Increase In Hematocrit Levels Research Articles

Modeling the Progression of Haematocrit Level over Time

AbstractHaematocrit Levels is defined as the proportion, by volume, of the blood that consists of red blood cells. This study was conducted to model the progress of haematocrit levels over time in kidney patients after their transplant and to determine how the progress depends on the age and gender of the patient and other factors. This is a longitudinal study, and haematocrit level was considered as a response while the covariates were time, gender, age, cardio-vascular problem during the years preceding the transplantation, and rejection symptoms during the first three months after the transplantation took place of the patients. Different statistical methods such as, multivariate regression model, two stage analysis and linear mixed effects model were employed to explore the progress of haematocrit over time. Models revealed that haematocrit levels in kidney transplant patients evolve over time. Gender and Age of the patient have significant effect on the evolution of haematocrit levels. Males tend to have a high increase in haematocrit levels over time than females. With regards to age, haematocrit levels tend to increase with increasing age. Moreover, it was observed that experience of cardio-vascular problems before trandplant and rejection symptoms did not have a significant effect on the progress of haematicrit levels. The growth of Haematocrit levels evolve over time follows a quartic time effect. Change in haematocrit levels varies according to gender and age of the patient. Patients starting with low haematocrit levels tend to have a larger increase over time.

PSIII-16 The Effects of Secondary Iron Injection to Suckling Piglets Injected with Two Levels of Iron at Birth on Growth Performance and Hematocrit Level in Suckling Period

Abstract This experiment was conducted to evaluate the effects of secondary iron injection in suckling piglets injected with 2 levels of iron at birth on growth performance and hematocrit level during the suckling period. Twenty suckling pigs from 5 litters were allotted into 2 treatments within litter (10 pigs per treatment) based on body weight and gender as follows: 1) Iron100b: intramuscular injection of 100 mg iron-dextran at birth (d 1-2 of age), and 2) Iron200b: intramuscular injection of 200 mg iron-dextran at birth. A 200 mg iron-dextran was injected to all piglets intramuscularly at d 14 after the first injection (d 15-16 of age; 11 d before weaning at d 26-27 of age). Body weight and hematocrit level were measured at d 0, 7, 14 (before second injection), 21, and 25 (weaning) after the first injection. No difference was observed in growth performance between the treatments. The Iron200b treatment had greater hematocrit levels than the Iron100b treatment at d 14 (P < 0.05; 32.50 vs. 37.40% for Iron100b and Iron200b, respectively), 21 (P = 0.06), and 25 (P < 0.05; 37.90 vs. 40.75%) after the first injection (d 0, 7, and 11 after second injection, respectively). The changes in hematocrit levels tended to be greater for the Iron200b treatment than the Iron100b treatment in d 7-14 (P = 0.08) and 0-14 (P = 0.06; 5.55 vs. 11.95%) after the first injection. After the second injection, the Iron100b treatment had greater increases (P < 0.05) in hematocrit levels than the Iron200b treatment for d 14-21 and 14-25 (5.40 vs. 3.35%) of the experiment. In conclusion, with the second injection, the 200 mg iron injection at birth had greater hematocrit levels than the 100 mg iron injection until weaning whereas the increase in hematocrit level by the second injection was greater in the 100 mg iron injection at birth than the 200 mg iron.

PSII-15 Effect of Secondary Iron Injection to Suckling Pigs on Growth Performance and Hematocrit Level in Suckling Period

Abstract The objective of this study was to evaluate the effects of secondary iron injection in suckling pigs on growth performance and hematocrit level in the suckling period. At d 1 of age, a total of 24 suckling pigs from 4 litters were allotted into 3 treatments within litter (8 pigs per treatment) based on body weight and gender as follows: 1) Control: no additional iron injection, 2) Iron100: secondary intramuscular injection of 100 mg iron-dextran, and 3) Iron200: secondary intramuscular injection of 200 mg iron-dextran. The initial 200 mg iron-dextran was injected intramuscularly on d 1 of age with a second injection given to the pigs on 11 d before weaning (d 16 of age). All piglets were weaned at d 27 of age. Body weight and hematocrit level were measured at d 0, 7, and 11 (weaning) post-injection. There was no significant difference in growth performance among the treatments. The Iron100 and Iron200 treatments had greater hematocrit levels than the Control treatment at d 7 and 11 post-injection (P < 0.05) with a greater hematocrit level in the Iron200 treatment than the Iron100 treatment at d 11 post-injection (P < 0.05; 34.25, 38.75, and 41.19% for Control, Iron100 and Iron200, respectively). For changes in hematocrit level, the Iron100 and Iron200 treatments had greater increases than the Control treatment in d 0-7 and d 0-11 post-injection (P < 0.05; -1.31, 4.31, and 5.75%) with no difference between the Iron100 and Iron200 treatments. In d 7-11 post-injection, the Iron200 treatment had a greater increase in hematocrit level than the Iron100 treatment with an intermediate value in the Control treatment (P < 0.05; 0.44, -0.06 and 1.38%). In conclusion, the secondary iron injection to suckling piglets did not affect growth performance until weaning whereas the injections increased hematocrit levels resulting in a greater value at weaning in the higher level of second iron injection.

