This study examined 4 soldiers with Plasmodium falciparum malaria who had a positive direct antiglobulin test, indicating Coombs'-positive hemolytic disease. In 3 patients, the positive Coombs' tests and hemolytic episodes seemed related to the administration of quinine used to treat relapsed malaria. Two of these patients experienced quinine-related skin reactions. The fourth patient had compensated hemolysis and a positive direct Coombs' test that was unrelated to quinine therapy. Coombs'-positive hemolytic disease is an unusual complication of malaria that clinical evidence suggests may be caused by quinine in some cases, though the mechanism is unknown.
This document describes a research project that aimed to sequence the aldolase B gene and discover new mutations that cause hereditary fructose intolerance (HFI). The researchers first attempted to amplify five fragments of the aldolase B gene via polymerase chain reaction (PCR) and analyze the results using gel electrophoresis. Fragment 5 was eventually successfully amplified from a plasmid, but fragments 2 and 4 could not be amplified from patient genomic DNA despite varying PCR conditions. Further optimization is still needed to amplify the fragments from genomic DNA and ultimately sequence the patient DNA to identify new mutations.
This document discusses several primary immunodeficiencies including agammaglobulinemia, common variable immunodeficiency, and selective IgA deficiency. It provides information on the epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of each condition. Key points include that agammaglobulinemia is caused by mutations in the BTK gene that halt B cell development, common variable immunodeficiency has unknown causes in most cases, and selective IgA deficiency involves a block in differentiation of B cells into IgA secreting plasma cells. Clinical features often involve recurrent respiratory and gastrointestinal infections. Treatment focuses on antibody replacement therapy and infection prophylaxis.
Isocitrate dehydrogenase mutations in hereditary diseaesamalreffat
NADPH production, which is vital for protecting cells from oxidative stress, depends on IDH enzyme.
If there is any mutation in this enzyme , it will adversely affects the cell.
Progretion of tumors and other diseases occurs consecutively.
1) The study found that 1.4% of E. coli strains isolated from acute diarrhea patients in Calcutta, India harbored the cdtB gene which encodes part of the cytolethal distending toxin (CDT).
2) Further analysis identified these cdtB-positive strains as enteropathogenic E. coli (EPEC). Among 138 EPEC strains screened, 6% were found to harbor the cdtB locus.
3) The cdtB-positive EPEC isolates belonged mostly to the O86a and O127a serogroups and showed genetically diverse pulsed-field gel electrophoresis profiles, suggesting they were not closely related clones.
This document summarizes research on the immunobiology of chronic lymphocytic leukemia (CLL). Key points include:
1. CLL results from the selection and transformation of B cells expressing B-cell receptors (BCRs) of restricted structure that can be polyreactive and autoreactive.
2. These BCRs bind to natural antigens as well as novel autoantigens generated during apoptosis.
3. CLL subgroups differ in retention of polyreactivity, with retention associated with worse clinical outcomes. Binding to autoantigens on apoptotic cells correlates with poor survival.
This document summarizes research on the immunobiology of chronic lymphocytic leukemia (CLL). Key points include:
1) CLL results from the transformation of B lymphocytes expressing antigen receptors (BCRs) of restricted structure that can be polyreactive and autoreactive.
2) These BCRs bind both natural antigens and novel autoantigens generated during apoptosis.
3) CLL subgroups differ in retention of polyreactivity, with retention associated with worse clinical outcomes.
This document provides a historical perspective on chronic myeloid leukemia (CML), summarizing key developments from its early descriptions in the 19th century to modern targeted therapies. Some of the major advances discussed include the discovery of the Philadelphia chromosome in 1960 linking CML to a chromosomal abnormality, identification of the BCR-ABL fusion gene in 1973, development of allogeneic stem cell transplantation as a curative treatment in the 1970s, introduction of interferon-alpha and tyrosine kinase inhibitors like imatinib in the 1990s-2000s, and ongoing research into second- and third-generation tyrosine kinase inhibitors. The CML story illustrates significant progress in understanding and treating the disease through scientific insights and innovations
1) The study aimed to use the PP65 antigenemia technique to diagnose active cytomegalovirus (CMV) infection in AIDS patients in Brazil and examine its occurrence in the region.
2) They found that 14 of 50 AIDS patients tested positive for PP65 antigenemia, indicating active CMV infection, while none of the 34 bone marrow transplant patients tested positive.
3) Having a CD4+ T-cell count below 100 cells/mm3 appeared to increase the risk of testing positive for PP65 antigenemia and active CMV infection, as more low CD4 count patients tested positive compared to higher CD4 count patients.
This document describes a research project that aimed to sequence the aldolase B gene and discover new mutations that cause hereditary fructose intolerance (HFI). The researchers first attempted to amplify five fragments of the aldolase B gene via polymerase chain reaction (PCR) and analyze the results using gel electrophoresis. Fragment 5 was eventually successfully amplified from a plasmid, but fragments 2 and 4 could not be amplified from patient genomic DNA despite varying PCR conditions. Further optimization is still needed to amplify the fragments from genomic DNA and ultimately sequence the patient DNA to identify new mutations.
This document discusses several primary immunodeficiencies including agammaglobulinemia, common variable immunodeficiency, and selective IgA deficiency. It provides information on the epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of each condition. Key points include that agammaglobulinemia is caused by mutations in the BTK gene that halt B cell development, common variable immunodeficiency has unknown causes in most cases, and selective IgA deficiency involves a block in differentiation of B cells into IgA secreting plasma cells. Clinical features often involve recurrent respiratory and gastrointestinal infections. Treatment focuses on antibody replacement therapy and infection prophylaxis.
Isocitrate dehydrogenase mutations in hereditary diseaesamalreffat
NADPH production, which is vital for protecting cells from oxidative stress, depends on IDH enzyme.
If there is any mutation in this enzyme , it will adversely affects the cell.
Progretion of tumors and other diseases occurs consecutively.
1) The study found that 1.4% of E. coli strains isolated from acute diarrhea patients in Calcutta, India harbored the cdtB gene which encodes part of the cytolethal distending toxin (CDT).
2) Further analysis identified these cdtB-positive strains as enteropathogenic E. coli (EPEC). Among 138 EPEC strains screened, 6% were found to harbor the cdtB locus.
3) The cdtB-positive EPEC isolates belonged mostly to the O86a and O127a serogroups and showed genetically diverse pulsed-field gel electrophoresis profiles, suggesting they were not closely related clones.
This document summarizes research on the immunobiology of chronic lymphocytic leukemia (CLL). Key points include:
1. CLL results from the selection and transformation of B cells expressing B-cell receptors (BCRs) of restricted structure that can be polyreactive and autoreactive.
2. These BCRs bind to natural antigens as well as novel autoantigens generated during apoptosis.
3. CLL subgroups differ in retention of polyreactivity, with retention associated with worse clinical outcomes. Binding to autoantigens on apoptotic cells correlates with poor survival.
This document summarizes research on the immunobiology of chronic lymphocytic leukemia (CLL). Key points include:
1) CLL results from the transformation of B lymphocytes expressing antigen receptors (BCRs) of restricted structure that can be polyreactive and autoreactive.
2) These BCRs bind both natural antigens and novel autoantigens generated during apoptosis.
3) CLL subgroups differ in retention of polyreactivity, with retention associated with worse clinical outcomes.
