Search

Abstract Many COVID-19 sufferers have a history of cardiovascular illnesses, which makes them more likely to develop severe COVID-19. Such patients were advised by experts to prioritize drug therapies based on their doctor’s commendations to avoid exacerbating their basic illnesses. Therefore, developing an analytical methodology for the concurrent estimation of medications prescribed for co-treating cardiovascular and COVID-19 illnesses is becoming critical in both bioavailability hubs and QC units. Herein, an inventive, rapid, and affordable HPTLC approach was developed, and its conditions were optimized employing the full factorial design approach for the concurrent estimation of aspirin, atorvastatin, atenolol, losartan, remdesivir, and favipiravir as co-administered medications, either with salicylic acid or not. Using the desirability function, the experimental design approach could forecast the best eluent system for optimal resolution results. On HPTLC-silica plates, the above-mentioned medications were separated utilizing an eluent system of ethyl acetate, methylene chloride, methanol, and ammonia (6:4:4:1 by volume), and their spots were detected at 232 nm. The proposed methodology was evaluated following ICH prerequisites and applied successfully to the medications’ dosage forms, human plasma, and buffered dissolution media with superb recovery proportions and no intrusiveness from formulations’ additives or plasma matrices. Five metrics were employed to appraise the suggested technique’s greenness: AGREE, eco-scale, Raynie and Driver, GAPI, and NEMI. The sensitivity, large sample capacity, and short run duration (15 min) of the proposed methodology confirm its appositeness for regular estimation of the above-mentioned medications.

Abstract The development of ion-selective sensors as green and energy-efficient substitutes is a promising trend in today’s analytical techniques. So, three distinct polyvinyl chloride sensors modulated by ionophores of cyclodextrins (α-, β-, and γ-cyclodextrins) were built, and their composition was optimized for rapid in-situ estimation of prucalopride succinate in different matrices. The experimental work was backed up by applying molecular docking, whose results were consistent with the practical findings, offering a creative strategy to reduce the experiment’s costs and duration. According to findings, the α-cyclodextrin sensor outperformed the other proposed sensors in terms of Nernstian slope (56.87 mV/decade), linearity range (1 × 10−6 M – 1 × 10−2 M), and detection limit (7.50 × 10−7 M). For the first time and with minimal sample pre-treatment, prucalopride was quantified with excellent recoveries in dissolution media, human urine, and formula milk samples employing the proposed α-cyclodextrin sensor. The proposed three sensors were validated following IUPAC guidelines. The proposed technique, represented by the proposed three sensors, has the following merits: high sample throughput, quick analysis, high selectivity, wide linearity ranges, and low detection limits, making it apt for routine prucalopride assessment, either in QC centers or in bioavailability units, at the most affordable price. Concerning the statistical assessment, there weren’t palpable disparities in functioning between the suggested technique and the published one. Concerning green assessment, the proposed technique surpassed the published techniques in both GAPI and analytical eco-scale metrics.

Abstract Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood–brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood–brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone regulated the levels and signaling activity of the CD44 receptor, decreasing stemness, invasive properties and proliferation of the CD44-TIC populations in vitro and in a patient-derived xenograft zebrafish model. This work proposes a novel, CPN- based, and surface moiety-driven selective way of targeting of TIC populations in brain cancer.

Abstract Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP366–374 and PA224–233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA224–233-specific than NP366–374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.

There is growing recognition among global health practitioners of the importance of rights-based family planning (FP) programming that addresses inequities. Despite Kenya achieving its national FP target, inequities in access and use of modern FP remain, especially amongst marginalised nomadic and semi-nomadic pastoralist communities. Few studies explore norms affecting FP practices amongst nomadic and semi-nomadic pastoralists and how these can influence social and behaviour change (SBC) interventions. We carried out 48 in-depth interviews and 16 focus group discussions with women and men from pastoralist communities in North Eastern Kenya in November 2018. Data were analysed thematically. Results from focus groups and interviews confirmed themes, while allowing differences between the qualitative approaches to emerge. We found that large family size was a descriptive and injunctive norm in both nomadic and semi-nomadic communities. The desire for around 10 children was sustained by religious beliefs and pastoralist ways of living. Despite a desire for large families, maintaining child spacing was encouraged and practised through breastfeeding and sexual abstinence. Most participants viewed modern FP negatively and as something used by “others”. However, it was acceptable in order to prevent severe negative health outcomes. Future FP research to inform interventions should continue to consider community fertility preferences and the rationale for these, including norms, religion and power dynamics. Targeted qualitative social norms research could inform multi-component SBC interventions in this context.

