bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated MCV in Patients with Hereditary Hemochromatosis.
Authors: Mikhail Sameh E. , Phatak Pradyumna D. 
Published: October 2019

Abstract
Background: Previous studies have reported that patients with Hereditary Hemochromatosis have higher red cell volumes than normal controls. The relationship of this abnormality to the degree of iron overload and to HFE genotype has not been systematically studied.
Method: We retrospectively compared the mean corpuscular volume (MCV) of patients with Hereditary Hemochromatosis with that of an age-, race- and sex-matched control population from the primary care clinic at our institution. We studied the relationship of MCV at diagnosis with serum transferrin saturation, serum ferritin level, phlebotomy-mobilizable iron stores and HFE genotype in our patients.
Results: The study population included 290 patients who were treated for Hereditary Hemochromatosis at our center. 122/290 were homozygous for C282Y; the mean MCV of this group was significantly elevated at 95.2 fL (control group was 89.2 fL; p<0.001) Among all patients with phlebotomy-mobilizable iron greater than four grams, regardless of HFE genotype, the mean MCV was 94.8 fL (significantly greater than control, p<0.001); there was no significant difference between those who are homozygous for the C282Y HFE mutation and those who are not. Among C282Y homozygous individuals, there was no significant correlation between the MCV versus serum transferrin saturation, serum ferritin and phlebotomy-mobilizable iron (r= 0.07, 0.207 and −0.005 respectively). In patients with mobilizable iron greater than four grams who were not C282Y homozygous there was weak correlation between the MCV versus serum transferrin saturation and serum ferritin (r= 0.39 and 0.37 respectively) and no significant correlation versus phlebotomy-mobilizable iron (r= 0.04).
Conclusion: Our study confirms the presence of elevated MCV levels in patients with Hereditary Hemochromatosis. The mean MCV was high in both C282Y homozygous individuals as well as those with elevated levels of body iron (>4 g) who were not homozygous for the C282Y HFE mutation. For the most part, the elevated MCV did not correlate with measures of body iron stores although there was a weak correlation with serum transferrin saturation and serum ferritin among iron-loaded individuals who were not homozygous for C282Y. Further studies of the factors that influence MCV in these patients may provide insights into the derangements of iron utilization that may occur in iron overload syndromes.
The Association between Acute Lead Exposure from Indoor Firing Ranges and Iron Metabolism.
Authors: Merkel Drorit , Hirshhoren Nir , Shochat Tzippora , Vivante Asaf 
Published: October 2019

Abstract
Objective: To assess the impact of short term indoor firing ranges lead exposure and its relationship to iron, ferritin, lead, zinc protoporphyrin and hemoglobin concentration among young adults.
Methods: We report of a clinical observation that was carried out in 30 young and healthy soldiers serving in the Israel Defense Forces (IDF) Counter Terrorist Unit (CTU). Blood samples were drawn for Lead (Pb), Zinc Protoporphyrin (ZPP),Iron, Hemoglobin (Hb) and ferritin prior to and after a 6 weeks period of intensive shooting practice in indoor firing ranges.
Results: A mean Blood lead level increase (p< 0.0001) with a mean Iron (p<0.0005) and mean ferritin (p<0.0625) decrease simultaneously after 6 weeks period of Lead dusts exposure were demonstrated. We found a trend for inverse correlation between pre-exposure low ferritin levels and post exposure high blood lead levels.
Conclusion: We found decreased iron and ferritin levels after short term lead exposure among young adults. This can be explained by competition of iron and lead absorption viatransporters like DMT1 suggesting that lead poisoning can cause iron depletion and that iron depletion can aggravate lead poisoning. This synergistic effect should come to every physicians mind especially when treating patients with a potential risk for each problem separately.
Lead (Pb), Zinc Protoporphryn (ZPP), Hemoglobin (Hb), Iron and Ferritin among the CTU soldiers before and after the indoor firing ranges lead exposer variable N Pre-exposure N Post-exposure Difference *P value Pb (mcg/dl) 29 10.3±2.3 30 18.9±3.6 8.8±2.6 0.0001 ZPP(mcg/dl) 29 42±7.5 30 42.9±8.1 0.03±6.5 NS Hb (g/dl) 30 15±0.7 30 14.8±0.9 0.2±0.2 NS MCV (fl) 30 88.7±2.5 30 89±2.7 0.3±0.2 NS Iron (mcg/dl) 29 108.5±43.6 30 77.4±24.4 −30.4±41.2 0.0005 Ferritin (mcg/l) 27 58.1±27.7 16 51±19.9 −6.1±10.7 0.0625 Correlation between Pre-exposure Ferritin levels and Post exposure Lead level.(Person correlation coefficient = −0.28 r=0.14 number of observations = 27) Correlation between Pre-exposure Ferritin levels and Post exposure Lead level.(Person correlation coefficient = −0.28 r=0.14 number of observations = 27)
Epoetin alfa 80,000 U Every Three Weeks (Q3W) in Anemic Cancer Patients (pts) Not Receiving Chemotherapy (CT) or Radiation Therapy (RT).