This document provides a historical perspective on chronic myeloid leukemia (CML), summarizing key developments from its early descriptions in the 19th century to modern targeted therapies. Some of the major advances discussed include the discovery of the Philadelphia chromosome in 1960 linking CML to a chromosomal abnormality, identification of the BCR-ABL fusion gene in 1973, development of allogeneic stem cell transplantation as a curative treatment in the 1970s, introduction of interferon-alpha and tyrosine kinase inhibitors like imatinib in the 1990s-2000s, and ongoing research into second- and third-generation tyrosine kinase inhibitors. The CML story illustrates significant progress in understanding and treating the disease through scientific insights and innovations
1) The study aimed to use the PP65 antigenemia technique to diagnose active cytomegalovirus (CMV) infection in AIDS patients in Brazil and examine its occurrence in the region.
2) They found that 14 of 50 AIDS patients tested positive for PP65 antigenemia, indicating active CMV infection, while none of the 34 bone marrow transplant patients tested positive.
3) Having a CD4+ T-cell count below 100 cells/mm3 appeared to increase the risk of testing positive for PP65 antigenemia and active CMV infection, as more low CD4 count patients tested positive compared to higher CD4 count patients.
Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi pa...iosrjce
The course of hepatitis B virus (HBV) infection is variable depending on many factors. In this study,
we investigated single nucleotide polymorphisms of interleukin-28B and interleukin-16 as possible host factors
which may determine the occurrence of hepatocellular carcinoma (HCC) in Saudi patients. Chronic hepatitis B
(CHB) patients (75), HCC patients (42), and healthy controls (70) were analyzed for polymorphisms of the IL16
and IL28B genes using PCR and restriction fragment length polymorphism (RFLP). Results showed that HCC
and chronic HBV patients had higher prevalence of rs11556218TG genotype than controls. The rs11556218GG
genotype was higher among HCC (14.4%) compared to chronic HBV (2.7%) patients. The IL-16 genotype
rs4072111CT was higher among HCC (47.6%) and chronic HBV (46.7%) patients than controls (28.6%). The
rs4072111TT genotype was higher among HCC patients compared to the other two groups. The T allele
frequency was higher among HCC patients than controls. The CT and TT of the IL-28B rs12979860 genotype
were significantly less frequent in chronic HBV and HCC patients. The IL-28B rs8099917 TG genotype was
more frequent among HCC (19%) compared to chronic HBV (8%) patients. However, no significant difference
was detected in the allele distribution.
1) The document analyzes 8 cases of late onset neutropenia (LON) in rheumatology patients treated with rituximab from a single center.
2) LON was defined as an absolute neutrophil count <1.0 x 109/L occurring at least 4 weeks after the last rituximab infusion. LON was identified in 8 patients (6% of those receiving rituximab).
3) The characteristics of LON were similar to reports in hematological malignancies, with LON appearing after a median of 23 weeks and recovering after a median of 6.5 days. Six patients were successfully rechallenged with rituximab without LON recurrence.
Infective endocarditis is a life-threatening disease caused by bacterial infection of the endothelium and cardiac valves, either native or prosthetic. In the present work the role of the new microbiological techniques (techniques of detection and amplification of the subunit 16 ribosomal sRNA by means of the chain reaction of the polymerase in blood or tissue, fluorescent in situ hybridization, and matrix-assisted laser is reviewed desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the diagnosis of infective endocarditis.
This study examined apoptosis of lymphocytes in patients with systemic lupus erythematosus (SLE). The percentage of apoptotic lymphocytes from SLE patients was significantly higher than healthy donors after 36 hours of incubation, indicating SLE patients have more lymphocytes undergoing apoptosis. A positive correlation was also found between lymphocyte apoptosis in SLE and disease activity markers like anti-dsDNA antibodies and prednisolone dosage. The percentage of CD4+ T cells was significantly lower in SLE patients compared to healthy donors.
This document summarizes a study investigating the association between genetic variants in genes encoding cytokines and susceptibility to schizophrenia. The study found a significant difference in genotype distribution and allele frequency of the TGFB1 ?869T[C polymorphism between schizophrenia patients and healthy controls. Carriers of the T allele had over two times higher risk of schizophrenia than those with the CC genotype. When analyzed separately by gender, the association was significant in females but only a trend in males. This is the first report showing an association between the TGFB1 ?869T[C polymorphism and schizophrenia.
This case report describes a case of refractory acute cellular rejection in a kidney transplant patient that was successfully treated with the monoclonal antibody rituximab. The patient developed sudden graft dysfunction 2 days post-transplant. Initial biopsy showed significant cellular infiltration but no antibody-mediated rejection. Further staining revealed 90% of infiltrating cells were CD20-positive. Treatment with steroids, plasmapheresis, and immunosuppression intensification failed to improve the graft. A single dose of rituximab led to improvement in graft function and disappearance of CD20-positive cells on follow-up biopsy. This highlights the importance of detailed cellular characterization in refractory rejection and targeting therapy to the specific cell population involved.
This document lists over 60 potential factors that are known to cause false positive HIV antibody test results. These factors include naturally occurring antibodies, viral infections like hepatitis B, autoimmune diseases, organ transplants, blood transfusions, and various medical treatments. False positives can also be caused by cross-reactivity with antibodies against other viruses or proteins as well as certain laboratory testing issues. Proper screening and confirmatory testing is necessary to avoid incorrect HIV diagnoses due to false positive initial test results from these many different sources.
This document discusses the use of intravenous immunoglobulin (IVIg) for various autoimmune diseases and cancer. It provides details on:
- How IVIg is prepared from blood donations and its definitive preparation process.
- Its clinical applications in treating severe immune deficiency diseases and various autoimmune conditions.
- Studies showing IVIg's effectiveness in treating autoimmune conditions like ITP, SLE, and experimental models of SLE.
- Mechanisms by which IVIg may exert anti-cancer effects like inhibiting tumor cell proliferation, invasion, and metastases in various cancer cell lines and mouse models. It also discusses a case report of a patient achieving remission of thymoma after IVIg treatment
2009 JCEM Detection of growth hormone doping by gene expression profiling of ...Selina Sutton
Gene expression profiling of peripheral blood from athletes administered growth hormone (GH) for 8 weeks found:
1) GH increased circulating insulin-like growth factor I (IGF-I) levels approximately 2-fold in both men and women.
2) Microarray analysis detected small changes in gene expression with GH, with a maximum 2-fold increase or decrease. 353 genes were differentially expressed in women and 41 in men.
3) The effect of GH on gene expression was similar in magnitude to natural variation between individuals, making it an unlikely approach for detecting GH doping.
This study demonstrates that anti-third party CTLs can efficiently kill B cell lymphomas through a novel TCR-independent mechanism that requires engagement of MHC class I molecules on the lymphoma cells with CD8 molecules on the CTLs. Using mutant cell lines and blocking antibodies, the researchers showed that lymphoma cell killing begins with conjugate formation between CTLs and tumor cells mediated by ICAM-1 and LFA-1 binding, followed by slower MHC-I dependent induction of apoptosis upon binding of MHC-I on tumor cells to CD8 on CTLs. This novel finding suggests MHC-I molecules can signal tumor cell death independent of antigen presentation when engaged by CD8, representing a new role for MHC-I in
1) WASp-deficient dendritic cells (DCs) show impaired activation of naive CD8+ T cells, especially at low antigen doses.
2) This is partly due to altered trafficking of antigen-bearing DCs from the periphery to lymph nodes. However, correcting DC migration does not fully rescue T cell activation.
3) In vitro and in vivo imaging revealed that cytoskeletal alterations in WASp-null DCs reduce their ability to form and maintain conjugates with naive CD8+ T cells in lymph nodes, contributing to defective T cell priming.