بعد الانهيارات التي شهدتها الشركات الكبيرة العالمية، وظهور ما يسمى بأساليب المحاسبة الإبداعية، ازداد الاهتمام بعملية المراجعة، حيث تعتبر المراجعة إحدى الركائز الأساسية لنظام الرقابة في الشركات؛ لكي تتمكن من تحقيق أهدافها بكفاءة. تهدف هذه الدراسة إلى التعرف على مدى كفاءة المراجعة الخارجية، ودراسة أثرها على ممارسات المحاسبة الإبداعية، كما تهدف الدراسة إلى التعرف على مدى استخدام إدارات الشركات لبعض أساليب المحاسبة الإبداعية من وجهة نظر المراجعين الخارجيين والأكاديميين بمدينة مصراته .اعتمدت الدراسة على المنهج الاستقرائي والمنهج الوصفي التحليلي؛ ولهذا فقد تم تصميم قائمة استبانة لغرض تجميع بيانات حول متغيرات الدراسة، والتي تم تحليلها باستخدام برنامج (SPSS) الإحصائي، وأسهمت هذه الدراسة في إثراء الجانب النظري الخاص بعملية المراجعة والمحاسبة الإبداعية، وتوصلت الدراسة إلى أن المراجعة الخارجية ذات كفاءة إلى حد ما، كما بينت الدراسة إلى وجود ممارسات لأساليب المحاسبة الإبداعية؛ وذلك حسب آراء عينة الدارسة، كما أظهرت الدراسة بأن كفاءة المراجعة الخارجية تلعب دورا مهما في الحد من ممارسات المحاسبة الإبداعية.

The in vitro susceptibilities of the isolates strain of Leishmania donovani (EMA, EAO, ZAA, HIH, MYIO and HYEA) to Sodium stibogluconate (SSG) and the experimental crude extract of Ambrosia maritime L. (Asteraceae) were determined for extracellular log-phase promastigotes and interacellular amastigotes in peripheral blood mononuclear cells (PBMCs). Susceptibility to reference drug (Pentostam) with different concentrations (1000, 500, 250, 125, 62.5 and 31.25) showed an increase in growth inhibition with the reduction in the concentration till then decrease in growth inhibition with the more reduction in concentration. While the Ambrosia maritima crude extract showed the decrease of growth inhibition with the increasing in concentration after 24, 48 and 72 hours. Ethanolic crude extract of A. maritime, it caused growth inhibition of L. donovani promastigotes at (1000, 500, 250, 125, 61.5, 31.25 mg/ mL), but the concentration 500ml/ml of the extract showed high biological activity 100% the study indicated that further analysis still to be done on the active crudes; bio-guided fractionation should also be conducted and may lead to the isolation of the major components in the active crude. Higher potency was observed against intercellular amastigots stage (IC50 is different for all parasites isolates EMA=1.339 to.541 EAO=1.473 to1.719, ZAA=1.447 to 1.719, HIH=1.465 to 1.686, MYIO= 1.280 to 1.559 and HYEA=1.473 to 1.707 mg/mL), a similar was observed for reference drug (SSG) (IC50 =1.945 to2.788mg/mL).

In this work, the application of silver nanoparticles (Ag NPs) for spectrophotometric determination of cefdinir (CFD) and cefepime HCl (CFP) was developed. The method was based on the ability of the alkaline degradation products of the cited drugs to reduce Ag+ ions to silver nanoparticles (Ag-NPs) in the presence of gelatin as a capping agent. The linear concentration ranges were 5.0-40 and 10-100 μg/mL for cefdinir and cefepime HCl, respectively. The lower detection limits were found to be 0.39 and 1.06 μg/mL for CFD and CFP, respectively, while the quantitation limits were found to be 1.18 and 3.21 μg/mL for CFD and CFP, respectively. The formed nanoparticles were characterized by ultraviolet-visible spectroscopy and transmission electron microscopy. The proposed method was applied successfully to determination of CFD and CFP in pure drugs, pharmaceutical preparations and human urine samples.

