Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that the true incidence of c-ALL is relatively uniform throughout the world is not supported by experience in tropical Africa, where ALL is uncommon under five years of age. A high rate of spontaneous somatic mutation in pre-B cells may initiate the development of c-ALL, but its progress could be determined by (i) a leukaemogenic agent causing a second genetic event, (ii) the effects of intense antigenic barrage, either stimulating or suppressing pre-B-cell mitosis, or (iii) genetic determinants. Epidemiological patterns in populations of low, intermediate and high socio-economic status may be classified I-III with increasing incidence of diagnosed T-ALL in children over five years and c-ALL in younger children, and subclassified A and B with decreasing incidence of BL. There may be two forms of AML, one similar to that seen in industrialized countries, the other occurring at high prevalence in African children of low socio-economic status, often presenting with chloroma, and perhaps associated with immune suppression secondary to malnutrition, malaria and other intercurrent infections. Uncontrolled exposure to petroleum and other chemicals, and the use of alkylating agents in treatment of neoplasms in young patients could emerge as important causes of ANLL in Africa. There are two varieties of CLL also, one similar to that seen in the western world, the other prevalent in adults below 45 years of age, especially women: transmission of a leukaemogenic agent is postulated, to which women are more susceptible due to immunosuppression during normal pregnancy. The human population and some subhuman primates of subSaharan Africa are the largest reservoir of HTLV-1, which shows association with B-CLL over 50 years of age and ATL.
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PMID:Possible aetiological factors in leukaemias in Africa. 289 24

Until recently, cALL has been uncommon in sub-Saharan Africa, but there is now emerging a peak of incidence at the age 3 to 5 years in west and southern Africa. Prognosis for African patients with cALL is poor because of a multitude of clinical, biological and social factors. AML is seen at high frequency (probably indicating truly high incidence) in male children 5-14 years, of whom up to a quarter present with chloroma. It is predicted that the incidence of AML in adults may rise in the near future, related to cigarette smoking, occupational and environmental exposures to benzene and other pollutants, and the prescription of alkylating agents to young people with malignant disease. CML shows no particular epidemiological features, except for a high frequency in young adults and children, reflecting the age structure of the whole population. There are two forms of B-CLL: one is seen most commonly in women of low socioeconomic status towards the end of the their reproductive life, and is probably related to an initially polyclonal expansion of B-cells in response of recurrent malaria and other infections; the other is seen over the age of 45 years, with men being affected twice as commonly as women, as in the western world.
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PMID:Leukaemias in Africa. 836 Dec 19

Pancytopenia is a common occurrence in pediatric patients. Though acute leukemias and bone marrow failure syndromes are usual causes of pancytopenia, etiologies such as infections and megaloblastic anemia also contribute. The aim of this study was to evaluate the clinico-hematological profile of varying degrees of childhood cytopenias with special reference to the non-malignant presentations. This is a retrospective study carried out in a tertiary care children's hospital. We retrospectively analyzed 109 pediatric patients who presented with pancytopenia for different etiologies. Acute leukemia (including ALL, AML and myelodysplastic syndrome) and aplastic anemia accounted for 21 per cent and 20 per cent cases respectively. Megaloblastic anemia was found in 31 (28.4 per cent) patients and was single most common etiological factor. Severe thrombocytopenia (platelet < or = 20 x 10(9)/l) occurred in 25.2 per cent of these patients. Various skin and mucosal bleeding occurred in 45.1 per cent of patients with megaloblastic anemia. Infections accounted for 23 (21 per cent) patients who presented with pancytopenia. Amongst infections, enteric fever occurred in 30 per cent patients. Malaria, kala-azar and bacterial infections were other causes of pancytopenia at presentation. The study focuses on identifying easily treatable causes such as megaloblastic anemia and infections presenting with pancytopenia. These conditions though look ominous but respond rapidly to effective therapy.
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PMID:Pancytopenia in children: etiological profile. 1601 64