Hepatitis-B and C in Sickle Cell Hemoglobinopathies of Western Odisha, Indiainventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
This journal article summarizes a study investigating the cytotoxic effects and molecular mechanisms of action of coumarins isolated from Calophyllum brasiliense (mammea A/BA and A/BB) in K562 leukemia cells. The study found that the coumarin mixture induced cytotoxicity in the cancer cells and apoptosis, as shown by TUNEL staining and caspase-3 activation. Genotoxic effects were also observed. Additionally, an in silico analysis found the coumarins complied with criteria for drug-likeness. The results support further development of these natural compounds as potential anticancer agents.
This case report describes a 57-year-old woman with newly diagnosed HIV who presented with axillary lymphadenopathy. Histopathological analysis of an excisional lymph node biopsy showed rare nests of Burkitt cells exclusively located within hyperplastic monocytoid B-cell areas, representing Burkitt microlymphoma (BmL). Follow-up PET/CT scans showed persistent lymphadenopathy, and a subsequent core needle biopsy confirmed Burkitt lymphoma (BL). This case provides novel insights into the early histopathogenesis of HIV-associated BL, showing that it can arise as nests of cells within prominent monocytoid B-cell areas seen in HIV lymphadenitis.
Genetics of fetal hemoglobin in tribal Indian patients sickle cell anemiaSujata Singh
This study investigated the association between genetic variants known to influence fetal hemoglobin (HbF) levels and HbF levels in 240 Indian patients with sickle cell anemia and 60 with sickle cell trait. Genotyping was performed for variants in the BCL11A, HMIP, and HBB genes. All three quantitative trait loci were associated with HbF levels, with the strongest association seen for the HBB Xmn1 variant. The BCL11A and HMIP variants were also associated with HbF levels and explained a percentage of trait variance. This is the first such study in India and indicates these genetic factors influence HbF levels and likely disease severity in this population.
This study identified risk factors for healthcare-associated bloodstream infections due to fluconazole-resistant Candida glabrata. The study found that prior fluconazole use and linezolid use were independent risk factors for infections caused by fluconazole-resistant C. glabrata. Prior cefepime use and metronidazole use were risk factors for infections caused by fluconazole-susceptible C. glabrata. The study was conducted between 2003-2007 at three hospitals and included 76 cases of fluconazole-resistant infection, 68 cases of fluconazole-susceptible infection, and 512 controls.
The most likely diagnosis based on the information provided is viral meningitis (B). A CSF with cloudy appearance, lymphocytic predominance, and glucose greater than half the serum level is characteristic of viral meningitis. Bacterial meningitis would show a higher white count with neutrophil predominance. Tuberculous meningitis typically has a lower glucose. Cryptococcal meningitis would have a very low glucose.
Multi drug resistant bacteria are a big problem in ICUs now a days. This is a successful case report where we treated an pleural infection b directly instilling the drug colistin in the pleura.
Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi pa...iosrjce
The course of hepatitis B virus (HBV) infection is variable depending on many factors. In this study,
we investigated single nucleotide polymorphisms of interleukin-28B and interleukin-16 as possible host factors
which may determine the occurrence of hepatocellular carcinoma (HCC) in Saudi patients. Chronic hepatitis B
(CHB) patients (75), HCC patients (42), and healthy controls (70) were analyzed for polymorphisms of the IL16
and IL28B genes using PCR and restriction fragment length polymorphism (RFLP). Results showed that HCC
and chronic HBV patients had higher prevalence of rs11556218TG genotype than controls. The rs11556218GG
genotype was higher among HCC (14.4%) compared to chronic HBV (2.7%) patients. The IL-16 genotype
rs4072111CT was higher among HCC (47.6%) and chronic HBV (46.7%) patients than controls (28.6%). The
rs4072111TT genotype was higher among HCC patients compared to the other two groups. The T allele
frequency was higher among HCC patients than controls. The CT and TT of the IL-28B rs12979860 genotype
were significantly less frequent in chronic HBV and HCC patients. The IL-28B rs8099917 TG genotype was
more frequent among HCC (19%) compared to chronic HBV (8%) patients. However, no significant difference
was detected in the allele distribution.
1) The document analyzes 8 cases of late onset neutropenia (LON) in rheumatology patients treated with rituximab from a single center.
2) LON was defined as an absolute neutrophil count <1.0 x 109/L occurring at least 4 weeks after the last rituximab infusion. LON was identified in 8 patients (6% of those receiving rituximab).
3) The characteristics of LON were similar to reports in hematological malignancies, with LON appearing after a median of 23 weeks and recovering after a median of 6.5 days. Six patients were successfully rechallenged with rituximab without LON recurrence.
Infective endocarditis is a life-threatening disease caused by bacterial infection of the endothelium and cardiac valves, either native or prosthetic. In the present work the role of the new microbiological techniques (techniques of detection and amplification of the subunit 16 ribosomal sRNA by means of the chain reaction of the polymerase in blood or tissue, fluorescent in situ hybridization, and matrix-assisted laser is reviewed desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the diagnosis of infective endocarditis.
This study examined apoptosis of lymphocytes in patients with systemic lupus erythematosus (SLE). The percentage of apoptotic lymphocytes from SLE patients was significantly higher than healthy donors after 36 hours of incubation, indicating SLE patients have more lymphocytes undergoing apoptosis. A positive correlation was also found between lymphocyte apoptosis in SLE and disease activity markers like anti-dsDNA antibodies and prednisolone dosage. The percentage of CD4+ T cells was significantly lower in SLE patients compared to healthy donors.
This document summarizes a study investigating the association between genetic variants in genes encoding cytokines and susceptibility to schizophrenia. The study found a significant difference in genotype distribution and allele frequency of the TGFB1 ?869T[C polymorphism between schizophrenia patients and healthy controls. Carriers of the T allele had over two times higher risk of schizophrenia than those with the CC genotype. When analyzed separately by gender, the association was significant in females but only a trend in males. This is the first report showing an association between the TGFB1 ?869T[C polymorphism and schizophrenia.
This case report describes a case of refractory acute cellular rejection in a kidney transplant patient that was successfully treated with the monoclonal antibody rituximab. The patient developed sudden graft dysfunction 2 days post-transplant. Initial biopsy showed significant cellular infiltration but no antibody-mediated rejection. Further staining revealed 90% of infiltrating cells were CD20-positive. Treatment with steroids, plasmapheresis, and immunosuppression intensification failed to improve the graft. A single dose of rituximab led to improvement in graft function and disappearance of CD20-positive cells on follow-up biopsy. This highlights the importance of detailed cellular characterization in refractory rejection and targeting therapy to the specific cell population involved.
This document lists over 60 potential factors that are known to cause false positive HIV antibody test results. These factors include naturally occurring antibodies, viral infections like hepatitis B, autoimmune diseases, organ transplants, blood transfusions, and various medical treatments. False positives can also be caused by cross-reactivity with antibodies against other viruses or proteins as well as certain laboratory testing issues. Proper screening and confirmatory testing is necessary to avoid incorrect HIV diagnoses due to false positive initial test results from these many different sources.
This document discusses the use of intravenous immunoglobulin (IVIg) for various autoimmune diseases and cancer. It provides details on:
- How IVIg is prepared from blood donations and its definitive preparation process.
- Its clinical applications in treating severe immune deficiency diseases and various autoimmune conditions.
- Studies showing IVIg's effectiveness in treating autoimmune conditions like ITP, SLE, and experimental models of SLE.
