Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

On the prediction of the phase distribution of bubbly flow in a horizontal pipe.

Horizontal bubbly flow is widely encountered in various industrial systems because of its ability to provide large interfacial areas for heat and mass transfer. Nonetheless, this particular flow orientation has received less attention when compared to vertical bubbly flow. Owing to the strong influence due to buoyancy, the migration of dispersed bubbles towards the top wall of the horizontal pipe generally causes a highly asymmetrical internal phase distributions, which are not experienced in vertical bubbly flow. In this study, the internal phase distribution of air-water bubbly flow in a long horizontal pipe with an inner diameter of 50.3 mm has been predicted using the population balance model based on direct quadrature method of moments (DQMOM) and multiple-size group (MUSIG) model. The predicted local radial distributions of gas void fraction, liquid velocity and interfacial area concentration have been validated against the experimental data of Kocamustafaogullari and Huang (1994). In general, satisfactory agreements between predicted and measured results were achieved. The numerical results indicated that the gas void fraction and interfacial area concentration have a unique internal structure with a prevailing maximum peak near the top wall of the pipe due to buoyancy effect.

Upregulation of lymphotoxin beta expression in liver progenitor (oval) cells in chronic hepatitis C.

BACKGROUND: Bipotent liver progenitor (oval) cells with the ability to differentiate into hepatocytes and biliary epithelium have recently been identified in human subjects with hepatitis C. Animal studies suggest that members of the tumour necrosis factor family, including lymphotoxin beta (LT-beta), regulate oval cell proliferation in liver disease, but its role in human liver disease is unclear. AIMS: This study seeks to establish a role for LT-beta in hepatitis C related liver injury and to provide evidence that its increased expression is related to the presence of oval cells. METHODS: Liver biopsy specimens were obtained from patients with chronic hepatitis C virus (HCV) infection (n=20). Control liver samples (n=5) were obtained from liver resection or transplant surgery. LT-beta expression in liver biopsy specimens was studied using quantitative real time polymerase chain reaction and immunohistochemistry. RESULTS: LT-beta mRNA levels were similar in control and HCV liver in the absence of fibrosis. In subjects with portal fibrosis, LT-beta mRNA levels were elevated 2.2-fold over control liver levels (p=0.04). In subjects with bridging fibrosis, LT-beta mRNA levels increased 4.4-fold over control liver levels (p=0.02). LT-beta mRNA levels in subjects with established cirrhosis were increased 3.3-fold compared with controls and 2.6-fold compared with mild liver damage (p=0.02). Immunohistochemical analysis established that LT-beta was expressed by oval cells, inflammatory cells, and small portal hepatocytes. CONCLUSIONS: In chronic HCV infection, LT-beta expression is observed in multiple hepatic cell types, including oval cells. LT-beta expression is significantly increased when fibrosis or cirrhosis is present, suggesting a role for LT-beta in the pathogenesis of chronic hepatitis C and a possible role in oval cell mediated liver regeneration.

A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver.

Several reliable and reproducible methods are available to induce oval cells in rat liver. Effective methods often involve inhibiting proliferation in hepatocytes using an alkylating agent, then subjecting the rat to partial hepatectomy (PH). The surgery is difficult to perform reproducibly in mice. Approaches that do not include partial hepatectomy, such as administration of D-galactosamine, are ineffective in mice. We found that a choline-deficient, ethionine-supplemented (CDE) diet, which is very effective in rats, leads to high morbidity and mortality when administered to mice. This article outlines an alternative protocol by which a CDE diet can be administered to mice. This diet is shown to be highly effective for oval cell induction, without causing high mortality. It takes less time and is at least as effective as other commonly used protocols for inducing oval cells in mice.

Hepatoblast-like cells populate the adult p53 knockout mouse liver: evidence for a hyperproliferative maturation-arrested stem cell compartment.

Although p53 regulates the cell cycle and apoptosis, gross embryonic development is normal in the p53 knockout (-/-) mouse. In this study, we comprehensively assessed liver development in p53 -/- mice (from embryonic day 15 to adult) for evidence of a cell cycle-induced perturbation in differentiation. Liver cell proliferation in the embryo and newborn is similar in p53 -/- and +/+ mice; in contrast, -/- adult hepatocytes divide at twice the rate of wild types. Developmental expression patterns of liver-specific markers that are up-regulated (e.g., phosphoenolpyruvate carboxykinase and aldolase B) and down-regulated (e.g., alpha-fetoprotein) are similar. Therefore, embryonic and perinatal liver development is normal in the absence of p53. However, the p53 -/- adult liver displays small blast-like cells, the majority being hepatic and some lymphoid. These cells appear in periportal regions and can infiltrate the parenchyma. The hepatic blast-like cells express both mature and immature liver markers, suggesting that differentiation of the liver stem cell compartment is blocked.

Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice.

Hepatic stem cells (oval cells) proliferate within the liver after exposure to a variety of hepatic carcinogens and can generate both hepatocytes and bile duct cells. Oval cell proliferation is commonly seen in the preneoplastic stages of liver carcinogenesis, often accompanied by an inflammatory response. Tumor necrosis factor (TNF), an inflammatory cytokine, is also important in liver regeneration and hepatocellular growth. The experiments reported here explore the relationship among the TNF inflammatory pathway, liver stem cell activation, and tumorigenesis. We demonstrate that TNF is upregulated during oval cell proliferation induced by a choline-deficient, ethionine-supplemented diet and that it is expressed by oval cells. In TNF receptor type 1 knockout mice, oval cell proliferation is substantially impaired and tumorigenesis is reduced. Oval cell proliferation is impaired to a lesser extent in interleukin 6 knockout mice and is unchanged in TNF receptor type 2 knockout mice. These findings demonstrate that TNF signaling participates in the proliferation of oval cells during the preneoplastic phase of liver carcinogenesis and that loss of signaling through the TNF receptor type 1 reduces the incidence of tumor formation. The TNF inflammatory pathway may be a target for therapeutic intervention during the early stages of liver carcinogenesis.

Cell block preparation on residual ThinPrep sample.

The liquid-based cytology system ThinPrep has overcome many of the deficiencies of the conventional Pap test. However, the cytologic appearances of the cells in the liquid-based medium are different and staffs of laboratories adopting the new system have to be specially trained. Even after the training sessions provided by the vendor, the cytology staff still face a sharp learning curve initially. One way to recognize the different appearances of cells in the liquid-based system is to look at paired split-sample cases from the same patient in laboratories offering the test as an adjunct to the conventional Pap test. Laboratories offering direct-to-vial testing may be able to overcome the difficulties with some cases by performing cell block sections of residual materials in the samples. The protocol for making cell blocks and its application in resolving difficulties with high-grade squamous and glandular epithelial lesions is illustrated in this report. Diagn. Cytopathol. 1999; 21:427-431.

Fine-needle aspiration cytology of mucocelelike tumors of the breast.

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.

Oval cell numbers in human chronic liver diseases are directly related to disease severity.

The risk of developing hepatocellular carcinoma is significantly increased in patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C infection. The precise mechanisms underlying the development of hepatocellular carcinoma in these conditions are not well understood. Stem cells within the liver, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma in animal models and may be important in the development of hepatocellular carcinoma in human chronic liver diseases. The aims of this study were to determine whether oval cells could be detected in the liver of patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C, and whether there is a relationship between the severity of the liver disease and the number of oval cells. Oval cells were detected using histology and immunohistochemistry in liver biopsies from patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. Oval cells were not observed in normal liver controls. Oval cell numbers increased significantly with the progression of disease severity from mild to severe in each of the diseases studied. We conclude that oval cells are frequently found in subjects with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. There is an association between severity of liver disease and increase in the number of oval cells consistent with the hypothesis that oval cell proliferation is associated with increased risk for development of hepatocellular carcinoma in chronic liver disease.

The diagnostic value of fine-needle aspiration cytology in the assessment of thyroid nodules: a retrospective 5-year analysis.

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.

Evaluation of the ThinPrep Papanicolaou test in clinical practice: 6-month study of 16,541 cases with histological correlation in 220 cases.

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.

Gadolinium chloride suppresses hepatic oval cell proliferation in rats with biliary obstruction.

Liver injury due to bile duct ligation (BDL) is histologically characterized by cholestasis, bile ductular proliferation, hepatocellular damage, portal fibrosis, and ultimately biliary cirrhosis. Stem cells within the liver may act as progenitor cells for small epithelial cells termed oval cells that can differentiate into bile duct cells or hepatocytes, whereas myofibroblasts are the principal source of collagen production in fibrosis. The aims of this study were to determine 1) whether BDL induces oval cell proliferation and 2) whether blockade of Kupffer cells affects oval cell proliferation, bile duct proliferation, and myofibroblast transformation in experimental biliary obstruction. Male Sprague-Dawley rats were divided into two groups to receive either a single dose of gadolinium chloride (a selective Kupffer cell blocking agent) or vehicle. One day later, the gadolinium- and vehicle-treated groups were further subdivided to receive either BDL or sham operation. The rats were sacrificed on day 7 postoperatively. Serum was collected for measurement of aspartate aminotransferase, gamma-glutamyl transpeptidase, and bilirubin levels. Liver tissue was taken for evaluation of fibrosis, bile ductular cells, oval cells, and myofibroblasts. BDL resulted in elevated aspartate aminotransferase, gamma-glutamyl transpeptidase, and bilirubin in serum, and gadolinium pretreatment did not modify these effects. BDL induced marked oval cell proliferation, which was completely prevented by gadolinium pretreatment. Gadolinium did not affect the induction of bile duct expansion or myofibroblasts after BDL. We conclude that experimental biliary obstruction induces oval cell proliferation, which can be prevented by gadolinium pretreatment. This suggests that bile ductular proliferation and myofibroblast transformation are not mediated by Kupffer cells and that ductular proliferation can proceed in the absence of oval cells. Alternatively, gadolinium may directly affect oval cell proliferation after BDL.