Objective: Vaccination hesitance for the COVID-19 booster dosage among hemodialysis patients is an important barrier in reducing morbidity and mortality linked to COVID-19 infection. Hence, this study aimed to explore the predictors of the third (booster) dose of COVID-19 vaccine intention among CKD patients on hemodialysis from the Kingdom of Saudi Arabia (KSA). Methods: This study was a multi-center cross-sectional study conducted at four dialysis centers in KSA from 13 February 2022 to 21 June 2022. The data was collected by the nephrologist in charge of the unit using a structured study questionnaire, which consisted of four parts; socio-demographic and clinical variables, questions about COVID-19 infection and subjective assessment of health state, COVID-19 booster dose vaccination intention and confidence in vaccines and preferences, and a health belief model. The study population consisted of 179 hemodialysis patients. Results: Participants in the study had conflicting health beliefs about their vulnerability to COVID-19 infection and the severity of the COVID-19 infection. Study participants expressed positive health beliefs about the advantages of the COVID-19 booster dose, and reported less perceived obstacles in receiving the vaccine. The influence of cues on action among the study population was high. A total of 140 (78.2%) hemodialysis patients expressed their intention to receive the COVID-19 booster dose. Patients who reported poor health in the self-rating of their health status had a substantially higher definite intention to take the COVID-19 booster dose, according to the chi-square test (11.16, df = 3, p = 0.01). There was a significant association between the constructs in the HBM model and COVID-19 vaccine (booster) intention. Marital status (OR = 1.67, CI 1.07–2.58) was found to be the strongest predictors of a definite intention to receive a COVID-19 booster dose. Confidence in the locally manufactured vaccine (OR = 0.33, CI 0.17–0.60), education (OR = 0.62, CI 0.41–0.93), and rating of health status (OR = 0.43 CI 0.25–0.74) were the strongest significant correlates of having no definite intention to take the COVID-19 vaccination. Conclusions: HBM constructs were found to be significantly associated with vaccination intention, which can be considered while planning policies to promote COVID-19 booster vaccination among hemodialysis patients. The study results could be utilized in drafting policies to improve COVID-19 booster dose vaccination uptake among hemodialysis population.

The study aimed to investigate the degree of employing the habits of mind in teaching by biology teachers in light of the variables of gender and experience in Jordan. The study used the descriptive method to answer the study questions. A questionnaire was developed after verifying its validity and reliability. The questionnaire was applied to a sample of (120) male and female teachers chosen from public and private schools in Wadi Al-Seer district in the capital, Amman. The results showed that the degree of employing habits of mind in teaching by biology teachers was medium. The results also showed a statistically significant difference between the biology teachers' estimates of the habits of mind according to the gender variable in favor of female teachers. The study also showed that there are no statistically significant differences for the biology teachers' estimates according to the variable of years of experience and the interaction between gender and years of experience. The study recommended the necessity of employing the habits of mind in teaching by biology teachers.

Innate lymphoid cells (ILCs) are a group of immune cells that are important for defense against pathogens, tissue repair, and lymphoid organogenesis. They share similar characteristics with various subsets of helper T cells but lack specific antigen receptors. Interleukin-7 (IL-7) and thymic stromal lymphopoietin (TSLP) are cytokines that engage the IL-7Rα and have major roles in dictating the fate of ILCs. Recent advances in the field have revealed transcriptional programs associated with ILC development and function. In this article, we will review recent studies of the role of IL-7 and TSLP in ILC development and function during infection and inflammation.

The data presented are related to the article entitled “Six Sigma quality approach for HPLC-UV method optimization” Ibrahim et al., 2019. The raw data of HPLC analysis of ascorbic acid (AS), paracetamol (PA) and guaifenesin (GU) are presented. Calibration standards were prepared at six concentrations levels (25%, 50%, 75%, 100%, 125% and 150%) each day and measured in triplicate. Validation standards were prepared at four concentration levels (25%, 60%, 100% and 150%) each day and measured in quintet. Three different series were used for method validation and prepared at the rate of one series per day. Keywords: Accuracy profile, HPLC, Ascorbic acid, Paracetamol, Guaifenesin