- Mechanisms by which IVIg may exert anti-cancer effects like inhibiting tumor cell proliferation, invasion, and metastases in various cancer cell lines and mouse models. It also discusses a case report of a patient achieving remission of thymoma after IVIg treatment
2009 JCEM Detection of growth hormone doping by gene expression profiling of ...Selina Sutton
Gene expression profiling of peripheral blood from athletes administered growth hormone (GH) for 8 weeks found:
1) GH increased circulating insulin-like growth factor I (IGF-I) levels approximately 2-fold in both men and women.
2) Microarray analysis detected small changes in gene expression with GH, with a maximum 2-fold increase or decrease. 353 genes were differentially expressed in women and 41 in men.
3) The effect of GH on gene expression was similar in magnitude to natural variation between individuals, making it an unlikely approach for detecting GH doping.
This study demonstrates that anti-third party CTLs can efficiently kill B cell lymphomas through a novel TCR-independent mechanism that requires engagement of MHC class I molecules on the lymphoma cells with CD8 molecules on the CTLs. Using mutant cell lines and blocking antibodies, the researchers showed that lymphoma cell killing begins with conjugate formation between CTLs and tumor cells mediated by ICAM-1 and LFA-1 binding, followed by slower MHC-I dependent induction of apoptosis upon binding of MHC-I on tumor cells to CD8 on CTLs. This novel finding suggests MHC-I molecules can signal tumor cell death independent of antigen presentation when engaged by CD8, representing a new role for MHC-I in
1) WASp-deficient dendritic cells (DCs) show impaired activation of naive CD8+ T cells, especially at low antigen doses.
2) This is partly due to altered trafficking of antigen-bearing DCs from the periphery to lymph nodes. However, correcting DC migration does not fully rescue T cell activation.
3) In vitro and in vivo imaging revealed that cytoskeletal alterations in WASp-null DCs reduce their ability to form and maintain conjugates with naive CD8+ T cells in lymph nodes, contributing to defective T cell priming.
Hepatitis-B and C in Sickle Cell Hemoglobinopathies of Western Odisha, Indiainventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
This journal article summarizes a study investigating the cytotoxic effects and molecular mechanisms of action of coumarins isolated from Calophyllum brasiliense (mammea A/BA and A/BB) in K562 leukemia cells. The study found that the coumarin mixture induced cytotoxicity in the cancer cells and apoptosis, as shown by TUNEL staining and caspase-3 activation. Genotoxic effects were also observed. Additionally, an in silico analysis found the coumarins complied with criteria for drug-likeness. The results support further development of these natural compounds as potential anticancer agents.
This case report describes a 57-year-old woman with newly diagnosed HIV who presented with axillary lymphadenopathy. Histopathological analysis of an excisional lymph node biopsy showed rare nests of Burkitt cells exclusively located within hyperplastic monocytoid B-cell areas, representing Burkitt microlymphoma (BmL). Follow-up PET/CT scans showed persistent lymphadenopathy, and a subsequent core needle biopsy confirmed Burkitt lymphoma (BL). This case provides novel insights into the early histopathogenesis of HIV-associated BL, showing that it can arise as nests of cells within prominent monocytoid B-cell areas seen in HIV lymphadenitis.
Genetics of fetal hemoglobin in tribal Indian patients sickle cell anemiaSujata Singh
This study investigated the association between genetic variants known to influence fetal hemoglobin (HbF) levels and HbF levels in 240 Indian patients with sickle cell anemia and 60 with sickle cell trait. Genotyping was performed for variants in the BCL11A, HMIP, and HBB genes. All three quantitative trait loci were associated with HbF levels, with the strongest association seen for the HBB Xmn1 variant. The BCL11A and HMIP variants were also associated with HbF levels and explained a percentage of trait variance. This is the first such study in India and indicates these genetic factors influence HbF levels and likely disease severity in this population.
This study identified risk factors for healthcare-associated bloodstream infections due to fluconazole-resistant Candida glabrata. The study found that prior fluconazole use and linezolid use were independent risk factors for infections caused by fluconazole-resistant C. glabrata. Prior cefepime use and metronidazole use were risk factors for infections caused by fluconazole-susceptible C. glabrata. The study was conducted between 2003-2007 at three hospitals and included 76 cases of fluconazole-resistant infection, 68 cases of fluconazole-susceptible infection, and 512 controls.
The most likely diagnosis based on the information provided is viral meningitis (B). A CSF with cloudy appearance, lymphocytic predominance, and glucose greater than half the serum level is characteristic of viral meningitis. Bacterial meningitis would show a higher white count with neutrophil predominance. Tuberculous meningitis typically has a lower glucose. Cryptococcal meningitis would have a very low glucose.
Multi drug resistant bacteria are a big problem in ICUs now a days. This is a successful case report where we treated an pleural infection b directly instilling the drug colistin in the pleura.
and Two Case Stories with Infective Episodes in Pacemaker Treated Patients.pdfMonica Franklin
1) The document describes two cases of infective episodes in pacemaker-treated patients caused by Cardiobacterium hominis and Cardiobacterium valvarum.
2) In the first case, C. hominis was cultured from blood samples taken two years apart, with a vegetation later found on the pacemaker lead requiring its removal.
3) The second case involved C. valvarum and a large vegetation on the aortic valve, treated with antibiotic therapy and valve replacement surgery.
This case report describes a 57-year-old male with a history of essential thrombocytosis who presented with leukocytosis and splenomegaly. Molecular testing found that he harbored both a BCR-ABL1 fusion gene, characteristic of chronic myelogenous leukemia (CML), as well as a CALR mutation, more common in essential thrombocytosis. He was diagnosed with CML with myelofibrosis arising from essential thrombocytosis. Treatment with imatinib resulted in a partial response initially and a complete cytogenetic response after a year, though the CALR mutation persisted. The report reviews 12 similar prior cases and discusses the importance of integrating clinical, morphological, and genetic data to classify these atypical myeloid
Acyclovir Induced Acute Kidney Injury In Acute Meningitis Patient: A Case Rep...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
This document describes a study that evaluated a carboplatin desensitization protocol for patients with a proven allergic reaction to carboplatin. Twenty-three patients with gynecologic malignancies who experienced hypersensitivity reactions to carboplatin and tested positive on a skin test were included. The study used a 6-hour carboplatin desensitization protocol with diluted concentrations of the drug. Twenty patients (87%) were successfully desensitized and tolerated 80 desensitization treatment courses with only one patient experiencing a mild reaction. The desensitization protocol was found to be safe and effective for allowing further carboplatin treatment in patients with a proven allergy to the drug.
Clinical cases from infection diseases hospital part 2drandreyst-p
New presentation shows real case from infection diseases hospital and allow you to challenge your knowledge in medicine. After presentation of each case you will see a slide with a question about diagnosis. Try to answer and if you would have problems go to next slide where you will find a hint. Goodluck! If you would interested in new cases please contact Dr Andrey Dyachkov cd4@inbox.ru
This document contains a chapter summary on the inflammatory response and sepsis as well as sample multiple choice questions that test understanding of the key concepts. It discusses that sepsis affects over 1 million people in the US each year and that cytokines are small hormone-like proteins secreted by cells that mediate inflammation. Recombinant human activated protein C has been approved by the FDA for treatment of severe sepsis.
This case study describes an 82-year-old woman with multiple medical conditions who was admitted to the hospital twice for pseudomembranous colitis (PMC). During her first admission, she was diagnosed with PMC and cystitis and treated with antibiotics. She later developed PMC again and was treated with metronidazole and vancomycin. During her second admission two months later, tests confirmed another PMC recurrence which was resistant to vancomycin and metronidazole treatment. She was ultimately treated successfully with fidaxomicin. The patient's age, multiple comorbidities and hospitalizations put her at high risk for PMC recurrence.
