The pattern of cervical smear abnormalities in marginalised women in Hong Kong.

INTRODUCTION: "Ripple Action" and "WE Stand" are projects co-organised by the Hong Kong Women Doctors Association. The two projects organise free cervical screening for low-income women, new immigrants from Mainland China, and ethnic minority women. The objective of this study was to analyse the pattern of cervical smear abnormalities in these marginalised women. METHODS: The study group consisted of 1189 marginalised women who participated in a free cervical screening campaign, including 324 low-income local Chinese, 540 new immigrants from Mainland China, and 325 ethnic minority women. The comparison group consisted of 1141 local Chinese who attended a well women clinic. The prevalence of cervical smear abnormalities was compared using Chi squared test. RESULTS: In the study group, 42.6% of women had never had a cervical smear. Compared with the comparison group, they had a significantly higher prevalence of cervical smear abnormalities (13.7% vs 1.4%; P<0.001), including atypical smear (10.8% vs 0.5%; P<0.001), low-grade lesion (1.8% vs 0.8%; P=0.036), and high-grade lesion (1.1% vs 0.1%; P=0.002). Logistic regression analysis showed that the strongest predictors for abnormal cervical smear were being South Asian (odds ratio=11.859; 95% confidence interval, 4.635-30.341), South-East Asian (6.484; 3.192-13.171), or new immigrant from Mainland China (6.253; 2.463-15.877). CONCLUSIONS: Marginalised women had a significantly higher prevalence of cervical smear abnormality than the general population and almost half had never had a cervical smear before. Outreach strategies are needed to enrol this population into screening programmes.

Separation of helper and suppressor T lymphocytes. II. Ly phenotypes and lack of DNA synthesis requirement for the generation of concanavalin A helper and suppressor cells.

Using a Ficoll velocity sedimentation gradient, we have been able to fractionate concanavalin A (Con A)-induced helper and suppressor cells into separate pools. Cells activated by Con A to mediate helper activity are Ly1+, do not require DNA synthesis for induction, and remain as small cells after activation. Suppressor cells are Ly23+, are found in the blast cell fraction and their induction is not inhibitable by prior treatment with mitomycin C or irradiation, both of which inhibit DNA synthesis. The implications of such findings are discussed.

T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.

B lymphocyte immune response gene phenotype is genetically determined.

We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ([GAT responder x GAT nonresponder]F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system which serves as a model for the human disease multiple sclerosis. We demonstrate here that encephalitogenic T cells, transduced with a retroviral gene, construct to express interleukin 4, and can delay the onset and reduce the severity of EAE when adoptively transferred to myelin basic protein-immunized mice. Thus, T lymphocytes transduced with retroviral vectors can deliver "regulatory cytokines" in a site-specific manner and may represent a viable therapeutic strategy for the treatment of autoimmune disease.

Insights into immune-response gene function using an Ia mutant mouse strain.

The class II genes of the major histocompatibility complex (MHC) encode the immune response-associated or Ia antigens. These highly polymorphic glycoprotein heterodimers have been shown to play a pivotal role in diverse immunological functions. Although the precise molecular and cellular interactions have yet to be elucidated, structural determinations on Ia molecules are known to control the immune response to foreign antigens. Several recent advances into our understanding of how Ia molecules function were made possible by the discovery of the B6,C-H-2bm12 (bm12) mouse strain. The bm12 strain carries a mutation that occurred spontaneously in one of its genes encoding an Ia polypeptide chain. Information from studies using bm12 include (1) insights into the evolution of class II genes and its functional significance; (2) the definition of multiple functional sites on Ia and their relative importance; and (3) the demonstration that Ia conformation is important in determining its functional capacity. These findings using the bm12 mutant are reviewed in the context of other recent studies of Ia recognition.

Characterization of a dominant anti-Ia idiotype using the IA mutant mouse strain B6.C-H-2bm12.

Initial studies of antibody recognition of Ia molecules using the IA mutant mouse strain bm12 suggested that two anti-Ia monoclonal antibodies (mAbs), 25-9-17 and 34-5-3, share several features: (1) indistinguishable serologic specificity including a lack of reactivity with Iabm12, (2) binding of the same spatial epitope (cluster), and (3) definition of a cross-reactive idiotype (CRI) as defined by xenogeneic antisera. In the present study we characterize a rabbit anti-idiotype (anti-Id) to 25-9-17 by affinity chromatography, and demonstrate that it detects at least two distinct idiotopes, one shared by 25-9-17 and 34-5-3 designated CRI (25-9-17) and one unique for 25-9-17 molecules. Experiments were also undertaken to determine whether CRI (25-9-17) represents a measurable component of allogeneic humoral responses to Iab antigens. By both absorption analyses of a polyspecific antiserum and production of antigenically-restricted antisera using bm12 mice, CRI (25-9-17) was found to represent a significant proportion of the antibodies to Iab. By several criteria it was shown that the CRI (25-9-17)+ molecules were among the antibodies defining the serologic lesion of bm12 mice. In preparation for future studies to alter in vivo T-cell responses involving recognition of Ia (e.g. graft vs host disease and allogeneic transplant rejection), various immunization protocols and mouse strains were tested for induction of Id (25-9-17) following in vivo administration of various anti-idiotypic reagents. Rabbit anti-Id (25-9-17) successfully induced CRI (25-9-17) positive molecules in all strains tested regardless of IA or Ig genotype. Moreover, some of these treated mice produced antibodies to an Ia determinant missing on bm12 cells, suggesting that they recognize the same serologic determinant as mAb 25-9-17.

