Predetermined Anti-Diabetic Drug Regimen Adjustments during Ramadan Fasting: An Observational Study of Safety

BACKGROUND: Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan. METHODS: In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen. RESULTS: No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B. CONCLUSION: The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.

Medicolegal significance of diffuse axonal injury [DAI]: a forensic, histopathological and immunohistochemical interpretation

In some head trauma cases, there is no obvious cause of death and no brain lesions detected despite the positive history and the short survival time. This study was conducted to evaluate immune-histochemistry for Beta-Amyliod Precursor Protein [beta-APP] in detection of DAI. It was carried on 50 autopsy cases, 39 males and 11 females, aging between the 2[nd] to the 5[th] decades of life. Survival period was around 3 hours up to 4 weeks. The cause of head injury was determined. Complete autopsy were done. Selected brain sections were prepared for examination with routine hematoxylin and eosin [H and E], special stains Phosphotungstic Acid Hematoxylin [PTAH] stain and beta-APP, Neuro Specific Enulase [NSE], S 100, Synapto- Physin, Glial Fibrillary Acid Protein [GFAP] immunohistochemistry. The brain was assessed grossly at two settings; before its removal from the skull and after 2 weeks of fixation in 10% buffered formalin. The results revealed that, there is no significant difference between age and sex, the causes of head injury were more common due to violent assaults, and motor vehicle accidents. OAI is not always associated with skull fractures. There is a highly significant difference for the presence of intracranial hemorrhage. Both H and E stain and PTAH stain can diagnose brain edema, OAI, as regards axonal swelling and damage after 6 hours post traumatic survival period. In early survival stage, [beta-APP] is highly significant for detection of axonal swelling as early as 3 hours survival period. GFAP stain has highly significant value in detecting the glial cells and gilosois in the late survival stage. The beta-APP is a more sensitive and accurate method for early detection of OAI. It should be considered as an important technique that could provide valuable medico-legal evidences

Tracing the effect of antidepressants therapy on handwriting documentaries

Handwriting is an acquired skill that is considered one of the most important parameters of personal identification. The production of handwriting involves a complex physical act between the brain and the moving hand and fingers in an extensive muscle and nerve system coordination to produce the finished writing. Some of the centrally acting drugs such as antidepressants can exhibit some interventions, which interfere with the process of writing. The aim of this work is to study the changes in the individual handwriting after different periods of therapeutic intake of the two main classes of antidepressant drugs from different technical points of view that are important in forensic document examination. In this study, 70 right-handed educated adult males and females were included by their handwritings. They were selected from the outpatients of the neuropsychiatric clinics in Kasr El-Aini hospitals. They were receiving regular antidepressants therapeutic regimen of one of the two targeted classes. Every subject was asked to present a personal handwriting document prior to the start of the treatment. A part of this document [about 4-5 lines] with its exact verbal contents was asked to be written by the same person. In all cases, the writing position was standardized regarding the posture of the writer and his position in front of the desk. The pen used was the same in all cases to facilitate the detection of the fine changes in the handwriting features. Groups were matched according to age, sex, treatment duration and the type of the used drug. It was shown that after drug intake there was a significant increase in tremors, pen pressure and word size in TCA users more than SSRI users. In addition, there were significant retouching and disturbance in word shape in TCA users more than SSRI users. Recorded changes were more obvious in males than females especially in patients aged more than 50 years. The results revealed direct relationship between duration of exposure to antidepressant drugs and their effects on handwriting parameters. Non significant increase in retouching, pen pressure, tremors and word size was recorded in TCA users when compared to SSRI users. [In conclusion, the effect of antidepressant drugs on the handwriting has to be considered while examining a document by the forensic expert, so as not to be misled by the drug intake and judge the document as a forged one

Spectrometric, thermal and electron microscope studies of iron complexes of adrenaline hydrogen tartrate and catecholamine