A simple RP-HPLC-PDA method for determination of atenolol (ATN) and trimetazidine (TMZ) in human urine and tablets has been developed. Analytes were separated on a Caltrex BI column (125× 4.0 mm, 5 μm) with 25mM potassium dihydrogen phosphate pH 3.3, methanol, and acetonitrile mobile phases. The PDA detector was operated at 210 nm for TMZ and 225 nm for ATN and the flow rate was 1.0 mL/ min. Linearity was obtained over a concentration range of (1.0-100 μg/mL) for both analytes in standard solutions and the method was successfully applied for determination of target analytes in their pharmaceutical tablets. Excellent linearity was also obtained over concentration ranges of (0.25-25 μg/mL) and (0.5-25 μg/mL) in human urine for TMZ and ATN, respectively. A simple liquid-liquid extraction was applied for urine sample clean-up and a gradient method was used for chromatographic separation. The lower limit of quantitation (LOQ) was 0.99 and 0.60 μg/mL for ATN and TMZ, respectively. The limit of detection (LOD) was 0.30 and 0.18 μg/mL for ATN and TMZ, respectively. Inter- and intraday precision and accuracy for ATN were within ±1.89% in pure form and within ±2.85% in urine samples. Inter- and intraday precision and accuracy for TMZ were within ± 3.99% in pure form and within ± 3.19% in urine samples.

The primary goal of language teaching is to enable students to understand the proper and clear language expression that he listens, or reads, or writes; in order to achieve a very lofty goal namely communication between human beings. It is recommended that we start teaching Arabic language to children since their early age. It is that a child spends hundreds and perhaps thousands of hours listening to his mother tongue, to recognize their voices, and to distinguish between them and finally to produce words and sentences. This is what we understand about early stages of Arabic language learning. DOI: 10.15408/a.v1i2.1144

The article presents information on a case study of a patient with acute leukemia with rare leukemic cells of unusual morphology. This 44-year-old male was presented with a 2-week history of a sore throat and a 4-day history of a rash. He was afebrile with a purpuric non-blanching papular rash affecting his legs and forearms. His tonsils were red and enlarged. The blood film showed infrequent pleomorphic blasts, some with bibbed nuclei. A bone marrow aspirate was of normal cellularity. The Myeloid: Erythroid ratio was 10: 1. Erythropoiesis was reduced but normoblastic. The majority of blasts had the cytological features of myeloblasts with a high nucleocytoplasmic ratio, a round nucleus and prominent nucleoli; some had 1 to 2 Auer rods. There was a minor population of leukemic cells with large basophilic granules; these comprised fewer than 0.5% of nucleated cells.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Bronchogenic carcinoma comprises >90% of primary lung tumors. The present study aimed to estimate the profile of patients with bronchogenic carcinoma and assess the cancer resectability in newly diagnosed patients. This is a single-center retrospective review conducted over a period of 5 years. A total of 800 patients with bronchogenic carcinoma were included. The diagnoses were mostly proven with either cytological examination or histopathological diagnosis. Sputum analysis, cytological examination of pleural effusion and bronchoscopic examination were performed. Lymph node biopsy, minimally invasive procedures (mediastinoscopy and video-assisted thoracoscopic surgery), tru-cut biopsy or fine-needle aspiration was used to obtain the samples for diagnosis. The masses were removed by lobectomy and pneumonectomy. The age range was between 22 and 87 years, with a mean age of 62.95 years. Males represented the predominant sex. Most of the patients were smokers or ex-smokers. The most common symptom was a cough, followed by dyspnea. Chest radiography revealed abnormal findings in 699 patients. A bronchoscopic evaluation was performed for the majority of patients (n=633). Endobronchial masses and other suggestive malignancy findings were present in 473 patients (83.1%) of the 569 who underwent fiberoptic bronchoscopy. Cytological and/or histopathological samples of 581 patients (91.8%) were positive. Small cell lung cancer (SCLC) occurred in 38 patients (4.75%) and non-SCLC was detected in 762 patients (95.25%). Lobectomy was the main surgical procedure, followed by pneumonectomy. A total of 5 patients developed postoperative complications without any mortality. In conclusion, bronchogenic carcinoma is rapidly increasing without a predilection for sex in the Iraqi population. Advanced preoperative staging and investigation tools are required to determine the rate of resectability., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Marie et al.)

