Decline In Hematocrit Research Articles

A Single Sea Lamprey Attack Causes Acute Anemia and Mortality in Lake Sturgeon

The effects of sea lamprey Petromyzon marinus parasitism on hematological variables have not been quantified for lake sturgeon Acipenser fulvescens. Our study objectives were to (1) assess changes in lake sturgeon hematology immediately after a single sea lamprey attack and after a 2-week recovery period and (2) assess changes in the histological condition of major hematopoietic organs. Lake sturgeon from four size-groups (470-570, 570-650, 650-760, and 950-1,500 mm fork length) were individually subjected to a sea lamprey attack in a series of 55 experimental trials. Survival of lake sturgeon after a single sea lamprey attack was size dependent, with fish in smaller size-groups exhibiting higher direct and indirect mortality than individuals in larger size-classes. The most sensitive blood chemistry variable was hematocrit: each 1% decline in hematocrit resulted in a 5.1% increase in mortality risk. Other important variables were plasma protein level, with a 10-g/dL decline resulting in a 4.2% increase in mortality risk; and hemoglobin, with a 1-g/dL decline resulting in a 2.9% increase in mortality risk. Most of the surviving lake sturgeon were unable to restore hemoglobin, hematocrit, and plasma protein to pre-attack levels by the end of the 2-week recovery period. We developed an index of histological spleen condition, which indicated that short-duration (< 5-d) sea lamprey attachments depleted red blood cell reserves faster than longer-duration attacks. Our study results indicate that sea lamprey parasitism has the potential to induce acute anemia in lake sturgeon and that nonlethal attacks on smaller (< 760-mm) fish can have serious physiological implications.

Higher-dose oxytocin and hemorrhage after vaginal delivery: a randomized controlled trial.

Higher-dose oxytocin is more effective than lower-dose regimens to prevent postpartum hemorrhage after cesarean delivery. We compared two higher-dose regimens (80 units and 40 units) to our routine regimen (10 units) among women who delivered vaginally. In a double-masked randomized trial, oxytocin (80 units, 40 units, or 10 units) was administered in 500 mL over 1 hour after placental delivery. The primary outcome was a composite of any treatment of uterine atony or hemorrhage. Prespecified secondary outcomes included outcomes in the primary composite and a decline of 6% or more in hematocrit. A sample size of 600 per group (N=1,800) was planned to compare each of the 80-unit and 40-unit groups to the 10-unit group. At planned interim review (n=1,201), enrollment in the 40-unit group was stopped for futility and enrollment continued in the other groups. Of 2,869 women, 1,798 were randomized as follows: 658 to 80 units; 481 to 40 units; and 659 to 10 units. Most characteristics were similar across groups. The risk of the primary outcome in the 80-unit group (6%; relative risk [RR] 0.93, 95% confidence interval [CI] 0.62-1.40) or the 40-unit group (6%; RR 0.94, 95% CI 0.61-1.47) was not different compared with the 10-unit group (7%). Treatment with additional oxytocin after the first hour was less frequent with 80 units compared with 10 units (RR 0.41, 95% CI 0.19-0.88), as was a 6% or more decline in hematocrit (RR 0.83, 95% CI 0.69-0.99); both outcomes declined with increasing oxytocin dose. Outcomes were similar between the 40-unit and 10-unit groups. Compared with 10 units, 80 units or 40 units of prophylactic oxytocin did not reduce overall postpartum hemorrhage treatment when administered in 500 mL over 1 hour for vaginal delivery. Eighty units decreased the need for additional oxytocin and the risk of a decline in hematocrit of 6% or more. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00790062. I.

