Malignancies in Immunoglobulin G4-related ophthalmic disease.

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

[Procedural skills training in a developing country: 10 tips]. / Vaardigheidstraining in ontwikkelingslanden: 10 tips.

Procedural skills training in a developing country is challenging, but can improve the quality of care for patients with an important regional health problem. A structured, brief, teach-the-teacher-based training course supports physicians in developing countries to acquire skills needed to perform a complex procedure independently. A case of a patient diagnosed with esophageal cancer is presented and 10 tips are given for training procedural skills in a developing country.

Emergency attendances and hospitalisations for complications after transrectal ultrasound-guided prostate biopsies: a five-year retrospective multicentre study.

INTRODUCTION: Transrectal ultrasound-guided (TRUS) prostate biopsy is an established procedure for diagnosis of prostate cancer. Complications after TRUS biopsy are not well reported in Hong Kong. This study evaluated the 5-year incidences of TRUS biopsy complications and potential risk factors for those complications. METHODS: This was a retrospective review of biopsies performed from 2013 to 2017 in two local hospitals, using data retrieved from electronic medical records. The primary outcome was the occurrence of complications requiring either emergency attendances or hospitalisations within 30 days after biopsy. Potential risk factors were examined using multiple logistic regression analysis. RESULTS: In total, 1699 men were included (mean age ± standard deviation: 67 ± 7 years; median prostate-specific antigen level: 7.9 µg/L [interquartile range, 5.5-12.6 µg/L]); 4.3% had pre-biopsy bacteriuria. Overall, 5.7% and 3.8% of post-biopsy complications required emergency attendances and hospitalisations, respectively. Gross haematuria and rectal bleeding requiring emergency attendances developed in 2.1% and 0.4% of men; 0.8% and 0.4% required hospitalisations. Furthermore, 1.5% of men developed acute urinary retention requiring hospitalisations; 1.9% and 1.2% had post-biopsy infections requiring emergency attendances and hospitalisations, respectively, and 0.9% had urosepsis requiring hospitalisations. Prostate volume >48 cc was associated with an increased risk of post-biopsy retention (odds ratio 2.75, 95% confidence interval: 1.23-4.17). CONCLUSIONS: The rate of overall complications after TRUS biopsy was low. The most common complications requiring emergency attendances and hospitalisations were gross haematuria and acute urinary retention, respectively. Prostate volume >48 cc increased the risk of post-biopsy urinary retention.

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.

Sexual violence cases in a hospital setting in Hong Kong: victims' demographic, event characteristics, and management.

INTRODUCTION: Rainlily, the first one-stop crisis centre in Hong Kong, was set up in 2000 to protect female victims of sexual violence. This study aimed to analyse the characteristics of sexual assault cases and victims who presented to two hospitals in Hong Kong. The data are invaluable for health care professionals and policymakers to improve service provision to these victims. METHODS: This retrospective analysis of hospital records was conducted in two acute hospitals under the Hospital Authority in Hong Kong. Sexual assault victims who attended the two hospitals between May 2010 and April 2013 were included. Characteristics of the cases and the victims, the use of alcohol and drugs, involvement of violence, and the outcome of the victims were studied. RESULTS: During the study period, 154 sexual assault victims attended either one of the two hospitals. Their age ranged from 13 to 64 years. The time from assault to presentation ranged from 1 hour to more than 5 months. Approximately 50% of the assailants were strangers. Approximately 50% of victims presented with symptoms; the most common were pelvic and genitourinary symptoms. Those with symptoms (except pregnancy) presented earlier than those without. The use of alcohol and drugs was involved in 36.4% and 11.7% of cases, respectively. Approximately 10% of the screened victims were positive for Chlamydia trachomatis. There were 11 pregnancies with gestational age ranged from 6 weeks to 5 months at presentation. Less than half of the victims completed follow-up care. CONCLUSIONS: Involvement of alcohol and drugs is not uncommon in sexual assault cases. Efforts should be made to promote public education, enhance coordination between medical and social services, and improve the accessibility and availability of clinical care. Earlier management and better compliance with follow-up can minimise the health consequences and impact on victims.

Seatbelt use by pregnant women: a survey of knowledge and practice in Hong Kong.

