Pediatr Transplant 2006 Jun; 10(4): 497-500 (Read article online)

Ohga S, Ichino K, Goto K, Hattori S, Nomura A, Takada H, Nakamura K, Hara T

Treatment of severe aplastic anemia (SAA) patients who lack human leukocyte antigen (HLA)-matched donors and failed immunosuppressive therapy (IST) is challenging. Recently, umbilical cord blood transplantation (CBT) after non-myeloablative therapy has been reported in adult but not in childhood SAA. However, most cases resulted in mixed donor chimerism and incomplete hematological recovery. We reported an 11-yr-old girl with recurred SAA 5 yr after IST who underwent unrelated donor CBT after a modified regimen. This patient had renal and cardiac dysfunction, and lacked suitable bone marrow donors. The 3.9 x 10(7)/kg CB cells from an HLA one-locus mismatched unrelated donor were infused after conditioning with total body irradiation (5 Gy), melphalan (120 mg/m(2)), and fludarabin (120 mg/m(2)). Hematological recovery was favorable in complete chimerism. A major complication was only skin graft-versus-host disease (grade I). CB could be an alternate stem cell source for childhood SAA after modified preparative regimen.

Atherosclerosis 2006 May 16; (Read article online)

Aessopos A, Farmakis D, Tsironi M, Diamanti-Kandarakis E, Matzourani M, Fragodimiri C, Hatziliami A, Karagiorga M

BACKGROUND: Homozygous sickle-cell anemia and beta-thalassemia are characterized by impaired endothelial function, while data on arterial stiffness have hitherto been conflicting. We sought to investigate aortic elastic properties and endothelial function in sickle-thalassemia, which combines molecular and clinical features of the above conditions. METHODS AND RESULTS: Forty-seven sickle-thalassemia patients, younger than 45 years, with preserved left ventricular (LV) function and no history of smoking, systemic or pulmonary hypertension, diabetes mellitus, dyslipidemia or thyroid disease, along with 40 healthy controls were studied. Aortic strain, distensibility and stiffness index were calculated by echocardiographically-obtained aortic root diameters. Brachial artery endothelial function was assessed by ultrasonographic evaluation of flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD). Left ventricle was assessed by echocardiography. Patients had an impaired FMD (4.2+/-2.9% versus 9.2+/-3.8% in controls, p<0.001) with a preserved NMD (16.9+/-5.6% versus 15.2+/-4.8% in controls, p>0.05). Aortic strain and distensibility were lower and aortic stiffness index was higher in patients compared to controls (8.1+/-4.6 versus 5.8+/-2.9, p<0.01). Indexed LV diameters and mass were higher in patients. Systolic LV function was preserved, while 14.9% of patients had an impaired relaxation transmitral inflow pattern. Patients' LV mass index and diastolic mitral E wave deceleration time were positively correlated with aortic stiffness index (p<0.001). CONCLUSION: Sickle-thalassemia is characterized by a complex vasculopathy, consisting of endothelial dysfunction and increased arterial stiffness, with a global effect on cardiovascular function.

Exp Parasitol 2006 May 19; (Read article online)

Hernandez-Valladares M, Naessens J, Musoke AJ, Sekikawa K, Rihet P, Ole-Moiyoi OK, Busher P, Iraqi FA

Tumor necrosis factor alpha (Tnf) plays a pleiotropic role in murine malaria. Some investigations have correlated Tnf with hypothermia, hyperlactatemia, hypoglycemia, and a suppression of the erythropoietic response, although others have not. In this study, we have evaluated parasitemia, survival rate and several pathological features in C57BL/6JTnf(-/-) and C57BL/6JTnf(+/+) mice after infection with Plasmodium chabaudi adami 408XZ. Compared to the C57BL/6JTnf(+/+) mice, C57BL/6JTnf(-/-) mice showed increased parasitemia and decreased survival rate, whereas blood glucose, blood lactate and body weight were not significantly different. However, C57BL/6JTnf(-/-) mice suffered significantly more from severe anemia and hypothermia than C57BL/6JTnf(+/+) mice. These results suggest that Tnf is an important mediator of parasite control, but not of anemia development. We hypothesize that the high mortality observed in the Tnf knock-out mice is due to increased anemia and pathology as a direct result of increased levels of parasitemia.