Blunt trauma induced splenic blushes are not created equal

BackgroundCurrently, evidence of contrast extravasation on computed tomography (CT) scan is regarded as an indication for intervention in splenic injuries. In our experience, patients transferred from other institutions for angioembolization have often resolved the blush upon repeat imaging at our hospital. We hypothesized that not all splenic blushes require intervention.MethodsDuring a 10-year period, we reviewed all patients transferred with blunt splenic injuries and contrast extravasation on initial postinjury CT scan.ResultsDuring the study period, 241 patients were referred for splenic injuries, of whom 16 had a contrast blush on initial CT imaging (88% men, mean age 35 ± 5, mean ISS 26 ± 3). Eight (50%) patients were managed without angioembolization or operation. Comparing patients with and without intervention, there was a significant difference in admission heart rate (106 ± 9 vs 83 ± 6) and decline in hematocrit following transfer (5.3 ± 2.0 vs 1.0 ± 0.3), but not in injury grade (3.9 ± 0.2 vs 3.5 ± 0.3), systolic blood pressure (125 ± 10 vs 115 ± 6), or age (38.5 ± 8.2 vs 30.9 ± 4.7). Of the 8 observed patients, 3 underwent repeat imaging immediately upon arrival with resolution of the blush. In the intervention group, 4 patients had ongoing extravasation on repeat imaging, 2 patients underwent empiric embolization, and 2 patients underwent splenectomy for physiologic indications.ConclusionsFor blunt splenic trauma, evidence of contrast extravasation on initial CT imaging is not an absolute indication for intervention. A period of observation with repeat imaging could avoid costly, invasive interventions and their associated sequelae.

Haematological changes in Bufo maculatus treated with sublethal concentrations of Cadmium

Adult &lt;em&gt;Bufo maculatus&lt;/em&gt; was exposed to sublethal cadmium concentrations of 0.25, 0.50, 1.00 and 2.00 mg/L. The toxicant from which the cadmium concentrations were prepared was cadmium chloride (CdCl2.H2O). There were three replicate tanks per treatment and three individuals per tank including control groups. The hematologic alterations based on the examination of blood indices during the 28 days of exposure showed that total erythrocyte count (TEC), hematocrit (Hct) and hemoglobin (Hb) concentration decreased (P&amp;lt;0.05) relative to controls. The decline was concentration- dependent as concentration of cadmium increased. The decline in hemoglobin and hematocrit in the experimental organism could be due to a decrease in the synthesis or release of erythrocytes into the circulation or an increase in the rate of erythrocyte destruction inflicted by cadmium toxicity. There was significant (P&amp;lt;0.05) elevation in total leuko- leukocyte count (TLC) with increase in the concen- cyte concentration of cadmium. The increase in total leukocyte count observed in this study could be attributed to a stimulation of the immune system in response to tissue damage caused by cadmium toxicity. The study has shown that the exposure of the &lt;em&gt;Bufo maculatus&lt;/em&gt; toad to cadmium can inflict alterations in the hematologic indices, which could induce unfavorable physiological changes in the amphibian, which may lead to death. There is, therefore, the need to protect amphibians in order to sustain the biodiversity in the Nigerian Niger Delta ecological zone.

Esophageal Pseudodiverticulosis Presenting with Massive Gastrointestinal Bleed

Purpose: Introduction: Esophageal intramural pseudodiverticulosis (EIP) is a rare benign disease of uncertain significance. We report a case of EIP which presented with massive self-limiting gastrointestinal bleed. Case: A 63 year old male presented to the emergency department with hematemesis and postural dizziness. His medical history was significant for coronary artery disease, diabetes mellitus, hypertension, esophageal candidiasis, alcohol and tobacco abuse. His heart rate was 111 per minute and BP was 104/70 mmHg without orthostasis. Abdominal examination did not reveal any significant abnormality. His hemoglobin was 12.7 gm/dl and hematocrit 40.2% compared to baseline values of 13.7 gm/dl and 44% respectively. In the emergency department he had two bouts of hematemesis with clots and a significant decline in hematocrit. He was volume resuscitated, started on esomeprazole infusion and transfused two units of packed RBC. After stabilization EGD was performed which revealed extensive pseudodiverticulosis of the esophagus from about 25 cm down to the distal esophagus. Erosive non-bleeding reflux induced distal esophagitis was also seen (Los Angeles Grade B). He remained stable during hospital stay without any recurrence of bleeding and was subsequently discharged on oral omeprazole. Discussion: EIP is a rare disease characterized by small sac like out pouching of the esophageal wall. Men between the ages of 50-70 years are most commonly affected and reflux esophagitis, diabetes mellitus and chronic alcoholism are well known associations. This benign esophageal disease is also known to be associated with candidial, herpetic and eosinophilic esophagitis. Our patient had a history of esophageal candidiasis which along with multiple other risk factors may have contributed to the pathogenesis of pseudodiverticuli. The pathophysiology of EIP remains unclear. The most widely accepted hypothesis is based on chronic mucosal inflammation resulting in squamous metaplasia of glandular epithelium with ductal dilatation and formation of pseudodiverticuli. Although esophagitis is a very commonly observed endoscopic finding, pseudodiverticulosis is extremely rare and this paradox is difficult to explain. Most patients present with dysphagia, odynophagia or chest tightness, hematemesis is rare. There are only two reported cases of EIP presenting with gastrointestinal bleeding. Endoscopy is the diagnostic test of choice and these small diverticular openings can be missed in the absence of detailed examination with adequate air insufflation. Treatment is aimed at relieving obstructive symptoms when present or treating underlying causes such as esophagitis in our case.

