Expectations and outcomes of varying treatment strategies for CML presenting during pregnancy.

Diagnosing chronic myeloid leukaemia (CML) during pregnancy is rare. Tyrosine kinase inhibitors (TKIs) have traditionally been contraindicated owing to their teratogenicity. Management decisions should consider the risks to mother and foetus of uncontrolled disease and teratogenic medications. Further cases are required to build upon the paucity of current literature. We report 22 cases of CML diagnosed during pregnancy from 2002 to date. Twenty-one pregnancies resulted in healthy babies and one patient miscarried. Some patients remained untreated throughout pregnancy but the majority received one or both of interferon-α and leucapheresis. One patient was started on imatinib at Week 26, and one on hydroxycarbamide in the third trimester. We report haematological parameters during pregnancy to provide clinicians with realistic expectations of management. There were no fetal abnormalities related to treatment during pregnancy. Seventeen patients achieved at least major molecular response on first-line TKI. A diagnosis of CML during pregnancy can be managed without significant consequences for mother or child. Leucapheresis and interferon-α are generally safe throughout pregnancy. Despite having been avoided previously, there is growing evidence that certain TKIs may be used in particular circumstances during the later stages of pregnancy. Future work should aim to further elucidate this safety profile.

Nanoparticles as a Novel Tool to Inhibit Inflammatory Cytokines in Human Lymphocytes and Macrophages of Coronary Artery Disease.

TNFα and NF-kB contribute in activation of pro-inflammatory signaling pathways and complications of coronary artery diseases (CAD). Current study highlights novel properties of Au (15 ± 2 nm), ZnO (77 ± 45 nm) and MgO (11 ± 4 nm) nanoparticles (NPs) as possible anti-inflammatory agents with greater efficacy and lower toxicity. Decrease in TNFα and NF-kB levels in Single Vessel Disease (SVD), Double Vessel Disease (DVD) and Triple-Vessel coronary artery disease (TVD) macrophage and lymphocyte cultures at varying concentrations of NPs has been studied to find an effective therapeutic concentration (ETC). Au and MgO NPs exhibits 5 µg/ml ETC compared to 1 µg/ml ZnO in all three CAD categories with negligible toxicity. ZnO remains most statistically significant (p < 0.001) in SVD and TVD cultures whereas MgO shows efficacy in DVD and TVD cultures with more than 50% reduction in TNFα and NF-kB levels at their respective ETCs. Au NPs exhibit prominent effect in DVD cultures. The mRNA expression results support the down-regulation of TNFα and NF-kB after NPs exposure in respective cultures. Findings of this prospective observational cohort study suggest use of NPs as an alternate anti-inflammatory agent in coronary artery and other diseases.

Knowledge, attitudes, and perceptions related to telemedicine among young doctors and nursing staff at the King Abdul-Aziz University Hospital Jeddah, KSA.

OBJECTIVE: To investigate the knowledge, perceptions, and attitude of young doctors and nurses at Kind Abdulaziz University Hospital (KAUH) Jeddah, KSA, regarding the effectiveness of telemedicine in dealing with the patients for either follow-up or continuous monitoring of chronic diseases. MATERIAL AND METHODS: This prospective cross-sectional study was carried out on the young doctors and nursing staff at KAUH. An online questionnaire addressing all the required fields, i.e., background essential demography, perceptions, acceptance, and knowledge regarding telemedicine's utility, was sent to the targeted population of health care workers. Completed responses were analyzed statistically as per study objectives. RESULTS: The response rate in our study was 85%. A total of 335 participants responded to our questionnaire. One hundred seventy-one (51.1%) were doctors, whereas one hundred sixty-four (48.9%) were the nursing staff. Among doctors, 50 (29.4%) were recent graduates, whereas, in the nursing side, 77 (46.7%) were the senior nursing students. The knowledge and attitude of the young nursing staff were relatively better than the senior staff taking part in the study and the trends were found statistically significant. CONCLUSION: Our study participants, being young, were enthusiastic, had good knowledge regarding the advantages and limitations of telemedicine in managing the selected groups of patients. Their perception and attitude were quite positive. This is an encouraging trend in the promotion of telemedicine as an established way of managing patients with special requirements in an effective way. The ongoing COVID-19 pandemic has highlighted the importance of telemedicine in emergencies to protect both patients and health care workers by reducing chronic patients' avoidable hospital visits.

Montelukast Reduces the Risk of Dengue Shock Syndrome in Dengue Patients.

