CentriMag left ventricular assist system: cannulation through a right minithoracotomy

The CentriMag left ventricular assist system can be used for perioperative or postcardiotomy circulatory support of the failing heart. The device resides at the patient's bedside, and the cannulae are usually inserted through a midline sternotomy, with the inflow cannula in the left ventricle or right superior pulmonary vein and the outflow cannula in the aorta. In a patient whose chest has been closed and who has a delayed need for temporary mechanical support, a less invasive method of left ventricular assist device cannula insertion is preferred. In these cases, the CentriMag cannulae can be inserted through a right minithoracotomy with the inflow cannula in the right superior pulmonary vein and the outflow cannula in the aorta, with no heparinization. Herein, we describe this approach in a patient who experienced postcardiotomy cardiogenic shock after aortocoronary bypass surgery. This technique may facilitate ambulation and recovery in selected patients.     

Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2

Erythropoietin (Epo), the hormone that is the principal regulator of red blood cell production, interacts with high-affinity receptors on the surface of erythroid progenitor cells and maintains their survival. Epo has been shown to promote cell viability by repressing apoptosis; however, the molecular mechanism involved is unclear. In the present studies we have examined whether Epo acts as a survival factor through the regulation of the bcl-2 family of apoptosis-regulatory genes. We addressed this issue in HCD-57, a murine erythroid progenitor cell line that requires Epo for proliferation and survival. When HCD-57 cells were cultured in the absence of Epo, Bcl-2 and Bcl-XL but not Bax were downregulated, and the cells underwent apoptotic cell death. HCD-57 cells infected with a retroviral vector encoding human Bcl-XL or Bcl-2 rapidly stopped proliferating but remained viable in the absence of Epo. Furthermore, endogenous levels of bcl-2 and bcl-XL were downregulated after Epo withdrawal in HCD-57 cells that remained viable through ectopic expression of human Bcl-XL, further indicating that Epo specifically maintains the expression of bcl-2 and bcl-XL. We also show that HCD-57 rescued from apoptosis by ectopic expression of Bcl-XL can undergo erythroid differentiation in the absence of Epo, demonstrating that a survival signal but not Epo itself is necessary for erythroid differentiation of HCD-57 progenitor cells. Thus, we propose a model whereby Epo functions as a survival factor by repressing apoptosis through Bcl-XL and Bcl-2 during proliferation and differentiation of erythroid progenitors.     

Human cytomegalovirus increases constitutive production of interleukin- 6 and leukemia inhibitory factor by bone marrow stromal cells

Human cytomegalovirus (CMV) infection is often associated with myelosuppression and acute inflammatory reaction in immunocompromised patients. We have previously documented that CMV exposure of bone marrow (BM) stromal cells reduces the capacity of these cells to support hematopoiesis because of a decreased production of colony- stimulating factors. This study examines the potential role of CMV on constitutive and lipopolysaccharide (LPS)-stimulated production of cytokines involved in inflammatory reaction, interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) by BM stromal cells. The release of IL- 6 was already detectable 2 hours post CMV-infection (2.5-fold increase in production) and the cumulative production of IL-6 after 5 days of infection was 23 +/- 1.2 ng/mL (ninefold increase in production). CMV was also able to induce a time-dependent production of LIF that was maximal 8 hours after CMV infection (2.5-fold increase in production). Concomitantly, there was no detectable release of granulocyte colony- stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) by CMV-infected stromal cells. The similar IL-6 and LIF production in the presence of polymyxin B ruled out the possibility that this increase could be caused by contamination of the viral stock by endotoxin. In addition, ultraviolet-inactivated virus behaved similarly to live virus and caused the release of IL-6 and LIF. However, heat-inactivated CMV was unable to induce IL-6 and LIF secretion by BM stromal cells. The production of IL-6 and LIF was also evaluated after stimulation by LPS. After 5 days of CMV exposure, the LPS-stimulated production of IL-6 and LIF was significantly lower than uninfected controls. This LPS-induced release of cytokine production was found to be dependent of viral replication. The experiments have shown that CMV is a potent inducer of IL-6 and LIF with differential effect on constitutive and LPS- stimulated cytokine production by stromal cells; we suggest that CMV induction of IL-6 and LIF during the first hours of infection could play a role in CMV-induced inflammatory reaction. Moreover, our results show that human CMV can disturb the balanced cytokine network involved in the regulation of hematopoiesis.     