Natural history of postpartum hematocrit recovery in an urban, safety-net population

Postpartum anemia is common after delivery, and postpartum blood transfusion is the leading indicator of severe maternal morbidity in the United States. Although hematologic changes during the antepartum period are well understood, little is known about postpartum hematologic changes. Therefore, we investigated the hematologic changes in the postpartum period in a large, contemporary cohort. This study aimed to characterize hematologic recovery in the postpartum period and evaluate the effect of demographics, medical conditions, and pregnancy characteristics on the recovery. In a contemporary cohort of deliveries in 2019 at a single institution, the hematocrit of postpartum women before hospital discharge was compared with the hematocrit of women at the postpartum follow-up. Our population was composed of a predominantly Hispanic population at an urban, safety-net hospital. All women received a complete blood count on postpartum day 1 and a spun hematocrit at their postpartum follow-up visit in our hospital system. All women were scheduled for a routine postpartum visit 2 to 3 weeks after delivery. All deliveries of a live-born infant with available postpartum hematocrit before hospital discharge and at postpartum follow-up were included. Demographics and pregnancy characteristics, along with medical conditions, were evaluated. To evaluate an uncomplicated cohort, those with multiple gestation, preeclampsia with severe features, chronic hypertension, and diabetes mellitus were excluded in the secondary analysis. Statistical analysis included chi-square, paired Student t test, Student t test for independent groups, and analysis of variance. Of 12,456 deliveries, 9003 met the inclusion criteria. The average number of days from discharge to follow-up was 21.73±10.39 days. The average hematocrit levels were 30.77±3.61 before discharge and 38.70±3.61 at postpartum follow-up. From discharge to postpartum follow-up, the hematocrit levels increased by an average of 7.93±3.24. In the cohort without complications, the average increase in hematocrit levels was 8.19±3.09. The rise in hematocrit levels was significantly lower for those with chronic hypertension (6.9±3.6), diabetes mellitus (7.3±3.3), and preeclampsia with severe features (6.9±3.7). The severity of anemia influenced the rise in hematocrit levels in the postpartum period. In women with postpartum anemia (hematocrit<30%), the rise in hematocrit levels was 9.49±2.97 in the uncomplicated cohort. Postpartum hemorrhage did not influence the rise in postpartum hematocrit levels; women receiving blood transfusion had a greater rise in hematocrit levels (9.01±3.29). Our study establishes the natural course of hematologic recovery in the postpartum period, and we found that women with asymptomatic postpartum anemia may have a hematocrit level of 37% to 39% at their postpartum follow-up approximately 3 weeks after hospital discharge. Women with preexisting and obstetrical complications experienced less hematologic recovery and adapted more slowly to postpartum physiological changes.

Effect of sodium–glucose cotransporter 2 inhibitors on hemoglobin and hematocrit levels in type 2 diabetes: a systematic review and meta-analysis

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes of patients with type 2 diabetes at high cardiovascular risk and chronic kidney disease. Recent studies showed an increase in hemoglobin and hematocrit after SGLT2i treatment. We did a systematic review and meta-analysis of randomized, double-blind, placebo-controlled studies of SGLT2i in patients with type 2 diabetes. We searched through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from January 2010 to January 2021. We included seventeen randomized, double-blind, placebo-controlled studies. The total number of evaluated patients was 14,748. The treatment arm consisted of canagliflozin, dapagliflozin, empagliflozin and ipragliflozin. SGLT2i therapy significantly increased hemoglobin levels when compared to placebo (MD 5.60g/L, 95% CI 3.73-7.47g/L, P < 0.00001, considerable heterogeneity-I2 = 94%). Each SGLT2i also led to a significant increase in the hematocrit level when compared to placebo (MD 1.32%, 95% CI 1.21-1.44, P < 0.00001, considerable heterogeneity-I2 = 99%). SGLT2i led to significant increases in hemoglobin and hematocrit levels when compared to placebo. In addition to their cardiovascular effect, SGLT2i also increases hemoglobin and hematocrit levels.