A significant percentage of dengue patients develop Dengue Shock Syndrome (DSS) which is characterized by increased vascular permeability, circulatory failure and often death. Montelukast, a cysteinyl leukotriene receptor antagonist regulates vascular permeability and we hypothesized that it may be effective in protecting against DSS. An open label, parallel, randomized controlled trial (RCT) was thus carried out at Mayo Hospital, Department of Medicine, Lahore. A total of 200 patients of dengue fever were recruited and randomized into two groups. The group A was treated with Montelukast 10 mg once daily for 5 days along with general supportive treatment. Group B received the standard supportive treatment and served as the control group. The frequency of DSS was compared in the two groups by Chi square test. A binary logistic regression analysis was conducted to assess the effects of montelukast treatment on onset of DSS after adjusting for gender, age, white cell count, platelet count, haematocrit, serum alanine transaminase (ALT) and aspartate transaminase (AST). Relative risk (RR), absolute risk reduction (ARR), relative risk reduction (RRR) and numbers needed to treat (NNT) were calculated. Significance level was set at p0.001, Odds ratio=5.01, 95% CI=2.17-11.60) even after adjusting for confounders. Montelukast reduced the absolute risk (ARR=22%) and the relative risk (RRR=71%) of DSS in dengue fever. Numbers needed to treat were 4.55. We thus conclude that treatment with oral montelukast may protect patients of dengue fever from DSS and greatly reduce mortality.

Montelukast Reduces the Risk of Dengue Shock Syndrome in Dengue Patients

@#A significant percentage of dengue patients develop Dengue Shock Syndrome (DSS) which is characterized by increased vascular permeability, circulatory failure and often death. Montelukast, a cysteinyl leukotriene receptor antagonist regulates vascular permeability and we hypothesized that it may be effective in protecting against DSS. An open label, parallel, randomized controlled trial (RCT) was thus carried out at Mayo Hospital, Department of Medicine, Lahore. A total of 200 patients of dengue fever were recruited and randomized into two groups. The group A was treated with Montelukast 10 mg once daily for 5 days along with general supportive treatment. Group B received the standard supportive treatment and served as the control group. The frequency of DSS was compared in the two groups by Chi square test. A binary logistic regression analysis was conducted to assess the effects of montelukast treatment on onset of DSS after adjusting for gender, age, white cell count, platelet count, haematocrit, serum alanine transaminase (ALT) and aspartate transaminase (AST). Relative risk (RR), absolute risk reduction (ARR), relative risk reduction (RRR) and numbers needed to treat (NNT) were calculated. Significance level was set at p<0.05. We found that only 9% of the patients in treatment group developed DSS compared to 31% patients in group B (p<0.001). The protective effect of montelukast treatment persisted (p>0.001, Odds ratio=5.01, 95% CI=2.17-11.60) even after adjusting for confounders. Montelukast reduced the absolute risk (ARR=22%) and the relative risk (RRR=71%) of DSS in dengue fever. Numbers needed to treat were 4.55. We thus conclude that treatment with oral montelukast may protect patients of dengue fever from DSS and greatly reduce mortality.

A Follow-Up Study of the Prevalence of Valvular Heart Abnormalities in Hyperprolactinemic Patients Treated With Cabergoline.

CONTEXT: Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate. OBJECTIVE: Our objective was to provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used. DESIGN: Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalized estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group. SETTING: Thirteen centers of secondary/tertiary endocrine care across the United Kingdom were included. RESULTS: There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97 mg (20-377) and 232 mg (91-551), respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.

Superparamagnetic bimetallic iron-palladium nanoalloy: synthesis and characterization.

Iron-palladium nanoalloy in the particle size range of 15-30 nm is synthesized by the relatively low temperature thermal decomposition of coprecipitated [Fe(Bipy)(3)]Cl(2) and [Pd(Bipy)(3)]Cl(2) in an inert ambient of dry argon gas. The silvery black Fe-Pd alloy nanoparticles are air-stable and have been characterized by EDX-RF, XRD, AFM, TEM, magnetometry, (57)Fe Mössbauer and impedance spectroscopy. This Fe-Pd nanoalloy is in single phase and contains iron sites having up to 11 nearest-neighboring atoms. It is superparamagnetic in nature with high magnetic susceptibility, low coercivity and hyperfine field.

Autografting as a risk factor for persisting iron overload in long-term survivors of acute myeloid leukaemia.