Iron was found to form coloured stable complexes with both adrenaline hydrogen tartrate and catechol as inhibitors for iron corrosion in aqueous solutions of different pH values [2.0-11.5]. The electrochemically formed complexes on the surface of the iron electrode in different media were separated and studied in comparison with the same complexes prepared by chemical method in the same media. The prepared complexes were studied using micro-, electro-and thermal analyses together with electron ionization mass [EI-MS] and IR spectral methods. Both chemically and electrochemically prepared complexes were found to be of the same structures. The electrochemically formed complex in different media was found to be as a chemisorbed layer on the surface of iron electrode. The aim of the present work is to compare the results of chemical and electrochemical techniques in preparation of stable iron chelates of both adrenaline hydrogen tatrate [AHT] and Catechol [Cat.] as inhibitors for iron corrosion. The morphology of the chemisorbed complex layers on the electrode surface was also tested by electron microscope [EMS] and characterized as an amorphous or crystalline adsorbents

Effect of chemical composition of zinc phosphating solution on phosphate coating properties

Phosphate coatings have a wide field of applications in industry. The applications of coatings are classified according to the film thickness and the type of solution employed. In this study the phosphating process in the zinc-phosphating-nitrate accelerator on steel gave a phosphating layer of suitable morphology which was investigated by different instruments like SEM/EDS and XRD. The crystal size and the thickness of phosphating layer were found to be iron content dependent. Therefore, adjusting of phosphate, zinc and iron concentrations is very important to get a suitable phosphating effective process. The aim of the present work is to control the iron concentration in the phosphating bath in order to improve the quality and adhesive properties of zinc phosphating coating on steel sheets that always used for military purposes in Helwan Engineering Company in Egypt

Investigation of molecula structure - chirality relationship of ephedrine and pseudoephedrine drug using thermal analyses and mass spectrometry techniques combined with MO-calculations

Two diastercoisomers ephedra drugs namely; ephedrine [eph.] and pseudoephedrine [psi-eph.] hydrochloride, have been investigated for their chirality using thermal analysis [TA] measurement [TG/DTA] and electron ionization mass spectrometry [EI-MS] at 70 eV. Monte Carlo conformational search technique was used for exploration of conformational space of ephedrine and psi-eph., using Amber force field molecular mechanics method. MO-calculations were performed using semi-empirical PM3 procedure on the obtained conformational sample for investigation of the different molecular properties. The calculations include bond length, bond order, charge distribution, ionization energy and heat of formation, in neutral and positively charged forms for the two drugs. The effect of diastereoisomerism on thermal analysis decomposition behavior of these drugs was studied. The obtained data confirmed the chirality and declared the structure reactivity relationship of these drugs

Electrochemical behavior of copper electrode in different solutions of adrenalin chydrogentatrate and catechol

Galvanic anodic polarization of copper electrode at different current densities in electrolytes of different pH values containing adrenaline hydrogen tartarte [AHT] and catechol [Cat.] have been studied. The effect of complex formation on the underlying anodic reactions and inhibition effect of these complexes on copper electrode is also studied. The cathodic deposition of copper in the prepared complexes on the surface of the cathode is involved to check their stability at different pH values and the effect of this stability on cathodic behavior of copper electrode

Kinetic spectrophotometric methods for the quantitation of sertraline drug in bulk and in formulations

Kinetic methods [fixed concentration, rate constant and fixed time] for the sensitive and accurate spectrophotometric microdetermination of sertraline basic drug have been described. The methods are based on the reaction between sertraline and iodine in 1,2-dichloroethane as a suitable medium. At a fixed time of 10 min, the spectrum of the formed inner and / or outer-sphere complexes [Drug. I+] I- / and or [Drug I2] is measured at a suitable selected lambdamax = 396 nm. The concentration of sertraline drug, in its pure form is calculated using the calibration equation for the fixed time method. Beer's law was obeyed in the concentration range of 1.6-48 microg ml[-1] and the recovery in average was 99.85%. The relative standard deviation RSD [n = 7] at 8 micro g ml[-1] is 0.65% and at 24 micro g ml[-1] is 0.88% within-day, and at 10 micro g ml[-1] is 0.67% and at 20 micro g ml[-1] is 0.84% for between-day, respectively. Therefore, the intera- and inter-day RSD values indicated the ruggedness of the fixed time kinetic method. The method is suitable for quantitative determination of sertraline in the concentration range of 6-20 microg ml[-1] in pharmaceutical formulation [Lustiral] after its separation as a basic form out of drug formulation additives like starch, glucose, ... etc without interference. The results obtained agreed well with the data obtained by an official method. The determination of sertraline by fixed concentration and rate constant methods is feasible with the calibration equations obtained but the fixed time method is more accurate