Age and Hydration of Competing Horses Influence the Outcome of Elite 160 km Endurance Rides

High elimination rates and the concern for horse welfare are important issues in endurance riding. An improved understanding of the causes of elimination could increase completion rates in this sport. We have identified pre-ride risk factors that allow an assessment of potential elimination before the ride. A longitudinal cohort study was performed among 49 healthy horses competing in the 160 km endurance ride at the 2016 World Championship of Endurance Riding in Samorin/Slovakia. Blood samples were drawn before the ride. For statistical evaluation, horses were categorized in three groups: finishers, lame and metabolically eliminated horses. Risk factors were calculated for each group using multinomial logistic regression. A 1% increase in hematocrit levels was associated with a higher OR for elimination (lameness: OR 1.26, p = 0.017; metabolic: OR 1.34, p = 0.010). Furthermore, increased potassium values correlated negatively with the race outcome. For a 1 mmol/l increase in potassium, the lameness OR was 4.21, p = 0.039 and metabolic OR was 1.15, p = 0.848. Eight-year-old horses had a 100% elimination rate and survival analyses showed a significantly higher hazard for elimination (p = 0.025). We thus conclude that age and hydration affect the outcome of elite endurance rides. Further investigation of age as a risk factor seems to be clinically relevant and adjustments of FEI qualification modes may be appropriate.

Dapagliflozin effects on haematocrit, red blood cell count and reticulocytes in insulin-treated patients with type 2 diabetes

Recent studies have shown that high-risk patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose cotransporter 2 (SGLT2) inhibitors have improved cardiovascular (CV) outcomes. In an exploratory analysis of data from the EMPA-REG study, elevations in haematocrit were shown to be strongly associated with beneficial CV effects. As insulin treatment has been shown to be antinatriuretic, with an associated increase in extracellular fluid volume, it is important to confirm whether haematocrit increase is maintained with concomitant insulin therapy. Here, we investigate the effect of the SGLT2 inhibitor dapagliflozin on haematocrit, red blood cell (RBC) counts and reticulocyte levels in high-risk patients with T2DM receiving insulin. A 24-week, double-blinded, randomised, placebo-controlled trial (ClinicalTrials.gov: NCT00673231) was reported previously with extension periods of 24 and 56 weeks (total of 104 weeks). Patients receiving insulin were randomised 1:1:1:1 to placebo or dapagliflozin at 2.5, 5 or 10 mg. Haematocrit, RBC and reticulocyte measurements were conducted during this study, and a longitudinal repeated-measures analysis was performed here to examine change from baseline during treatment. Dapagliflozin treatment in combination with insulin resulted in a dose-dependent increase in haematocrit levels and RBCs over a 104 week period. There was a short-term increase in reticulocyte levels at the start of treatment, which dropped to below baseline after 8 weeks. SGLT2 inhibition with dapagliflozin leads to a sustained increase in haematocrit in patients receiving chronic insulin treatment.

Dietary vitamin D supplementation improves haematological status following consumption of an iron-fortified cereal: an 8-week randomised controlled trial