Growth characteristics of circulating hematopoietic progenitor cells from patients with essential thrombocythemia

Peripheral blood mononuclear cells from five patients with essential thrombocythemia (ET) were cultured in vitro to evaluate restricted megakaryocytic (CFU-Meg), myeloid (CFU-GM), and erythroid (BFU-E) progenitor cell development. Varying concentrations of aplastic canine serum served as the source of megakaryocyte colony-stimulating activity, and cultured megakaryocyte ploidy distributions were determined by Feulgen staining and microfluorometry. Megakaryocyte colony growth was strikingly abnormal in all five patients evaluated. Four of the 5 had a marked expansion in the concentration of circulating CFU-Meg and 3 of 4 manifested abnormalities in cultured megakaryocyte colony size (2 unusually large and 1 small). Unstimulated megakaryocyte colony growth was substantially increased in three patients. However, the fraction of megakaryocyte progenitors in cell cycle was near or below normal in all instances. Endomitotic megakaryocyte development was disordered in each of the four ET patients in whom it was evaluable. In normal subjects, mean megakaryocyte ploidy values vary biphasically with aplastic canine serum concentration and peak at 13.2 N following 12 to 15 days of culture. In contrast, day 12 mean ploidy values in cultures from the ET patients remained low at all aplastic canine serum concentrations and reached a maximum averaging only 8.4 N. Three patients were evaluated serially at extended culture durations of up to 21 days. The cultured megakaryocyte ploidy was unchanged during this interval for two of the patients. For the third patient, ploidy increased steadily, reaching abnormally high ploidy values by day 21. Progenitor cell expansion was limited to the megakaryocyte line in three patients. However, two patients had substantial increases in CFU-GM, one of whom also had a marked increase in BFU-E. There was no significant unstimulated colony growth by either CFU-GM or BFU-E. These data indicate that ET is usually characterized by an expansion in the concentration of circulating CFU-Meg in vivo which manifest both disordered replication and endoreduplication in vitro.     

Opioid Use Disorder: Challenges During Acute Hospitalization

Opioid use is a major public health concern increasing the volume of need for medical care and the national tragedy of accidental overdose deaths. Patients with opioid use disorders have higher numbers of emergency department visits, acute hospitalizations, and complications secondary to opioid use. Acute care nurse practitioners are challenged to manage increasingly complicated patient encounters related to opioid use. This article addresses effective strategies for inpatient management of opioid use disorder including identification and the use of measurement-based tools, as well as providing supportive care.     

Increase in Suicides Associated With Home Eviction and Foreclosure During the US Housing Crisis: Findings From 16 National Violent Death Reporting System States, 2005–2010

Objectives. We aimed to determine the frequency, characteristics, and precipitating circumstances of eviction- and foreclosure-related suicides during the US housing crisis, which resulted in historically high foreclosures and increased evictions beginning in 2006.Methods. We examined all eviction- and foreclosure-related suicides in the years 2005 to 2010 in 16 states in the National Violent Death Reporting System, a surveillance system for all violent deaths within participating states that abstracts information across multiple investigative sources (e.g., law enforcement, coroners, medical examiners).Results. We identified 929 eviction- or foreclosure-related suicides. Eviction- and foreclosure-related suicides doubled from 2005 to 2010 (n = 88 in 2005; n = 176 in 2010), mostly because of foreclosure-related suicides, which increased 253% from 2005 (n = 30) to 2010 (n = 106). Most suicides occurred before the actual housing loss (79%), and 37% of decedents experienced acute eviction or foreclosure crises within 2 weeks of the suicide.Conclusions. Housing loss is a significant crisis that can precipitate suicide. Prevention strategies include support for those projected to lose homes, intervention before move-out date, training financial professionals to recognize warning signs, and strengthening population-wide suicide prevention measures during economic crises.In 2010, 36 364 persons in the United States died by suicide (age-adjusted rate = 12.08 per 100 000 population), making it the second leading cause of death for US adults aged 25 to 34 years, and fourth for adults aged 35 to 54 years.1 Furthermore, the overall suicide rate in the United States has increased over the past decade,2 especially among adults aged 35 to 64 years.3 Suicide carries enormous costs to society, such as emotional trauma for friends and family members (including heightened risk of subsequently attempting suicide themselves), and medical and work loss costs estimated at $34.6 billion a year.Persons who engage in suicidal behavioral typically have multiple risk factors for suicide such as depression, substance abuse, or chronic or acute life stressors such as financial problems. In some instances, a precipitating event prompts an attempt in an already vulnerable person. Several studies of US and international economic cycles have found that suicides increase in step with adverse economic events.4,5 For example, a recent study examining the impact of austerity measures taken in England during the European financial crisis on unemployment and subsequent suicides attributed more than 1000 excess suicides to these economic conditions between 2008 and 2010.6 Another found that in Greece, one of the worst-hit economies in Europe, suicide mortality rates among men have increased by more than 22% since 2007.7 Similar trends were observed in several countries (e.g., Japan, Hong Kong, South Korea) following the Asian monetary crisis of 1997.8An analysis of US business cycles and suicide rates between 1928 and 2007 recently demonstrated that suicide rates in the United States have also generally increased and decreased along with economic conditions.4 The findings demonstrated that US suicide rates peaked during the Great Depression, and decreased during times of economic expansion and low unemployment. Working-age adults were most affected. One recent study attributed up to 25% of the US suicide rate increase seen over the past decade specifically to rising unemployment.9There were other important dimensions of the recent US economic downturn that may be associated with the observed increase in suicides. Beginning in late 2006, the US experienced a housing crisis characterized by historically high rates of home foreclosure10 and increased evictions.11 Media reports of suicides associated with eviction or foreclosure appeared in national news outlets during this time,12–14 although little information exists about the frequency or characteristics of these events. Although the full impact of the housing crisis on public health is not yet known, several studies have documented adverse effects associated with mortgage delinquency such as 2 or more times greater odds of major depression15,16 and 8 times greater odds of elevated depressive symptoms related to acute stress.17 In addition, a recent study found higher suicide rates in regions experiencing higher rates of foreclosure.18 These findings suggest that eviction or foreclosure may be related to elevated risk of suicide. However, to date, no study has described or directly investigated suicides associated with home eviction and foreclosure.We determined the frequency and circumstances of suicide deaths linked to eviction (i.e., renters evicted for financial reasons) and foreclosure (i.e., homeowners losing homes to foreclosure) in the years 2005 through 2010 with data from 16 states participating in the National Violent Death Reporting System (NVDRS). Within this sample, we also examined the extent to which eviction or foreclosure was perceived as a key stressor contributing to the decedent’s suicide versus acting in concert with other stressors. Furthermore, we calculated the frequency of eviction or foreclosure suicides relative to other suicides during this time period, and the percentage of all suicides associated with financial stressors that were eviction or foreclosure related.     