Ann Hematol 2006 May 20; (Read article online)

Müller-Berndorff H, Haas PS, Kunzmann R, Schulte-Mönting J, Lübbert M

We retrospectively studied 89 consecutive patients diagnosed with primary myelodysplastic syndrome (MDS) over a period of 10 years to (1) identify prognostic factors for overall survival (OS) and leukemia-free survival (LFS); (2) to assess and compare the Bournemouth-, Spanish-, Düsseldorf-, Lille-, and the International prognostic scoring systems (IPSS); and to (3) compare the French-American-British (FAB) and World Health Organization (WHO) classifications. The median age of patients was 63 years (range, 26-85). Karyotype analyses were done in 85 patients (96%). Median OS was 3 years; 67 patients (75%) have died, and 28 (31%) had progression to acute myeloid leukemia (AML). Major independent prognostic variables for both OS and LFS (multivariate analysis) were percentage of bone marrow (BM) blasts (P<0.0001), and in patients with cytogenetic data available, cytogenetic risk groups by Lille-score (OS, P=0.031/LFS, P=0.002) and IPSS (OS, P=0.024). All five prognostic scoring systems successfully discriminated risk groups as regards OS and LFS, but in patients with cytogenetic data available, the major independent prognostic score for OS (P<0.0001) and LFS (P=0.006) was the IPSS. The FAB and WHO classifications also successfully discriminated between risk groups. The new WHO subgroups [refractory cytopenia with multilineage dysplasia (RCMD), with (RCMD-RS) or without ringed sideroblasts] showed a significantly (P=0.0454) different prognosis for OS, but not for LFS (P=0.0839), in comparison to the subgroups having erythroid dysplasia only (RA/RARS). Risk stratification into refractory anemia with excess blast-I (RAEB-I) and RAEB-II tended to yield different prognoses for OS and LFS. The 5q-minus syndrome strongly predicted for a good prognosis. In patients treated with the demethylating agent decitabine (n=24), IPSS "poor risk" cytogenetics were unable to predict for the expected worse prognosis when compared to "intermediate-risk" cytogenetics. In conclusion, we confirm in a single-center patient cohort that the use of the WHO classification improves the predictive value of the FAB classification and that, in patients with cytogenetic data available, the IPSS can be used for clinical decision-making.

Kyobu Geka 2006 May; 59(5): 355-8 (Read article online)

Sasaki Y, Shibata T, Hirai H, Motoki M, Bito Y, Takahashi Y, Suehiro S

We report a 61-year-old man with aplastic anemia who underwent successful off-pump coronary artery bypass (OPCAB) after being admitted for angina pectoris. Coronary angiography showed severe stenosis of the left main coronary artery. Preoperative WBC was 2,200/microl, neutrophil 704/microl, Hb 8.1g/dl, and PLT 16,000/microl. We conducted OPCAB on double vessels using left internal thoracic and radial artery grafts. Thirty units of platelets were transfused intraoperatively with little perioperaive hemorrhage. Because of high grade fever, we injected 150 microg granulocyte colony-stimulating factor (G-CSF) every 3 days postoperatively to prevent major infection. The combination of appropriate perioperative management and OPCAB yielded an effective result for a patient with severe hematological disorders causing pancytopenia.