1. The document provides an overview of cytology cases and diagnoses, including examples of LSIL, HSIL, and ASC from Pap smear samples.
2. Case examples also include diagnoses of ALK positive diffuse large B-cell lymphoma from lymph node biopsy samples and Hodgkin lymphoma with LCH from cervical lymph nodes.
3. The final case discusses a diagnosis of progressive transformation of germinal centre from cervical lymph node biopsy in a patient with history of ALL.
This study analyzed blood cultures from neonatal intensive care unit patients from 1997 to 2001 in Tripoli Medical Center, Libya. A total of 1431 blood culture sets from 1092 patients were positive for bacterial growth in 801 sets, representing 648 cases of neonatal bacteraemia. The most common causative agents were members of the Enterobacteriaceae family including Serratia, Klebsiella, and Enterobacter species as well as coagulase-negative and positive Staphylococci. Antibiotic susceptibility testing found high levels of resistance among the most frequent pathogens, though resistance to newer antibiotics like aztreonam and imipenem was less common. Resistance in Staphylococcus to anti-stap
1. A 55-year-old man presented with left eye ptosis and diplopia, symptoms of third cranial nerve palsy. Laboratory tests found elevated white blood cell count. Bone marrow biopsy revealed granulocytic hyperplasia and a positive test for the Philadelphia chromosome, confirming a diagnosis of chronic myelogenous leukemia (CML).
2. This is the first reported case of CML initially presenting solely as third cranial nerve palsy. While cranial neuropathies have been reported in other types of leukemia and lymphoma, this nerve palsy manifestation has not previously been associated with CML.
3. CML may present atypically with isolated cranial nerve pals
Hematological toxicities of anticancer agents (management strategies)Pranav Sopory
This document provides a summary of hematological toxicities caused by anti-cancer agents and their management strategies. It discusses chemotherapy-induced neutropenia, thrombocytopenia, and anemia. It describes common chemotherapy drugs that cause these side effects and their frequencies. Management strategies for neutropenia include use of granulocyte colony-stimulating factors like filgrastim and pegfilgrastim. Febrile neutropenia is discussed as a medical emergency requiring prompt treatment. Thrombocytopenia caused by chemotherapy is also summarized.
A 23-year old female presents with a rash, bruising, nosebleeds, and heavy menstruation. Her physical exam and labs reveal an isolated thrombocytopenia. Her peripheral smear shows decreased platelet numbers and slightly larger platelets, suggesting early release from the bone marrow in response to peripheral destruction. Further history and testing are needed to determine the cause of the thrombocytopenia.
The document discusses various aspects of haematopoiesis including:
- Haematopoiesis is the complex process of blood cell formation regulated by growth factors and nutrients.
- It occurs in bone marrow and other organs like the liver and spleen.
- Various in vitro and in vivo models are used to study haematopoiesis and induce anemia like using cyclophosphamide, phenylhydrazine, and haloperidol.
- Experiments on rats and rabbits evaluate the effects of test substances on haematological parameters during induced anemia and recovery.
Successful treatment of two cases of Elizabethkingia meningoseptica septicemi...Apollo Hospitals
Elizabethkingia meningoseptica is emerging as a cause of hospital acquired infection particularly in immunocompromised adults. The treatment of this bacterium is difficult since it is intrinsically resistant to a number of antibiotics. Here we report two cases of septicemia in patients who were critically ill and were successfully treated with appropriate antibiotics. Cotrimoxazole, quinolones, and rifampicin seem to be drugs effective against E. meningoseptica. Antibiotic susceptibility results are ineffective in guiding treatment. The bacterium particularly colonizes water pipelines and tap faucets and occurrence of infection by this bacterium should direct attention towards eradicating the source of this bacterium.
This document summarizes a study examining drug-induced hepatotoxicity in acute lymphoblastic leukemia patients undergoing chemotherapy. The study found that liver enzymes including bilirubin, ALT, ALP, and GGT increased significantly after one month of induction chemotherapy compared to before treatment. Additionally, hematological parameters like hemoglobin, RBC count, and neutrophil count improved after chemotherapy, while blast cells decreased. The study concludes that chemotherapy can cause hepatotoxicity in ALL patients during the induction phase.
The document discusses multi-drug resistant Gram-negative pathogens and current and emerging therapeutic approaches. It provides an overview of colistin, tigecycline, and fosfomycin - discussing their mechanisms of action, pharmacokinetics, clinical efficacy, and safety. Colistin is an old antibiotic that is seeing renewed use for resistant infections. Tigecycline is used off-label for extremely drug resistant infections but has limitations. Fosfomycin has broad-spectrum activity against resistant bacteria including ESBL producers.
CLASSIFICATION OF H1 ANTIHISTAMINICS-
FIRST GENERATION ANTIHISTAMINICS-
1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE,PROMETHAZINE,HYDROXYZINE 2)MODERATELY SEDATIVE- PHENARIMINE,CYPROHEPTADINE, MECLIZINE,CINNARIZINE
3)MILD SEDATIVE-CHLORPHENIRAMINE,DEXCHLORPHENIRAMINE
TRIPROLIDINE,CLEMASTINE
SECOND GENERATION ANTIHISTAMINICS-FEXOFENADINE,
LORATADINE,DESLORATADINE,CETIRIZINE,LEVOCETIRIZINE,
AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE. Mechanism of action of 2nd generation antihistaminics-
These drugs competitively antagonize actions of
histamine at the H1 receptors.
Pharmacological actions-
Antagonism of histamine-The H1 antagonists effectively block histamine induced bronchoconstriction, contraction of intestinal and other smooth muscle and triple response especially wheal, flare and itch. Constriction of larger blood vessel by histamine is also antagonized.
2) Antiallergic actions-Many manifestations of immediate hypersensitivity (type I reactions)are suppressed. Urticaria, itching and angioedema are well controlled.3) CNS action-The older antihistamines produce variable degree of CNS depression.But in case of 2nd gen antihistaminics there is less CNS depressant property as these cross BBB to significantly lesser extent.
4) Anticholinergic action- many H1 blockers
in addition antagonize muscarinic actions of ACh. BUT IN 2ND gen histaminics there is Higher H1 selectivitiy : no anticholinergic side effects
Selective alpha1 blockers are Prazosin, Terazosin, Doxazosin, Tamsulosin and Silodosin majorly used to treat BPH, also hypertension, PTSD, Raynaud's phenomenon, CHF
Can Traditional Chinese Medicine Treat Blocked Fallopian Tubes.pptxFFragrant
There are many traditional Chinese medicine therapies to treat blocked fallopian tubes. And herbal medicine Fuyan Pill is one of the more effective choices.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
GASTROINTESTINAL INFECTIONS AND GASTRITIS
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Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
- Video recording of this lecture in English language: https://youtu.be/RvdYsTzgQq8
- Video recording of this lecture in Arabic language: https://youtu.be/ECILGWtgZko
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Spontaneous Bacterial Peritonitis - Pathogenesis , Clinical Features & Manage...Jim Jacob Roy
In this presentation , SBP ( spontaneous bacterial peritonitis ) , which is a common complication in patients with cirrhosis and ascites is described in detail.
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Nutritional deficiency Disorder are problems in india.