Low-Dose Heparin Retention in Temporary Hemodialysis Double-Lumen Catheter Does Not Increase Catheter Occlusion and Might Reduce Risk of Bleeding

Background: The objective of this study was to assess the impact of heparin concentration retained in temporary double-lumen catheters on bleeding risk. Methods: Activated partial thromboplastin time (aPTT) was measured in patients hemodialyzed via double-lumen catheters. Heparin solutions of 5,000 U/ml (group 1, n = 95) and 1,000 U/ml (group 2, n = 89) were randomly retained in catheters after placement and each hemodialysis (HD) session. Blood transfusion, bleeding episodes, and changes of hematocrit were recorded. Results: The aPTT at the beginning of HD or 10 min after heparin lock was significantly prolonged, which was more prominent in the 5,000 U/ml group, whereas the aPTT declined to baseline values at the end of HD or before the next dialysis session in both groups. Infection and occlusion rates were similar in both groups. More patients suffered from major bleeding and prominent decline of hematocrit in the 5,000 U/ml group. Conclusions: Low-dose heparin (1,000 U/ml) retention in double-lumen catheters for temporary HD maintains comparable catheter patency and might reduce the bleeding risk.

Femoral vascular complications entail an increased risk of death at 1 year only if there is a significant hematocrit decline associated

Femoral vascular complications entail an increased risk of death at 1 year only if there is a significant hematocrit decline associated

Amelioration of Radiation-Induced Hematological and Biochemical Alterations in Swiss Albino Mice by Panax ginseng Extract

This study was carried out to observe the radioprotective effect of Panax ginseng root extract (PGE) against radiation-induced hematological and biochemical alterations in blood and liver of mice. Materials and methods. Adult Swiss albino mice were exposed to 6 Gy gamma radiation in the presence (experimental) or absence (control) of PGE to study the quantitative and qualitative alterations in the blood and liver. Radiation exposure resulted in a significant decline (P<.001) in erythrocyte count, hemoglobin (Hb), and hematocrit (Hct) in peripheral blood. Maximum changes in all the parameters were observed on day 3 after irradiation. In contrast, PGE-pretreated irradiated animals showed a significant increase in erythrocyte, Hct, and Hb values compared with irradiated controls. Furthermore, a significant elevation in lipid peroxidation level over normal was recorded in irradiated control mice, whereas this increase was considerably lesser in PGE pretreated animals. Likewise, pretreatment with PGE caused a significant increase in glutathione levels in serum as well as in liver in comparison to irradiated controls. From this study, it is clearly evident that PGE provides protection against radiation-induced hematological and biochemical alterations in Swiss albino mice.

M1548: The Syndrome of a Drop in Hematocrit: Clinical Features and Outcomes

Hematocrit declines without overt gastrointestinal (GI) bleeding are common during inpatient encounters. Though GI bleeding is often implicated after large hematocrit declines, overt GI bleeding should be heralded by passage of hematochezia, melena, or hematemesis. We hypothesized that inpatients having a hematocrit decline without overt GI bleeding have unique clinical features and hence evaluated a cohort of these patients.

Aconitase Modulates Erythroid Signaling through a Novel MEK-ERK Regulatory Pathway.