Structure investigation of piroxicam and tenoxicam using thermal analyses, mass spectrometry and semi-empirical MO calculations

Steroidal and non-steroidal anti-inflammatory agents such as oxicam group [e.g. piroxicam [Pir] and tenoxicam [Ten] were investigated using thermal analyses [TA] measurements [TGA, DTGA, DTA and DDTA] in comparison with El mass spectral [MS] fragmentation at 70 eV. Semi-emperical molecular orbital [MO] calculations have been carried out using PM3 described by Stewart on Pir and Ten both as neutral molecules and the corresponding positively charged molecular ions. These calculations included molecular geometries such as bond length, bond order, bond strain, atomic charge distribution and hybridization, and heat of formation of these drugs. Thermal analyses reveal a high response of Pir and Ten to temperature variation with a cleavage of six bonds in aliphatic side chains around O, S, and N heteroatom, leaving aromatic radicals as final products, which become volatile at high temperature. TA mostly involved fragmentation of SO2 gas molecule at first followed by C, N, and O containing fragments as CH3CN, CHO, NHCONHCO, and NHCO. The MS fragmentations indicate the presence of the same final products as given by TA technique. Mass fragmentation pathways refer to the loss of more or less the same fragments via cleavage of seven bonds of Pir and nine bonds of Ten molecular ions, in parallel and many consecutive steps as explained by geometries values calculated by MOC. These may refer to the instability of Pir and Ten molecular ions in comparison with their neutral forms. This instability is explained by comparison of the calculated partial charges on their atoms and/or their heat of formation values. The best pathway in both TA and MS techniques is that starts with the loss of SO2 gas molecule and followed by the loss of HCO and CH3CN molecules. The partial charge values and the stereo structures of ionic and neutral form refer to a distinct phenomenon of collection of voluminous charge density on SO2 group covering in space most atoms behind. It is explained by the highest electron withdrawing abilities of the heteroatom, two O and S in this group as a result of their high electro negativities. This rationalized the starting of fragmentation process in TA and MS with the loss of SO2 gas molecules. Therefore, a MOC was applied to declare both TA and MS observations

Neopterin levels in patients with post hepatitis C chronic liver disease

Hepatitis C virus causes biochemical, immunological and histological changes in host immuno response against the virus. Neopterin [NPT] is a valuable marker of cell-mediated immunity that reflects the degree of T helper-1 [Th-I] immune activation. Evaluation of the significance of serum neopterin as a marker of cellular immune response in patients with different states of post hepatitis C chronic liver disease. Seventy patients with post hepatitis C chronic liver disease were included in the current study: 40 patients with chronic hepatitis C and 30 patients with liver cirrhosis in addition to 15 healthy individuals as a control group. Patients were assessed and evaluated by laboratory instigations and liver biopsy to determine the severity of the disease. Serum neoterin level was significantly elevated in patients with chronic hepatitis C virus infection and cirrhosis compared to the control group with distinctly higher concentrations in the cirrhotic stage than those in he non-cirrhotic stage of disease. Neopterin may be an early and valuable biochemical marker of cellular immunity which is activated upon simulation of cells by interferon. Measurements of immune activation by NPT could potentially be helpful surrogate markers in progression of liver disease

Genetic polymorphisms of DNA repair gene XRCC1 and susceptibility to acute leukemia