Authors: Shasha Daniel , Dawkins Fitzroy , Wilhelm Francois E. 
Published: October 2019

AbstractAnemia is reported at rates approaching 40% in cancer pts not receiving CT or RT. In two previous studies in anemic cancer pts not receiving CT or RT, epoetin alfa administered at 40,000 U sc once weekly1 or 60,000 U sc every two weeks2 was shown to be both safe and effective (hematopoietic response [HR] rates of 76.9% and 76.8%, respectively) in treating anemia. The primary objective of the current study was to evaluate the HR to epoetin alfa 80,000 U SC Q3W in this population; transfusions and quality of life were evaluated as well. Eligible pts had a non-myeloid malignancy, baseline hemoglobin (Hb) ≤ 11 g/dL, no CT administration within 8 weeks or RT within 4 weeks of study entry, and no plans to receive these therapies during the study period. Study drug was to be administered at Weeks 1, 4, 7, and 10, with follow-up continuing to Week 13. Epoetin alfa dose was reduced for Hb > 12 g/dL or Hb increase > 1.5 g/dL in any 3-week period; dose was withheld for Hb > 13 g/dL, then reduced when Hb ≤ 12 g/dL. All pts were to receive supplemental ferrous sulfate 325 mg po qd as tolerated. The primary efficacy endpoint was the proportion of pts achieving HR, defined as a ≥ 2 g/dL Hb increase and/or Hb ≥ 12 g/dL during the study, independent of transfusion within 28 days. 51 pts were enrolled (safety population) and 49 met the criteria for efficacy analyses (received ≥ 1 dose of epoetin alfa and had ≥ 1 post-baseline Hb value). Mean age was 71.0 ± 10.5 years, 53% of pts were female, 94% of pts had baseline ECOG status of 0 or 1, and mean baseline Hb was 10.3 ± 0.6 g/dL. The most common tumor types were breast (n=12, 24.5%) and prostate (n=12, 24.5%). HR was achieved in 37/49 (75.5%) pts. Mean time to first HR was 5.76 weeks. Hb change from baseline ≥ 1 g/dL was achieved in 39/49 (79.6%) pts, in a mean 3.77 weeks. 24 of 51 pts (47.1%) had at least one dose reduction or withhold. From Day 29 to end of study, 2/49 (4.1%) pts received PRBC transfusion. Statistically significant quality of life improvements from baseline in all 3 LASA scales (Energy Level, Daily Activities, and overall Quality of Life) were noted at Weeks 7 and 13/WD. Improvements were also seen with the FACT-An subscales, although not all changes were statistically significant at Weeks 7 and 13/WD. Adverse events occurring in ≥ 5% of the safety population were arthralgia (5 of 51 pts, 9.8%), back pain (3 of 51 pts, 5.9%), and vomiting (3 of 51 pts, 5.9%). One non-clinically relevant thrombotic vascular event of chest pain was reported. One pt died during the study, and 2 pts died during study follow-up; all deaths were considered unrelated to epoetin alfa therapy. In this population of cancer pts with anemia not receiving CT or RT, epoetin alfa 80,000 U sc administered Q3W safely increases Hb and improves pt quality of life. This extended dosing regimen further expands the flexible dosing options for epoetin alfa in this pt population.
AMD3100 and G-CSF Synergize To Promote Repopulating Stem Cell Mobilization in Fanca −/− and Fancc −/− Mice.