Perforation of metastatic melanoma to the small bowel with simultaneous gastrointestinal stromal tumor

The gastrointestinal tract (GIT) is a common site of metastases for malignant melanoma. These metastatic tumors are often asymptomatic. We describe a case of a 58-year-old male who presented with a sudden onset of generalized abdominal pain. The patient's past medical history was significant for lentigo melanoma of the right cheek. Laparotomy was performed and two segments of small bowel, one with a perforated tumor, the other with a non-perforated tumor, were removed. Histology and immunohistochemical staining revealed the perforated tumor to be a metastatic malignant melanoma and the non-perforated tumor was found to be a gastrointestinal stromal tumor (GIST). The patient was discharged 7 d postoperatively. To the best of our knowledge, this is the first reported case in the literature of a simultaneous metastatic malignant melanoma and a GIST. Surgical intervention is warranted in patients with symptomatic GIT metastases to improve the quality of life or in those patients with surgical emergencies.     

The interaction of signal transduction pathways in FRTL5 thyroid follicular cells: studies with stable expression of beta 2-adrenergic receptors.

Multiple signal transduction pathways interact in FRTL5 cells to promote thyroid follicular cell differentiated function and cell proliferation. In these cells, TSH is a tissue-specific mitogen that promotes DNA synthesis primarily through activation of adenylate cyclase. To further test the role of adenylate cyclase in regulating cell growth and differentiated function we have introduced into FRTL5 the human beta 2-adrenergic receptor (BAR) complementary DNA and have studied the ability of isoproterenol, alone and in combination with insulin-like growth factor I (IGF-I), to stimulate cAMP accumulation, iodide transport, [3H]thymidine incorporation into DNA, and cell growth. Wild-type FRTL5 were infected with a PLJ retroviral construct containing the BAR in either a sense (FRTL BAR) or antisense (FRTL RBAR) orientation, and cell populations were selected on the basis of resistance to the antibiotic geneticin. FRTL BAR expressed approximately 1.3 x 10(5) high affinity binding sites per cell for the beta 2-specific ligand, CGP-12177, while neither FRTL5 wild-type nor RBAR cells demonstrated any specific binding. FRTL BAR had significantly higher levels of intracellular cAMP, [3H]thymidine incorporation, and iodide uptake in the absence of added isoproterenol than FRTL RBAR or wild-type cells. In FRTL BAR, but not RBAR cells, isoproterenol stimulated a dose-dependent accumulation of cAMP, iodide uptake, [3H]thymidine incorporation, and cell growth. FRTL BAR and RBAR cells were equally responsive to TSH and to IGF-I. Isoproterenol enhanced the ability of IGF-I to stimulate [3H]thymidine incorporation in BAR but not RBAR cells. Isoproterenol partially inhibited the ability of TSH to stimulate cAMP generation and DNA synthesis. These studies demonstrate that activation of adenylate cyclase through the BAR introduced into FRTL5 cells by retroviral infection reproduces the range of biological effects in these cells stimulated by TSH and suggest that activation of adenylate cyclase is sufficient to stimulate thyroid differentiated function and cell growth. FRTL BAR cells will provide an interesting model system with which to study the heterologous regulation of both TSH and BARs through activation of a common signal transduction pathway, adenylate cyclase.     

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs.     

Allergic responses to biting and stinging insects

Biting and stinging insects are classified under the major division of arthropods. The arthropods consist of eighty-five per cent of the animal kingdom. Since we share so much of this earth's surface with these small creatures, it is evident that they must often affect our lives. Man may be helped by some activities or hindered by others. On the positive side, arthropods help in the pollination of plants, destroying the dead animals and plants, and help to return the organic materials to the soil. The value of bee products such as honey and wax is estimated to be as high as fifty million dollars each year in the United States. On the negative side, arthropods can cause disease and varied allergic reactions. This article will deal chiefly with the allergic responses. Most of the allergic reactions are minor annoyances, but some are serious and can result in death.