INTRODUCTION: The use of motor vehicles is common during pregnancy. Correct seatbelt use during pregnancy has been shown to protect both the pregnant woman and her fetus. This survey aimed to evaluate the practices, beliefs, and knowledge of Hong Kong pregnant women of correct seatbelt use, and identify factors leading to reduced compliance and inadequate knowledge. METHODS: A self-administered survey was completed by postpartum women in the postnatal ward at the United Christian Hospital, Hong Kong, from January to April 2015. Eligible surveys were available from 495 women. The primary outcome was the proportion of pregnant women who maintained or reduced seatbelt use during pregnancy. Secondary outcomes were analysed and included knowledge of correct seatbelt use, as well as contributing factors to non-compliance and inadequate knowledge. RESULTS: There was decreased compliance with seatbelt use during pregnancy and the decrease was in line with increasing gestation. Pregnant women's knowledge about seatbelt use was inadequate and only a minority had received relevant information. Women who held a driving licence and had a higher education level were more likely to wear a seatbelt before and during pregnancy. Women with tertiary education or above knew more about seatbelt use. CONCLUSIONS: Public health education for pregnant women in Hong Kong about road safety is advisable, and targeting the lower-compliant groups may be more effective and successful.

Prevalence of Maternal Affective Disorders in Chinese Mothers of Preschool Children with Autism Spectrum Disorders.

OBJECTIVES: To evaluate the prevalence of affective disorders and identify their associated factors among Chinese mothers of preschool children diagnosed with autism spectrum disorders. METHODS: This cross-sectional study was conducted at the Autism Spectrum Disorders Multidisciplinary Clinic of the United Christian Hospital from August 2012 to June 2013. All mothers of a consecutive series of preschool children diagnosed with autism spectrum disorders at their first visit to the clinic were recruited. Information regarding the child-related, maternal, and environmental factors was collected. Psychiatric diagnoses were made according to the Chinese-Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders. Independent factors associated with maternal affective disorders were determined by univariate and multivariate analyses. RESULTS: Of the 121 subjects, the point prevalence of affective disorders as a group was 29.8%. The point prevalence of major depressive disorders, adjustment disorders, anxiety disorders, and bipolar affective disorders was 14.9%, 10.7%, 3.3% and 0.8%, respectively. A higher level of disruptive and self-absorbed behaviours in the children (as assessed by the Developmental Behaviour Checklist), a higher level of affiliate stigma (as assessed by 22-item Affiliate Stigma Scale), and a history of psychiatric disorders were independently associated with current affective disorders. CONCLUSION: Psychiatric disorders, predominantly affective disorders, are common among Chinese mothers of preschool children with autism spectrum disorders. Identification of independent factors associated with maternal affective disorders can aid in the early detection of cases and planning of early intervention programmes to address both child and maternal psychological needs.

Imaging of the heart: historical perspective and recent advances.

Correct diagnosis must be made before appropriate treatment can be given. The aim of cardiac imaging is to establish cardiac diagnosis as accurate as possible and to avert unnecessary invasive procedures. There are many different modalities of cardiac imaging and each of them has advanced tremendously throughout the past decades. Echocardiography, as the first-line modality in most clinical circumstances, has progressed from two-dimensional, single-planed M-mode in the 1960s to three-dimensional speckle tracking echocardiography nowadays. Cardiac computed tomography angiogram (CCTA) has revolutionised the management of coronary artery disease as it allows clinicians to visualise the coronary arteries without performing an invasive angiogram. Because of the high negative predictive value, CCTA plays an important reassuring role in acute chest pain management. The greatest strength of cardiovascular magnetic resonance (CMR) is that it provides information in tissue characterization. It is the modality of choice in assessing myocardial viability and myocardial infiltration such as haemochromatosis or amyloidosis. Each of these modalities has its own strengths and limitations. In fact, they are complementing each other in different clinical settings. Cardiac imaging will continue to advance and, not long from now, we will not need invasive procedures to make an accurate cardiac diagnosis.

Improving delivery of segments with small MU in step-and-shoot IMRT.

The purpose of this study is to describe four new delivery schemes for intensity-modulated radiation therapy (IMRT). In the first two schemes the order in which segments are delivered is varied from fraction to fraction. The last two delivery schemes employ fixed order of segments. The obtained results indicate that the suggested approaches can significantly reduce the so-called "overshoot" and "undershoot" phenomena and the associated discrepancies between planned and delivered monitor units.

Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin.

AIM: To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C. METHODS: 19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals. RESULTS: 8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes. CONCLUSION: Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

Hypomethylation of chromosome 1 heterochromatin DNA correlates with q-arm copy gain in human hepatocellular carcinoma.