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Dr. Tan's Balance Method.pdf (From Academy of Oriental Medicine at Austin)GeorgeKieling1
Home
Organization
Academy of Oriental Medicine at Austin
Academy of Oriental Medicine at Austin
Academy of Oriental Medicine at Austin
About AOMA: The Academy of Oriental Medicine at Austin offers a masters-level graduate program in acupuncture and Oriental medicine, preparing its students for careers as skilled, professional practitioners. AOMA is known for its internationally recognized faculty, award-winning student clinical internship program, and herbal medicine program. Since its founding in 1993, AOMA has grown rapidly in size and reputation, drawing students from around the nation and faculty from around the world. AOMA also conducts more than 20,000 patient visits annually in its student and professional clinics. AOMA collaborates with Western healthcare institutions including the Seton Family of Hospitals, and gives back to the community through partnerships with nonprofit organizations and by providing free and reduced price treatments to people who cannot afford them. The Academy of Oriental Medicine at Austin is located at 2700 West Anderson Lane. AOMA also serves patients and retail customers at its south Austin location, 4701 West Gate Blvd. For more information see www.aoma.edu or call 512-492-303434.
1. Coombs'-Positive Hemolytic Disease in Malaria
MARVIN M. ADNER, M.D., LESLIE B. ALTSTATT, M.D., and
MARCEL E. CONRAD, M.D., F.A.C.P.
Washington, D. C.
Qrr^vrADv I n a stu(
ly of 131 soldiers evacu-
3UMMARY a t e d f r o m Vietnam with drug-re-
sistant Plasmodium falciparum malaria, 4 patients
were found with a positive direct antiglobulin
test of the immunoglobulin (Ig) G type. In three
patients the positive Coombs' tests seemed tem-
porally related to the administration of quinine
for relapsed malaria and were associated with
hemolysis. Two of these patients had a quinine-
related dermatitis, one developed blackwater
fever within hours after the initiation of quinine
therapy, and another had a panagglutinin in
quinine-free red cell eluates. The fourth patient
had compensated hemolysis and a positive direct
Coombs' test which seemed unrelated to quinine
therapy. The indirect Coombs' test was negative
in all subjects, and no antiquinine antibodies were
found in sera or red cell eluates from these pa-
tients.
Coombs'-positive hemolytic disease is an un-
usual complication of malarial infections. Clini-
cal observations in man suggest that quinine has
a causal role in the hemolytic reaction. The mech-
anism by which this drug-induced hemolysis oc-
curs is not known.
MALARIA FREQUENTLY CAUSES anemia of
greater severity than can be attrib-
uted to the destruction of parasitized red
blood cells. It has been postulated that an
autoimmune-type hemolysis occurs, but the
evidence to support this hypothesis is
largely indirect (1).
This report describes four soldiers with
Plasmodium falciparum malaria who had
a positive direct antiglobulin test. Three of
these patients developed an acute hemo-
lytic episode shortly after quinine therapy
was initiated.
SUBJECTS AND METHODS
The subjects of this study were four white
soldiers with a positive direct Coombs' test who
were evacuated from Vietnam to Walter Reed
General Hospital because of P. falciparum ma-
laria.
The direct antiglobulin tests were performed
with commercial Coombs' sera.* f These anti-
globulin sera gave negative reactions with a
red blood cell preparation containing 10%
reticulocytes. Red cell eluates were prepared
by ether extraction (Patient 2) (2) and by heat-
ing (Patients 1, 3, and 4) (3). The specificity
of the antibody in eluates from Patient 1 was
tested with two commercial red cell panels
(Identigen® J and Ten-Cell® panel f). The class
of protein in the eluate was determined by the
immunodiffusion method of Ouchterlony (4)
using rabbit antihuman immunoglobulin (Ig) G,
IgA, IgM, transferrin, and whole serum.J The
quinine concentration of red cell eluates of
Patient 1 was determined by a fluorometric
method (5). The gamma globulin neutraliza-
tion test (6) was performed with IgG prepared
by purification of human fraction II on
diethylaminoethanol cellulose.
Indirect Coombs' tests were performed with
a 4% suspension of pooled 0+ red cells (Spec-
trogen®f) and test sera prepared in the fol-
lowing manner: [1] red cells suspended in a 1:5
dilution of compatible fresh normal serum (di-
luent = triethanolamine-buffered saline, pH 7.3,
containing added calcium and magnesium) plus
test sera; [2] red cells suspended in the diluted
fresh normal serum containing 1, 10, 25, 50, or
100 mg/100 ml quinine sulfate plus test
sera; [3] red cells suspended in buffered
Received July 17, 1967; revision accepted Sep-
tember 12, 1967.
From the Department of Hematology, Walter
Reed Army Institute of Research, Washington,
D. C.
Requests for reprints should be addressed to Lt.
Col. Marcel E. Conrad, MC, USA, Department of
Hematology, Walter Reed Army Institute of Re-
search, Washington, D. C. 20012.
* Ortho Pharmaceutical Corp., Raritan, N. J.
f Spectra Biologicals, Inc., East Brunswick, N. J.
j Hyland Laboratories, Los Angeles, Calif.
33
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2. 34 ADNER, ALTSTATT, AND CONRAD Annals of
Internal Medicine
FIGURE 1. Laboratory values during the clinical course in Case 1 (see text).
saline containing 1, 10, 25, 50, or 100 mg/100
ml quinine sulfate plus test sera; [4] red cells
suspended in the diluted fresh normal serum
plus test sera that had been incubated with
equal volumes of quinine sulfate for 30 min
at 37 C; [5] red cells incubated in buffered
saline containing 50 mg/100 ml quinine sulfate
(1 part cells/20 parts quinine solution) for 2
hr at 37 C, washed once in saline, and resus-
pended in the diluted fresh normal serum plus
test sera.
The pooled 0+ red cells were treated with
trypsin by the method of Morton and Pickles
(7). The trypsinized cells and test sera were
then prepared as described above [1 to 5]. De-
tection of incomplete antibodies was performed
according to the method of Dacie and Lewis
(8).
CASE REPORTS
PATIENT 1
This 21-year-old soldier developed P. falci-
parum malaria in Vietnam during October
1965. (See Figure 1 for clinical course.) Sub-
sequently, he had five malarial relapses that
were treated with quinine sulfate and chloro-
quine. In March 1966 he became febrile with
parasitemia (2,500/mm8
) and was treated with
quinine sulfate. After 3 days of therapy the
symptoms of malaria and the parasitemia dis-
appeared. However, the hematocrit, which was
38% at the time of institution of quinine
therapy, fell to 25% by the sixth day of treat-
ment. The patient had a positive direct anti-
globulin test, decreased plasma hemoglobin-
binding capacity (6 mg/100 ml), and hyper-
bilirubinemia (1.3 mg/100 ml, indirect fraction;
0.2 mg/100 ml, direct fraction); and a bone
marrow aspirate revealed a marked normo-
blastic erythroid hyperplasia. Therapeutic
blood levels of quinine had been attained
(7 mg/liter), and this drug was continued for
a total of 14 days of therapy. During this period
the hematocrit stabilized at 30% with 10%
reticulocytes, and the direct red cell anti-
globulin test remained positive. After dis-
continuation of the quinine therapy the
hematocrit increased to normal levels, the
reticulocyte count decreased, and the direct
antiglobulin test became negative. During the
next 5 months the patient had no malarial
relapses nor evidence of hemolytic disease.
Methemoglobin reduction test was normal 3
months after the hemolytic episode.