Authors: Pulliam Anna C. , Hobson M. Joe , Yang Fengchun , Broxmeyer Hal E. , Clapp D. Wade 
Published: October 2019

Abstract
Fanconi Anemia (FA) is an autosomal recessive DNA repair disorder clinically characterized by congenital abnormalities, progressive bone marrow (BM) failure and a propensity for malignancies. It is advantageous to bank FA patients’ cells for autologous treatment of pancytopenia, transplantation following chemotherapy or future gene therapy trials. Because the amount of cells able to be collected by BM harvesting is limited and the process is often problematic in children, mobilization of stem cells into the circulation would be an ideal means of collecting repopulating hematopoietic stem and progenitor cells (HSPC). Traditional mobilization protocols utilizing granulocyte colony-stimulating factor (G-CSF) as a mobilizing agent result in poor yields of phenotypic HSPC in FA patients. We have shown that analogous to the human patients with FA, administration of recombinant G-CSF is not sufficient to effectively mobilize myeloid progenitors from the BM of Fancc −/− mice (Broxmeyer et al, JEM, 2005). Antagonists to chemokine receptors, together with G-CSF, can enhance mobilization of murine wild type (WT) HSPC. AMD3100 is a selective antagonist of CXCR4, which is thought to function in the retention of HSPC in the BM. We hypothesized that the combination of AMD3100 and G-CSF would enhance mobilization of HSPC in Fanca −/− and Fancc −/− mice. Peripheral blood was collected to assess the number of myeloid progenitors and HSPC repopulating ability. Myeloid progenitor numbers were assessed using progenitor assays. Either G-CSF or AMD3100 alone resulted in poor mobilization of hematopoietic progenitors. In contrast, administration of AMD3100 and G-CSF together increased the number of colonies of myeloid progenitors up to 18 fold above that of either G-CSF or AMD3100 alone in both Fanca −/− and Fancc −/− mice. The stem cell activity of mobilized peripheral blood cells was evaluated using competitive repopulation assays, in which a common pool of isogenic ‘competitor cells’ and ‘test cells’ from mice of different genotypes or treatment conditions are co-transplanted. Fanca −/− and Fancc −/− cells mobilized with both G-CSF and AMD3100 yielded a 3–4 fold increase in peripheral blood chimerism as compared to the cells mobilized with G-CSF or AMD3100 alone. The latter mice also had a decreased survival. Phenotypic analysis of the peripheral blood of primary recipients confirmed the engraftment of multi-lineage test cells. Transplantation of chimeric bone marrow into secondary recipients maintained the test cell chimerism, confirming that long-term repopulating cells were mobilized. Collectively, these data from two FA murine models demonstrate that the AMD3100 and G-CSF protocol is an effective strategy to mobilize FA deficient repopulating HSPC. This has potential implications for more efficient banking of FA patients’ HSPC for future use or for use in gene transfer protocols.
Aplastic Anemia Due to Exposure to Benzene in Diamond Workers in Surat (India).
Authors: Shah Kiran C. , Naik Prashant K. 
Published: October 2019

Abstract
Benzene, used as a solvent in many industries is a known carcinogen which can lead to variety of hematological manifestations, like macrocytic anemia, aplastic anemia, myelodysplasticsyndrome and leukemia. However benzene induced aplastic anemia in diamond industry has not been reported so far in literature. We report series of cases of aplastic anemia from a single diamond factory, in Surat, India. All cases were diagnosed in June and July 2005. Benzene was used to remove whitener applied on diamonds before cutting them by Laser technology (Sarin technology from Israel). Diamond workers used benzene without any protective measures. Each worker used to clean about hundred diamonds daily by taking benzene in their hands. Most of the workers were using benzene for more than one year. The working environment used to have strong smell of benzene, however exact level of benzene in ppm was not determined. Out of 37 workers working in eight hour shift in a closed airconditioned room, eleven of them developed blood dyscrasia. Initially four patients presented with fever and pancytopenia. After confirmation of aplastic anemia in all of them remaining workers from same factory and other diamond factories using benzene were screened. From the same factory seven more cases of mild aplastic anemia were detected. Few cases of mild blood dyscrasia were detected from other diamond factories too. All cases were thoroughly examined clinically & investigated to rule out other causes of pancytopenia. Biochemical tests, liver functions, serum Iron, B12 study, tests for PNH, bone marrow aspiration & trephine biopsy and cytogenetics in severe cases were done. Three cases were treated with ATG and cyclosporine transfered to state capital, Ahmedabad. One patient died during treatment and two recovered. Two other cases were treated with cyclosporine alone and both of them recovered. No cases of MDS or leukemia detected from same factory so far. Since July 2005 benzene is no more used in diamond industry in India. After removing the workers from the exposure all other cases recovered. A close follow up for one year showed no recurrence or progression.
Hematological Characteristics of Infants and Young Children Presenting with Different Levels of Malarial Anemia at a Rural District Hospital in Western Kenya.
Authors: Novelli Enrico M. , Ong’echa John Michael , Davenport Greg , Keller Christopher C. , Were Tom , Ouma Collins , Otieno Richard , Rosano Caterina , Kaplan Sandra , Perkins Douglas J. 