Adoptive transfer of murine experimental autoimmune encephalomyelitis in SJL.Thy-1 congenic mouse strains.

For the purpose of tracking the migration of donor T cells in chronic relapsing EAE (CREAE), a Thy-1 congenic mouse strain on the SJL genetic background was generated. T cells from these distinguished from those of SJL (Thy-1.2+) by staining with specific anti-Thy-1 antibodies. In adoptive EAE, SJL.Thy-1a mice exhibited similar chronic remitting and relapsing cycles as in SJL mice. Reciprocal transfer of adoptive EAE had also been successfully carried out between the two Thy-1 disparate strains. The lack of alloreactivity against the Thy-1 antigen was further demonstrated by the absence of reactivity in the vitro mixed lymphocyte cultures and in vivo skin graft rejection between the two strains. The establishment of the SJL.Thy-1a mouse strain should prove to be a valuable tool for further dissecting the complex process of relapsing EAE.

Homing of T cells to the central nervous system throughout the course of relapsing experimental autoimmune encephalomyelitis in Thy-1 congenic mice.

Chronic relapsing experimental allergic encephalomyelitis (EAE) was induced in Thy-1.1 congenic SJL/J mice by the adoptive transfer of myelin basic protein (MBP)-responsive lymph node cells from Thy-1.2 SJL/J mice. The Thy-1 congenic mouse strain was constructed on the SJL (Thy-1.2) background by the initial cross with the AKR (Thy-1.1) strain and does not reject Thy-1.2+ T cells. Quantitative immunocytochemical analysis of the central nervous system (CNS) of Thy-1.1 recipients showed preferential trafficking of Thy-1.2+ T cells to the meninges and white matter, beginning prior to onset of clinical signs. At 7 days post-transfer (dpt), Thy-1.2+ donor cells constituted 2.5% of the infiltrating cells and reached peak values (ca. 10%) during the first attack. At later stages (up to ten relapses), Thy-1.2+ T cells constituted 2-5% of the infiltrate. In control mice injected with irrelevant antigen-stimulated Thy-1.2+ T cells, only the occasional Thy-1.2+ T cell could be demonstrated up to 14 dpt. This is the first study showing unequivocally the presence of MBP-stimulated, adoptively transferred T cells within the CNS of recipients throughout the course of EAE, particularly during later relapsing stages. These results indicate that the persistent presence of antigen-specific T cells may be required for the recruitment of non-CNS antigen-responsive immune cells.

A combination of adoptive transfer and antigenic challenge induces consistent murine experimental autoimmune encephalomyelitis in C57BL/6 mice and other reputed resistant strains.

Adoptive EAE was induced in SJL mice by the transfer of MBP-primed and in vitro-stimulated donor lymph node cells into naive syngeneic recipients. Priming donor mice with OVA instead of restimulating MBP-primed donor cell with OVA resulted in no transfer of EAE. This apparent lack of disease, however, could be overcome if the recipients were subsequently challenged with MBP. When this transfer-challenge technique was applied to BALB/c and C57BL/6 mice, these reputed (MBP)EAE-resistant strains developed consistent and severe disease similar to that seen in susceptible strains. In fact, a survey of eleven (MBP)EAE-resistant strains, defined on the basis of their inability to mount an encephalitogenic response in recipient mice following the transfer of MBP-primed and in vitro activated lymph node cells, revealed that EAE could be induced in all these strains. Since the surveyed strains represented a wide spectrum of genetic backgrounds as well as the common MHC congenic haplotypes (H-2b,d,k,m,r,s,v), it is concluded that the machinery for recognition of MBP, i.e. MHC genes and the appropriate T cell receptors, is functionally intact in these resistant mice. While MHC and T cell receptor genes are required for T cell responses, they are not the limiting factors that confer resistance in murine EAE.

Universal screening of human immunodeficiency virus infection in pregnant women in Hong Kong: prospective study.