AbstractVitamin D, a secosteroid, has recently been implicated in the stimulation of erythroid precursors and ultimately the rate of erythropoiesis. However, there are a paucity of randomised controlled trials (RCT), investigating the effect of vitamin D supplementation iron status, especially in populations at risk of iron deficiency. An eight-week, double-blind RCT was carried out in 50 female (mean age (± SD): 27 ± 9 years), iron-deficient (plasma ferritin concentration &lt; 20 μg/L) participants, randomised to consume an iron-fortified cereal containing 9 mg of iron, with either a vitamin D supplement (1,500 international units (IU)/day, 38 μg/day) or placebo. The effect of dietary vitamin D supplementation on haematological indicators was investigated. Blood samples were collected at baseline, 4-weeks and 8-week timepoints for measurement of iron and vitamin D status biomarkers. The effect of intervention was analysed with a mixed-model repeated measures ANOVA using IBM SPSS statistical software (Version 21, IBM Corporation, New York, USA). Significant increases were observed in two haematological parameters: haemoglobin concentration and haematocrit level from baseline to post-intervention in the vitamin D group, but not in the placebo group. The increase from baseline to post-intervention in haemoglobin concentration in the vitamin D group (135 ± 11 to 138 ± 10 g/L) was significantly higher than in the placebo group (131 ± 15 to 128 ± 13 g/L) (P ≤ 0.05). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42.0 ± 3.0 to 43.8 49 ± 3.4%) compared to the placebo group (41.2 ± 4.3 to 40.7 ± 3.6%) (P ≤ 0.05). Despite non-significant changes in plasma ferritin concentration, this study demonstrates that dietary supplementation with 1,500IU vitamin D, consumed daily with an iron-fortified cereal led to improvement in haemoglobin concentration and haematocrit levels in women with low iron stores. Further long-term studies are required, however, these findings suggest a potential role for improvement of vitamin D status as an adjunct therapy for recovery of iron status in iron-deficient populations.

Predictor of Dengue Shock Syndrome Among Pediatric Dengue Infection in Limited Resource Setting

Introduction: Indonesia has the most dengue outbreaks in the ASEAN region. Lack of diagnostic modality and poor sanitation especially in rural area hinders proper and prompt management of Dengue Fever.&#x0D; Aim: Finding the early, simple, and reliable predictor of Dengue Shock Syndrome (DSS) in Indonesia.&#x0D; Materials and Methods: A retrospective study reviewing the medical record of pediatric patient with dengue infection from 1 January 2016 to 31 March 2016 were conducted. Age, gender, dengue signs, and simple laboratory result were collected. The data acquired were then analyzed using logistic regression for multivariate analysis (P&lt;0,05) to find the severity predictor.&#x0D; Results: 80 cases of dengue infection were included, mean age was 7,7 ± 3.4 years old, the average length of hospital stay was 4.59 days. 28.75% of patients had DSS. From the multivariate analysis, it is found that lethargy (p= 0.00; OR 21.23), bleeding (p= 0.01; OR 0,04), cold extremities (p=0.00;OR=22.35), and increased haematocrit level (p=0.01;OR=4.72) has significant relationship with DSS while other indicator did not.&#x0D; Conclusion: Patients presenting with lethargy, cold extremities, and increase in haematocrit level should be treated promptly and intensively as they are more likely to develop DSS compared to patients who did not.

Low hematocrit levels: a risk factor for long-term outcomes in patients requiring prolonged mechanical ventilation after cardiovascular surgery. A retrospective study

While low-risk patients who undergo elective surgery can tolerate low hematocrit levels, the benefits of higher hematocrit levels might outweigh the risk of transfusion in high-risk patients. Therefore, this study...

Vitamin D3 supplementation for 8 weeks leads to improved haematological status following the consumption of an iron-fortified breakfast cereal: a double-blind randomised controlled trial in iron-deficient women.

The effect of 38 µg (1500 IU) daily vitamin D3 supplementation, consumed with an Fe-fortified breakfast cereal for 8 weeks, on haematological indicators in Fe-deficient female subjects was investigated. Fifty Fe-deficient subjects (plasma ferritin concentration &lt;20 µg/l; mean age: 27·4 (sd 9·4) years) were randomised to consume an Fe-fortified breakfast cereal containing 9 mg of Fe daily, with either a vitamin D3 supplement or placebo. Blood samples were collected at baseline, interim (4 weeks) and post-intervention (8 weeks) for measurement of Fe and vitamin D status biomarkers. The effect of intervention was analysed using mixed-model repeated-measures ANOVA. Significant increases were observed in two main haematological indices: Hb concentration and haematocrit level from baseline to post-intervention in the vitamin D group but not in the placebo group. The increase from baseline to post-intervention in Hb concentration in the vitamin D group (135 (sd 11) to 138 (sd 10) g/l) was significantly higher compared with the placebo group (131 (sd 15) to 128 (sd 13) g/l) (P=0·037). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42·0 (sd 3·0) to 43·8 (sd 3·4) %) compared with the placebo group (41·2 (sd 4·3) to 40·7 (sd 3·6) %) (P=0·032). Despite the non-significant changes in plasma ferritin concentration, this study demonstrates that 38 µg supplemental vitamin D, consumed daily, with Fe-fortified breakfast cereal led to improvement in Hb concentration and haematocrit levels in women with low Fe stores. These findings may have therapeutic implications in the recovery of Fe status in Fe-deficient populations at a healthcare level.