Abstract 75Erythropoiesis is a complex developmental program regulated in part by erythropoietin (EPO) and iron levels. We have previously shown that erythroid iron deprivation causes diminished enzymatic activity of the multifunctional aconitase proteins (Bullock et al., ASH 2007 #707). In addition, pharmacological inhibition of aconitase impairs erythroid growth and maturation in a lineage-selective manner without compromising ATP levels, suggesting a novel, non-metabolic regulatory role for aconitase in erythropoiesis (Talbot et al., ASH 2008 #3865). The nature of this regulatory role was addressed in the present study by examining the connection between aconitase activity and erythroid signal transduction. The impact of aconitase inhibition by fluoroacetate (FA) on several candidate pathways was assessed in primary human erythroid progenitors by standard immunoblotting. This approach consistently implicated the mitogen activated protein kinases (MAPKs) ERK1/2, whose phosphorylation was strongly induced both at early (30 minutes) and late (4 days) time points. In addition, phosphorylation of the other MAPKs p38 and JNK was unchanged, ruling out a non-specific stress response. To determine why aconitase inhibition augmented ERK1/2 phosphorylation, the effects of FA were determined on the upstream kinases MEK1/2. Surprisingly, phosphorylation of MEK1/2 showed no changes at earlier time points (up to 24 hours) and decreases at later time points (2–4 days). Activation of ERK/1/2 in the absence of MEK1/2 activation suggests an unconventional pathway in which aconitase regulates dephosphorylation, scaffolding, or subcellular localization. The inhibition of erythropoiesis by FA could result from increased ERK1/2 activity or diminished MEK1/2 activity. The first mechanism predicts phenotypic rescue by addition of MEK inhibitor (U0126), whereas the second mechanism predicts increased inhibition. In fact, U0126 alone recapitulated the anti-proliferative and anti-differentiative effects of FA on primary erythroid cultures, and the combination of U0126 and FA caused increased inhibition of growth and differentiation, arguing in favor of MEK1/2 repression as a mechanism for FA. Our findings establish that aconitase modulates signaling through the MEK-ERK pathway, perturbation of which may block erythropoiesis. To expand our studies on the in vivo role of aconitase in erythropoiesis, the impact of aconitase blockade was assessed in two additional murine models: phenylhydrazine (PHZ)-induced stress erythropoiesis and Polycythemia vera (PV). In both systems, erythropoiesis was found to be extremely sensitive to aconitase blockade. In the first system, adult C57Bl/6 female mice were treated with continuous FA infusion plus bolus intraperitoneal PHZ. FA-treated mice developed a much more severe anemia in response to PHZ than did non-FA-treated mice despite receiving 50% less PHZ. Their anemia showed a lower nadir (red cell count of 3.56 M/ul vs. 4.75 M/ul, p=0.0013, n=6) and a more prolonged trough. Their reticulocytosis was delayed and diminished. In the second system, PV female mice carrying one copy of the JAK2 V617F allele were treated with continuous FA infusion. Decreased red indices were observed by day 11 of treatment, with a decline in hematocrit from 51.3% to 42.5% in PV mice (p=0.0002, n=4), compared with a decline from 44.6% to 37.9% in wild type mice (p=0.04, n=4). No effects were observed on platelet and leukocyte counts. Interestingly, the rate of decrease of the red cell parameters was greater in the PV mice, suggesting that erythropoiesis driven by JAK2 V617F is highly responsive to changes in aconitase activity levels. We conclude that aconitase functions as a modifier of erythroid signaling to regulate proliferation and differentiation. Indeed, our results indicate that aconitase activity regulates steady state, stress, and JAK2 V617F-driven erythropoiesis, most likely through its novel modulation of MEK-ERK signaling. This novel function may provide an alternate targeting strategy in the treatment of Polycythemia vera. Disclosures:No relevant conflicts of interest to declare.

Administration of a Novel GDF Trap Prevents Anemia Induced by Renal Insufficiency and Augments Recovery From Blood Loss.

