Acute leukemia and lymphoma in pregnancy, a retrospective study from a tertiary center in Malaysia.

INTRODUCTION: Most evidence about the management of cancer and hematological malignancy in pregnancy are derived from retrospective observational studies with a small sample size. Availability of sufficiently large data has enabled evidence-based decision-making in this clinical dilemma. MATERIALS AND METHODS: Retrospective study looking into patients diagnosed with acute leukemia or lymphoma in pregnancy from 1st January 2014 to 1st January 2020 in Ampang General Hospital including newly or previously diagnosed and relapsed disease RESULTS: 37 cases of acute leukemia or lymphoma in pregnancy occurred in 34 patients. Majority of acute leukemia or lymphoma in pregnancy diagnosed in 1st trimester or in the setting of previously established or relapsed disease was therapeutically terminated. Thirteen pregnancies treated with antenatal chemotherapy resulted in livebirths except one stillbirth. More adverse obstetric outcomes are observed in pregnancies that did not receive antenatal chemotherapy, but association did not reach statistical significance. There was no significant difference in fetal outcome between cohort with and without antenatal chemotherapy. No treatment related mortality was observed in pregnancies with antenatal chemotherapy. Overall survival for newly diagnosed acute leukemia in pregnancy is significantly better with antenatal chemotherapy versus no antenatal chemotherapy. CONCLUSION: Treatment with chemotherapy in 2nd trimester of pregnancy onwards appears to have tolerable risks with favorable obstetric and fetal outcome. Deferment of treatment for acute leukemia in pregnancy to after delivery may cause increased risk of maternal and fetal adverse outcome.

A case report of transverse myelitis in a patient with human immunodeficiency virus.

Acute or subacute transverse myelitis is a rare disease caused by inflammation of the spinal cord. The extensive differential diagnosis of this disease require physician to timely decide the necessary investigations and plan for effective treatment. We report a case of anomalous multifactorial transverse myelitis in a patient with human immunodeficiency virus (HIV) who responded well with multimodal therapy. The patient was given immunosuppressive agent and plasma exchange for the demyelinating disease as well as antibiotics for neurosyphilis, antiviral for cytomegalovirus (CMV) neurologic disease, and highly active antiretroviral therapy (HAART). Three months after his first presentation, patient showed full neurology recovery and suppressed HIV viral load.

Combined nicotine patch with gum versus nicotine patch alone in smoking cessation in Hong Kong primary care clinics: a randomised controlled trial.

BACKGROUND: The prevalence of daily cigarette smoking has dropped to 10% in Hong Kong (HK) in 2017, however, smoking still kills 5700 persons per year. Studies suggest that abstinence rates are higher with combined NRT than single NRT, although local data on safety and benefits of combined NRT are lacking. The aim of this study is to compare the effectiveness of combined NRT with single NRT among HK Chinese. METHODS: This is a one-year, two-arm, parallel randomised trial. Five hundred sixty smokers, who smoked ≥10 cigarettes/day for ≥1 year, were randomized to combined and single NRT. Combined NRT group received counseling and nicotine patch & gum. Single NRT group received counselling and nicotine patch. Primary outcome was abstinence rate measured as self-reported 7-day point prevalence with CO validated at 52 weeks. Secondary outcomes included smoking abstinence rates at 4, 12, & 26 weeks. Crude odds ratio and p-value were reported from logistic regression without adjustment; for trend analysis, adjusted odds ratio (AOR) and p-value were reported from Generalized Estimating Equation (GEE) (controlling for time). All AORs were adjusted for age, sex, baseline CO and clusters. RESULTS: Abstinence rates at 4, 12, 26 and 52 weeks were all higher in the combined NRT group (35.8, 21.9, 16.8, 20.1%) compared with the single NRT group (28, 16.8, 11.2, 14.3%). At 4 weeks, combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.00 to 2.05) than the single NRT group. From GEE analysis, combined NRT group had a significantly higher abstinence rate (23.6%) than the single NRT group (17.6%) across repeated measures at all-time points. Combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.15 to 1.77). No significant difference in the side effect profile was detected between groups. CONCLUSIONS: Smokers given 8 weeks of combined NRT were more likely to quit smoking at 4, 12, 26 and 52 weeks compared with single NRT. Combined NRT was as well tolerated as single NRT and it should be further promoted in our community. TRIAL REGISTRATION: NCT03836560 from ClinicalTrial.gov , 9 Feb 2019.