Recombinant human erythropoietin does not affect several microvascular parameters in well-trained cyclists.

Recombinant human erythropoietin (rHuEPO) has been used as a performance‐enhancing agent by athletes in a variety of sports. The resulting increase in hematocrit levels leads to increased blood viscosity and can affect blood flow, potentially increasing the athlete's risk of developing health complications. However, the actual effects of using rHuEPO on microvascular blood flow and post‐occlusive reactive hyperemia are currently unknown. We therefore evaluated the effect of rHuEPO on the cutaneous microcirculation in well‐trained cyclists using laser speckle contrast imaging (LSCI). This study was part of a randomized, double‐blind, placebo‐controlled, parallel trial designed to investigate the effects of rHuEPO in 47 well‐trained adult cyclists (age 18–50 years). Subjects received a weekly dose of either rHuEPO or placebo for 8 weeks, and LSCI was performed at baseline, after a maximal exercise test in week 6, and before maximal exercise in week 8. Endpoints included basal blood flux, maximum post‐occlusion reperfusion, and time to return to baseline. Despite an increase in hematocrit levels in the rHuEPO‐treated group, we found no statistically significant difference in microvascular function measured between the rHuEPO‐treated group and the placebo group. Our results suggest that the increased hematocrit levels in rHuEPO‐treated well‐trained cyclists are not associated with changes in microvascular blood flow or post‐occlusive reactive hyperemia measured using LSCI.

The effect of blood cell count on coronary flow in patients with coronary slow flow phenomenon

Objective The coronary slow flow phenomenon(CSFP)is a coronary artery disease with a benign course, but its pathological mechanisms are not yet fully understood. The purpose of this controlled study was to investigate the cellular content of blood in patients diagnosed with CSFP and the relationship of this with coronary flow rates. Methods Coronary angiographies of 3368 patients were selected to assess thrombolysis in myocardial infarction(TIMI) frame count(TFC) values. Seventy eight of them had CSFP, and their demographic and laboratory findings were compared with 61 patients with normal coronary flow. Results Patients'demographic characteristics were similar in both two groups. Mean corrected TFC(c TFC) values were significantly elevated in CSFP patients(P< 0.001). Furthermore, hematocrit and hemoglobin values, and eosinophil and basophil counts of the CSFP patients were significantly elevated compared with the values obtained in the control group(P= 0.005,P= 0.047,P= 0.001 and P= 0.002). The increase observed in hematocrit and eosinophil levels showed significant correlations with increased TFC values(r= 0.288 and r= 0.217). Conclusion Significant changes have been observed in the cellular composition of blood in patients diagnosed with CSFP as compared to the patients with normal coronary blood flow. The increases inhematocrit levels and in the eosinophil and basophil counts may have direct or indirect effects on the rate of coronary blood flow. Key words: Basophil; Eosinophil; Hematocrit; Hemoglobin; Coronary slow flow

Ingestion of glucose and Vitamin C affects orthostatic stress-induced cardiovascular responses in young men

Aim: We hypothesized that coadministration of glucose and Vitamin C will reduce the orthostatic tolerance in normal young male volunteers. Materials and Methods: In a randomized controlled crossover fashion, nine nonobese, young men ingested nothing (control), and glucose (75 g) alone and with Vitamin C (1 g) 10 min before standing on 3 separate days of appointment. We measured the supine and standing blood pressure, heart rate, hematocrit, and blood glucose levels. The orthostatic tolerance was evaluated as the time to presyncope during motionless standing or until presyncopal symptoms were observed. Results: During the first 60 min of standing, 89%, 78%, and 0% of patients experienced the presyncopal symptoms when ingested nothing, glucose alone, and glucose + Vitamin C, respectively. Ingesting glucose alone did not affect the orthostatic tolerance (61.4 ± 1.4 vs. 63.0 ± 1.7 min; P > 0.05) while ingesting glucose with Vitamin C significantly improved the orthostatic tolerance (86.6 ± 2.2 vs. 63.0 ± 1.7 min; P < 0.001). Increases in the systolic blood pressure (SBP) and heart rate induced by standing were significantly enhanced when glucose + Vitamin C was ingested, while changes in diastolic blood pressure were not significantly affected. Ingestion of glucose alone or with Vitamin C led to a comparable significant increase in blood glucose levels after standing. However, a significant increase in hematocrit level was observed after standing when glucose + Vitamin C but not when glucose alone was ingested. Conclusion: The present study reveals that the oral glucose loading with Vitamin C ingestion improves the orthostatic tolerance, and the improvement is associated with an enhanced SBP, heart rate, and hematocrit level.

