Bone-destroying candida infection following left ventricular assist device explant

Infections associated with left ventricular assist devices (LVADs) constitute an important clinical issue because they are difficult to completely eradicate without removal of the LVAD itself and can sometimes be fatal. We encountered a case of extracorporeal LVAD-related candida infection in a patient who was successfully weaned from LVAD support. Although the patient appeared to have recovered from the infection, the patient was readmitted to our institute due to a relapse of candida infection 9 months after LVAD removal. Although the patient did not demonstrate any systemic sign of infection on admission, computed tomography images clearly showed that the residual apical cuff of the LVAD inflow cannula, which was infected with Candida albicans during the initial admission, resulted in re-infection that involved the chest wall with destruction of the adjacent rib.     

Surgical Strategies for Cervical Spinal Neurinomas

Cervical spinal neurinomas are benign tumors that arise from nerve roots. Based on their location, these tumors can also take the form of a dumbbell-shaped mass. Treatment strategies for these tumors have raised several controversial issues such as appropriate surgical indications and selection of surgical approaches for cervical dumbbell-shaped spinal neurinomas. In this report, we review previous literature and retrospectively analyze cervical spinal neurinoma cases that have been treated at our hospital. Surgical indications and approaches based on tumor location and severity are discussed in detail. Thus, with advances in neuroimaging and neurophysiological monitoring, we conclude that appropriate surgical approaches and intraoperative surgical manipulations should be chosen on a case-by-case basis.     

Mechanisms related to the pathophysiology and management of central hypothyroidism

Central hypothyroidism (CH) is defined as hypothyroidism due to insufficient stimulation of the thyroid gland by TSH, for which secretion or activity can be impaired at the hypothalamic or pituitary levels. Patients with CH frequently present with multiple other pituitary hormone deficiencies. In addition to classic CH induced by hypothalamic-pituitary tumors or Sheehan syndrome, novel causes include traumatic brain injury or subarachnoid hemorrhage, bexarotene (a retinoid X receptor agonist) therapy, neonates being born to mothers with insufficiently controlled Graves disease, and lymphocytic hypophysitis. Growth hormone therapy, which may be used in children and adults, is now also recognized as a possible cause of unmasking CH in susceptible individuals. In addition, mutations in genes, such as TRHR, POU1F1, PROP1, HESX1, SOX3, LHX3, LHX4 and TSHB, have been associated with CH. The difficulty in making a clear diagnosis of CH is that the serum TSH levels can vary; values are normal in most cases, but in some might be low or slightly elevated. Levels of endogenous T(4) in serum might also be subnormal. Appropriate doses of levothyroxine for T(4) replacement therapy have not been confirmed, but might need to be higher than presently used empirically in patients with CH and should be adjusted according to age and other hormone deficiencies, to achieve free T(4) concentrations in the upper end of the normal range.     

Src family kinases and nitric oxide production are required for hepatocyte growth factor-stimulated endothelial cell growth

Hepatocyte growth factor (HGF) is a potent mitogen for vascular endothelial cells (EC); however, signal transduction pathways for HGF-stimulated EC growth remain unclear. In the present study we investigated the role of Src family kinases and nitric oxide (NO) in HGF-stimulated EC growth. Human umbilical vein endothelial cells (HUVEC) were stimulated with HGF and NO was measured by an NOx analyzing HPLC system. Activation of ERK1/2 and p38 MAPK was assessed by Western blot. NO production in HUVEC increased 1.8-fold by HGF. A Src family kinases inhibitor PP1 inhibited HGF-stimulated NO production by 71%. HUVEC growth increased 1.9-fold in cell number by HGF. PP1 and Nitro-L-arginine methylester (L-NAME) inhibited HGF-stimulated HUVEC growth by 51 and by 71%. ERK1/2 and p38 MAPK were phosphorylated by HGF and a MEK inhibitor PD98059 and a p38 MAPK inhibitor SB203580 inhibited HGF-stimulated HUVEC growth by 66% and by 58%; however, HGF-induced phosphorylation of ERK1/2 and p38 MAPK was not inhibited by L-NAME, indicating that NO is not an upstream activator of ERK1/2 and p38 MAPK. These findings demonstrated that Src family kinases regulate HGF-stimulated NO production in HUVEC and that HGF stimulates HUVEC growth through NO-dependent and NO-independent pathways.     

Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia

A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.