Early diagnosis and appropriate staging workup are crucial for cancer patients. Whole-body magnetic resonance imaging (WB-MRI) has been proposed as another practical whole-body approach for assessing local invasiveness and distant metastases in patients newly diagnosed with cancer. The current study aimed to evaluate the efficacy of WB-MRI in assessing metastasis in patients newly diagnosed with cancer using histopathologic data as the reference method. A prospective observational study was performed from April 2018 to July 2020. MRI sequences were utilized to acquire anatomical and functional images in three orthogonal planes. The discovery was classified as nodal, skeletal and visceral metastases. Patient-based analysis was used for visceral metastasis and region-based for skeletal, systemic and lymph node metastases. A total of 43 consecutive patients (mean age, 56±15.2 years) were assessed successively. In 41 patients, there was a concordance between the WB-MRI and histological confirmation. The most prevalent site of metastasis was the skeletal system (18 patients). There were 12 individuals with liver metastasis, 10 with lung metastasis and 4 with peritoneal metastasis, with just one brain metastatic lesion found. On WB-MRI, 38 lymph node groups were deemed positive. Out of the total, 66 skeletal locations contained metastases. The accuracy of WB-MRI for nodal, skeletal and visceral metastases was (98.45, 100 and 100%, respectively). In conclusion, WB-MRI in three orthogonal planes, including the diffusion-weighted MRI with background body signal suppression sequence, may be utilized efficiently and accurately for assessing metastasis staging and may thus be utilized in patients with newly diagnosed cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Rashid et al.)

This retrospective study was done to assess the prevalence of congenital hypothyroidism among children born in Arar city, Kingdom of Saudi Arabia during years 2008 to 2014. Data were collected from newborns registry in Central hospital. The prevalence of congenital hypothyroidism was 2.6 per 10,000 live births with no gender difference.

A myelodysplastic syndrome (MDS) was suspected in a middle-aged man who presented with neutropenia and macrocytosis. The correct non-neoplastic diagnosis was not made for 5 years. It is of crucial importance to exclude treatable causes of cytopenia and dysplasia when MDS is suspected.

A 56-year-old woman presented with acute myeloid leukemia 3 years after presenting with carcinoma of the breast. Detailed investigations led to a precise diagnosis.

A young man presented with systemic symptoms and marked eosinophilia. Subsequently cyclical weight gain and edema contributed to a diagnosis.

A case history of a man, who was found to have an asymptomatic lymphoplasmacytic lymphoma with an IgM paraproteinaemia and subsequently acquired HIV infection, is presented. After seroconversion there was a reduction in CD4+ cell count in the peripheral blood and bone marrow, together with an increase in CD 138+ cells in the marrow and disease progression with increasing paraprotein levels and falling haemoglobin. Following antiretroviral therapy (HAART) there was a reduction in viral titres, an increase in peripheral blood CD4+ cell counts together with a reduction in paraprotein and an improvement in haemoglobin. This case suggests that CD4+ cells play a role in controlling B cell proliferation and consequently that CD4 suppression contributes to the increased incidence of lymphoma in patients with HIV infection. We also discuss treatment options for this patient for should his LPL progress and require treatment in the future.

The case of a 44 year old Ashkenazi Jewish woman of Russian origin who presented with a typical clinical and haematological picture of favism is reported. There was initial difficulty in confirming glucose-6-phosphate dehydrogenase (G6PD) deficiency because the enzyme concentrations were normal at presentation, but later fell to a concentration compatible with heterozygosity for the Mediterranean type of G6PD deficiency. The diagnosis was also later confirmed by gene analysis. The reasons for the difficulties in the initial confirmation of the diagnosis and the normal G6PD enzyme activity at presentation are discussed.

The optimum dose and duration of treatment with thalidomide for relapsed or refractory multiple myeloma are not known. Long term responses were seen in 5 patients given low doses of thalidomide (100-200 mg) with or without pulsed dexamethasone, for between 48 and 108 weeks. The responses were sustained for between 23 and 67 weeks after stopping treatment. We recommend that the lowest effective dose (LED) and optimum duration of therapy with thalidomide should be determined within the framework of a well conducted clinical trial in order to answer these important questions.