We studied the iron status of 32 evaluable adult acute myeloid leukaemia (AML) survivors who were entered into the UK Medical Research Council acute myeloid leukaemia (AML) 10 and 12 trials at our institution between 1988 and 1998. Patients were required to have been independent of all blood products for at least 3 years. As a group, the median first serum ferritin level was 1323 mug/l (NR 19-300 mug/l) at a median of 1321 days from the last transfusion confirming the presence of significant iron overload persisting for some years after completion of all therapy and blood products. There was a general trend for the serum ferritin level to fall with time, but the fall was less pronounced in men and carriers of the C282Y mutation. Recipients of autologous stem cell transplantation (SCT) had a higher median first serum ferritin level (3245 mug/l) than patients who received chemotherapy alone (1148 mug/l) or allogeneic SCT (1334 mug/l) because of increased use of transfused blood. Nine of the 10 recipients of autologous SCT underwent venesection. No evidence of end organ damage was seen in any patient. Serial monitoring of serum ferritin and assessment of the C282Y status may be useful in all long-term AML survivors, especially autograft recipients.

Isolation of genomic DNA from blood using a novel filter-based DNA purification technology.

A novel DNA purification technology is described that enables the purification of pure dsDNA from blood. When compared to existing DNA purification methods, the Whatman BioScience Purification System (WBPS) offers a fast and convenient way to recover high yields of DNA. WBPS is based on a unique filter system that entraps DNA within a matrix. This allows the process to be performed in a single unidirectional reaction vessel, reducing user interaction and multiple centrifugation steps.

High frequency of positive surveillance for cytomegalovirus (CMV) by PCR in allograft recipients at low risk of CMV.

Cytomegalovirus (CMV) causes significant morbidity and mortality following allogeneic haemopoietic stem cell transplantation. A pre-emptive strategy for ganciclovir therapy is widely used, where treatment is commenced on finding positive evidence of CMV replication. Surveillance by PCR has increased the sensitivity for CMV detection, but it is not known whether this may detect cases with evidence of CMV DNAemia who have a low probability of CMV disease. We reviewed our experience of CMV infection and disease since introducing CMV surveillance by PCR. All 30 allografts received bedside leucodepleted CMV-negative blood products. Seven of 10 CMV-positive recipients of a CMV-positive graft developed CMV DNAemia, with three developing clinical disease requiring ganciclovir treatment. In contrast, of 11 low risk patients (CMV-negative recipients of CMV-negative grafts), six developed evidence of CMV DNAemia although only one had clinical evidence of CMV disease requiring ganciclovir. Transfusion records confirmed that four of these had received exclusively CMV-negative blood products. The aetiology of the CMV DNAemia in these cases is unclear. It is suggested that before commencing ganciclovir therapy, confirmatory CMV antigenaemia testing is carried out on samples which test positive for CMV DNA, unless there is high clinical suspicion of CMV disease.

Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial.

In the context of limited effectiveness of iron supplementation programs, intermittent iron supplementation is currently under debate as a possible alternative strategy that may enhance the effectiveness of operational programs. This field-based trial assessed the outcome of twice weekly iron supplementation compared to daily in Pakistan. A double-blind, randomized, clinical trial was conducted in Northern Pakistan. Anemic pregnant women (n = 191) were assigned to receive daily (200 mg ferrous sulfate) or twice weekly (2 x 200 mg ferrous sulfate) iron supplementation. Hemoglobin was measured at baseline and at 4-wk intervals for up to 12 wk. Serum ferritin was measured at baseline and 8 or 12 wk. Analysis was by intention to treat. The two groups did not differ in age, parity, sociodemographic characteristics, hemoglobin or serum ferritin concentrations at baseline. Women who received iron daily had a greater rise in hemoglobin compared with women who received iron twice weekly (17.8 +/- 1.8 vs. 3.8 +/- 1.2 g/L, P < 0.001). The serum ferritin concentrations increased by 17.7 +/- 3.9 microgram/L (P < 0.001) in the daily supplemented group and did not change in the twice weekly group. Daily iron supplementation remained superior to twice weekly supplementation after controlling initial hemoglobin Z-scores and duration of treatment. The body mass index (BMI) modified the effect of daily versus twice weekly iron supplementation. For every unit increase in BMI, the difference between the two treatment groups was reduced by 0.0014 (final hemoglobin Z-score; P = 0.027). We recommend continuation of daily iron supplementation as opposed to intermittent iron supplementation in pregnant women in developing countries.

Ecstasy-induced very severe aplastic anaemia complicated by invasive pulmonary mucormycosis treated with allogeneic peripheral blood progenitor cell transplant.