Abstract 4037Poster Board III-973This study investigated the effect of inhibiting GDF signalling via administration of a soluble form of a modified activin type II receptor (ACE-536) in anemia models.Anemia is a debilitating complication associated with several chronic diseases, including chronic kidney disease (CKD), and results in fatigue, shortness of breath, decreased quality of life and increased risk of mortality. Recombinant human EPO (rhEPO) is the most commonly prescribed therapy for CKD induced anemia. However, approximately one-third of patients treated with rhEPO are hyporesponsive, requiring high doses to obtain minimal increases in hemoglobin, and 5-10% of CKD-anemia patients are fully non-responsive to treatment. Moreover, there is increasing evidence to suggest that hyporesponsive patients have significantly increased risk for adverse drug reactions to rhEPO, including cardiovascular events. Therefore, novel, non-EPO based therapies to correct anemia may provide an alternative to EPO-based therapies to treat anemia. Various members of the TGF-β superfamily have been implicated in erythropoiesis. We have developed ACE-536, a soluble GDF-trap derived from the Type II activin receptor fused to the Fc region of IgG1, which binds to and inhibits several ligands in the TGF-β superfamily. Elsewhere, we report that administration of ACE-536 leads to rapid increases in red blood cells (RBC) in normal mice. Here, we report on the effects of ACE-536 in two disease models of anemia.To study the effects in a model of anemia related to renal insufficiency, nephrectomized (CKD) or sham-operated (SHAM) C57BL/6 mice were randomized to receive ACE-536 at 10 mg/kg or an equal volume of vehicle control (TBS; tris-buffered saline) for 4 weeks. Compared to baseline values, the SHAM-TBS group maintained the same red blood cell mass by the end of the four-week treatment period, whereas the CKD-TBS mice showed a significant decline (-6%; P<0.001). In contrast, SHAM and CKD mice receiving ACE-536 displayed a 24% and 19% increase in total red blood cells (P<0.001), respectively. Hemoglobin and hematocrit measurements also increased accordingly with treatment. The SHAM-TBS group exhibited no change in either parameter over the four-week treatment period, while the CKD-TBS group showed a significant decline in both hemoglobin and hematocrit (P<0.05 and P<0.001, respectively). Finally, SHAM and CKD mice receiving ACE-536 showed a significant increase in hemoglobin (P<0.001 and P<0.01, respectively) and hematocrit (P<0.001 and P<0.05, respectively) compared to their respective baseline values.We next investigated the effect of ACE-536 in recovery from blood loss to determine its role in a more acute model of anemia. Blood loss in Sprague-Dawley rats was achieved by removing 20% of total blood volume which, at 24 hours, resulted in a 14% decrease in total red blood cells and hemoglobin. At this point rats were randomized to receive ACE-536 at 10 mg/kg or an equal volume of TBS. Two days post randomization, hematological parameters returned to baseline levels in the ACE-536 treated rats; however, these same parameters remained significantly lower in the TBS treated group until day 6. Therefore, targeting the TGF-β signaling pathway with ACE-536, a novel, GDF-trap, is a viable therapeutic approach for the prevention and treatment of anemia induced by CKD and blood loss, and represents a potential alternative to EPO-based therapy. Disclosures:Cadena:Acceleron Pharma: Employment. Mitchell:Acceleron Pharma: Employment. Ucran:Acceleron Pharma: Employment. Liharska:Acceleron Pharma: Employment. Sako:Acceleron Pharma: Employment. Monnell:Acceleron Pharma: Employment. Kumar:Acceleron Pharma: Employment. Underwood:Acceleron Pharma: Employment. Pearsall:Acceleron Pharma: Employment.

Ultra-Minilaparotomy Myomectomy: A Minimally Invasive Surgical Approach for the Treatment of Large Uterine Myomas

Background: In recent years, a growing number of more conservative methods for the treatment of uterine myomas has been reported. However, only a small number of techniques is used for the treatment of large myomas. Aims: In the present retrospective study, we report our experience with a group of patients who consecutively underwent ultra-minilaparotomy myomectomy for single or multiple large myomas, with diameter greater than 5 cm, with emphasis on the safety and efficacy of this procedure. Methods: Forty-one women underwent an ultra-minilaparotomy myomectomy that involved a <4 cm transverse skin incision, with or without laparoscopic assistance. Results: Mean operating time was 92.4 min, the mean hemoglobin decline was 2.0 g/dl and the mean hematocrit decline was 5.7%. The mean time to discharge was 84.3 h. No patient underwent a second surgery for early postoperative complications. Postoperative fever occurred in 4 patients, especially in patients who underwent ultra-minilaparotomy without assisted laparoscopy. There were two cases of severe anemia with recourse to blood transfusion. Conclusion: The results of this study suggest that ultra-minilaparotomy myomectomy with or without laparoscopic assistance might represent a safe and effective minimally invasive alternative to standard open myomectomy in the treatment of large myomas.

Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator

AbstractCurcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borderline iron deficiency, with reductions in spleen and liver iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or plasma iron. Against this backdrop of subclinical iron deficiency, curcumin exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of microcytic anisocytotic red blood cells, and decreases in spleen and liver iron content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central role in regulation of systemic iron balance. These results demonstrate that curcumin has the potential to affect systemic iron metabolism, particularly in a setting of subclinical iron deficiency. This may affect the use of curcumin in patients with marginal iron stores or those exhibiting the anemia of cancer and chronic disease.

Tolerance of Acute Anemia: The Anesthesiology Perspective

SUMMARY Anesthesiologists have to face anemia in a variety of surgical interventions and have had the challenge of assuring positive patient outcomes. As such, treatment of acute anemia has traditionally resulted in increased exposure to allogeneic blood transfusions. Enhancing our knowledge of the hemoglobin molecule, its functions and reserve, allows the anesthesiologist to utilize compensatory mechanisms to achieve a positive outcome, with the reduction or elimination of patient's exposure to allogeneic blood transfusions. Since the inception of anesthesiology as a medical specialty, one of the most important issues for anesthesiologists has been oxygen delivery and consumption. Anemia has been a long-time challenge for the anesthesiologist. Anemia is defined as a decline of hemoglobin concentration or hematocrit. During acute normovolemic anemia, compensatory mechanisms are elicited at both the macrocirculatory (systemic) and microcirculatory level. Acute normovolemic hemodilution (ANH) is the intentional dilution of blood (a state of anemia) caused by controlled withdrawal of surgical patient's blood for reinfusion within 8 hours during and following surgical blood loss. This technique provides fresh whole blood for transfusion and avoids the pitfalls of predonated blood. ANH is an iatrogenic condition where dilutional anemia is used to the advantage of a patient for blood conservation, i.e. as an alternative for allogeneic blood transfusion. The effects of ANH-induced anemia on various organ systems and functions are discussed in addition to the effect of anesthesia and anesthetic depth.

The Relationship Between Anemia, Change in Hematocrit Over Time and Change in Health Status in Patients With Heart Failure After Myocardial Infarction

Background Studies have identified anemia as a potential therapeutic target in patients with heart failure, with the goal of improving survival and health status. However, whether changes in hematocrit are associated with changes in health status is unknown. Methods and Results We studied 1382 patients with heart failure after myocardial infarction who had serial hematocrits and health status assessments with the Kansas City Cardiomyopathy Questionnaire (KCCQ). Linear regression models assessed the relationship between change in hematocrit and change in health status between 1 month (baseline) and 3 months after hospitalization. During follow-up, 12.6% of patients experienced a greater than 2% decline in hematocrit, 32.5% experienced a greater than 2% improvement in hematocrit, and 54.9% had no significant hematocrit change. After multivariable adjustment there was a highly significant interaction ( P = .007) between baseline hematocrit and change in hematocrit, suggesting that the effects of changes in hematocrit on health status vary as a function of patients' initial hematocrits. Patients with severe anemia initially (hematocrit ≤ 33%) experienced marked decrements in health status (−4.4 point KCCQ change per 1% hematocrit decline, P = .006) with further declines in hematocrit, but only modest health status gains with hematocrit improvements (0.6 point KCCQ change per 1% hematocrit improvement, P = .3). Less pronounced changes were observed among patients with a baseline hematocrit greater than 33% to 39%, and no significant changes were seen in patients with hematocrit levels greater than 39%. Conclusion Among anemic patients with heart failure, a decrease in hematocrit is associated with marked decline in health status, whereas health status gains associated with hematocrit improvements are modest.