White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism.

BACKGROUND: Individuals with autism have impairments in 3 domains: communication, social interaction and repetitive behaviours. Our previous work suggested early structural and connectivity abnormalities in prefrontal-striato-temporal-cerebellar networks but it is not clear how these are linked to diagnostic indices. METHOD: Children with autism (IQ > 70) aged 6 to 14 years old and matched typically developing controls were studied using diffusion tensor imaging. Voxel-based methods were used to compare fractional anisotrophy (FA) measures in each group and to correlate FA measures in the autism group with the diagnostic phenotype described by the Autism Diagnostic Interview - Revised (ADI-R) algorithm for ICD-10. RESULTS: After controlling for the effects of age and white matter volume, we found that FA in the autism group was significantly lower than controls in bilateral prefrontal and temporal regions, especially in the right ventral temporal lobe adjacent to the fusiform gyrus. FA was greater in autism in the right inferior frontal gyrus and left occipital lobe. We observed a tight correlation between lower FA and higher ADI-R diagnostic algorithm scores across white matter tracts extending from these focal regions of group difference. Communication and social reciprocity impairments correlated with lower FA throughout fronto-striato-temporal pathways. Repetitive behaviours correlated with white matter indices in more posterior brain pathways, including splenium of the corpus callosum and cerebellum. CONCLUSIONS: Our data support the position that diagnostic symptoms of autism are associated with a core disruption of white matter development.

Psychometric properties of the Chinese (Cantonese) Tinnitus Handicap Inventory.

OBJECTIVES: To establish the reliability and validity of the Chinese (Cantonese) version of the Tinnitus Handicap Inventory to measure the self-perceived handicapping effect and severity of the condition in patients with chronic tinnitus. DESIGN: Cross-sectional psychometric validation study. SETTING: Audiology clinics in a hospital setting. PARTICIPANTS: Subjects were 114 adult Chinese who attended the audiology clinics with a complaint of tinnitus. MAIN OUTCOME MEASURES: Test-retest and internal consistency reliability; construct validity. RESULTS: The Chinese version of the Tinnitus Handicap Inventory and its subscales showed good internal consistency reliabilities (alpha = 0.72-0.94) that are comparable to those of the original version. High correlations were observed between the Tinnitus Handicap Inventory and psychological distress, tinnitus-related problem ratings and severity ratings. Factor analysis showed that the Chinese version of the Tinnitus Handicap Inventory has a unifactorial structure. A high degree of test-retest reliability was observed (intraclass correlation coefficient = 0.88). CONCLUSIONS: The results suggest that the Chinese (Cantonese) version of the Tinnitus Handicap Inventory is a reliable and valid measure of general tinnitus-related distress that can be used in clinical settings to quantify the impact of tinnitus on daily life.

The cytotoxic and genotoxic potential of 5-aminolevulinic acid on lymphocytes: a comet assay study.

BACKGROUND: 5-aminolevulinic acid (ALA) and its hexylester (ALA-H) are the drugs currently used in photodynamic therapy (PDT). The side effect, especially the long-term side effect of these drugs is a problem of concern in this field, which has not been clearly understood yet. PURPOSE: The normal lymphocytes and nasopharyngeal carcinoma (NPC) cells were used as the cell models to evaluate the side effects of ALA or ALA-H in the absence of light or under sub-lethal doses of light. METHODS: The cytotoxic and DNA-damaging effects of ALA or ALA-H on lymphocytes and NPC cells were studied by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the alkaline comet assay. ALA at 0.75 mM concentration and ALA-H at 10-microM concentrations were selected in the studies. This is because under these concentrations, ALA- or ALA-H-mediated PDT can destroy most NPC cells in vitro. The intracellular distributions of the protoporphyrin IX (PpIX), induced by the ALA or ALA-H, were measured by the confocal laser scanning microscope to provide more information for understanding the DNA damage. RESULTS: The incubation of 0.75 mM ALA or 10 microM ALA-H alone (without light) did not cause DNA damage as well as the considerable cytotoxic effect on NPC cells. However, after ALA (0.75 mM) incubation and without light irradiation, the serious cytotoxicity and remarkable DNA damage were found in lymphocytes. When the lymphocytes were incubated with ALA-H (10 microM) alone (in the absence of light), no DNA damage could be detected and a slight cytotoxic effect was found. Both ALA and ALA-H induced PpIX in the lymphocytes. The fluorescence images of PpIX intracellular localization demonstrated that the PpIX diffused into the nuclear region in ALA-(0.75 mM)-incubated lymphocytes but not existed in the nucleus of ALA-H(10 microM)- incubated lymphocytes, providing an explanation for the facts that ALA (0.75 mM) induced the DNA damage while ALA-H (10 microM) did not. CONCLUSION: These results suggested that the genotoxic potential of lymphocytes seems high for ALA (0.75 mM) and could be excluded for ALA-H (10 microM).