Defective DNA repair has been reported to be a risk factor for various malignancies. Polymorphisms of DNA repair genes could alter protein structure and may impair DNA repair capacity. Genetic polymorphisms of XRCC1 gene could lead to defective base excision repair [BER] pathway resulting in impaired DNA repair capacity and increased risk of acute leukemia. To determine the possible effect of XRCC1 gene polymorphisms 194Arg to Trp and 399Arg to Gin on the risk of development of acute leukemia in a group of Egyptian patients. The study was also extended to evaluate the association between these polymorphisms and disease outcome. Polymorphisms of XRCC1 codon 194 [Arg to Trp] and codon 399 [Arg to Gin] were genotyped in 35 patients with acute lymphoblastic leukemia [ALL], 35 patients with acute myeloid leukemia [AML] and 70 healthy controls using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Individuals with heterozygous XRCC1 194 Arg/Trp variant demonstrated a significant increased risk of AML than controls [Odds Ratio [OR] 3.5, 95% confidence interval [CI], 1.3-9.5]. The frequency of homozygous XRCC1 399 Gin/Gin variant was statistically higher in ALL patients than controls [OR 3.69, 95% CI, 1.19-11.4]. Stratification for sex with regard to codon 194Trp carriers showed that males had 3.2-fold increased risk of ALL than females with borderline significance. In case of codon 399Gln polymorphism, a highly significant risk of ALL among females was observed with 7.5-fold increased risk. The frequency of XRCC1 haplotype A [399Gln carriers and 194Trp carriers] was significantly higher in both ALL and AML patients than controls [OR5.2, 95% CI, 1.6-16.7, p-value <0.01 for ALL] [OR 3.2, 95% CI, 0.9-11.1, p-value=0.055 for AML]. The polymorphic variant of XRCC1 194Trp has a significant unfavorable effect on disease outcome among ALL and AML patients [p-value 0.002 and 0.05 respectively]. Acute lymophoblastic leukemia patients carrying the 399Gln allele experienced a significant unfavorable outcome than ALL patients carrying the wild-type allele [p-value<0.01]. An increased risk of AML among carriers of XRCC1 194Trp and an increased risk of ALL among patients with XRCC1 399Gln variant genotypes were observed. Combined presence of XRCC1 194Trp and 399Gln variants [haplotype A] had significantly higher risk of both ALL and AML. The polymorphic variants of XRCC1 codons 194 and 399 had significant unfavorable effect on disease outcome of both AML and ALL

Study of reaction mechanism between piroxicam and tenoxicam drugs with iodate and N-bromosuccinamide oxidants and their microdetermination by spectrophotometric and potentiometric measurements

Piroxicam [Pir] and tenoxicam [Ten] are specified as nonsteriodal anti-inflammatory drugs. They are used in the symptomatic management of osteoarthritis, rheumatoid arthritis and in short term management of soft-tissue injury. Therefore, their reactions with oxidants, Iodate and N-bromosuccinamide [NBS] are suggested, discussed and used for microdeterminations of these essential biomedical drugs. A sensitive Spectrophotometric method has been suggested and used in comparison with a potentiometric one to follow these reactions mechanisms aiming to apply them in microdetermination of piroxicam [Pir] and tenoxicam [Ten]. No interference from excipients was observed in both techniques. The Spectrophotometric procedure was better than the potentiometric one, because of the sensitivity of the former to detect lower concentration ranges [50 to 1100 micro g ml[-1]] of the pure standard drugs and the detection of high concentration range [300 to 3980 micro g ml[-1]] by the latter. The high molar absorptivity [e = 0.25-0.29 x 10[3] L.mol[-1] cm[-1]] and Sandell sensitivity [1.2 - 13 micro g cm[-2]] refer to the high selectivity of the Spectrophotometric method. The between -day precision of the potentiometric procedure refers to the greater stability and good reliability of this procedure in high concentration [% recovery = 99 to 102%]. These procedures were applied for successful microdetermination of Pir and Ten in many pharmaceutical preparations, such as tablets and capsules. The values of SD [0.03 to 0.6 for five replicates] and RSD [0.6 to 1.2%] refer to reproducibility and precision of the applied procedures. The results of analyses of these drugs were compared with those obtained by the application of the official method using Ringbom, t-test and f-test. These results gave t- value of 2.776 and f-value of 6.31 at 95% confidence level. The obtained results also refer to the robustness of the proposed procedures