Very severe aplastic anaemia (vSAA) is rare. We report a case of Ecstasy-induced very severe aplastic anaemia which did not respond to immunosuppressive therapy, developing invasive pulmonary mucormycosis. The patient underwent an HLA-identical sibling peripheral blood progenitor cell transplant (PBPCT) with rapid neutrophil engraftment. During engraftment he developed life-threatening adult respiratory distress syndrome (ARDS). This case serves to illustrate a novel aetiology of vSAA where the infective complications responded to prompt haematopoietic engraftment.

Transfer of cytokine-inducing bacterial products across hemodialyzer membranes in the presence of plasma or whole blood.

Cytokine production by peripheral blood mononuclear cells (PBMC) is a sensitive indicator of cytokine-inducing substances which may cross from contaminated dialysate into the blood compartment. The objective of this study was to compare the transfer of cytokine-inducing substances from dialysate contaminated with a culture filtrate from Pseudomonas aeruginosa across dialyzers with low (hemophan) or intermediate ultrafiltration coefficients (modified cellulose triacetate, CTA), under conditions where either 10% plasma or whole blood was circulated in the blood compartment. Eight paired experiments of in vitro dialysis were carried out at 37 degrees C using a countercurrent recirculating loop dialysis circuit with either a new CTA or hemophan dialyzer. 10% plasma in standard tissue culture medium was circulated through the blood compartment and bicarbonate dialysate was circulated in the dialysate compartment. The dialysate was challenged sequentially by log-fold dilutions (10(2), 10(3) or 10(4)) of a Ps. aeruginosa culture filtrate. Samples were drawn from the blood compartment 5 and 15 minutes after each challenge and incubated with suspensions of PBMC in the absence or presence of polymyxin B, in order to block endotoxin. After 24 h at 37 degrees C, total interleukin-1 alpha (IL-1 alpha) was measured by RIA. Although the dialysate contained potent cytokine-inducing substances, there was no significant IL-1 alpha production by PBMC incubated with the plasma mixture from the blood compartment in the majority of experiments with both dialyzers and with each of the three dilutions of the bacterial challenge. Eight experiments were also performed with CTA dialzyers using heparinized whole blood in the blood compartment. Samples of whole blood and dialysate were drawn at baseline, after one hour of dialysis with uncontaminated dialysate and 15 minutes and three hours after dialysis with dialysate contaminated with Ps. aeruginosa filtrate. There was no significant IL-1 alpha production by PBMC isolated from the whole blood 1 h after dialysis with uncontaminated dialysate, and 15 min and 2 h after adding the Ps. aeruginosa filtrate to the dialysate side. In contrast, production of IL-1 alpha by PBMC from the same donors incubated with samples from the dialysate were 263 +/- 50, 1074 +/- 306, 2333 +/- 774 and 2602 +/- 702 pg/2.5 x 10(6) PBMC, respectively at the same four time points. These data suggest that although the Ps. aeruginosa culture filtrate present in the dialysate was a potent inducer of IL-1 alpha, neither dialyzer permitted transfer of cytokine inducing substances from the dialysate into the blood compartment.

Cytokine production by human peripheral blood mononuclear cells stimulated by a Pseudomonas aeruginosa culture filtrate: role of plasma and polymyxin B.

The lack of consensus regarding the significance of transmembrane passage of bacterial products across hemodialysis membranes can be related to several methodological differences in the various studies, including the choice of circulating fluid in the blood compartment of the model, nature and concentration of the bacterial products employed to challenge the dialysate compartment and whether cytokine production by PMBC or the limulus amebocyte lysate (LAL) assay was used as the index of transfer and the cytokine used as the read-out. In this study, we examined the production of interleukin-1 alpha (IL-1 alpha), interleukin-1 receptor antagonist (IL-1Ra) and interleukin-8 (IL-8) by peripheral blood mononuclear cells (PBMC) incubated with a Pseudomonas aeruginosa culture filtrate. Further, the effects of 10% autologous human plasma and Polymyxin B sulfate (PmB) on cytokine production by PBMC were also characterized. The results of our study indicate that the Ps. aeruginosa culture filtrate had both PmB suppressible and PmB non-suppressible components and that the addition of 10% human plasma significantly enhanced cytokine production by both PmB suppressible and PmB non-suppressible components. The enhancing effect of plasma was most evident at low concentrations of the filtrate. The inhibitory effect of PmB was most evident in samples cultured in the presence of 10% plasma. There was a direct correlation between the production of IL-1 alpha and IL-1Ra suggesting that both pro-inflammatory cytokines and cytokine-specific inhibitory proteins are concurrently produced. There results have direct relevance to selection of study conditions for in vitro models used to study the transmembrane passage of bacterial products across hemodialysis membranes.