Fine needle aspiration of breast masses: an analysis of 1533 cases in private practice.

The diagnostic efficacy of fine needle aspiration cytology of breast masses and the causes for unsatisfactory specimens in private practices were investigated in Hong Kong. All specimens that were submitted to the histopathology unit at the Canossa Hospital between 1 January 1996 and 30 April 1997 formed the basis of this report. A total of 1533 specimens were received from 1447 patients; 274 (17.8%) cases were unsatisfactory for assessment, 1080 (70.4%) were benign, 51 (3.3%) atypical, 19 (1.2%) suspicious, and 67 (4.4%) malignant. The specimens were submitted by 105 doctors, who each performed between 1 and 561 smears. The proportion of unsatisfactory samples was high for doctors who performed an occasional fine needle aspiration (48%; overall mean, 25%). Histological correlation was available in 165 cases. The overall sensitivity was 79%, specificity 98%, positive predictive value (including the 'suspicious' category) 92%, and negative predictive value 94%. Two false positive cases that were reported as suspicious were found to be fibroadenomata following subsequent excision biopsy. No adverse clinical outcomes were recorded for the false positive cases. There were six false negative cases (reported as a cyst in one case, benign in two cases, and atypical in three cases). The results compared favourably with published data and affirmed the effectiveness of the test in private practice.

The association between murine cytomegalovirus induced hepatitis and the accumulation of oval cells.

The accumulation of oval cells is an early event in the development of hepatocellular carcinoma induced by certain experimental regimes involving hepatocarcinogens. Oval cells have also been observed during chronic hepatitis induced by alcohol and iron overload. In this study, livers of murine cytomegalovirus (MCMV) infected mice were examined to determine whether hepatitis induced by this virus could initiate oval cell proliferation. BALB/c and C57BL/6 mice were infected with MCMV and studied 4, 8, 10 and 12 months later, alongside control (uninfected) mice. The livers were examined histochemically, immunocytochemically and by in situ hybridization to identify oval cells, inflammatory cells and proliferating cells. Oval cells were seen in the periportal regions of livers from MCMV infected BALB/c mice. These increased in number from 4 to 12 months after infection in parallel with increases in the numbers of inflammatory cells, even though cells expressing MCMV antigens were no longer evident in these samples. Proliferating oval cells and hepatocytes were identified by PCNA staining, indicating an increased level of liver regeneration in the infected livers. C57BL/6 mice are less susceptible to persistent MCMV hepatitis and had fewer oval cells than BALB/c mice. Thus the study demonstrates an association between MCMV induced hepatitis, inflammation, and presence of oval cells.

5' sequences direct developmental expression and hormone responsiveness of tyrosine aminotransferase in primary cultures of fetal rat hepatocytes.

Tyrosine aminotransferase (TyrAT) is one of several gluconeogenic enzymes which appear postnatally in humans and rodents in response to increased glucocorticoid and glucagon levels and decreased insulin. Primary cultured fetal rat hepatocytes older than day 15 of gestation (>E15) transcribe the TyrAT gene in response to the synergistic effect of dexamethasone and N6,2'-O-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP), whereas less mature hepatocytes (E15 hepatocytes, and not

The oval-shaped cell as a candidate for a liver stem cell in embryonic, neonatal and precancerous liver: identification based on morphology and immunohistochemical staining for albumin and pyruvate kinase isoenzyme expression.

