of > 20 cm. The mean lung shunting also increased with increasing vascularity grades, as assessed by hepatic angiography. The difference between any two vascularity grades was statistically significant (p = 0.0001-0.0148). Similar analysis by subgroups in colorectal liver metastases was impossible because of the small number of patients. Lung shunting decreased in HCC patients after the tumors were treated, but it might increase or decrease when the disease recurs. CONCLUSION: The lung shunting was influenced by the type, size and vascularity of the hepatic tumor. The change in lung shunting with the status of the tumor after treatment further suggests a neoplastic nature of the blood vessels involved in the arteriovenous shunt.

Carcinoma, Hepatocellular

Production of a baculovirus-derived gp50 protein and utilization in a competitive enzyme-linked immunosorbent assay for the serodiagnosis of pseudorabies virus.

The pseudorabies virus (PRV) gp50 envelope glycoprotein gene was cloned and expressed in a recombinant baculovirus. An anti-gp50 Mab (1842) recognized a protein of approximately 40 kDa in immunoblotting assays from infected insect cell lysates, while this product was not present in cells infected with wild-type baculovirus. The recombinant protein was purified by lectin affinity chromatography, utilizing lectins specific for O-linked oligosaccharides (Artocarpus integrifolia and Glycine max). Competitive (c) ELISAs, using either crude or lectin-purified antigen, were devised for the detection of antibodies to PRV in sera, and were capable of monitoring sero-conversion by day 14 post-infection. Furthermore, a specificity of 100% and sensitivity of 98% (crude lysate antigen) or 96% (lectin-purified antigen) was found for a panel of 80 swine sera, using the cELISA, as compared to a serum neutralization (SN) test. These studies demonstrated that recombinant PRV gp50 protein shows promise as a cELISA antigen, for serodetection of PRV.

Animals

The modulation of choline phosphoglyceride metabolism in human colon cancer.

Colorectal cancer has a high incidence of morbidity and mortality in the North American population. Elevated levels of plasmalogens have been reported in some neoplastic tissues including colon tumors, but the mechanism for this increase has not been defined. Since changes in plasmalogen level are usually associated with changes in the other phospholipid subclasses, a general increase in all phospholipid subclasses may also be found in colonic neoplasms. In this study, the levels of the major phospholipids, including their plasmalogen and diacylphospholipid subclasses, were found to be elevated in human malignant colonic tissues. Since phosphatidylcholine is the most prominent type of phospholipid found in both malignant and control tissues, the mechanism for its accumulation during malignancy was investigated. Decreases in phospholipase C and D activities were observed in tumor samples, but an enhancement of the CTP: phosphocholine cytidylyltransferase activity was also detected. Immunoblotting analysis revealed that the elevated cytidylyltransferase activity was caused by a three-fold increase in the level of enzyme protein during tumor development. Based on these enzyme studies, we conclude that the high level of phosphatidylcholine in colon tumors resulted from a decrease in its turnover and an increase in its expression.

Colon

Immunologic cytofluorometric studies in adolescents with anorexia nervosa.

OBJECTIVE: To assess lymphocyte stimulation and lymphocyte phenotype evaluation in adolescent patients with anorexia nervosa (AN). METHOD: In vitro lymphocyte stimulation and flow cytometric phenotype studies were done on 26 hospitalized patients with AN receiving nutritional rehabilitation. The laboratory assessment consisted of lymphocyte subset analysis and in vitro lymphoproliferative responses to mitogens and antigens. RESULTS: Flow cytometric phenotype analysis showed that only a minority of the patients had abnormal phenotype and immune responses, moreover their immune systems were not significantly impaired. DISCUSSION: The cytofluorometric study of immune function does not show significant alterations in adolescents hospitalized for anorexia nervosa.

Adolescent

Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours.

A uniform distribution of yttrium-90 (90Y) microspheres throughout the entire liver has always been assumed for dose calculation in treating hepatic tumours. A simple mathematical model was formulated which allows estimation of the activities of a therapeutic dose of 90Y microspheres partitioned between the lungs, the tumour and the normal liver, and hence the radiation doses to them. The doses to the tumour and normal liver were verified by intra-operative direct beta-probing. The percentage of activity shunted to the lung and the tumour-to-normal tissue ratio (T/N) were obtained from gamma scintigraphy using technetium-99m-labelled macroaggregated albumin (MAA) which simulates the 90Y microspheres used in subsequent treatment. The intrahepatic activity was partitioned between the tumour and the normal liver based on the T/N and their masses determined from computerized tomography slices. The corresponding radiation doses were computed using the MIRD formula. The estimated radiation doses were correlated with the doses directly measured using a calibrated beta-probe at laparotomy by linear regression. The radiation doses to the tumour and the normal liver, estimated using the partition model, were close to that measured directly with coefficients of correlation for linear regression: 0.862 for the tumours and 0.804 for the normal liver compartment (P<0.001). The partition model permits a distinction between the radiation doses received by the tumour and the normal liver to be made and the doses thus estimated are close to the actual doses received. The optimal doses to the tumour and normal liver and hence the required quantity of 90Y microspheres to be administered can be easily predetermined.

Brachytherapy

Acute pulmonary effects of three nebulizers for administering aerosol pentamidine: comparison of Parineb to Fisoneb and Respirgard II.

We conducted a prospective, unblinded, nonrandomized, multiple crossover study to assess the acute pulmonary effects of a new jet nebulizer-Parineb, comparing it to Respirgard II (jet nebulizer) and Fisoneb (ultrasonic nebulizer) for administering aerosol pentamidine (AP). Twenty-three HIV patients received AP at 60 mg dissolved in 3 ml sterile water with Parineb and Fisoneb and 300 mg dissolved in 5 ml sterile water with Respirgard II on three successive clinic visits. Twelve patients known to develop bronchospasm with AP received 200 micrograms of salbutamol as premedication for all three nebulizers. Eleven subjects received AP without bronchodilator premedication. All subjects had a reduction in flow rates with AP. No significant difference was noted in the reduction of flow rates between the three nebulizers in those patients without prior history of bronchospasm with AP. However, there was a significantly greater reduction in flow rates with Parineb in patients with known AP-induced bronchospasm despite premedication with bronchodilator. This decrease in flow rates with Parineb was not felt by patients based on the subjective rating of cough using a visual analog score when compared to the other two nebulizers. Parineb should be used cautiously in individuals with known AP-induced bronchospasm.

Administration, Inhalation