Using comparative genomic hybridization (CGH) analysis, we, and others, have shown that there is a high and consistent incidence of chromosome 1q copy gain in human hepatocellular carcinoma (HCC). Chromosome 1 rearrangements, that involved peri-centromeric breakpoints, have also been frequently reported in karyotypic studies of HCC. Satellite DNA hypomethylation has been postulated as the mechanism underlying the induction of chromosome 1 peri-centromeric instability in many human cancers and in individuals with the rare recessive disorder ICF (immunodeficiency, centromeric heterochromatin instability, facial anomalies). In this study, we have investigated the role of DNA hypomethylation in 1q copy gain in HCC by examining the methylation status of chromosome 1 heterochromatin DNA (band 1q12). Thirty-six histologically confirmed samples of HCC were studied (24 paired tumor and adjacent nontumorous liver tissues, and 12 tumor only). Hypomethylation of satellite 2 (Sat2) DNA in 1q12 was analyzed by Southern blotting using methyl-sensitive enzyme digestion. In parallel, all cases were analyzed by CGH. A strong correlation between hypomethylated Sat2 sequences and 1q copy gain with a 1q12 breakpoint was found (P < 0.001). We postulate that such hypomethylation alters the interaction between the CpG-rich satellite DNA and chromatin proteins, resulting in heterochromatin decondensation, breakage and aberrant 1q formation. Spectral karyotyping further supported the presence of fragile 1q12 in HCC. Of particular interest was the finding of Sat2 DNA hypomethylation in 5 of 24 adjacent nontumorous liver tissues examined. These tissues showed no evidence of malignancy on histological examination nor did they display any CGH abnormalities. Our findings suggest a role for Sat2 demethylation in the early stages of the stepwise progression of liver carcinogenesis.

An assessment of intraocular pressure rise in patients with gas-filled eyes during simulated air flight.

PURPOSE: To investigate the safety of aircraft flight for patients with small volumes of residual postoperative intraocular gas. DESIGN: Nonrandomized comparative trial. PARTICIPANTS: Seventeen eyes (nine gas filled and eight control eyes) of nine patients and one eye of one control subject were tested. METHODS: Patients with postoperative intraocular gas and the control subject were tested in the controlled environment of a hypobaric chamber to simulate the cabin depressurization associated with a typical commercial aircraft flight. Before, during, and after a simulated flight, the intraocular pressure (IOP) in the gas-containing and contralateral eyes was tested using the Perkins (Edinburgh, UK) and Tono-Pen XL (Jacksonville, FL) tonometers. MAIN OUTCOME MEASURES: The absolute and percentage change in IOP with varied cabin pressurization. RESULTS: Of the nine patients with intraocular gas, seven had 10% to 15% gas volume and two had 20% gas volume. In the 10% to 15% gas volume group, the IOP rose by an average of 109% from baseline during ascent to an average cabin altitude of 7429 feet above sea level. The IOP dropped to an average of 30% above baseline IOP during the cruise phase and further decreased to an average of 38% below baseline IOP on return to baseline altitude. In the 20% gas volume group, the IOP rose by an average of 84% from baseline during ascent to an average cabin altitude of 3400 feet above sea level. The IOP dropped to an average of 42% below baseline IOP on return to baseline altitude. The IOP in the contralateral control eyes did not vary with altitude changes. No patient experienced pain or visual loss during the experiments. CONCLUSIONS: Our results demonstrate that IOP may rise significantly in gas-filled eyes during simulated air flight, supporting the current conservative recommendation against air travel for most patients with intraocular gas bubbles. Further testing is warranted to develop a more objective measure of intraocular gas volume estimation and to define better the tolerability of aircraft flight for patients with intraocular gas.

High-frequency ultrasonography findings in persistent hyperplastic primary vitreous.

PURPOSE: To identify anatomic correlates in eyes with persistent hyperplastic primary vitreous (PHPV) by using high-frequency ultrasonography. METHOD: Three main groups of patients were studied by means of high-frequency ultrasonography over a 19-month period. Group I included 9 eyes of 9 patients with newly diagnosed unilateral PHPV. Group II included 4 eyes of 4 patients with unilateral PHPV that had been previously surgically treated. Group III included 22 eyes and was a control group of patients without PHPV. This group consisted of the 5 contralateral normal eyes of 5 patients with unilateral PHPV in the fellow eye, both eyes of one patient with uncomplicated unilateral cataracts, the affected eye of one patient with unilateral uncomplicated cataract, the affected eye of one patient with isolated retinal coloboma, and 13 normal eyes of 7 young adults. Group I and II patients also had B-scan ultrasonography performed and had any intraoperative findings noted. RESULTS: Characteristic features of PHPV, such as centrally dragged ciliary processes and swollen anteriorly displaced lens, were observed only in those eyes with PHPV. A new echographic finding of a double linear echo was observed in the region of the pars plana or plicata only in eyes with PHPV. This finding was confirmed intraoperatively to be consistent with a thickened adherent anterior hyaloid face and not to be an anteriorly inserted peripheral retina. CONCLUSION: High-frequency ultrasound can be reliably used to distinguish characteristic features of PHPV. To our knowledge this is the first such description of the use of high-frequency ultrasonography in PHPV eyes. Furthermore, the presence of a thickened adherent anterior hyaloid face may help explain the well-recognized complications of peripheral retinal tears and retinal detachments during and after surgical intervention.