PATIENT 2
This 34-year-old soldier developed malaria
in November 1965 and had two relapses during
the next 60 days. (See Figure 2 for clinical
course.) Each episode responded to quinine,
and the patient developed a mild pruritic, ery-
thematous, macular eruption during the second
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3. Volume 68, No. 1
January 1968
COOMBS-POSITIVE HEMOLYTIC DISEASE IN MALARIA
35
FIGURE 2. Laboratory values during the clinical course in Case 2 (see text).
relapse. Chloroquine produced clinical improve-
ment of a third relapse, but parasitemia per-
sisted. On February 17, 1966, parasitemia in-
creased, fever occurred, and quinine therapy
was started. Four hours later the patient de-
veloped hemoglobinuria. The hematocrit de-
creased from 38 to 16%, the total serum bili-
rubin increased to a peak level of 18 mg/100
ml (indirect bilirubin, 9.2 mg/100 ml), and the
direct Coombs' test was positive. The patient
had marked depletion of multiple coagulation
factors. The plasma quinine level was 6.5 mg/
liter. He became oliguric. Quinine therapy was
stopped, and treatment with pyrimethamine,
chloroquine, sulfadiazine, heparin, cortico-
steroids, and osmotic diuretics was initiated.
Renal function improved, and the rate of
hemolysis decreased. The Coombs' test became
negative on February 21, but the hematocrit
remained at 20% without reticulocytosis. A
bone marrow aspirate showed marked megalo-
blastic changes, and antimalarial drug therapy
was stopped; we believed that the megaloblastic
changes were caused by the antifolic action
of pyrimethamine. Reticulocytosis recurred
spontaneously, and the hematocrit became nor-
mal. During the next 3 months the patient had
no malarial relapses or evidence of hemolytic
anemia. Methemoglobin reduction test was nor-
mal 3 months after the hemolytic episode.
PATIENT 3
This 24-year-old soldier developed malaria
in November 1965. The initial episode and
relapses were treated with quinine, pyrimeth-
amine, and chloroquine. The patient was ad-
mitted to Walter Reed General Hospital during
the third relapse. A pruritic, erythematous,
urticarial eruption developed and persisted on
quinine therapy after other drugs were dis-
continued. The patient developed a mild ane-
mia with a positive direct Coombs' test, reticu-
locytosis, indirect hyperbilirubinemia, and de-
creased plasma hemoglobin-binding capacity
(20 mg/100 ml). No parasites were present in
thick peripheral blood smears. Heterophil and
cold agglutinin studies were normal. Methemo-
globin reduction test was normal. The skin rash
and the hemolytic anemia improved markedly
within 1 day after cessation of quinine therapy.
The patient had no relapses during the next
3 months of observation.
PATIENT 4
This 24-year-old soldier was evacuated from
Vietnam in November 1965 after an initial
malarial infection that responded to 3 days of
chloroquine therapy. On admission to Walter
Reed General Hospital the patient was asymp-
tomatic, and a thick smear of blood showed no
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4. 36 ADNER, ALTSTATT, AND CONRAD Annals of
Internal Medicine
parasites. The splenic tip was palpable; the
hematocrit was 38% with 1% reticulocytes. The
white blood count was 9,700 cells/mm* with a
differential count that showed 47 neutrophils,
2 bands, 1 metamyelocyte, 33 lymphocytes, 3
monocytes, and 12 eosinophils. Stool specimens
contained no ova or parasites. During January
1966 the patient had a malarial relapse that
responded to 2 weeks of quinine therapy. Dur-
ing the next 3 months the patient had per-
sistent eosinophilia but no parasitemia. A bone
marrow aspirate showed mild normoblastic ery-
throid hyperplasia, eosinophilia, and malarial
merozoite and ring forms. The hematocrit was
49%, reticulocyte count, 1.4%, and the direct
Coombs' test, strongly positive. An autologous
^Cr red blood cell survival showed a half-life
of 21 days (normal half-life, 26 to 35 days).
Methemoglobin reduction test was normal. The
patient remained asymptomatic until July 1966.
Then he had a relapse of malaria that re-
sponded to combinational therapy with qui-
nine, pyrimethamine, and sulfadiazine. Sub-
sequently, eosinophilia, evidence of hemolysis,
and parasitemia have not been found.
SPECIAL LABORATORY STUDIES
Blood specimens from 131 patients evac-
uated from Vietnam because of P. falci-
parum malaria were examined. The in-
direct Coombs' test was negative in all
specimens, but the direct antiglobulin test
was positive in blood from four subjects.
In three (Patients 1, 3, and 4) the gamma
globulin neutralization test showed that
the positive reaction was caused by an im-
munoglobulin (Ig) G antibody on the sur-
face of the red blood cells. The positive
antiglobulin reaction was inhibited by in-
cubation of the Coombs' sera with an equal
volume of 1% IgG before the addition of
red blood cells. Concentrations of IgG less
than 0.1 to 0.4 mg/100 ml did not inhibit
the reaction. The gamma globulin neu-
tralization test was not used to study Pa-
tient 2.
Eluates of the Coombs'-positive red cells
from Patient 1 contained antibody activity.
These eluates showed a positive indirect
antiglobulin reaction when incubated with
any of the cells in two commercial red cell
panels. The panels included cord cells but
no Rh-null cells. An eluate was concen-
trated twentyfold and shown to contain
IgG and transferrin but not IgA or IgM.
Fluorometric analysis showed no quinine
in the concentrated eluate. Thus, Patient
1 had an IgG antibody on his red cells
that acted as a panagglutinin in the
absence of quinine. Eluates from the
Coombs'-positive red blood cells of Patients
2, 3, and 4 failed to show antibody activity.
Numerous serum samples from these
patients drawn during the periods when
the Coombs' tests were positive and the
following 2 to 3 months after the Coombs'
test became negative were tested for un-
usual antibody activity. In no instance was
there any evidence of abnormal antibody
activity against normal red cells and tryp-
sinized red cells suspended in saline or in
varying concentrations of quinine sulfate.
Incubation of the sera with varying con-
centrations of quinine did not bring out
any antibody activity against normal red
cells. The results of the laboratory studies
are summarized in Table 1.
DISCUSSION
The anemia of malaria is more profound
than can be caused by the destruction of
parasitized erythrocytes. The evidence that
an immune-type hemolysis may be respon-
sible for the disproportionate anemia has
been summarized by Zuckerman (1). Al-
though most attempts to demonstrate ab-
normal red cell antibodies have been un-
successful, there are a few reports of a
positive Coombs' test in malarious patients
(9-11). Heidelberger and Mayer (12)
showed that incubation of malarial sera
with normal human erythrocytic stromal
antigen resulted in the fixation of comple-
ment. In addition, the sera of rats infected
with Plasmodium berghei contain hemag-
glutinins against trypsinized normal rat
erythrocytes (13, 14).