Published: October 2019

Abstract
In areas of intense P. falciparum exposure, such as western Kenya, the most lethal complication of malaria is severe malarial anemia (SMA). The pathogenesis of SMA is multi-factorial and not fully understood. Our ongoing studies are, therefore, investigating the hematological manifestations of MA in a cohort of children presenting at a rural district hospital in western Kenya. A total of 619 children aged 3–33 mos. were categorized into 5 groups: SMA (Hb<6.0g/dL); moderate MA (MdMA; 6.0≤Hb<8.0g/dL); mild MA (MlMA; 8.0≤Hb<11.0g/dL); uncomplicated malaria (UM, Hb≥11.0g/dL), and healthy aparasitemic controls (HC). Parasite density, CBC, and reticulocyte count was obtained on all subjects (see table).
HC (n=62) UM (n=36) MlMA (n=139) MdMA (n=161) SMA (n=221) P valuea Data are presented as mean±SEM. aDifferences between the groups were compared using the Kruskal-Wallis test. *Denotes p<0.05 (Mann-Whitney U test) relative to the HC group. Parasitemia (/μL) 0 82471±15925 51711±5300 51513±5798) 62934±6416 0.107 Hb (g/dL) 1.81±0.11 11.66±0.14 9.27±0.07* 6.86±0.05* 4.78±0.06* <0.001 MCV (fL) 71.87±0.71 73.42±1.12 68.57±0.63* 69.25±0.76* 71.34±0.67 0.001 Reticulocyte count (%) 1.57±0.20 1.64±0.24 2.55±0.16* 4.21±0.29* 5.50±0.31* <0.001 RPI 1.83±0.33 1.90±0.49 1.44±0.09 1.50±0.10 1.15±0.07* 0.001
Peripheral blood smears (n=150) were randomly selected from all groups for examination of RBC and WBC morphology, and identification of any clinically significant abnormalities, such as presence of hemozoin (Hz). The majority of the children with malaria had inadequate bone marrow responses (77.6%), as determined by the reticulocyte production index (RPI). Relative to the UM group, the SMA group had increased microcytosis (p<0.005). Moreover, numbers of nucleated RBC (nRBC) and Hz-laden monocytes correlated with increasing degrees of anemia (p=0.08 and p<0.005, respectively). In contrast, levels of parasitemia, prevalence of high-density parasitemia (≥10,000 parasites/ml) and reactive lymphocytes did not differ among the four malaria groups. No significant increases were observed in the number of schistocytes, acanthocytes or spherocytes in any of the groups. Macrocytosis was rarely observed and sickle cells were not detected. These findings illustrate that parasitemia is not associated with the severity of anemia in this population. Conversely, the number of Hz-containing monocytes was a strong predictor of anemia severity, suggesting that SMA results from more chronic malaria infections. Finally, although nRBC were most commonly associated with SMA, the RPI was not appropriately increased for the degree of anemia, illustrating that these children have suppressed and/or ineffective erythropoiesis.
Successful Treatment of Pure Red Cell Aplasia (PRCA) Associated to Phenitoin without Blood Transfusions in a Jehovah’s Witness Patient.
Authors: Argote Victoria E. Ferrer , Ayala-Alcantara Noe , Ramos-Peñafiel CHristian O. 