Calcimimetic (Cinacalcet) and Hemodiafiltration versus Conventional Treatment of Secondary Hyperparathyroidism in Children With End-Stage Renal Disease on Regular Hemodialysis

Background Control of metabolic derangements related to bone disease is one of the important goals in management of patients with chronic kidney disease. Traditional treatment using calcium containing phosphate binders and active vitamin D 3 analogues can lead to hyperphosphatemia and hypercalcemia with increase in calcium phosphorus product and metastatic calcifications. Other methods of therapy such as calcimimetics and hemodiafiltration are additional options of treatment that can lead to better control of metabolic bone disease with avoidance of these complications. Methods Our study was a case-control study which was performed over 6 months on 33 children with end stage renal disease on regular hemodialysis. They were randomly divided into 3 groups: The first group (11 cases) on regular hemodialysis and received Cinacalcet (Mimpara) 30 mg/day in addition to conventional care (vitamin D and phosphorus binders) as needed, the Second group (13 cases) on hemodiafiltration (HDF) for at least 6 months and received conventional care only, and the third group (9 cases) [control group] on regular hemodialysis received conventional care only. Monthly follow up of serum calcium, phosphorus and alkaline phosphatase was done in addition to baseline and 3-monthly parathormone level (intact PTH). Results The mean age of whole study population was 10.6 ± 3.9 years (range 3-17 years), and the mean weight was 20.2 ± 7.3 kg (range 8-39.1 kg). 􀀥oth groups I and II, but not group III, showed a statistically significant increase in hematocrit level and a statistically significant decrease in alkaline phosphatase and PTH after the study period. There was a significant percent reduction of PTH level in group I patients compared to those in group III. There was no statistically significant difference between percentage of achievement of the NFK-K/DOQI recommended goals in the three groups. Conclusions On spite of the costs of cinacalcet and hemodiafiltration, patients with resistant hyperparathyroidism should use one of these modalities to avoid complications of the metabolic bone disease. The cost of cinacalcet and HDF should be calculated in the context that they will save in other items, as decreasing the dose of erythropoietin and vitamin D analogues and decreasing the complications, and consequently therapy of bone disease.

Effects of delayed cord clamping in very-low-birth-weight infants

Delayed cord clamping (DCC) may be beneficial in very-preterm and very-low-birth-weight infants. This study was a randomized unmasked controlled trial. It was performed at three centers of the NICHD (National Institute of Child Health and Human Development) Neonatal Research Network. DCC in very-preterm and very-low-birth-weight infants will result in an increase in hematocrit levels at 4 h of age. Infants with a gestational age of 24 to 28 weeks were randomized to either early cord clamping (<10 s) or DCC (30 to 45 s). The primary outcome was venous hematocrit at 4 h of age. Secondary outcomes included delivery room management, selected neonatal morbidities and the need for blood transfusion during the infants' hospital stay. A total of 33 infants were randomized: 17 to the immediate cord clamping group (cord clamped at 7.9±5.2 s, mean±s.d.) and 16 to the DCC (cord clamped at 35.2±10.1 s) group. Hematocrit was higher in the DCC group (45±8% vs 40±5%, P<0.05). The frequency of events during delivery room resuscitation was almost identical between the two groups. There was no difference in the hourly mean arterial blood pressure during the first 12 h of life; there was a trend in the difference in the incidence of selected neonatal morbidities, hematocrit at 2, 4 and 6 weeks, as well as the need for transfusion, but none of the differences was statistically significant. A higher hematocrit is achieved by DCC in very-low-birth-weight infants, suggesting effective placental transfusion.