Arch Gynecol Obstet 2006 Jun; 274(3): 165-169 (Read article online)

Lapaire O, Irion O, Koch-Holch A, Holzgreve W, Rudin C, Hoesli I,

Objective: Although elective cesarean section (ECS) is the currently recommended modality for delivering women infected with the human immunodeficiency virus (HIV), historical evidence suggests that they are at higher risk of postoperative complications than noninfected women. Those risks have to be carefully balanced against the presumed minimal benefit of ECS, especially in the case of low viral load and high CD4 counts. We therefore compared the incidence and type of post-ECS complications in HIV-infected women, most with low viral loads and high CD4 cell counts, with those in matched noninfected women treated by the same surgical teams. Study design: A Swiss 8-center, prospective, matched case-control study compared minor and major post-ECS complication prevalence, hospital stay and confounding factors (surgeon experience) between HIV-infected and noninfected women. Results: Minor complications in the 53 matched pairs were eightfold more frequent overall in infected women. More frequent specific minor complications were anemia, blood loss and urinary tract infection. Yet the surgeons performing ECS in infected women were more experienced. Complications prolonged hospital stay in infected women. Major complication rates did not significantly differ between the groups. Conclusion: HIV-positive women have a higher risk of post-ECS morbidity, even with high CD4 counts and low viral load. Therefore, the blanket recommendation of ECS in HIV-infected women requires a review.

J Paediatr Child Health 2006 May; 42(5): 316-318 (Read article online)

Borgia F, Pasquale LD, Cacace C, Meo P, Guarneri C, Cannavo SP

Subcutaneous fat necrosis of the newborn is an uncommon, self-limiting panniculitis that usually occurs in full-term infants as a consequence of perinatal asphyxia. The cutaneous involvement may be associated with metabolic complications such as hypoglycaemia, thrombocytopenia, hypertriglyceridemia, anemia and hypercalcaemia. The delayed onset of hypercalcaemia, 1-6 months after the development of the skin manifestations, imposes a prolonged follow-up to avoid its acute toxic effects on cardiovascular and renal systems and the more durable metastatic calcifications.

Cancer Chemother Pharmacol 2006 May 23; (Read article online)

Ardavanis A, Mavroudis D, Kalbakis K, Malamos N, Syrigos K, Vamvakas L, Kotsakis A, Kentepozidis N, Kouroussis C, Agelaki S, Georgoulias V,

Purpose: To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. Patients and treatment: Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performance status of 0-1, 30 (83%) had visceral disease and 83% had received prior taxanes while 50% anthracyclines. Treatment consisted of pegylated liposomal doxorubicin (40 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 15) every 4 weeks. Results: In an intention-to-treat analysis 2 (6%) complete and 12 (33%) partial responses were observed (overall response rate 39%; 95% CI: 23-54.8%); 8 (22%) and 14 (39%) patients experienced stable and progressive disease, respectively. The median TTP was 6.5 months and the median survival time 14.2 months. The 1-year survival rate was 54.1%. Grade 3 and 4 neutropenia occurred in 21 (58%) patients, grade 3-4 anemia in four (11%) and grade 4 thrombocytopenia in one (3%). Two (6%) patients developed febrile neutropenia. Non-hematologic toxicity was mild and easily manageable. There was no clinically important cardiac toxicity or treatment-related deaths. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated salvage regimen in patients with metastatic breast cancer which merits further evaluation.

Infect Immun 2006 Jun; 74(6): 3190-203 (Read article online)