Published: October 2019

Abstract
A 17 year-old Jehovah’s Witness girl was admitted to the neurosurgery ward with a subarachnoid hemorrhage Fisher IV, Hunt and Hess II, due to an arteriography-confirmed aneurism of the left posterior comunicating artery (LPCA). CT scan showed hemorrhages of the left lateral, 3rd and 4th ventriculi. Her blood counts were normal. She underwent surgery and during the procedure she developed neurologic deterioration due to brain edema. The procedure was stopped and she was started on prophylactic Phenitoin. Her hemoglobin levels began to drop progressively until they reached 3.6 gr/dL with 0.8% reticulocytes while her platelet and WBC counts remained within normal ranges (278 and 5.9 × 109/L respectively) with a normal differential count. No bleeding site was found, and hemorrhage was discarded as cause of the anemia. The serum iron was 218, the IBC 213 and the saturation index 102.5 (37.3%), all within normal values. The bone marrow aspirate showed a slight increase of the cellularity with normal megakariocytes and granulocytes with slight eosinophilia and a total absence of the erythroid series. The lymphocytes were also normal. This image was consistent with a PRCA. The existence of a thymoma as well as several viral infections including Parvovirus, EBV, HIV, HB and HC were discarded as cause of the PRCA. Phenitoin was stopped and treatment with steroids, cyclosporine, mesterolone and erythropoietin 8,000 U/d SC was started. Despite the evidence of very deep anemia with dispnea and prostration, which required red cell transfusions, the patient and her parents absolutely refused them for religious reasons and the supportive treatment was enhanced. Her clinical status improved after 48 hours and the Hb began to increase progressively. She was discharged one month later with a Hb of 13.1 gr/dL, Ht 39.6%, with a corrected reticulocyte count of 1.8%, 6.2 × 109/L WBC with a normal differential count and 284 × 109/L BP. Even though no tests could be done to confirm phenitoin as the triggering factor of the PRCA, the temporal association between its use and the development of the anemia very strongly suggests a causal association even though it can not be assured. The results we had with erythropoietin, high-dose iron, oxygen and parenteral feeding were very rewarding. Jehovah’s Witnesses patients with severe anemia like this one have a poor prognosis and pose a strong therapeutic challenge that may discourage the medical staff to continue a struggle that seems hopeless. We feel that by accepting it and sharing experiences like this one we can help these patients who will rather die than accept blood derivatives.
Early and Standard Intervention with Epoetin Alfa (PROCRIT®) 120,000 Units (U) Every Three Weeks (Q3W) in Patients with Cancer Receiving Chemotherapy - Results of a Planned Interim Analysis.
Authors: Glaspy John , Moyo Victor , Kamin Marc , Wilhelm Francois E. 
Published: October 2019

Abstract
Epoetin alfa has been used for chemotherapy-induced anemia (CIA) for over a decade, has an established efficacy and safety profile, and offers the flexibility of three times a week (TIW) or weekly (QW) dosing to match patient needs. Newer erythropoiesis stimulating therapies (ESTs) are being used for the treatment of CIA at dosing intervals of up to once every three weeks to coincide with commonly used chemotherapy regimens. A recent study suggested that initiating epoetin alfa every other week produced a similar hemoglobin (Hb) response as QW initiation1. We are conducting the first study to evaluate the efficacy and safety of initiating epoetin alfa Q3W for the treatment of CIA.
This 16-week study was designed to enroll 180 patients with non-myeloid malignancy, planned myelosuppressive chemotherapy for at least 9 weeks during the study, and with baseline Hb ≥ 11.0 and ≤ 12.0 g/dL. Patients were randomized to begin epoetin alfa 120,000 U SC immediately (early intervention) or when their Hb decreased to < 11 g/dL (standard intervention). In both groups, dosing was reduced to 80,000 U Q3W if Hb was > 12.0 g/dL at the time of a dosing visit or increased by more than 1.5 g/dL in a 3-week period. If a patient’s Hb was < 10.0 g/dL at any dosing visit after the first dose, the regimen was changed to 40,000 U QW. The objective of this planned interim analysis was to explore the safety and efficacy of the 120,000 U Q3W regimen.
We report results for the first 46 patients who received study drug and had at least one post-baseline Hb (26 early intervention and 20 standard intervention patients). Mean Hb values over time for patients receiving epoetin alfa Q3W are presented in the table below. Standard intervention patients had a mean Hb increase of 1.7 g/dL after two doses (week 7). Early intervention patients had weekly mean Hb values in the 11.0 to 12.0 g/dL range while receiving Q3W dosing. By week 5, weekly mean Hb levels were similar between the two groups. Eighteen patients (11 early and 7 standard) had at least one dose reduction to 80,000 U Q3W. Eleven patients (6 early and 5 standard) converted to 40,000 U QW. Epoetin alfa was well tolerated in both groups. A total of 4 (2 early and 2 standard) out of 47 treated patients (8.5%) experienced clinically relevant thrombotic vascular events.
The results of this interim analysis suggest that epoetin alfa can be initiated at 120,000 U Q3W in cancer patients with CIA, potentially offering the same Q3W initiation dosing option as the newer ESTs, yet with the added advantage of established TIW and QW dosing.
Mean Hb (g/dL) Over Time (N)* Week on Study Early Intervention (N=26) Standard Intervention (N=20) *Hb values censored after patients switched to 40,000 U QW Baseline (1) 11.5 (26) 10.4 (20) 4 11.7 (26) 10.9 (19) 7 11.6 (24) 12.1 (14) 10 11.6 (21) 11.8 (11) 13 11.9 (15) 12.3 (8) 16 12.3 (8) 11.8 (2)