Evidence for immune hemolysis in ma-
laria is largely indirect. Autoagglutination
and microspherocytosis of nonparasitized
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5. Volume 68, No. 1
January 1968
COOMBS'-POSITIVE HEMOLYTIC DISEASE IN MALARIA
37
TABLE 1. Summary of Studies of Four Patients with Malaria with Positive Coombs' Tests
Patient Evidence of Hemolysis Quinine
Therapy
at Time of
Hemolysis
Direct
Coombs'
Test
Gamma Globulin
Neutralization
Test
Antibody Activity
Eluate Serum
1
Rapidly developing anemia
Decreased plasma hemo-
globin-binding capacity
Reticulocytosis
Hyperbilirubinemia
Normoblastic erythroid
hyperplasia of bone marrow
+ +++ + + 0
2
Rapidly developing anemia
Absent plasma hemoglobin-
binding capacity
Hyperbilirubinemia
Hemoglobinuria
+ +++ (-)• 0 0
3
Anemia
Decreased plasma hemoglobin-
binding capacity
Reticulocytosis
Hyperbilirubinemia
+ ++ + 0 0
4
Decreased red cell
autosurvival
Erythroid hyperplasia
of bone marrow
0 +++ + 0 0
* Study not performed.
red cells have been observed in blood speci-
mens from malarious patients with acute
intravascular hemolysis (15). Transfusion
of labeled red blood cells from a patient
with blackwater fever had a shortened sur-
vival in a normal recipient. Conversely,
normal erythrocytes are prematurely de-
stroyed in malarious subjects (16). Marked
splenic erythrophagocytosis of nonparasi-
tized erythrocytes is frequently found in
malaria (17). These observations suggest
that the red blood cell is sensitized in ma-
laria, perhaps in a manner that is not usu-
ally demonstrated by available techniques.
Although quinine therapy cannot be im-
plicated in every case of blackwater fever,
the frequent association of hemolytic crisis
and the initiation of quinine therapy can-
not be disregarded (18-20). Quinine causes
a dose-related anemia in rabbits in vivo
and makes red blood cells more susceptible
to in vitro hemolysis (21, 22). However, the
administration of quinine to many patients
with malaria and the relative rarity of
blackwater fever make it unlikely that the
hemolysis is caused solely by a direct toxic
effect of quinine upon erythrocytes. Qui-
nine-associated hemolytic anemia has been
reported only in pregnant or malarious pa-
tients. This may indicate that quinine acts
upon previously sensitized or damaged
erythrocytes to accelerate or precipitate he-
molysis. Glucose 6-phosphate dehydrogenase
deficiency has been suggested as a precipi-
tating factor, but our patients showed no
evidence of this enzymatic defect (23). The
possibility that this is an immune response
to quinine is suggested by the usual occur-
rence of blackwater fever in patients after
multiple courses of quinine therapy and
the positive Coombs' test in certain pa-
tients with intravascular hemolysis. Ad-
ditional credence for this hypothesis is
obtained from previous reports of a
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6. 38 ADNER, ALTSTATT, AND CONRAD Annals of
Internal Medicine
quinine-dependent complement-fixing anti-
body in the sera of patients receiving qui-
nine therapy (24, 25). The failure to dem-
onstrate a similar antibody in our patients
indicates that this is a complex problem
that requires further investigation.
ACKNOWLEDGMENT
We wish to acknowledge the helpful assist-
ance of Lt. Col. Kevin G. Barry, MC, USA,
Maj. Paul F. Gilliland, MC, USA, and Capt.
Max M. Inman, MC, USA, Department of Me-
tabolism, Walter Reed Army Institute of Re-
search, who made the clinical information and
specimens reported in this study available to us.
REFERENCES
1. ZUCKERMAN, A.: Autoimmunization and other
types of indirect damage to host cells as fac-
tors in certain protozoan diseases. Exp.
Parasit. 15: 138, 1964.
2. RUBIN, H.: Antibody elution from red blood
cells. J. Clin. Path. 16: 70, 1963.
3. LANDSTEINER, K., MILLER, C. P.: Serological
studies on the blood of primates. II. The
blood groups in anthropoid apes. / . Exp.
Med. 42: 853, 1925.
4. OUCHTERLONY, O.: Antigen-antibody reactions
in gels. IV. Types of reactions in coordinated
systems of diffusion. Acta Path. Microbiol.
Scand. 32: 231, 1953.
5. BRODIE, B. B., UDENFRIEND, S.: The estimation
of quinine in human plasma with a note on
the estimation of quinidine. / . Pharmacol.
Exp. Ther. 78: 154, 1943.
6. DACIE, J. V.: Differences in the behaviour of
sensitized red cells to agglutination by anti-
globulin sera. Lancet 2: 954, 1951.
7. MORTON, J. A., PICKLES, M. M.: Use of trypsin
in the detection of incomplete anti-Rh anti-
bodies. Nature (London) 159: 779, 1947.
8. DACIE, J. V., LEWIS, S. M.: Practical Hematol-
ogy, 3rd ed. Grune & Stratton, Inc., New
York, 1963, p. 178.
9. DEMIRAG, B., SOZER, C: Hemolytic anemia fol-
lowing malaria. Ann. Paediat. (Basel) 186:
86, 1956.
10. VANDEPITTE, J. M.: Le facteur Rh et sa rela-
tion avec la fievre bilieuse hemoglobinurique.
Ann. Soc. Belg. Med. Trop. 29: 501, 1949.
11. ZOUTENDYK, A., GEAR, J.: Auto-antibodies in the
pathogenesis of disease. S. Afr. Med. / . 25:
665, 1951.
12. HEIDELBERGER, M., MAYER, M.: Normal human
stromata as antigens for complement fixation
in the sera of patients with relapsing vivax
malaria. Science 100: 359, 1944.
13. Cox, H. W., SCHROEDER, W. F., RISTIC, M.:
Hemagglutination and erythrophagocytosis
associated with the anemia of Plasmodium
berghei infection of rats. / . Protozool. 13:
327, 1966.
14. KREIER, J., SHAPIRO, H., DILLEY, D., SZILVASSY,
I., RISTIC, M.: Autoimmune reactions in rats
with Plasmodium berghei infection. Exp,
Parasit. 19: 155, 1966.
15. GEAR, J.: Autoantigens and autoantibodies in
the pathogenesis of disease with special ref-
erence to blackwater fever. Trans. Roy. Soc.
Trop. Med. Hyg. 39: 301, 1946.
16. FOY, H., KONDI, A., REBELO, A., SOEIRO, A.:
Survival of transfused red cells in black-
water fever circulation and of blackwater red
cells in normal circulation. Trans. Roy. Soc.
Trop. Med. Hyg. 38: 271, 1945.
17. ZUCKERMAN, A.: Recent studies on factors in-
volved in malarial anemia. Milit. Med. 131
(suppl. 9): 1201, 1966.
18. FINDLAY, G. M.: Recent Advances in Chemo-
therapy, vol. II, 3rd ed. The Blakiston Di-
vision, McGraw-Hill Book Co., Inc., New
York, 1951, p. 191.
19. FOY, H., KONDI, A.: The correlation between
blackwater fever, malaria, quinine and ata-
brine. Ann. Trop. Med. Parasit. 44: 309,1950.
20. LECCIARDELLO, A. T., STANBURY, J. B.: Acute
hemolytic anemia from quinine used as an
abortifacient. New Eng. J. Med. 238: 120,
1948.
21. GREWAL, R. S.: Role of quinine in hemolysis.
Brit. J. Pharmacol. 13: 175, 1958.
22. PONDER, E., ABELS, J. C: Effects of quinine hy-
drochloride on the resistance of rabbit red
cells. Proc. Soc. Exp. Biol. Med. 34: 162,
1936.
23. LARIZZA, P., BRUNETTI, P., GRIGNANI, F.: [En-
zyme-deficient hemolytic anemia.] (It.) Hae-
matologica 45: 1, 1960.
24. LEDDY, J. P.: Immunological aspects of red cell
injury in man. Seminars Hemat. 3: 48, 1966.
25. MUIRHEAD, E. E., HOLDEN, E. R., GROVES, M.:
Drug dependent Coombs (antiglobulin) test
and anemia. Arch. Intern. Med. (Chicago)
101: 87, 1958.
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