Floral expression of a gene encoding an E2-related ubiquitin-conjugating protein from Arabidopsis thaliana.

An Arabidopsis thaliana gene (UBC6) encoding a homologue to ubiquitin-conjugating enzymes has been isolated which is capable of encoding a protein of 183 amino acids of ca. 21 kDa. Northern analysis indicates that the gene is expressed in flowers, seeds and, to a somewhat lesser extent, in 10-day seedlings but not in mature leaves, callus and pre-flowering plants. This pattern of expression is confirmed using transgenic Arabidopsis plants containing a UBC6 promoter-GUS gene fusion construct. These plants display GUS activity in mature anthers prior to dehiscence, in developing embryos, sepals and the style after pollination.

Aspects of 5-alpha reductase deficiency, a review.

Two forms of 5 alpha-reductase deficiency have been described and two genes have been cloned. In view of the psychoendocrinological complexity of the primary form, the early diagnosis preferably in infancy, is crucial. Rearing up those who are assigned as females to the male gender identity could minimize the risk of gender identity and role disorders when puberty is reached.

Low birth weight: an outcome of poor socio-obstetric interaction.

PIP: Factors contributing to low birth weight (LBW) include poverty, ignorance, and inability to use health care services. Early marriage and low family income lead to poor maternal nutrition reserves, which lead to reduced fetal nutrition. Poor maternal nutrition is also the result of ignorance, short birth intervals, multi-parity, and lack of prenatal care. Both heavy manual labor and smoking contribute to placental ischemia, which, along with reduced fetal nutrition, leads to intrauterine growth retardation (IUGR). In developing countries, IUGR accounts for over 66% of all LBW neonates. About 7 million Indian babies annually are LBW. This study examined the incidence of LBW among 178 mothers delivering single births at the maternity hospital associated with the Department of Community Medicine of SKIMS, Srinagar, Kashmir, India, during 1989-90. 26.40% (47) of the 178 births were LBW (2500 g). Among 71 first-borns, marriage age was found to be statistically significantly associated with LBW. 31.82% of mothers younger than 20 years had LBW babies, compared to only 6.12% of mothers older than 20 years. The impact ratio, which measured excess LBW, was 4.20. Birth interval was statistically significantly associated with LBW outcome. 55.81% of women with a birth interval of less than 18 months had LBW babies, compared to 20.31% of mothers with longer birth intervals. The impact ratio was 1.75. Gravidity was also statistically associated with LBW babies. 34.58% of multigravida mothers had LBW babies, compared to 14.08% of primigravidae. The impact ratio was 1.46. Presence of prenatal care was statistically associated; the impact ratio was 1.42. 31.30% of illiterate women had LBW babies, compared to only 17.46% among literate women, which indicated significant associations with LBW. Other significant factors were manual labor, maternal smoking, and monthly family income. Reduction of LBW by 10-30% nationally by the year 2000 will be difficult and best accomplished by a high risk approach supplemented by health and nutrition education.^ieng

Gonococcal outer-membrane protein PIB: comparative sequence analysis and localization of epitopes which are recognized by type-specific and cross-reacting monoclonal antibodies.

Comparison of the inferred amino acid sequence of outer-membrane protein PIB from gonococcal strain P9 with those from other serovars reveals that sequence variations occur in two discrete regions of the molecule centred on residues 196 (Var1) and 237 (Var2). A series of peptides spanning the amino acid sequence of the protein were synthesized on solid-phase supports and reacted with a panel of monoclonal antibodies (mAbs) which recognize either type-specific or conserved antigenic determinants on PIB. Four type-specific mAbs reacted with overlapping peptides in Var1 between residues 192-198. Analysis of the effect of amino acid substitutions revealed that the mAb specificity is generated by differences in the effect of single amino acid changes on mAb binding, so that antigenic differences between strains are revealed by different patterns of reactivity within a panel of antibodies. The variable epitopes in Var1 recognized by the type-specific mAbs lie in a hydrophilic region of the protein exposed on the gonococcal surface, and are accessible to complement-mediated bactericidal lysis. In contrast, the epitope recognized by mAb SM198 is highly conserved but is not exposed in the native protein and the antibody is non-bactericidal. However, the conserved epitope recognized by mAb SM24 is centred on residues 198-199, close to Var1 , and is exposed for bactericidal killing.