Oval cells observed in some experimental models of hepatocarcinogenesis can function as stem cells capable of differentiating into hepatocytes and bile ductular cells. Using markers which characterise embryonic hepatocytes, we showed that oval cells display different patterns of gene expression, suggesting some are more mature than others. In this study we looked for oval cells in developing liver, predicting that they are abundant in embryonic liver and decline in number during development. Albumin (ALB) serves as a liver-specific marker, and the isoenzymes of pyruvate kinase, M2-PK and L-PK, are used to identify immature and mature hepatocytes, respectively. Small oval-shaped cells expressing ALB, M2-PK and L-PK are found near the vascular spaces and portal areas in 20-day gestation (E20), E21, newborn, 3-day and 1-week-old rat liver. Similar cells expressing ALB and M2-PK, but not L-PK are seen only periportally in adult liver. These are abundant in early embryonic liver and decrease in number during development until only a few, located periportally, persist in the adult. Oval cells, located periportally a few days after commencing a choline-deficient, ethionine-supplemented diet, co-express ALB and M2-PK. Their similarity with respect to markers, morphology and location suggests that oval-shaped cells may be the progenitors of oval cells.

Improved Papanicolaou smear reporting through the use of automated data entry.

The implementation of an automated data entry and report generation system using an optical scanner and commercially available image processing program is described. This method could be easily adapted for use in other fields of medical research where the compilation of a large amount of repetitive data is involved, such as the filling in of questionnaires. Using an optical scanner for data entry improves the efficiency of report generation, thereby improving the turnaround time of reports. Reports are standardised and more easily understood by referring doctors. Data is also standardised and validated and is more amenable for quality assurance analysis, in the reminder service for patients, and gives a performance analysis of smear takers.

The accuracy of Papanicolaou smear predictions: cytohistological correlation of 283 cases.

The Papanicolaou smear is a highly effective screening test for the detection of cervical neoplastic changes. The success of the test has resulted in unrealistic expectations of the accuracy of the test by both referring medical practitioners and the public. However, as with any pathological test, it has irreducible false negative and positive rates. This report is a comparison between interpretations based on cytological and histological tests and was undertaken to estimate the sensitivity of the Papanicolaou test as practised in Hong Kong. The overall absolute concordance rate for the study was 51.2%. The concordance rates within one diagnostic category were 63.9% and 74.6% for low- and high-grade squamous intraepithelial lesions respectively. The overall sensitivity of the test was 91.7% with a positive predictive value of 93.5%. Ten percent of the error rate was attributed to laboratory error; the remainder was attributed to sampling error and poor smear preparation. Forty-five percent of cases of atypical squamous cells of undetermined significance showed evidence of cervical intraepithelial neoplasia on subsequent biopsy. Follow-up biopsies of low-grade squamous intraepithelial lesions also showed as many lesions from cervical intraepithelial neoplasia grade I as from grades II and III. These findings suggest that colposcopies and biopsies should be performed as soon as possible rather than to repeat the smears in 3 to 6 months. The results of the study may provide guidelines for formulating follow-up recommendations.

Spectrum of histological changes reactive to prosthetic breast implants: a clinopathological study of 84 patients.

A wide range of host reactions can be produced in response to prosthetic breast implants. Although the spectrum of histological changes is well described in the literature, the chronology and relative occurrence of these changes are not well documented. Examination of 161 capsulectomy specimens from 84 women suggested the following chronological sequence of tissue response: fibrous scar tissue; histiocyte response; foreign body giant cell reaction to extruded or exposed material including polyurethane and Dacron patch; synovial-like metaplasia; and calcification. Fibrous scar tissue was seen in all implants. Histiocytic response was noted in 107/161 of the specimens and a foreign body giant cell reaction to polyurethane was seen only in the two Meme implants. Synovial-like metaplasia was less common than previously reported, occurring in 45/161 of specimens after a mean in situ duration of 11.7 years. This peculiar process was seen only in association with a prominent histiocytic response and was not associated with calcification. Dystrophic calcification, which has been reported as occurring rarely in implant capsules, was seen in 15/161 of our specimens after a mean in situ duration of 17.7 years.

Chronic iron overload in rats induces oval cells in the liver.

Liver damage induced by a variety of agents including hepatocarcinogens, alcohol, and virus induces proliferation of oval cells. In this study, iron overloading of the liver is used as a means of inducing liver damage over an extended period to ascertain whether it promotes the appearance of oval cells. Rats were fed a 2% carbonyl-iron-supplemented diet for 3 or 6 months. Extensive iron deposits appeared periportally in hepatocytes and some Kupffer cells. Iron deposition was less pronounced pericentrally. Small oval-like cells, morphologically and immunocytochemically similar to CDE-derived oval cells, were identified and quantified. They first emerged periportally and subsequently in small tracts or foci nearer central regions and stained positively for alpha-fetoprotein, pi-class glutathione S-transferase, and the embryonic form of pyruvate kinase. They contained very few iron deposits and were classified as iron free. The major difference between CDE- and iron-overload-derived oval cells was that the latter were negative for transferrin. This study shows that cellular changes occurring in iron-overloaded rat liver are similar to those observed in rats placed on a hepatocarcinogenic diet and in rats chronically exposed to alcohol.