Thalidomide is an effective treatment for relapsed multiple myeloma (MM), but is associated with a significant side effect profile at higher doses. In a recent study, only half of the enrolled patients were able to tolerate the maximum dose of 800 mg/day [Singhal, S., et al. (1999) "Antitumor activity of thalidomide in refractory multiple myeloma", New Engl. J. Med. 341, 1565-1571]. Moreover, the dose-response relationship has not been defined. We report our use of low dose thalidomide in a small cohort of 12 patients-eight with relapsed or refractory MM and four with plasma cell leukaemia (PCL). Five of the 12 (42%) patients had a partial response, showing a median fall in their PP/BJP of 80% (63-90%) at a median dose of 175 mg (100-300 mg) with negligible side effects. Three of four patients with PCL showed an impressive response to treatment with thalidomide as a single agent. No patient who failed to show any evidence of response at low dose (<150 mg/day) responded to higher doses. In this study, thalidomide induces a similar rate of response at a lower and better tolerated dose than previously reported and produced "best ever" responses in patients with resistant PCL.

Multiple myeloma (MM) in three human immunodeficiency virus (HIV)-infected patients is reported. HIV infection predisposes to the development of high-grade B-cell lymphomas, but few cases of plasma cell tumours in association with HIV have been reported. The coincidence of HIV infection and neoplasia highlights the distinct roles of immunodeficiency and infection with herpesviridae, including HIV itself, in the pathogenesis of HIV-related tumours. In addition, a number of cytokines (e.g., interleukin-6 [IL-6]) and angiogenic factors (e.g., vascular endothelial growth factor [VEGF] and basic fibroblastic growth factor [bFGF]) may play a role in the initiation, maintenance, and progression of multiple myeloma (MM). Infection was the first clinical consideration to the cause of the illness in two of our HIV-seropositive patients. The diagnosis of MM may be difficult in patients with advanced HIV infection as they often have renal failure, bone marrow plasmacytosis, repeated infections, and polyclonal hypergammaglobulinaemia, due to HIV infection itself, opportunistic pathogens, and/or medication.

A variety of abnormalities in the number, morphology and function of blood and bone marrow cells may be found in Plasmodium falciparum and P. vivax malaria. In a non-immune individual, the nature of such abnormalities depends on the time after infection. In others it is determined by the pattern and intensity of malaria transmission in the area and the extent of host immunity. Severe anaemia may occur in children with chronic falciparum malaria and low parasitaemia as well as in patients with complicated acute falciparum malaria with high parasitaemia. However, the mechanisms underlying the anaemia in these two situations appear to be different. The possible roles of parasite products, T-cell-derived cytokines produced in response to the infection, macrophage activation and hyperplasia, macrophage-derived factors such as tumour necrosis factor-alpha, and macrophage dysfunction in the pathogenesis of the haematological abnormalities are discussed., (Copyright 2000 Harcourt Publishers Ltd.)

We report two siblings with Rothmund-Thomson syndrome (RTS); the older sister died of acute myeloblastic leukaemia and the younger sister has a slowly progressive leucopenia. Her prognosis is guarded in view of the increased incidence of neoplasms in this condition. More than 200 cases of RTS have now been reported worldwide.1 This is the first report of siblings with haematological disease and RTS.

Some patients with haematological neoplasms have features which overlap between a myelodysplastic syndrome and a myeloproliferative disorder. Two such patients are reported, both having sideroblastic erythropoiesis and thrombocytosis and one sequentially developing features of atypical chronic myeloid leukaemia, idiopathic myelofibrosis and acute megakaryoblastic leukaemia. The prevalence of thrombocytosis among cases of refractory anaemia with ring sideroblasts may be as high as 15-20% and has implications for choice of therapy.

A 66-year-old female with dermatomyositis (DM) who had received immunosuppressive therapy with azathioprine developed acute myeloid leukaemia (AML). Cytogenetic analysis revealed a complex karyotype including monosomy 7, and trilineage dysplastic features strongly suggestive of a treatment-related aetiology. The literature on azathioprine-associated AML is reviewed.

We report the case of a female patient who at presentation fulfilled the diagnostic criteria of dermatomyositis and also had an autoimmune haemolytic anaemia. Although autoimmune haemolysis is a well recognized feature of a number of autoimmune disorders, it has not previously been described in association with dermatomyositis.