Cernetich A, Garver LS, Jedlicka AE, Klein PW, Kumar N, Scott AL, Klein SL

To examine the hormonal and immunological mechanisms that mediate sex differences in susceptibility to malaria infection, intact and gonadectomized (gdx) C57BL/6 mice were inoculated with Plasmodium chabaudi AS-infected erythrocytes, and the responses to infection were monitored. In addition to reduced mortality, intact females recovered from infection-induced weigh loss and anemia faster than intact males. Expression microarrays and real-time reverse transcription-PCR revealed that gonadally intact females exhibited higher expression of interleukin-10 (IL-10), IL-15Ralpha, IL-12Rbeta, Gadd45gamma, gamma interferon (IFN-gamma), CCL3, CXCL10, CCR5, and several IFN-inducible genes in white blood cells and produced more IFN-gamma than did intact males and gdx females, with these differences being most pronounced during peak parasitemia. Intact females also had higher anti-P. chabaudi immunoglobulin G (IgG) and IgG1 responses than either intact males or gdx females. To further examine the effector mechanisms mediating sex differences in response to P. chabaudi infection, responses to infection were compared among male and female wild-type (WT), T-cell-deficient (TCRbetadelta(-/-)), B-cell-deficient (muMT), combined T- and B-cell-deficient (RAG1), and IFN-gamma knockout (IFN-gamma(-/-)) mice. Males were 3.5 times more likely to die from malaria infection than females, with these differences being most pronounced among TCRbetadelta(-/-), muMT, and RAG1 mice. Male mice also exhibited more severe weight loss, anemia, and hypothermia, and higher peak parasitemia than females during infection, with WT, RAG1, TCRbetadelta(-/-), and muMT mice exhibiting the most pronounced sexual dimorphism. The absence of IFN-gamma reduced the sex difference in mortality and was more detrimental to females than males. These data suggest that differential transcription and translation of IFN-gamma, that is influenced by estrogens, may mediate sex differences in response to malaria.

Gynecol Oncol 2006 May 17; (Read article online)

Fracasso PM, Blessing JA, Molpus KL, Adler LM, Sorosky JI, Rose PG

OBJECTIVE.: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with advanced or recurrent endometrial cancer who had received one prior platinum therapy. METHODS.: Eligible patients were to have measurable disease and one prior chemotherapy regimen which could include cisplatin or carboplatin. Oxaliplatin 130 mg/m(2) was administered intravenously over 2 h. This treatment was repeated every 21 days until progression of disease or adverse effects prohibited further therapy. RESULTS.: Fifty-four patients were entered on study, of which 52 were eligible and 50 had had prior platinum therapy. The overall response rate was 13.5%, with three patients (5.8%) achieving a complete response and four patients (7.7%) achieving a partial response. Median duration of response was 10.9+ (range: 4.1-50.3+) months. Stable disease was reported in 15 (28.8%) patients, with an associated median duration of 5.4 (range: 2.2-19.6) months. Drug-related toxicities consisted of anemia, nausea and vomiting, and neurotoxicity. CONCLUSIONS.: Oxaliplatin at the dose and schedule employed has limited activity in patients with advanced or recurrent endometrial carcinoma who have had previous platinum therapy.

Genes Cells 2006 Jun; 11(6): 685-700 (Read article online)

Nakajima O, Okano S, Harada H, Kusaka T, Gao X, Hosoya T, Suzuki N, Takahashi S, Yamamoto M

Molecular defects in erythroid 5-aminolevulinate synthase (ALAS-E), the first enzyme in the heme biosynthetic pathway, cause X-linked sideroblastic anemia (XLSA). However, ring sideroblasts, the hallmark of XLSA, were not found in ALAS-E-deficient mouse embryos, indicating that simple ALAS-E-deficiency is not sufficient for ring sideroblast formation. To investigate the developmental stage-specific pathogenesis caused by heme-depletion, we attempted a complementation rescue of ALAS-E-deficiency. We exploited transgenic mouse lines expressing human ALAS-E at approximately half that of wild-type levels. In these hypomorphic embryos, most of the primitive erythroid cells were transformed into ring sideroblasts. The majority of the circulating definitive erythroid cells became siderocytes, enucleated erythrocytes containing iron deposits, and definitive ring sideroblasts were also observed. These iron-overloaded cells suffered from an alpha/beta globin chain imbalance. Despite the iron overload, transferrin receptors were highly expressed in the erythroid cells, suggesting they contribute to the formation of ring sideroblasts and siderocytes. These results indicate that a partially depleted heme supply provokes ring sideroblast formation. The experimental generation of ring sideroblasts in animals would contribute to our understanding of the iron metabolism and its disorder in erythroid cells.

