Background: Due to the high prevalence and incidence of leprosy in the Philippines, there is a continuing need to detect and document the occurrence of dapsone-induced hemolytic anemia. Objective: The aim of this study is to determine the incidence of dapsone-induced hemolytic anemia in non-glucose-6-phosphate dehydrogenase deficient leprosy patients receiving multidrug therapy (MDT) in Southern Philippines Medical Center. Methodology: This is a retrospective study through chart review of leprosy patients treated with MDT regimen at Southern Philippines Medical Center from January 2016 to December 2018. The demographic profile, clinical characteristics, hemoglobin and hematocrit concentrations before and after initiation of MDT, the presence of symptoms of anemia, and the occurrence of dapsone-induced hemolytic anemia in leprosy patients were collected. The main outcome measure for this study was the incidence rate of dapsone- induced hemolytic anemia. Statistical-based analysis were used for continuous and categorical data which were summarized using means and standard deviations, and frequencies and percentages, respectively. Results: There was a decrease in the mean hemoglobin and hematocrit levels noted in the majority of patients after initiation of MDT from baseline 143.46 g/dl and 0.44, respectively, to 94 g/dl and 0.28 on the third month of MDT. The incidence rate of dapsone-induced hemolytic anemia during the 3-year period was 20 cases per 100. Conclusion The relatively high incidence rate of dapsone-induced hemolytic anemia highlights the importance of frequent monitoring of hemoglobin and hematocrit concentrations in leprosy patients being treated with multidrug therapy.
Hansen&rsquo ; s disease ; leprosy ; Dapsone ; hemolytic anemia

Sudden acute arterial occlusion can result from a multitude of pathological processes. Although the appearance and the secondary effects of an acute arterial occlusion are similar regardless of the underlying cause, the treatment and prognosis are different. Therefore, establishing a correct diagnosis is crucial. Acute arterial occlusion is most frequently a complication of ischemic cardiac disease, with an atrial fibrillation occurring in most patients. An identifiable noncardiac source of the acute arterial occlusion can be found in 5~10% of patients. Howerver, in these cases, the specific source of the occlusion cannot be determined clinically or even at autopsy. Possible hypercoagulable states should be suspected and appropriately evaluated, particularly in patients with no history of antecedent occlusive disease who present with sudden arterial occlusions, or in patients with malignant disease. Protein C and protein S deficiencies are frequently described as a cause of the hypercoagulable states. We reported 3 cases of acute arterial occlusion associated with protein C and S deficiencies.
Acute Disease ; Atrial Fibrillation ; Autopsy ; Diagnosis ; Heart Diseases ; Humans ; Pathologic Processes ; Prognosis ; Protein C* ; Protein S ; Protein S Deficiency

Authors investigated the possible role of intravascular hypercoagulable states on the etiology of Kegg-Clave-Perthes diesease. Forty-five patients with Legg-Clave-Perthes disease(31 avascular stages and 14 reossification stages) and twenty-two normal control patients were subjected to study for evaluation of coagulation and fibrinolysis system by means of the tests which included antiphospholipid antibody(APA), Protein C, Protein S and antithrombin- III (AT- III) for evaluation of coagulation system, and tissue type PIasminogen activator(tPA), Plasminogen activator inhibitor(PAI), D-dimer for fibrinolytic system. APA increased significantly in Legg-Clave-Perthes patients(p=0.016) as compared with control group, while Protein C(p=0.040) and Protein S(P=0.0001) decreased significantly in Legg-Clave- Perthes disease. AT- III increased in Legg-Clave-Perthes disease(p=0.0000). In contrast, there were no statistically significant differences in PAI, tPA, D-dimer between the Legg-Clave-Perthes disease and control group. There were no differences in all parameters between the avascular stage and reossification stage in patients with Legg-Clave-Perthes disease, Suggestive of possible inherent effect in coagulation system(hypercoagulable states) which does not change with time. Based on the above findings authors presumed that hypercoagulable state may contribute to the development of Legg-Calve-Perthes disease. However, to elucidate the etiology of Legg-Calve-Perthes disease, further extensive investigation should be followed, which include the familial tendency of hypercoagulable state, relationship with other multifactorial causes such as alcohol and steroids, and confirmation of intravascular thrombosis or decreased blood perfusion in the femoral head. Also, the significance of abnormally elevated AT-III on the disease should be answered.
Fibrinolysis ; Head ; Humans ; Legg-Calve-Perthes Disease ; Perfusion ; Plasminogen Activators ; Protein C ; Protein S ; Steroids ; Thrombosis

OBJECTIVETo evaluate the associations between polymorphisms of methionine synthase(MTR) A2756G and methionine synthase reductase(MTRR) G66A and risk of coronary artery disease.