New Drugs for the Treatment of Diabetes Mellitus

The cardiovascular disease (CVD) risk associated with diabetes mellitus (DM) has become increasingly evident, accounting for ≈80% of deaths among patients with this disease1 and making CVD risk modification a key therapeutic objective in diabetic patients. Indeed, in some clinical contexts, DM has been elevated to a coronary heart disease risk equivalent for risk reduction strategies.1–4 The rapidly increasing global burden of DM,5 coupled with the associated CVD risk, underscores the imperative for continued generation and application of evidence-based therapies to reduce CVD risk in this high-risk cohort. In this 2-part series, we first review the CVD effects of the thiazolidinedione medications, the most broadly investigated class of antihyperglycemic drugs evaluated in the context of CVD risk. In the second part, we review the modulators of the incretin axis that have most recently achieved US Food and Drug Administration approval, with a focus on CVD considerations; introduce selected drugs in advanced development; summarize glucose control strategies for cardiovascular patients; and discuss the regulatory review of glucose-lowering medications. Ciglitazone, the first thiazolidinedione, was discovered in a compound-screening program for lipid-lowering agents and serendipitously observed to lower glucose in experimental animals, but it failed in clinical testing as a result of toxicities.6 Troglitazone became the first thiazolidinedione approved to treat type 2 DM (T2DM) in 1997, with little understanding of its mechanism of action. Subsequently, the peroxisome proliferator–activated (PPAR)-γ receptor, a nuclear receptor that regulates gene transcription, was identified as the thiazolidinedione target of action.7 PPAR-γ is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors8 that, when activated, dimerizes with the retinoid X receptor and binds to DNA (PPAR-response element) to regulate gene transcription through coordinate transactivation and transrepression.9 PPAR-γ is expressed most prominently in adipocytes, regulating adipogenesis10 and glucose …

Microvascular free‐tissue transfer for head and neck reconstruction in Jehovah's Witness patients

Jehovah's Witnesses' religious convictions disallow blood transfusion. Major surgery in these patients is therefore problematic. The objective of this study is to describe our experience with microvascular reconstruction of complex head and neck defects in Jehovah's Witness patients. This was a retrospective review of all Jehovah's Witnesses' patients undergoing head and neck free-flap reconstruction at a tertiary academic referral center from 1997 to 2006. Five Jehovah's Witnesses patients underwent a total of 7 free-flap reconstructions (6 radial, 1 rectus). Four flaps were immediate: 1 osteocutaneous radial forearm, 2 fasciocutaneous radial forearm, and 1 rectus abdominus myocutaneous. One fasciocutaneous radial forearm flap was staged. Two patients were planned secondary reconstructions, both facsciocutaneous radial forearm. Iron supplements and/or erythropoietin were administered perioperatively in 6 of the 7 microvascular reconstructions. Selective external carotid embolization was performed preoperatively in 1 patient. Hematocrit levels were 36% to 46% preoperatively and 30% to 41% postoperatively. Immediate postoperative hematocrit decline was 5.2% (3.0% to 6.0%). No transfusions or blood products were administered. Our case series supports the feasibility of head and neck free-flap reconstruction in these challenging patients.

Antioxidant enzymes activities and bilirubin level in adult rat treated with lead