World J Gastroenterol 2006 May 21; 12(19): 3114-8 (Read article online)

Zhou J, Fan J, Wang Z, Wu ZQ, Qiu SJ, Huang XW, Yu Y, Sun J, Xiao YS, He YF, Wang YQ, Tang ZY

AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune(R), rapamycin) in a consecutive cohort of 248 liver allograft recipients. METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n=11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n=18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n=7) after OLT. RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n=2), anemia (n=8), and oral aphthous ulcers (n=7) found in our cohort were easily manageable. CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

Acta Histochem 2006 May 19; (Read article online)

Richter S, Makovitzky J

Multiple myeloma (MM) is a neoplastic disorder characterized by proliferation of a single clone of plasma cells derived from B cells, which proliferates in the bone marrow and frequently invades the adjacent bone, producing skeletal destruction that results in bone pain and fractures. Patients with MM can furthermore present with anemia, hypercalcemia and renal failure. Non-secretory multiple myeloma (NSMM) is characterized by the absence of a monoclonal (M) protein in both the serum and urine. The reported incidence is 1-5% of all multiple myeloma cases. Development of amyloid tumors in NSMM has been described in the literature only occasionally. The clinical features of a 49-year-old female patient with NSMM and amyloid tumors in the breast, lung and rib are presented in this report. Conventional histology, Congo red staining with and without potassium permanganate pretreatment, aldehyde bisulfite-toluidine blue (ABT) reaction, sialic acid specific topo-optical reaction, toluidine blue topo-optical reaction as well as immunohistochemistry were performed. An attempt is made to explain the lack of monoclonal immunoglobulins in the serum and urine, although extensive organ amyloidosis of AL type (kappa-light chains) has been found. It is assumed that the plasmocytic plasma cells possess an excretory mechanism, which allows the pathologic immunoglobulins to be secreted either as amyloid proteins polymerizing into amyloid fibrils, or as immunoglobulin fragments that are subject to degradation as soon as they are excreted out of the tumor cell. In this paper, we review the occurrence of amyloid tumors in non-secretory multiple myeloma and, in a single case report, we confirm the existence of carbohydrate residues, including sialic acids and sulfated GAGs, in amyloid deposits.

Leuk Res 2006 May 20; (Read article online)

Smolej L

In March issue of Leukemia Research, Nishida et al. describe a case report of an elderly patient with chronic lymphocytic leukemia in whom fludarabine-induced autoimmune hemolytic anemia (AIHA) was treated with rituximab and subsequently prednisone. This letter raises several questions about the type and cost-effectiveness of the therapy and suggests a different therapeutic approach.

Rev Esp Anestesiol Reanim 2006 Apr; 53(4): 208-13 (Read article online)

Gredilla E, Gimeno M, Canser E, Martínez B, Pérez Ferrer A, Gilsanz F

OBJECTIVE: To assess the efficacy and safety of treatment with intravenous iron for postpartum anemia or postoperative anemia after gynecological surgery. PATIENTS AND METHODS: A prospective study enrolling patients entering our recovery care unit from June through December 2004 with hemoglobin levels less than 10 g x dL(-1) after vaginal childbirth or cesarean section or after another form of gynecological surgery. Three 200 mg doses of intravenous iron sucrose (Venofer) were administered on consecutive days. Fifteen days after the last dose, the patient came for follow-up tests and was asked about side effects. The results were analyzed with a Student t test for matched samples. RESULTS: A total of 250 obstetric and 52 gynecological surgery patients were enrolled; 156 and 33 completed the study in each group, respectively. Hemoglobin increased after treatment by 3.2 g x dL(-1) in the obstetric patients and by 2.7 g x dL(-1) in patients who underwent gynecological surgery. The increase was significant in both groups (P<0.001); the 95% confidence interval was 2.918-3.519 for the obstetric patients and 2.220-3.071 for the gynecological surgery patients. The incidence of side effects was low (13 obstetric patients and 1 gynecological surgery patient). Most side effects were related to pain at the injection site (in 12 of the 14 women). CONCLUSIONS: Intravenous iron sucrose is safe and effective for treating puerperal anemia and following gynecological surgery. The low incidence of serious side effects and the rapid recovery of hemoglobin levels make this a safe, effective drug for treating anemia.