Axitinib Induces Paradoxical Erythropoietin Synthesis in Metastatic Renal Cell Carcinoma

TO THE EDITOR: In a recent letter, Alexandrescu et al reported thoughtful data to address the occurrence of erythrocytosis after treatment with tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib for metastatic cancers. In addition, it has been previously reported that patients with von Hippel-Lindau (VHL) disease treated with semaxanib, a TKI targeting vascular endothelial growth factor receptor 2 (VEGFR-2) and cKit, may experience a supra-additive increase in hematocrit level. Experimental studies showing hepatic erythropoietin (EPO) synthesis related to VEGF blockage could explain this iatrogenic polycythemia. We report a case of polycythemia in a patient treated for metastatic renal cell carcinoma with axitinib, another TKI targeting VEGFR-2. Our findings were the opposite of those in the report by Alexandrescu et al. A 52-year-old man, with no significant past medical history, underwent a right radical nephrectomy for clear renal cell carcinoma. In October 2002, a partial response was achieved with interferon-alfa treatment for lung metastases. In March 2004, the lung metastases progressed in number and size, and the patient subsequently was enrolled onto an axitinib phase II trial. Oral axitinib was administered continuously at the fixed dose of 5 mg twice daily. Minor adverse effects were reported, including diarrhea and asthenia. During the initiation of the second cycle (week 5), we observed an increase in hematocrit, which was confirmed during the subsequent cycles. An isotopic measurement of RBCs confirmed the diagnosis of polycythemia. Treatment was continued for 36 months, with a documented complete response by the third cycle. However, repeated therapeutic phlebotomies for polycythemia remained necessary. There was no alternative cause of polycythemia, including the absence of clinical evidence of VHL disease. In addition, no somatic VHL mutation in the tumor sample was found in polymerase chain reaction analysis. Endogenous EPO blood levels and VEGF-A levels were monitored, and results are listed in Table 1. Tam et al demonstrated that erythropoiesis is regulated by endogenous VEGF. In Tam’s preclinical study, high-grade VEGF blockage induced the repression of adult hepatic EPO production. The absence of VEGFR-2 expression on hepatocytes suggests the participation of liver sinusoidal endothelial cells with homeostatic VEGFR-2– dependant paracrine signaling. In our observation, axitinib treatment was associated with a paradoxical VEGF increase, as reported both in vivo and in a cohort of patients with metastatic gastrointestinal stromal tumors treated with sunitinib, another TKI with VEGFR-2 inhibition. However, we speculate that axitinib mimics VEGF starvation in organs (such as the liver) through VEGFR-2 blockade, and leads to hepatic EPO production. Finally, we cannot exclude an axitinib interaction with the hypoxiainducible factor pathway, which induces nitric oxide release, cutaneous vascular flow modification, and increased systemic EPO expression. Further investigation in clinical trials is warranted to determine the utility of EPO blood level as a marker of VEGF/ VEGFR modulator activity.

Efficacy of the Long-Acting Repeatable Formulation of the Somatostatin Analogue Octreotide in Postoperative Dumping

Several studies have established symptomatic and mechanistic benefits of the somatostatin analogue octreotide in patients with dumping syndrome, but clinical use is hampered by the requirement for subcutaneous administration 3 times daily. We compared the efficacy of subcutaneous octreotide with that of the long-acting repeatable (LAR) octreotide formulation, which is administered monthly, in patients with dumping syndrome. The study included 30 consecutive patients with postoperative dumping, evidenced by oral glucose tolerance test (OGTT) results and insufficient response to dietary measures. OGTT, dumping severity score (summary of scores 0-3 for 8 early and 6 late dumping symptoms), and quality-of-life data were evaluated at baseline, after 3 days of subcutaneous administration of octreotide (0.5 mg), and then after 3 monthly intramuscular injections of octreotide LAR (20 mg). Both formulations of octreotide significantly reduced total dumping severity scores (21.7 +/- 1.6 at baseline, 11.2 +/- 1.2 for subcutaneous and 14.0 +/- 1.8 for LAR formulations; P < .05). This reduction was associated with significant improvements in the increase in pulse rate (13.8 +/- 5.8 at baseline vs -0.3 +/- 2.2 and 1.9 +/- 1.7; P < .05) as well as the increase in hematocrit level (4.0 +/- 1.4 at baseline vs 0.3 +/- 0.9. and 0.4 +/- 1.0; P < .05), and the lowest glycemia level in the OGTT (54.1 +/- 6.7 at baseline vs 98.9 +/- 7.1 and 67.8 +/- 5.9; P < .05). LAR octreotide administration significantly improved patients' quality of life. Patients' evaluations of their overall treatment efficacy was higher on LAR compared with the subcutaneous formulation (83% vs 52%; P = .01). Gallbladder stones occurred in 4 patients. Monthly administration of LAR octreotide improves OGTT results, symptoms, and quality of life in patients with postoperative dumping.