OBJECTIVE: To evaluate universal screening with an opt-out approach of pregnant women for human immunodeficiency virus infection. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: All women booked or delivered in Kwong Wah Hospital from 1 January 1999 to 30 November 1999 were recruited. MAIN OUTCOME MEASURES: Numbers of women who received the human immunodeficiency virus antibody screening test, refused the test (and the reasons why), tested positive, and tested positive with confirmation by immunoblot study. RESULTS: A total of 5597 women were recruited and 5459 screening tests performed in this study. Of the 16 screened positive cases, three were confirmed by immunoblot study. The overall acceptance rate for the test was 97.5%. The acceptance rate among the 5191 women recruited through the hospital's booking clinic was not significantly different from that among the 406 women who did not go through the hospital's booking clinic (97.6% versus 96.6%). CONCLUSION: Universal screening of pregnant women for human immunodeficiency virus infection with an opt-out approach is practical, feasible, and clinically acceptable in Hong Kong.

Consensus statement on iodine deficiency disorders in Hong Kong.

This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.

Effect of fetal diagnosis on the outcomes of second-trimester pregnancy termination for fetal abnormalities: a pilot study.

OBJECTIVE: To explore whether the outcomes of second-trimester pregnancy termination for fetal abnormalities are affected by fetal diagnoses. METHODS: This was a retrospective review of cases undergoing second-trimester pregnancy termination for the fetal diagnoses of hemoglobin Barts, trisomy 21, and trisomy 18 during the period from 1999 to 2006. The affected pregnancies were terminated by vaginal misoprostol. The outcome measures were: (1) abortion within 24 hours after misoprostol commencement, (2) histology-confirmed incomplete abortion, and (3) experience of significant side effects during termination (temperature over 39 degrees C or need for metoclopramide for vomiting). RESULTS: One hundred and twenty cases were available for analysis. After adjusting for maternal age, parity, history of cesarean delivery, body mass index, gestation, and fetal hydrops, pregnancy termination for trisomy 21 was associated with a higher risk of incomplete abortion than trisomy 18 and hemoglobin Barts (odds ratio 5.25, 95% confidence interval 1.24-22.19, p = 0.024). The chance of abortion within 24 hours and experience of significant side effects were not found to be associated with fetal diagnosis. CONCLUSIONS: Pregnancy termination for trisomy 21 is associated with a higher risk of incomplete abortion. Fetal diagnosis affects the outcome of pregnancy termination.

The effect of gestational age on the outcome of second-trimester termination of pregnancies for foetal abnormalities.

OBJECTIVE: To explore the effect of gestational age on the outcome of second-trimester termination of pregnancies for foetal abnormalities. METHOD: A retrospective study was conducted on 280 pregnancies terminated for foetal abnormalities in the second trimester using vaginal misoprostol. The gestational age at termination was divided into three groups: 13-16 weeks, 17-20 weeks and 21-23 weeks. The likelihood of (1) abortion within 24 h of commencement of misoprostol, (2) incomplete abortion and (3) experiencing significant side effects was compared among these three gestational groups after adjusting for maternal age, parity and body mass index (BMI). RESULTS: Compared to termination after 20 weeks, pregnancy termination for foetal abnormality before 17 weeks of gestation was associated with higher chance of incomplete abortion (OR 2.2, 95% CI 1.07-4.61, p = 0.032) and lower chance of experiencing significant side effects (OR 0.11, 95% CI 0.01-0.91, p = 0.041). CONCLUSION: Women undergoing pregnancy termination for foetal abnormalities in the early second trimester should be informed of possible higher chance of incomplete abortion.

Meconium peritonitis: prenatal diagnosis, postnatal management and outcome.

OBJECTIVES: Prenatal ultrasonography (USS) is a routine screening test for fetal abnormalities. Its accuracy for detecting meconium peritonitis (MP), which may carry high mortality, is important for prenatal counseling. The aim of this study was to assess the accuracy of prenatal USS for diagnosing MP and predicting patient outcomes. METHODS: The prenatal and postnatal medical records of all patients referred to our institutions with confirmed MP were reviewed, with emphasis on prenatal USS findings, results of postnatal investigations, operative findings, outcomes, and possible causes of MP. RESULTS: From January 2000 to November 2004, seven fetuses were confirmed to have MP at birth. Three MP patients (3/7, 43%) were diagnosed prenatally because of USS showing ascites and calcification/dilated or hyperechoic bowel loops. One (1/7, 14.3%) suspected cystic MP was confirmed by prenatal MRI. In the other three cases, USS showed only ascites. All patients had postnatal contrast CT scans. Two patients' CT scans showed persistent intestinal perforation not visible with prenatal USS, and required emergency operations. All patients survived and prospered, and were sweat test negative. CONCLUSIONS: Prenatal USS allows suspected MP babies to be transferred to a tertiary centre for delivery and appropriate management. In this way, the chances of survival of these babies can be excellent if they are not associated with cystic fibrosis (CF). Prenatal MRI can improve the low diagnostic yield of prenatal USS for MP. Postnatal contrast CT scan is required to define persistent intestinal perforation invisible with prenatal USS.