Detection of bcl-2 translocation in patients with chronic hepatitis C and its possible relation to antiviral therapy: preliminary study

It has been suggested that t[14;18] translocation of bcl-2 to the immunoglobulin heavy chain [IgH] locus may contribute to the pathogenesis of lymphoproliferative disorders [LPD] related to hepatitis C virus [HCV] infection. The present study aimed to assess the prevalence of bcl-2 translocation in Egyptian chronic HCV patients and to investigate the effect of combination antiviral therapy of interferon alpha and ribavirin on t[14;18]. Fifty five chronic HCV patients were studied for the prevalence of t[14;18]. These patients were classified into 2 groups, 33 non treated HCV patients and 22 treated HCV patients with antiviral therapy as well as control group of age and sex matched individuals. The bcl-2/IgH rearrangement was detected in peripheral blood mononuclear cells [PBMCs] by nested polymerase chain reaction. All patients have undergone HCV viral determination by real time PCR. Bcl-2/IgH translocation was detected in 21 [38.2%] of all 55 chronically infected HCV patients. Considering all patients with chronic HCV-infection, bcl-2 rearrangement was slightly more frequent in the non treated group than in those who underwent treatment with interferon plus ribavirin but the difference was not statistically significant, although treated patients showed biochemical and virologic response at the end of 6 months of antiviral therapy. In conclusion, t[14;18] in PBMCs is a frequent finding in chronic HCV infection

Spectrophotometric assay of levodopa and alpha-methyldopa in pharmaceutical products and in biological samples of schizophrenic patients using copper complex and tri-iodide reagent

Two simple, rapid and sensitive spectrophotometric methods are proposed for the determination of levodopa [LD] I, and alpha-methyldopa [alpha -MD] II. The first method is based on coupling of 4-aminoantipyrine [4-AAP] with LD and a alpha -MD to give new ligands that react with copper-tetramine complex to give intense colored chelates of ratios [1:1:1, LD or alpha -MD: 4-AAP: copper tetramine]. The colored products are quantified spectrophotometrically at 520 and 545 nm for LD and a alpha -MD, respectively. The optimization of the experimental conditions is described. The method has been used for the determination of 19.72-69.02 and 31.24-98.94 micro g ml[-1] of drugs I and II, respectively. The accuracy of the method is indicated by the values of recovery [100 +/- 0.2%] and the precision is supported by the low standard deviation [SD 0.17-0.22] and relative standard deviation [RSD=0.59-1.54%]. The second method is based on the formation of ion-pair iodinated inner sphere or outer sphere colored complexes between the drug and iodine or tri-iodide negative ions at pH 5 and room temperature [25 +/- 3°C]. This method has been used for the determination of LD within the concentration range 39.44-78.88 micro g ml[-1] with SD=022-0.24 and recovery percent=100 +/- 0.3%. The sensitivity of the two methods is indicated by Sandell factor of 0.014- 0.016 g cm[2]. The results of the two methods are compared with those of the official method. The interference from common drug additives, degradation products and excepients was also studied. The proposed methods were applied successfully to the determination of LD and alpha-MD in dosage forms. The second method was also successfully applied for the analysis of LD and carbidopa [CD] synthetic mixture of concentration of these drugs similar to that of Aldomost drug form of LD, and also the determination of these drugs in urine of some schizophrenic patients with good precision and accuracy. The reliability of the methods was established by parallel determinations against the official British pharmacopoeia method

Investigation of malonanilide and its dinitro-isomers using thermal analyses, mass spectrometry and semi-empirical MO calculation