Correlation of placental microsomal activities with protein detected by antibodies to rabbit cytochrome P-450 isozyme 6 in preparations from humans exposed to polychlorinated biphenyls, quaterphenyls, and dibenzofurans.

Placental tissues were obtained from Chinese women in Taiwan who had been exposed to contaminated rice oils containing polychlorinated biphenyls and their thermal degradative products. Exposure via the diet occurred 4-5 years prior to pregnancy. Placental microsomal fractions from eight of the nine exposed subjects studied showed marked elevation of benzo(a)pyrene hydroxylation and 7-ethoxyresorufin O-deethylation activities related to control subjects. Placental microsomes from exposed subjects were found to contain a protein that cross-reacted with antibodies raised to rabbit cytochrome P-450 isozyme 6, an isozyme induced by polycyclic aromatic hydrocarbons. This protein was not observed with microsomal samples from control subjects. A significant correlation was found between the relative amounts of the immunoreactive protein and benzo(a)-pyrene hydroxylation and 7-ethoxyresorufin O-deethylation activities. The 7-ethoxyresorufin O-deethylation activities were inhibited by alpha-naphthoflavone, a compound known to inhibit activities of rabbit cytochrome P-450, isozyme 6.

Biosynthesis of dolichol and cholesterol during embryonic development of the chicken.

The polyisoprenol dolichol, in its phosphorylated form, serves as the lipid intermediate in N-linked glycoprotein synthesis, and shares the portion of its biosynthetic pathway with cholesterol. The synthesis of dolichol and cholesterol was followed over the course of development by incubating chicken embryos with [3H] acetate for 24-h intervals. Dolichol and cholesterol were isolated from the non-saponifiable lipids and identified by gel filtration and thin-layer chromatography. It was found that the rate of acetate incorporation into these two compounds per g of embryo decreased from days 8 to 14 of development. In the whole embryo, over the course of development the ratio of the rates of acetate incorporation into dolichol to that into cholesterol decreased markedly. These results suggest that mechanisms exist for controlling the differential rates of dolichol and cholesterol synthesis during development. When labeled organs from day 10 embryos were analysed, it was found that the ratio of the rates of synthesis of dolichol to cholesterol in brain was about 14-fold lower than that in liver and heart. Similar values for the rates of synthesis of these two compounds were obtained when isolated organs were labeled in vitro. These data suggest that these three organs are capable of synthesizing dolichol and cholesterol de novo, and that each organ independently regulates the rates of synthesis of dolichol and cholesterol.

Changes in thyroid function in nonthyroid illness.

Nonthyroid illness can cause changes in thyroid function that have been described as low triiodothyronine (T(3)) and low thyroxine (T(4)) states. Reduced peripheral conversion of T4 to T(3) explains the low serum T(3) concentration. The explanation for the low serum T(4) level is multifactorial; whether free-thyroxine (FT(4)) level is normal or reduced remains controversial. Cytokines such as tumor necrosis factor alpha, which are produced by the immune system during severe illness, may inhibit thyroid function directly and be responsible for the changes in pituitary-thyroid function.

Improved method for the isolation and cultivation of human scalp dermal papilla cells.