Stem cell transplantation is curative in a number of otherwise fatal hematological diseases. In Pakistan, SCT was started in October 1995 at Dr Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over 350 allogeneic stem cell transplants have been carried out in these latter two centers. Another 50 autologous procedures were carried out in all centers. In 2004, a third center started transplants at the Aga Khan Hospital. The main indications for transplant are aplastic anemia, beta-thalassemia major and hematological malignancies. HLA-identical sibling donors provide stem cells for the recipient. In 70% of cases, a matched donor is identified. In sharp contrast to the rest of the world, the majority of transplants are allogeneic, donor-recipient pairs are CMV positive and fungal infection, tuberculosis and malaria are particular problems. The early results are promising, with transplant-related mortality reported to be 10-20%, whereas long-term survival is reported to be 78, 72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively. Financial constraints, poor socioeconomic status, poor transfusion services, trained human resources and difficulty in keeping pace with technological advances are major hurdles in the growth of transplant medicine. Government support is badly needed to strengthen existing facilities and to develop more centers.
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PMID:The stem cell transplant program in Pakistan--the first decade. 1872 82

Farnesyltransferase inhibitors (FTIs) have mainly been used in cancer therapy. However, more recently, investigations on these inhibitors revealed that FTIs can be used for the treatment of other diseases such as Progeria, P. falciparum resistant malaria, Trypnosomatid, etc. Hence the development of novel FTIs is an important task for the drug discovery program. Initially, numerous peptidomimetic FTIs were developed from the template of CAAX (CVIM was the first pharmacophore model used as a peptidomimetic). Later, many non-peptidomimetic FTIs have been discovered with the structural modification of the peptidomimetics. The structural analysis of those developed FTIs by various researchers suggested that the presence of a heterocycle or a polar group in place of the thiol group is required for interaction with the Zn(2+) ion. The bulky naphthyl, quinolinyl, phenyl, phenothazine, etc in this position provide better hydrophobicity to the molecules which interact with the aromatic amino acid moieties in the hydrophobic pocket. A hydrophilic region with polar groups is necessary for the polar or hydrogen bonding interactions with the amino acids or water molecules in the active site. Many FTIs have been isolated from natural products, which possessed inhibitory activity against farnesyltransferase (FTase). Among them, pepticinnamin E (9R), fusidienol (9T), gliotoxin (9V), cylindrol A (9X), etc possessed potential FTase inhibitory activities and their structural features are comparable to those of the synthetic molecules. The clinical studies progressing on FTIs showed that tipifarnib in combination with bortezomib is used for the treatment of patients with advanced acute leukemias. Successful phase I and II studies are undergoing for tipifarnib alone or in combination with other drugs/radiation for the treatment of multiple myeloma, AML, breast cancer, mantle cell lymphoma, solid tumors, non-small cell lung cancer (NSCLC), pancreatic cancer, glioblastoma, etc. Phase I pharmacokinetic (maximum tolerated dose, toxicity) and pharmacodynamic studies of AZD3409 (an orally active double prodrug) is progressing on patients with solid malignancies taking 500 mg once a day. A phase II study is undergoing on lonafarnib alone and in combination with zoledronic acid and pravastatin for the treatment of Hutchinson-Gilford Progeria syndrome (HGPS) and progeroid laminopathies. Lonafarnib therapy improved cardiovascular status of children with HGPS, by improved peripheral arterial stiffness, bone structure and audiological status in the patients. Other important FTIs such as BMS-214662, LB42908, LB42708, etc are under clinical studies for the treatment of various cancers. This review concluded that the quantitative structural analysis report with an elaborative study on the natural product compounds provides ideas for development of novel molecules for the FTase inhibitory activity. The fragment based analysis is also needed to select the substituents, which provides significant inhibitory activities and can also have good pharmacokinetic properties in the clinical studies.
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PMID:Farnesyltransferase inhibitors: a comprehensive review based on quantitative structural analysis. 2405 35