Lead toxicity is closely related to its accumulation in several tissues and its interference with bioelements, whose role is critical for several biological processes. Recently, oxidative stress has been proposed as a possible mechanism involved in lead toxicity. This study was carried out to investigate the effect of dose-dependent lead exposure on haematological and oxidative stress parameters. Adult male ‘Wistar’ rats (150–200 g) were divided into three groups: group [Pb 5] and group [Pb 15] received respectively 5 mg Pb 2+ ( n = 16 ) and 15 mg Pb 2+/kg b.w. ( n = 16 ) as lead acetate solution i.p. for a period of seven days. Group [T] ( n= 16) served as control and received 15 mg Na +/kg b.w. as sodium acetate solution i.p. for the same period. All animals were sacrificed 24 h after the last injection. Blood superoxide dismutase (SOD) and blood glutathione peroxidase (GPx) activities and plasma bilirubin level were measured. Liver was quickly excised for the estimation of alteration in lipid peroxidation indices (MDA). Lead exposure induces, in both treated groups, a marked decline in haematocrit and haemoglobin levels ( p < 0.01 ) when compared to control. The results show also a significant decrease ( p < 0.01 ) in SOD activity, but only in group [Pb 15]. SOD activity did not decrease in group [Pb 5] in comparison with control ( p > 0.05 ). However, lead exposure caused a light increase in GPx activity in group [Pb 15], which remains non-significant ( p > 0.05 ) compared to control. Group [Pb 5] did not record significant changes in the activity of GPx. Lead exposure for a period of seven days resulted in a significant ( p < 0.05 ) increase in bilirubin level in group [Pb 15] compared to control. The bilirubin level from rats of group [Pb 5] did not reach a statistical significance. Changes in liver MDA content in lead-exposed rats from [Pb 5] and [Pb 15] groups did not reach a statistical ( p < 0.05 ) significance. It is concluded that lead induces oxidative stress in a dose-dependent manner. No dose-dependent response was observed in blood GPx activity and liver MDA content. These results could be due to the short duration of the treatment. To cite this article: A. Annabi Berrahal et al., C. R. Biologies 330 (2007).

Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies

The aim of this study is to evaluate the fetal hematocrit (Hct) decrease along repeated intravascular intrauterine fetal transfusions (IUTs) and test the hypothesis that, after consecutive IUTs, there is a lower Hct drop off. From July 1996 to June 2006, pregnancies submitted to IUT for fetal hemolytic anemia treatment had their data assessed. The daily rate of decrease in fetal Hct was calculated by dividing the difference between the posttransfusion Hct of the previous IUT and the pretransfusion Hct of the current IUT, by the number of days between the transfusions. Fetuses with other abnormalities or submitted to intraperitoneal transfusions were excluded. Eighty-one women were submitted to IUT during the alluded period, ensuing 296 intrauterine transfusions. The perinatal survival was 89.9% (n = 80), with 92.0% (n = 69) of nonhydropic fetuses survival. Hydropic fetuses showed higher hematocrit drop off than nonhydropic ones (P < 0.01). Compared to the interval between the first and second IUT, the daily fetal Hct decline was lower after the third one (P < 0.05). Stratifying by the presence of hydrops, nonhydropic fetuses showed a smaller decrease at the third and fourth intervals (P < 0.01 and P < 0.05, respectively). Among hydropic fetuses, there is a trend of smaller Hct decrease along successive IUTs (interval 3, P = 0.08; interval 4, P = 0.07; and interval 5, P = 0.10). Following some IUTs, fetal hematocrit decrease is lower and larger intervals between the transfusions could be accomplished. Multicenter studies should investigate an algorithm for timing subsequent IUTs, considering Doppler values, estimated fetal hematocrit decline and other parameters.

Health-Related Quality of Life of Predialysis Patients with Chronic Renal Failure

Background: Health-related quality of life (HQOL) of predialysis patients with chronic renal failure (CRF) has received less attention than that of dialysis patients. We investigated changes in SF-36 over 1 year and examined associations between clinical parameters and SF-36 in predialysis CRF patients. Methods: Subjects were 471 predialysis CRF patients. SF-36 and clinical parameters were measured every 8 weeks for 48 weeks. Of the 471 subjects, 294 underwent one or more follow-ups. We analyzed the pooled dataset of the 294 CRF patients and 2002 subjects from Japanese general population using analysis of covariance. Results: After adjustment for age and sex, the 1-year declines in SF-36 domains were significantly greater in the predialysis patients than in the general population. For a 10% decline in hematocrit from the baseline survey value, the decline in vitality of SF-36 was 4.5 points (p = 0.003), while for a 10% increase in serum creatinine from the baseline survey value, respective declines in physical functioning, role-physical and mental health were 1.2 (p = 0.004), 1.9 (p = 0.035), and 1.0 points (p = 0.008). Conclusion: Among these predialysis CRF patients, the decline in HQOL was faster than that in the general population, and was associated with an increase in serum creatinine and decline in hematocrit.