Medicina (B Aires) 2006; 66(2): 155-64 (Read article online)

Caramelo C, Peña Deudero JJ, Castilla A, Justo S, De Solis AJ, Neria F, Peñate S, Gonzalez-Pacheco FR

New, critically important data have been recently generated about the response to hypoxia. This response can be schematized in three main systems or functions, ie, detectional or oxygen sensing, regulatory, which controls gene expression and effector. The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In the presence of oxygen, the alpha subunit of HIF-1 (HIF-1alpha) is modified by hydroxylases, that represent the central point of the oxygen sensing mechanism. This type of hydroxylation induces HIF-1alpha catabolism by the proteosome. On the contrary, in hypoxia, or in the presence of certain growth factors that increase HIF-1alpha synthesis, HIF-1alpha translocates to the nucleus, where it binds HIF-1beta, and thence acts on transcription of genes carrying hypoxia responsive elements (HRE) on their promoters. These genes regulate the synthesis of an ample series of proteins, which span from respiratory enzymes and transporters to hormones regulating circulation and erythropoiesis. The role of HIF-1alpha is not restricted to the mere induction of adaptation to decreased oxygen: instead, it significantly participates in cell repairing mechanisms. A simple list of some of the stimulatory or inhibitory alterations of pathophysiological importance involving the HIF-1 system, would include: chronic lung disease, smoking adaptation, anemia/hemorrhage, ischemia/reperfusion, growth, vascularization and cell resistance of tumors, preeclampsia and intrauterine growth retardation, retinal hyper o hypovascularization, drug intoxications, bowel inflammatory disease and wound repair. This list illustrates by itself the importance of the mechanism herein reviewed.

Behav Brain Res 2006 May 18; (Read article online)

Felt BT, Beard JL, Schallert T, Shao J, Aldridge JW, Connor JR, Georgieff MK, Lozoff B

BACKGROUND: Iron deficiency anemia (IDA) has been associated with altered cognitive, motor, and social-emotional outcomes in human infants. We recently reported that rats with chronic perinatal IDA, had altered regional brain iron, monoamines, and sensorimotor skill emergence during early development. OBJECTIVE: To examine the long-term consequences of chronic perinatal IDA on behavior, brain iron and monoamine systems after dietary iron treatment in rats. METHODS: Sixty dams were randomly assigned to iron-sufficient (CN) or low-iron (EID) diets during gestation and lactation. Thereafter, all offspring were fed the iron-sufficient diet, assessed for hematology and behavior after weaning and into adulthood and for brain measures as adults (regional brain iron, monoamines, dopamine and serotonin transporters, and dopamine receptor). Behavioral assessments included sensorimotor function, general activity, response to novelty, spatial alternation, and spatial water maze performance. RESULTS: Hematology and growth were similar for EID and CN rats by postnatal day 35. In adulthood, EID thalamic iron content was lower. Monoamines, dopamine transporter, and dopamine receptor concentrations did not differ from CN. EID serotonin transporter concentration was reduced in striatum and related regions. EID rats had persisting sensorimotor deficits (delayed vibrissae-evoked forelimb placing, longer sticker removal time, and more imperfect grooming chains), were more hesitant in novel settings, and had poorer spatial water maze performance than CN. General activity and spatial alternation were similar for EID and CN. CONCLUSION: Rats that had chronic perinatal IDA showed behavioral impairments that suggest persistent striatal dopamine and hippocampal dysfunction despite normalization of hematology, growth and most brain measures.