Interaction of DNA polymerase I (Klenow fragment) with DNA substrates containing extrahelical bases: implications for proofreading of frameshift errors during DNA synthesis.

Frameshift mutagenesis occurs through the misalignment of primer and template strands during DNA synthesis and involves DNA intermediates that contain one or more extrahelical bases in either strand of the DNA substrate. To investigate whether these DNA structures are recognized by the proofreading apparatus of DNA polymerases, time-resolved fluorescence spectroscopy was used to examine the interaction between the Klenow fragment of DNA polymerase I and synthetic DNA primer-templates containing extrahelical bases at defined positions within the template strand. A dansyl probe attached to the DNA was used to measure the fractional occupancies of the polymerase and 3'-5' exonuclease sites of the enzyme for DNA substrates with and without the extrahelical bases. The presence of an extrahelical base at the first position from the primer 3' terminus increased the level of partitioning of the DNA substrates into the 3'-5' exonuclease site by 3-7-fold, relative to the perfectly base-paired primer-template, depending on the identity of the extrahelical base. The ability of different extrahelical bases to promote partitioning of DNA into the 3'-5' exonuclease site decreased in the following order: G > A approximately T > C. The results of partitioning measurements for DNA substrates containing a bulged adenine base at different positions within the template showed that an extrahelical base is recognized up to five bases from the primer 3' terminus. The largest effects were observed for the extrahelical base at the third or fourth positions from the primer terminus, which increased the level of partitioning of DNA into the 3'-5' exonuclease site by 8- and 18-fold, respectively, relative to that of the perfectly base-paired substrate. Steady-state fluorescence measurements of analogous primer-templates containing 2-aminopurine (AP) at the primer 3' terminus indicate that extrahelical bases increase the degree of terminus unwinding, especially when close to the terminus. In addition, steady-state kinetic measurements of removal of AP from the primer-templates indicate that the exonucleolytic cleavage activity of Klenow fragment is correlated with the increased level of partitioning of bulged DNA substrates to the 3'-5' exonuclease site relative to that of properly base-paired DNA. The results of this study indicate that misalignment of primer and template strands to generate an extrahelical base strongly promotes transfer of a DNA substrate to the 3'-5' exonuclease site, suggesting that the premutational intermediates in frameshift mutagenesis are subject to proofreading by the polymerase.

Identification and immunohistochemical localization of protein precursors to human axillary odors in apocrine glands and secretions.

OBJECTIVES: To determine the cellular localization in male and female axillary tissue for apocrine secretion odor-binding proteins 1 (ASOB1) and 2 (ASOB2) and the electrophoretic pattern of female apocrine proteins and to begin characterization of the ASOB1 protein. DESIGN: Immunohistochemical techniques were used with biopsy samples from axillary tissue of male and female subjects. Immunological techniques and microsequencing were used to characterize several of the proteins in male and female apocrine secretions. SETTING: A university medical center. PARTICIPANTS: Healthy male and female volunteers who donated apocrine secretions and/or axillary tissue. RESULTS: Specific immunoreactivity was localized only to the apocrine glands in both sexes. Furthermore, only preabsorption with a mixed apocrine secretion sample eliminated all immunoreactivity. The electrophoretic pattern of proteins in female apocrine secretions is similar to that in male secretions. Western blotting of the separated proteins from female samples using serum samples containing antibodies to ASOB1 and ASOB2 yielded identical results to those found with separated proteins from male samples. Partial sequence data obtained from the N-terminus of ASOB1 suggested that it shares homology with the alpha-chain of apolipoprotein J (Apo J). Apocrine secretion odor-binding protein 1 is not immunologically similar to ApoJ, but 2 other apocrine secretion proteins are. CONCLUSIONS: Male and female subjects appear to have the same glycoprotein carriers for (E)-3-methyl-2-hexenoic acid localized to the apocrine glands. The N-terminal sequence for ASOB1 may be homologous to Apo J, but it is not immunologically similar to it. However, 2 other proteins in the apocrine secretion appear to be the monomer and dimer forms of Apo J.