METHODSLiteratures in Medline reporting the relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of coronary artery disease from January 1990 to May 2010 were searched. A total of 14 relevant articles were selected and 13 of them met the criteria. A Meta-analysis was performed to estimate the pooled odds ratio (OR) to evaluate the relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of coronary artery disease. All analyses were performed using the STATA statistical software.

RESULTSAmong the 13 studies, eight case-control studies containing 2143 cases of coronary artery disease and 2270 controls were included in the analysis of MTR A2756G and risk of coronary artery disease. Meanwhile, five case-control studies with 811 cases of coronary artery disease and 387 controls were included in the analysis of MTRR G66A and risk of coronary artery disease. In the analysis of MTRR G66A related to the risk of coronary artery disease, there were 246 GG carries, 397 AG carriers and 168 AA carriers in the group of coronary artery disease, against 102 GG carriers, 203 AG carriers and 82 AA carriers in the control group. Compared with the MTRR GG carriers, the risk of coronary artery disease decreased significantly by 27% (OR = 0.73, 95%CI: 0.54 - 0.99) and 25% (OR = 0.75, 95%CI: 0.56 - 1.00) (Egger's test t = -0.19, P = 0.862) in the MTRR 66 AG and AG/AA carriers, respectively, and also decreased in the MTRR AA carriers but significant difference was observed (OR = 0.84, 95%CI: 0.42 - 1.68). There was no significant association between coronary artery disease and MTR A2756G.

CONCLUSIONThese results suggest that MTRR66 may play a role in coronary artery disease susceptibility. MTRR 66 A allele carries are associated with a statistically significant decreased risk of coronary artery disease susceptibility.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Alleles ; Coronary Artery Disease ; genetics ; Ferredoxin-NADP Reductase ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans

OBJECTIVE: We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. METHODS: Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. RESULTS: The patients with AD were older than the normal controls (AD 74.03+/-7.90 yr vs. control 68.28+/-6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29+/-6.32% vs. 76.03+/-9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45+/-6.09% vs. 6.03+/-5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. CONCLUSION: The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.
Alzheimer Disease ; Cell Cycle ; Cell Cycle Checkpoints ; Flow Cytometry ; G1 Phase ; Humans ; Lymphocytes ; Neurons ; S Phase ; Sirolimus

Acute Disease ; Adult ; Female ; Humans ; Mesenteric Ischemia ; etiology ; surgery ; Pregnancy ; Pregnancy Complications ; surgery ; Protein S Deficiency ; complications ; Remission Induction

Elevated plasma homocysteine ( Hcy) is a risk factor for cognitive dysfunction and Alzheimer disease, although the mechanism is still unknown. Both folate and betaine, a choline metabolite, play essential roles in the remethylation of Hcy to methionine. Choline deficiency may be associated with low folate status and high plasma Hcy. Alterations in DNA methylation also have established critical roles for methylation in development of the nervous system. This study was un-dertaken to assess the effect of choline and folate deficiency on Hcy metabolism and genomic DNA methylation status of the liver and brain. Groups of adult male Sprague Dawley rats were fed on a control, choline-deficient ( CD) , folate-deficient ( FD) or choline/folate-deficient ( CFD) diets for 8 weeks. FD resulted in a significantly lower hepatic folate ( 23%)(p < 0.001) and brain folate ( 69%)(p < 0.05) compared to the control group. However, plasma and brain folate remained unaltered by CD and hepatic folate reduced to 85% of the control by CD ( p < 0.05) . Plasma Hcy was signi-ficantly increased by FD ( 18.34 +/- 1.62 micrometer) and CFD ( 19.35 +/-3.62 micrometer) compared to the control ( 6.29 +/-0.60 micrometer) ( p < 0.001) , but remained unaltered by CD. FD depressed S-adenosylmethionine ( SAM) by 59% ( p < 0.001) and ele-vated S-adenosylhomocysteine ( SAH) by 47% in liver compared to the control group ( p < 0.001) . In contrast, brain SAM levels remained unaltered in CD, FD and CFD rats. Genomic DNA methylation status was reduced by FD in liver ( p< 0.05) . Genomic DNA hypomethylation was also observed in brain by CD, FD and CFD although it was not signifi-cantly different from the control group. Genomic DNA methylation status was correlated with folate stores in liver ( r = - 0.397, p < 0.05) and brain ( r = - 0.390, p < 0.05) , respectively. In conclusion, our data demonstrated that genomic DNA methylation and SAM level were reduced by folate deficiency in liver, but not in brain, and correlated with folate concentration in the tissue. The fact that folate deficiency had differential effects on SAM, SAH and genomic DNA methylation in liver and brain suggests that the Hcy metabolism and DNA methylation are regulated in tissue-specific ways.
Adult ; Alzheimer Disease ; Animals ; Betaine ; Brain ; Choline ; Choline Deficiency ; Diet ; DNA Methylation* ; DNA* ; Folic Acid ; Homocysteine* ; Humans ; Liver ; Male ; Metabolism ; Methionine ; Methylation ; Nervous System ; Plasma* ; Rats* ; Rats, Sprague-Dawley ; Risk Factors ; S-Adenosylhomocysteine ; S-Adenosylmethionine

Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues. Apoptotic cell death plays an important role in the proliferation and turnover of cells in various tumors. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. Flowcytometric analysis of the cellular DNA content appears to be a useful clinical prognostic indicator in colorectal cancer. The relationship of apoptotic index(AI) and proliferative indices have being investigated. We analyzed the tumor DNA content and AI in 84 patients who underwent resection for colorectal cancer between January 1989 and December 1994 in order to evaluate the prognostic significance of apoptosis, DNA ploidy and index using in situ apoptosis detection method and flowcytometry. The mean value of AI was 32.4, and median value 21. In the cellular DNA, forty-two percent of the tumors were diploidy, fifty-eight percent aneuploidy. The mean value of DNA index(DI) was 1.38, G0/G1 72%, S phase fraction 21.7%, G2/M 6.3%, and proliferative fraction 28%. There was no significant difference between AI and tumor invasion, LN metastasis, DNA ploidy, DI.(p>0.05) There was no significance between overall survival and AI, DNA ploidy, DI. But patients who had tumors with low DNA index had a significantly longer disease free survival than high DNA index.(p<0.05) As a result, this study shows that AI is a less useful as prognostic factor and DNA index is a more important prognostic factor in patients undergoing surgery for colorectal cancer.
Aneuploidy ; Apoptosis ; Cell Death ; Colorectal Neoplasms* ; Diploidy ; Disease-Free Survival ; DNA* ; Drug Therapy ; Heating ; Hot Temperature ; Humans ; Neoplasm Metastasis ; Ploidies ; S Phase

Thromboembolic events are rare among systemic complications of inflammatory bowel disease; however, they are a significant cause of mortality when they occur. Several reports have considered thromboembolic events in patients with ulcerative colitis presenting with venous or arterial thromboembolism, such as cerebral thrombosis, deep vein thrombosis, pulmonary thromboembolism, portal vein thrombosis, or mesenteric vein thrombosis. However, increased coagulability related to Crohn's disease is extremely rare compared with that of ulcerative colitis. We report a case of a 42-year-old man with complicated portal hypertension that occurred due to extensive portal vein and mesenteric vein thrombosis. He had a monozygotic twin brother who was also in remission with Crohn's disease. The patient showed protein C and protein S deficiencies; however, he recovered with early anticoagulation therapy.
Colitis, Ulcerative ; Crohn Disease ; Humans ; Hypertension, Portal ; Intracranial Thrombosis ; Mesenteric Veins ; Portal Vein ; Protein C ; Protein S ; Pulmonary Embolism ; Siblings ; Thromboembolism ; Thrombosis ; Twins, Monozygotic ; Venous Thromboembolism ; Venous Thrombosis

The cyclin-dependent kinase (cdk) inhibitor p27Kip1 gene is a powerful molecular determinant of cell cycle progression. Loss of expression of p27Kip1 has recently been shown to be predictive of disease progression in several human malignancies. The prognostic value and expression of p27Kip1 have been incompletely studied in bladder cancer. In this study, we investigated the relationship between p27Kip1 protein expression and clinicopathologic parameters in 50 cases of carcinoma of the urinary bladder by conducting immunohistochemical analysis and DNA flow-cytometry. Malignant bladder tissue demonstrated a heterogeneous pattern of p27Kip1 immunoreactivity. In addition, there was progressive loss of expression with increasing tumor grade. The expression of p27Kip1 protein was unrelated to stage, DNA ploidy and S phase fraction (SPF). SPF was unrelated with tumor grade and DNA ploidy. The results indicate that p27Kip1 is frequently expressed in well differentiated transitional cell carcinomas of the urinary bladder but less often expressed in muscle-invasive transitional cell carcinomas. The expression of p27Kip1 and its prevalence in low-grade tumors may reflect growth regulatory influences and potential inhibiting action in tumor progression and novel predictive markers of the biological potential of bladder tumors.
Carcinoma, Transitional Cell ; Cell Cycle ; Cyclin-Dependent Kinase Inhibitor p27* ; Disease Progression ; DNA ; Humans ; Phosphotransferases ; Ploidies ; Prevalence ; S Phase ; Urinary Bladder Neoplasms ; Urinary Bladder*