In this paper malonanilide compound [M 1], and its dinitro-isomers [M 2 - M 4] compounds were investigated. The evaluation has been performed using thermal analyses [TA] measurements in comparison with electron ionization [EI] mass spectral [MS] fragmentation. Knowledge gained from experimental work was combined with theoretical calculations for neutral molecules, using the Modified Neglect of Diatomic Overlap [MNDO] semi-empirical MO calculations. The theoretical calculations include molecular geometry, bond order, charge distribution and heats of formation. For all the studied compounds, the major fragmentation pathways in TA and MS [including intermediates] is a CO-CH 2 bond rupture, followed by ketene [COCH 2] loss to form the nitroaniline structure. The MNDO procedure provides a basis for fine distinction among sites of initial bond cleavage, which is crucial to the rationalization of subsequent fragmentation of the molecule. Also, the thermal behavior decomposition due to ortho effect for o,o-dinitromalonanilide is discussed in terms of experimental and the MO calculations

Spectrophotometric determination of levodopa, carbidopa and alpha-methyldopa

The dopamine derivatives participate in the regulation of a wide variety of physiological functions in human body and in medication life. A sensitive spectrophotometric method is developed for the determination of levodopa [LD], carbidopa [CD] and alpha methyldopa [MD]. It proposed on the bases of metal complex formation of these compounds with copper tetramine then coupling with 4-aminoantipyrine. The optimum conditions [pH, time, ratio and sequence of addition] are established. The method permits the determination of LD, CD and MD as a rectlinear relation in calibration curve over a concentration range 19.72 to 69.02, 13.79 to 63.34 and 31.24 to 98.94 micro g ml -1, respectively. The obtained data of SD [0.174 to 0.59], CV [0.68 to 1.16%] and correlation coefficient [0.995 to 0.999] reflect the reliability, reproducibility and accuracy of this procedure. The method is applicable to the assay of LD and MD in pharmaceutical drugs [Levocare and Aldomet respectively], and the results are in a good agreement with those obtained by the official method. The method was simple, rapid, reproducible and accurate to follow of medication of schizophrenic patient

Prevalence of activated protein C resistance, factor V Leiden and prothrombin 20210A mutations among patients with venous thromboembolism

Venous thromboembolism [VTE] is a multifactorial disease. Multiple interactions between genetic and environmental factor contribute to the development of the disease. Factor V [F V] Leiden and factor II[F II] G 20210A mutations are two frequent genetic risk factors involved in VTE. The goal of this case control study which was carried on 30 young patients with VTE and 20 age matched controls was to determine the prevalence of activated protein C resistance [APC-R], FV Leiden mutation as well as F II 20210A mutation as risk factors for VTE in the studied groups. Both patients and control groups were subjected to proper history taking including personal and family history, routine laboratory and coagulation tests including liver function [SGOT, SGPT], random blood sugar, total cholesterol, PT, and APPT. Our results revealed the history of immobilization was the only acquired risk factor which showed a statistically significant difference [p=0.01] between the two studied group. Actifed protein C sensitivity ratio and the normalized sensitivity ratio [APC-SR and APC-SR] were all significantly lower in the patients' group as compared to the control group with p values of 0.002 and 0.002 respectively. Factor V Leiden was detected in 30% of patients and 5% of controls with F II 202140A mutation was only detected in 6.7% of significantly lower APC-SR and n-APC-SR when compared to patients without the emulation with p values < 0.001. Simultaneous detection of both studied mutation was not recorded in any of our cases