We present an improved method for the isolation and cultivation of human scalp anagen hair follicle dermal papilla cells. Following treatment of the isolated dermal papilla with collagenase, incubation in Chang's medium mediates accelerated growth of the papilla cells when compared with other media such as DMEM, M199, and EMEM. Upon reaching confluency, the cells cultured in this fashion exhibit a multilayer-forming property that is dependent on normal proteoglycan synthesis. The papilla cells maintain this morphologic behavior for as long as 7 weeks in culture, or after being subcultured six times. During this time, the cells continue to synthesize extracellular matrix components associated with the human anagen follicle in situ. These include chondroitin sulfate, laminin, and type IV collagen. Type III collagen and keratan sulfate are poorly expressed by the papilla both in situ and in vitro. Heparan sulfate proteoglycan, a matrix component of the papilla in situ, is poorly expressed in vitro. Earlier reports suggested that the expression of extracellular matrix components is not maintained in culture. We show that the expression of these molecules is not dependent on the secondary culture medium, but continues in DMEM and M199 after primary culture in Chang's medium. Our results suggest that initial exposure of the dermal papilla to Chang's medium either selectively permits the outgrowth of papilla cells having extracellular matrix components similar to those found in situ, or stabilizes the expression of extracellular matrix components among the entire cultured cell population.

Appearance of beta-lactamase activity in animal cells upon liposome-mediated gene transfer.

A restriction fragment, 875 bp, which encodes for a beta-lactamase activity, was isolated from the Escherichia coli plasmid pBR322 DNA and entrapped in liposomes. The incubation of the DNA-liposomes with avian, murine, and human cultured cells results in the uptake of the DNA with the efficiency of around 2000 molecules per cell. Extracts of the recipient cells show a beta-lactamase activity as demonstrated by spectroscopic and microbiological methods. These results indicate the expression of a prokaryotic gene in eukaryotic cells.

Lack of specific inhibition of DNA repair in WI-38 human diploid fibroblasts by sodium saccharin.

The ability of sodium saccharin (NaS) to inhibit the repair of DNA damaged by UV irradiation was examined in cultured WI-38 human diploid fibroblasts. Cesium chloride density gradient ultracentrifugation was used to measure DNA repair and DNA replication. NaS (10-10,000 micrograms/ml) did not specifically inhibit UV light-induced DNA repair. At doses of NaS (1785 and 10,000 micrograms/ml) that caused a 62-67% inhibition of semiconservative DNA replication, there was little or no inhibition of DNA repair synthesis. In cell cultures not exposed to UV irradiation, NaS failed to induce DNA repair. RNA synthesis and protein synthesis were unaffected by NaS at all doses tested. The inhibition of semiconservative DNA replication at higher doses of NaS may be a manifestation of cytotoxicity. In contrast to results with NaS, WI-38 cells were very sensitive to DNA repair inhibition by the well-studied inhibitor quinacrine-HCl. These results do not support mechanisms of saccharin-induced tumorigenesis involving either direct induction of DNA damage or inhibition of the repair of DNA damage caused by other agents.

Quantification of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activity in human placentae: development of a protocol suitable for studying effects of environmental exposures on human metabolism.

Several issues regarding measurement of placental AHH and 7ECD activity were studied, and standardized procedures that appeared more suitable than previous assay procedures for measurement of MFO induction in epidemiological studies were adopted. In the AHH assay, deletion of the rat-liver supernatant eliminated a possible extraneous contribution to measurement of low levels of AHH activity and did not substantially affect measurement of higher levels of activity. Increasing the protein concentration of placentae homogenate from 2 to 6 mg, and the length of the incubation time from 20 to 60 min, allowed for accumulation of more BaP products, potentially maximizing the detection of low levels of AHH activity. Use of tissue homogenates made the procedure more convenient and did not appear to interfere with interindividual comparisons of activity. Assay of homogenates of fresh and frozen tissue from the same placenta gave similar results, so that frozen tissue was adopted for convenience and replicability. Although a potential problem for specimens with high AHH activity, degradation of product(s) was modest in AHH assays of human placenta. The efficiency of extraction of fluorescent products declined with increasing protein concentrations in the reaction mixture of AHH assays, but it was stable for a range of product concentrations, and could be controlled by the use of a constant amount of protein per assay. Recovery of product for the 7ECD assay was more complete and was not affected by protein concentration. Additionally, the 7ECD activity was easily detected in every placenta, regardless of smoking exposure. However, in this study the AHH assay appeared to be better at discriminating between non-smokers and smokers. These observations, and the potential differences in the spectrum of agents causing induction of mixed-function oxidases, suggest that both assays are potentially useful measures of human MFO induction in clinical or epidemiological studies.

Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.

Our studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed "Yu-Cheng" in Chinese. Based on data from experimental animal models, we examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. We also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. Our results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6 [derived from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced rabbit lung]. No other cytochrome P-450 isozyme was detected in placental preparations, and the form 6 homolog was found only in placentae from exposed women. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties (Kd and Bmax). The EGF receptor autophosphorylation effect correlated well with the decrease in birthweight observed in offspring of exposed women, suggesting that this biochemical event might provide a good marker of effect for the toxic halogenated aromatics.

Inversion 14q in acute lymphoblastic leukemia of B-lineage.

Many types of leukemia are associated with specific chromosomal rearrangements. Inversion 14(q11q32) has been reported to be specifically associated with post-thymic T-cell malignancies, including T-chronic lymphocytic leukemia. T-prolymphocytic leukemia, and adult T-cell leukemia/lymphoma. We have previously reported its occurrence in T-cell acute lymphoblastic leukemia. Recently, we encountered a case of acute lymphoblastic leukemia with inv(14)(q11q32), which surprisingly showed a B-cell immunophenotype (CD10+CD19+HLA-DR+Ig mu-).

Concomitant partial tetrasomy 3q and trisomy 18 in Waldenström macroglobulinemia.

We report a 54-year-old female patient with Waldenström macroglobulinemia who shows concomitant partial tetrasomy 3q in the form of an additional isochromosome 3q, and trisomy 18. To our knowledge, isochromosome 3q has not been reported in chronic lymphoproliferative disorders. A review of the literature on karyotypic aberrations in Waldenström macroglobulinemia suggests that additional copies of the long arm of chromosome 3 and chromosome 18 may play a possible role in the pathogenesis of a subset of this disorder.

Stimulation of human scalp papilla cells by epithelial cells.

Evidence for the growth stimulatory properties of human keratinocyte-derived conditioned medium on human scalp dermal papilla cells and a mouse fibroblast cell line (Balb/c 3T3) is presented. There was no mitogenic effect on human keratinocytes. This conditioned medium induced a 2-5-fold increase in mitogenic activity in papilla cells relative to sham-conditioned medium as measured by 3H-thymidine incorporation. The papilla cell growth-stimulating activity of the conditioned medium was sensitive to heat, and from size exclusion the molecular weight was greater than 3000 Da.

Stereoselective metabolism of benzo[a]pyrene and 7-methylbenzo[a]pyrene by liver microsomes from sprague-Dawley rats pretreated with polychlorinated biphenyls.

The dihydrodiols formed from the metabolism of benzo[a]pyrene (BaP) and 7-methylbenzo[a]pyrene (7-MBaP) by liver microsomes from male Sprague-Dawley rats treated with polychlorinated biphenyls (PCBs, Aroclor 1254) have been examined by circular dichroism (CD) spectropolarimetry. Comparisons with optically pure enantiomers obtained via high performance liquid chromatography (HPLC) resolution of diastereomeric di-(-)-menthoxyacetates indicated that the trans-4,5-, 7,8- and 9,10-dihydrodiols formed from BaP metabolism are predominantly R,R-enantiomers with optical purities greater than 98%. The major enantiomers of the metabolically formed 7-MBaP-trans-4,5- and 9,10-dihydrodiols and 7-hydroxymethyl-BaP-trans-9,10-dihydrodiol have Cotton effects very similar to those of BaP-4R,5R- and 9R,10R-dihydrodiols, respectively. These 7-MBaP-trans-4,5- and 9,10-dihydrodiol metabolites therefore contain predominantly the R,R-enantiomers. The optical purity of metabolically formed 7-MBaP-trans-4,5-dihydrodiol was determined to be 30.8% enriched in (-)-enantiomer. The optical purity of the 9,10-dihydrodiol was not determined due to the lack of synthetic standards. The major trans-7,8-dihydrodiol enantiomer formed from 7-MBaP metabolism is a (+)-enantiomer (optical purity 60.4%) which has Cotton effects opposite in sign to that of the (-)-7R,8R-dihydrodiol formed from BaP metabolism. The results indicate that a methyl substituent on a polycyclic aromatic hydrocarbon may alter the stereoselective properties of the microsomal drug-metabolizing enzyme systems toward the substrate molecule.