Aims: To investigate the value of bone marrow biopsy in the diagnosis of mycobacterial infection., Methods: The culture results of 433 bone marrow samples taken between 1983 and 1992 were reviewed. The histopathology reports on bone marrow trephine specimens of culture positive samples and all those on HIV positive patients sent in 1992 were also reviewed., Results: Fifty one specimens yielded Mycobacterium spp, 47 were obtained from HIV positive patients. Of the isolates, 42 were Mycobacterium avium-intracellulare (MAI), five were M tuberculosis (MTB), and the remaining four comprised a variety of atypical mycobacteria. All MAI positive samples were obtained from HIV positive patients, with the bone marrow being the only culture positive specimen in one third. Bone marrow yielded MTB only in patients from whom it was also isolated in other specimens. Eleven of 47 trephine specimens from positive bone marrow showed granulomata and nine showed acid-fast bacilli. No acid-fast bacilli were seen in the absence of granulomata., Conclusion: Bone marrow biopsy for mycobacterial culture should be reserved for severely immunosuppressed patients and should not be advocated for immunocompetent patients with suspected tuberculosis. Bone marrow biopsy still has a role in the investigation of pyrexia of unknown origin in HIV positive patients, despite the advent of mycobacterial blood culture techniques, particularly if these can be processed safely in automated systems.

This paper presents changes in the bone marrow of patients with malaria; it is based primarily on observations of bone marrows of 89 Gambian children with P. falciparum malaria and includes a review of the literature. Erythroid hyperplasia with dyserythropoiesis was found to be more common in patients with severe anemia and low grade parasitemia than in those with acute malaria. The dyserythropoietic changes are illustrated both with light photomicropraphs and with electron micrographs. The significance of the dyserythropoiesis and possible causes are discussed. Other changes in these patients with acute malaria include lymphocytosis in the bone marrow and reactive lymphocytes, monocytosis and mild neutrophilia in the peripheral blood. Giant metamyelocytes were also commonly seen in bone marrow of patients but were thought to be part of dysmyelopoiesis and not due to B12 or folate deficiency. Phagocytosis of erythrocytes, parasitized cells and nucleated cells was more commonly seen in macrophages in acute malaria, while phagocytosis of small particles such as merozoites was observed in neutrophils. Megakaryocytes were found to be increased in number in patients with acute malaria; a proportion of these cells had rounded nuclei, probably indicating accelerated platelet turnover.

Iron and folate status were evaluated in a group of 106 Gambian children with malaria and variable degrees of anaemia. In children with malaria, normal or increased levels of red cell folate were found in 75 patients at presentation and in 15 patients 1-2 weeks after treatment with anti-malarials alone, despite the presence of giant metamyelocytes and megaloblasts in the bone marrow in some cases. Twenty-eight per cent of patients were found to have deficient bone marrow iron stores but malaria could not be directly implicated as the cause of this deficiency. Iron deficiency could also not be implicated as the sole cause of dyserythropoiesis in patients with malarial anaemia. Excess storage iron and the presence of ring sideroblasts were found in the bone marrow in some cases. It is concluded that the morphological changes including dyserythropoiesis, occasional megaloblasts, giant metamyelocytes and ring sideroblasts seen in the bone marrows of these children are manifestations of disturbed marrow function in malaria and are not related to haematinic deficiency. Because of the high rate of iron deficiency found in these patients it is recommended that Gambian children with severe anaemia should receive iron therapy after adequate treatment of malaria.

The performances of two commercial screening tests for glucose-6-phosphate dehydrogenase deficiency (Sigma fluorescent spot test and Sigma colorimetric method) were assessed in order to determine their usefulness in a routine haematology laboratory. As a first step, three ranges for enzyme activity were determined as follows: a 'normal' range determined from the 95% confidence limit of assays carried out on 114 normal adult males, a deficient range calculated as 25% of the upper limit of normal or less, and an intermediate range between the lower and upper values of these ranges. These values were 4.9-11.8 u/g Hb, 0-2.9 u/g Hb and 3.0-4.8 u/g Hb respectively. A separate normal range was also determined for females and was 5.5-12.8 u/g Hb. The two screening tests were then assessed against these values and the kits were found to be equally reliable at predicting normals and deficients but less reliable at detecting all female heterozygotes. The criteria for using the different procedures were evaluated. It is concluded that screening procedures are useful only when a large number of tests are routinely performed or in the absence of facilities for assays, as they offer no advantage in cost or time over the assay procedure. The colorimetric test (single vials) is easier and cheaper to use if isolated tests are performed, whereas the fluorescent spot test (with some modifications) is more useful for carrying out numerous tests simultaneously.