Med Care 2006 Jun; 44(6): 560-567 (Read article online)

Schrag D, Xu F, Hanger M, Elkin E, Bickell NA, Bach PB

BACKGROUND:: Fragmentation across sites of care may impede efficient healthcare delivery. OBJECTIVES:: The objectives of this study were to evaluate fragmentation of hospital care for chronically ill New York City (NYC) residents and its association with enrollment in the New York State (NYS) Medicaid program. RESEARCH DESIGN:: We conducted a cross-sectional study using the NYS Department of Health's Statewide Planning and Research Cooperative System discharge database. We identified 53,031 NYC residents admitted 3 or more times to acute care hospitals between 2000 and 2002 with the same principal diagnosis of a specific chronic illness (diabetes, sickle cell anemia, psychosis, substance abuse, cancer, gastrointestinal disease, chronic obstructive pulmonary disease/asthma, coronary artery disease, or congestive heart failure). We also evaluated a larger cohort of 225,421 patients with >/=3 admissions for a specific chronic illness coded as either the principal or a secondary diagnosis. A generalized logit model was used to examine the relationship between fragmentation and each patient's primary insurance adjusted for diagnosis and demographic characteristics. MEASURES:: Fragmentation was characterized as high, moderate, or low based on the number of distinct hospitals a patient visited relative to the patient's total number of hospitalizations over the 3-year interval. RESULTS:: Among frequently hospitalized NYC residents with select chronic conditions, 17.1% experienced highly fragmented care. This rate was 9.9% for patients with commercial insurance, 24.4% for those with Medicaid, and 9.7% for those with Medicare. The unadjusted odds ratio describing high fragmentation of Medicaid enrollees compared with commercially insured patients was 3.82 (95% confidence interval [CI], 3.50-4.18) and, although attenuated, remained significant after adjustment for demographic characteristics (odds ratio, 1.33; 95% CI, 1.20-1.47). The strongest predictor of fragmentation was a diagnosis of psychosis (OR, 2.81; 95% CI, 2.43-3.25) or substance abuse (OR, 7.58; 95% CI, 6.55-8.77). CONCLUSIONS:: In NYC, Medicaid enrollment is associated with greater fragmentation of hospital care, but this is largely attributable to the preponderance of Medicaid enrollees with diagnoses of psychosis and substance abuse. Strategies to improve the efficiency of healthcare delivery should focus on patients with mental illness who are frequently admitted to general hospitals.

World J Surg 2006 May 15; (Read article online)

Moore EE, Cheng AM, Moore HB, Masuno T, Johnson JL

BACKGROUND: The greatest need for blood substitutes worldwide is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes derived from hemoglobin. The hemoglobin-based oxygen carriers (HBOCs) tested currently in advanced clinical trials are polymerized hemoglobin solutions. METHODS: In the USA, the standard approach to restoring oxygen delivery for hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. Allogeneic RBCs, however, may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II in hospital clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with an HBOC-in lieu of stored RBCs-attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, an HBOC has been shown to obviate stored RBC-provoked polymorphonuclear neutrophil (PMN) priming, endothelial activation, and systemic release of interleukins (IL) 6, 8, and 10. In a 2-event rodent study of shock-induced PMN-mediated acute respiratory distress syndrome (ARDS), the simulated prehospital administration of an HBOC markedly attenuated lung injury. RESULTS: Based on this background and work by others, we have initiated a US multicenter prehospital trial in which severely injured patients with major blood loss [systolic blood pressure (SBP) 500 injured patients have been enrolled in this multicenter trial, and the final interim analyses support the original target of 720.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2006 Apr; 23(2): 392-5 (Read article online)

Xie L, Yang H, Sun D, Wen Z, Tan W

This paper reports an in vivo study on the biophysics characteristics of reticulocytes. Anemia was induced by injection of phenylhydrazine in rabbits. The measurements, including electrophoresis rate, hematolytic rate, fluorescent polarization and the changing anisotropic value, were performed in vivo for 72 hours in the process of reticulocytes growing into erythrocytes. It was shown that there were obvious changes in the biophysics characteristics of reticulocytes in this course. Therefore, the findings are of significance to basic, theoretical and clinical studies.