Modulation of total ceramide and constituent ceramide species in the acutely and chronically hypoxic mouse heart at different ages

Ceramide has been implicated in regulatory processes vital for cell survival under different stressors, most notably hypoxia. Little has been done to investigate the contributions of the different ceramide species to the regulation of cell survival. This study aims to highlight the patterns of variation in total ceramide and its species in the growing and hypoxic mouse heart. Mus musculus mice were placed in a hypoxic environment at birth. Control animals remained in room air. The hearts were extracted at different time points: 1 day, 1 week, 4 weeks, and 8 weeks. The total ceramide content and the amounts of component species were assayed by a modified diacylglycerol kinase assay and high-performance liquid chromatography–tandem mass spectroscopy, respectively. Data was collected from both ventricles in hypoxic and control conditions. There was significant polycythemia in the hypoxic versus control animals with a nearly twofold increase in hematocrit levels. Hypoxic right ventricle (RV) mass significantly increased over that of controls at different age groups. When ceramide content was compared in the hypoxic versus control animals, there was a significant increase at day 1 and a significant decrease at week 4 in the left ventricle, whereas a significant decrease was found in the RV at 1 week, 4 weeks, and 8 weeks. There was also a differential involvement of the RV with regard to levels of N-palmitoyl- d-erythro-sphingosine (C16-Cer) and its synthetic precursor dihydro- N-palmitoyl- d-erythro-sphinganine (DHC-16-Cer). The decrease in C16-Cer observed in both hypoxic and control RV's over time was paralleled by a significant increase in DHC-16-Cer in hypoxic (142.1 ± 15.0 pmol; p < 0.05) but not control (52.8 ± 4.0 pmol) RV's suggesting a role for DHC-16-Cer in the RV adaptive response to hypoxia. Another species, N-arachidoyl- d-erythro-sphingosine (C20-Cer), was specifically and significantly decreased in the hypoxic RV. These studies support the presence of distinct roles for different ceramide species and their precursors. A better assessment of cyanotic congenital heart disease in light of the mechanism and timing of cardiomyocyte death, will lead to punctual interventions and even novel cardioprotective strategies.

Cardiovascular Issues in Hypogonadism and Testosterone Therapy

A systematic literature search was conducted to investigate the cardiovascular issues related to hypogonadism and testosterone therapy. Vascular cells contain sex steroid hormone receptors. Testosterone can exert effects on the vascular wall, either by itself or through aromatization as estrogen. Hypogonadism is associated with central obesity; insulin resistance; low levels of high-density lipoprotein (HDL); high cholesterol levels; and high levels of low-density lipoprotein (LDL), triglycerides, fibrinogen, and plasminogen activator-1. Some observational studies show a correlation between low testosterone and cardiovascular disease (CVD), and others show no correlation. Interventional studies do not reveal a direct long-term relation between testosterone therapy and CVD. Short-term data suggest cardiovascular benefits of testosterone. Testosterone therapy has beneficial and deleterious effects on cardiovascular risk factors. It improves insulin sensitivity, central obesity, and lowers total cholesterol and LDL. In some studies, testosterone therapy has an HDL-lowering effect, and in other studies this effect is insignificant. This should not be assumed to be atherogenic because it might be related to reverse cholesterol transport and effects on the HDL(3) subfraction. The cardiovascular effects of testosterone therapy may be neutral to beneficial. There is no contraindication for testosterone therapy in men with CVD and diagnosed hypogonadism with or without erectile dysfunction. Caution should be exercised regarding occasional increases in hematocrit levels, especially in patients with congestive heart failure. Conversely, evidence does not support testosterone therapy in aging men for the purpose of cardiovascular benefit, despite claims to this effect. Further research on the cardiovascular benefits and risks of testosterone is strongly recommended.