When mononuclear cells derived from the blood of unsensitized adult Caucasians are incubated for 22 hours with supernatants from cultures of Plasmodium falciparum, there is a substantial stimulation of the phagocytic capacity of the adherent monocytes for anti-D sensitized red cells. This stimulatory effect is dependent on (i) a heat-stable factor in such supernatants, (ii) the presence of T lymphocytes in the mononuclear cell preparations and (iii) the occurrence of DNA synthesis in the mononuclear cell cultures. It is proposed that the malaria culture supernatant contains a mitogen which acts on non-allergized T lymphocytes and that the stimulation of such lymphocytes probably causes the release of a lymphokine which enhances the phagocytic activity of cells of the mononuclear phagocyte system.

The presence of an IgG antibody to autologous schizont-infected red blood cells (SIRBC) in the sera of Gambian children with acute malaria and a positive direct anti-globulin test (DAT) was demonstrated by two methods: IgG quantitation using 125I-labelled anti-IgG and phagocytosis of these SIRBC. A similar antibody could not be demonstrated in sera of children with acute malaria and a negative DAT. When a laboratory strain of parasite was used there was a more variable pattern of IgG uptake but the highest was from sera of immune adult Gambians and Gambian children with acute malaria and a positive DAT. The uptake of IgG by SIRBC may be a useful test to determine the specificities of antibodies against different isolates of P. falciparum.

Five cases of severe megaloblastic anaemia in Gambians are described. Three of the patients were found to have pernicious anaemia. The difficulties in diagnosis and the various features of pernicious anaemia in Negroes are discussed. A brief review of the literature is included.

Haematological studies in a group of Gambian children with severe anaemia due to Plasmodium falciparum malaria revealed marked dyserythropoietic changes in erythroblasts and evidence of increased ineffective erythropoiesis. In some cases, the bone marrow also showed a few giant metamyelocytes and ring sideroblasts. The results of deoxyuridine suppression tests indicated that these haematological disturbances were not a consequence of vitamin B12 or folate deficiency within marrow cells.

The direct antiglobulin test (DAT) was performed on 243 subjects in Kenya. A high incidence of positive DAT was found in children with malaria of whom 70% had RBCs coated with IgG, C3 and C4 either separately or together. Only 12% of paediatric patients with conditions other than malaria had a positive DAT. Most positive DATs in association with malaria occurred in children between 18 months and five years of age. There was a lower incidence of positive DAT in Kikuyu children from an area of low malarial transmission than in children from other tribal groups who reside in areas of high malaria endemicity. A high rate of positive DAT was also found in patients with visceral leishmaniasis. Interestingly there was an association of IgG and C4 but without C3 on red cells of five patients with visceral leishmaniasis and two schoolchildren from an area endemic for visceral leishmaniasis. This combination was not found on other patients.

Neutrophilia, monocytosis, eosinopenia and reactive lymphocytes were found in the peripheral blood of infants and children with acute malaria at presentation. These changes were mostly reversed by days 3 and 7 after starting treatment. Mild rebound eosinophilia was seen in three cases after starting treatment. In patients with low grade malaria and anaemia, peripheral blood counts did not alter significantly after treatment. Two patients with mild eosinophilia at presentation were subsequently found to have strongyloidiasis and the eosinophil count rose markedly in one after treatment of malaria. Bone marrows were hypercellular in all cases. There was a low mean percentage of myeloid precursors in the marrow of all children as compared with the normal. This was due to increased lymphocyte percentage in those with acute malaria and to marked erythroid hyperplasia in those with low grade malaria. Phagocytosis of parasitized and non-parasitized red cells by bone marrow macrophages was seen most frequently in children with high parasitaemias, but erythroblast phagocytosis was more commonly seen in those with low grade malaria. There was no absolute correlation between the presence or absence of erythrophagocytosis in marrow macrophages and the presence or absence of a positive direct antiglobulin test (DAT) in children with malaria. This indicates that immunological mechanisms cannot be implicated as the sole cause of erythrophagocytosis in these bone marrows.