Aberrant p15 promotor methylation in acute leukaemia

The p15 gene is one of the tumour suppressorgenes located on chromosome 9p21. In acute leukemias alterations involving the p15 gene have been reported. Commonly, these alterations involve the c[p]g islands that are commonly aberrantly methylated and result in the transcriptional loss of this gene. To detect this aberrant methylation, we used methylation specific pcr which is a novel method of pcr that can rapidly assess the methylation status of virtually any c[p]g island. The study included 30 patients: 17 cases of the novo all and 13 cases of de novo aml. Aberrant p15 gene mehylation was detected in 47.1% of cases of all and in 69.2% of casaes of AML. There was no statistically significant difference between methylated and unmethylated cases regarding the clinical and haematological data other than the peripheral blood blast cell count. On following up the patients to detect the response to therapy, there was a statistically significant difference in the response to therapy between methylated and unmethylated cases [p< 0.05]. Methylated case had a higher incidence of relapse or death [in all methylated cases 35.4% of the studied cases relapsed and 61.6% in aml patients] while the inidence of remission was 11.7% for all methylated cases and 7.7% for aml cases. Unmethylated all cases achieved remission in 41.2% of the studied group and unmethylated cases of AML reached remission in 61.6%. Aberrant p15 methylation may have important prognostic implications for clinical monitoing. And risk assessment. Also it opens new strategies of treatment using demethylating agents that can reverse this epigenetic change

Continuous renal replacement therapies in ICU patients with septic shock: impact on inflammatory mediators removal

Continuous renal replacement therapies are widely used for patients with acute renal failure specially in critically ill patients in ICU. It has been suggested that hemofiltration may also eliminate toxic mediators thought to be important in the pathophysiology of sepsis. The present study examined whether hemofiltration can eliminate inflammatory mediators in patients with sepsis. A total of 28 consecutive patients with septic shock, as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. All patients had renal affection. Patients were randomly assigned to receive hemofiltration in addition to usual ICU care [n = 17] [group 1], or to usual care plus hemodiafiltration [n =11 [group 2]. We measured the plasma concentrations of complement fraction C3a, IL-6 and TNF -a at baseline, 2 hours and 24 hours after these procedures. C3a showed a fall in concentration between baseline and 2 hrs, which not reached statistical significance during hemofiltration [from median 495.5 to 363 ng/ml, P =.48] and statistical significance during hemodiafiltration [from median 524 to 379.7 ng/ml, P = <0.05]. Furthermore, during HF C3a showed a significant fall in concentration during the interval between 2 hrs and 24hrs [from median, 363 to 274.6 ng/mL, p<0.05], HDF [from median, 379.7 to 215.8 ng/mL, p<0.05]. TNF showed a fall in concentration between baseline and 2 hrs, which reached statistical significance during hemofiltration [from median 397.9 to 332.8 pg/ml, P =0.035] and statistical significance during hemodiaflltration [from median 430.7 to 347.2 pg/ml, P 0.02]. However, during HF TNF showed a non significant change in concentration during the interval between baseline and 24hrs [from median, 397.9 to 410.4 pg/mL, p = 0.6], HDF [from median, 430.7 to 405.6 pg/mL, p = 0.5]. IL-6 showed a fall in concentration between baseline and 2 hrs, which reached statistical significance during hemofiltratio in [from median 1051 to 843.6 pg/ml, P =0.03] and statistical significant during hemodiaflltration [from median 1111.3 to 859 pg/ml, P 0.025]. However, during HFJL-6 showed a non significant change in concentration during the interval between baseline and 24hrs [from median, 1051 to 905 pg/ml, p = 0.13], HDF [from median, 1111.3 to 901.9pg/mL, p = 0.07]. No correlation were detected between inflammatory mediators removal and changing the size of hemofilter [surface area 0.7 and 1.35 square meter] p>0.05. or changing hemofiltration rate [from 1 to 2 liters/hour]. p>0.05. In conclusion, short-term hemofiltration with a highly biocompatible membrane in patients with septic multiple organ dysfunction syndrome and renal failure may even eliminate some of the mediators from septic plasma like C 3a. Filtration of the classic cytokines IL-6 and TNF-a is presumably of minor importance, but clearance of the first few hours may occur so we cannot advocate the use of continuous therapies as a treatment in sepsis for removal of inflammatory mediators only, but in presence of renal affection, these slow renal replacement therapies results in fewer cardiovascular side effects than intermittent techniques, Furthermore, continuous hemofiltration allows better control of fluid balance and simultaneous continuation of total parenteral nutrition in addition to reduction of anaphylatoxin concentrations which could be of clinical importance, since beneficial therapeutic effects in sepsis have been correlated with a fall of anaphylatoxin concentrations