Separation of helper and suppressor T lymphocytes. III. Positive and negative effects of mixed lymphocyte reaction-activated T cells.

Using a Ficoll velocity sedimentation gradient, we provide evidence to show that stimulatory and inhibitory activities induced in mixed lymphocyte culture belong to two distinct subpopulations of T cells. Slow- to medium-sedimenting, nonproliferating cells enhance the humoral response of normal cells to SRBC whereas fast-sedimenting cells inhibit that response. Cytotoxic lymphocytes are found in the same fractions as suppressor cells but appear to be differentiable from the latter in terms of maturation kinetics and specificity.

Cell-cell interactions in the T cell proliferative response. I. Analysis of the cell types involved and evidence for nonspecific T cell recruitment.

In the antigen-induced T cell proliferative response, it has been firmly established that antigen-specific T cell activation signals are provided by a specialized antigen-presenting cell (APC). However, the number of responding T cell populations involved has not been clearly delineated. This problem can be analyzed by plotting the logarithm of the number of cultured cells against the logarithm of the response. This yields a straight line, the slope of which indicates the minimum number of interacting cell populations that are required to give the response. In the antigen-induced T cell proliferative response, this number is 3. Based on their ability to shift the slopes of the log cell number-log response line, two of the populations were identified to be T cells. The third cell, which was present in irradiated spleens, possessed certain properties of the APC. Of the two T cells, one was antigen-specific and the other could come from normal unprimed animals. The frequency of antigen-specific proliferating T cells in primed animals was estimated to be only 1 in 1.3 x 10(3), and a large proportion of the proliferation was shown to be due to unprimed cells. Furthermore, without the need to use antigen-pulsed macrophages, this slope analysis demonstrated convincingly that the successful interaction between APCs and proliferating T lymphocytes is determined by products of the I-region immune response genes.

Direct cloning and extended culture of antigen-specific MHC-restricted, proliferating T lymphocytes.

The development of antigen-specific, T-cell lines has been a subject of intensive investigation by many laboratories interested in the problems of the nature of the T-cell receptor and the mechanism of major histocompatibility complex (MHC) restriction. We describe here a modification of the soft agar cloning technique which has allowed us to rapidly generate and expand proliferating T-lymphocyte clones directly from murine lymph nodes. Using this technique, we demonstrate that such T-cell clones are antigen specific and require I--A compatible antigen-presenting cells for stimulation.

Ductus venosus Doppler study in fetuses with homozygous alpha-thalassemia-1 at 12 to 13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 are anemic from the first trimester of pregnancy. We investigated ductus venosus Doppler velocimetry in these affected fetuses at 12-13 weeks of gestation. DESIGN: Prospective observational study. SUBJECTS: Women referred for the prenatal diagnosis of homozygous alpha-thalassemia-1 before 14 weeks of gestation. METHODS: All fetuses underwent pulsed Doppler investigations following color flow mapping at 12 or 13 weeks of gestation. Homozygous alpha-thalassemia-1 was diagnosed by DNA or hemoglobin study. The ductus venosus Doppler indices--Vmax (peak velocity during ventricular systole), Vmin (minimum forward velocity during atrial systole), TAMX (time-averaged maximum velocity), PIV (pulsatility index for veins, Vmax-Vmin/TAMX), PLI (preload index, Vmax-Vmin/Vmax) and Vmax/Vmin ratio--were compared between the affected fetuses and fetuses unaffected by homozygous alpha-thalassemia-1. RESULTS: Between June 1998 and October 1999, 102 eligible women were recruited. Fetal ductus venosus Doppler study was successful in 96 pregnancies (94%). Of these, 20 fetuses were affected by homozygous alpha-thalassemia-1. None of them showed hydropic changes at the time of Doppler study. The affected fetuses had significantly higher ducts venosus Vmax (30% increase), Vmin (50% increase) and TAMX (20% increase) and significantly lower Vmax/Vmin ratio, PIV and PLI values. CONCLUSION: Fetuses affected by homozygous alpha-thalassemia-1 at 12-13 weeks had increased forward flow velocities in the ductus venosus throughout the cardiac cycle. The increase of venous return is consistent with our previous report of cardiac dilatation and an increase of cardiac output in the affected fetuses at this stage as a compensatory mechanism for anemia and hypoxia. However, extensive overlap of the ductus venosus Doppler indices between affected and unaffected fetuses precludes its use in predicting anemia at 12-13 weeks.