Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients

Aggressive surgical management of spinal metastatic disease can provide improvement of neurological function and significant pain relief. However, there is limited literature analyzing such management as is pertains to individual histopathology of the primary tumor, which may be linked to overall prognosis for the patient. In this study, clinical outcomes were reviewed for patients undergoing spinal surgery for metastatic breast cancer. Respective review was done to identify all patients with breast cancer over an eight-year period at a major cancer center and then to select those with symptomatic spinal metastatic disease who underwent spinal surgery. Pre- and postoperative pain levels (visual analog scale [VAS]), analgesic medication usage, and modifed Frankel grade scores were compared on all patients who underwent surgery. Univariate and multivariate analyses were used to assess risks for complications. A total of 16,977 patients were diagnosed with breast cancer, and 479 patients (2.8%) were diagnosed with spinal metastases from breast cancer. Of these patients, 87 patients (18%) underwent 125 spinal surgeries. Of the 76 patients (87%) who were ambulatory preoperatively, the majority (98%) were still ambulatory. Of the 11 patients (13%) who were nonambulatory preoperatively, four patients were alive at 3 months postoperatively, three of which (75%) regained ambulation. The preoperative median VAS of six was significantly reduced to a median score of two at the time of discharge and at 3, 6, and 12 months postoperatively (P < 0.001 for all time points). A total of 39% of patients experienced complications; 87% were early (within 30 days of surgery), and 13% were late. Early major surgical complications were significantly greater when five or more levels were instrumented. In patients with spinal metastases specifically from breast cancer, aggressive surgical management provides significant pain relief and preservation or improvement of neurological function with an acceptably low rate of complications.     

TMB-8 prevents the hydroosmotic response to ADH in rabbit cortical collecting tubules.

Both AVP and dDAVP effect a transient increase in cytosolic free calcium (iCa2+) in cortical collecting tubule (CCT) cells. To investigate the physiological role of this increase in iCa2+, we examined the effect of TMB-8, a putative inhibitor of iCa2+ release, on the initial and sustained phase of AVP- and dDAVP-stimulated water permeability (Pf) in isolated, perfused CCTs. Pretreatment of tubules with TMB-8, 50 microM, suppressed the increase in osmotic water permeability (Pf) induced by 10 microU/ml AVP and dDAVP, but had no effect on the sustained phase of the response. When increased to 100 microM. TMB-8 inhibited the sustained phase of AVP action. A similar pattern was observed on AVP-stimulated adenyly cyclase activity in rabbit renal membranes. Pretreatment of tubules with 50 microM TMB-8 attenuated the initial increase in Pf in response to cholera toxin but not to 8-Br-cAMP or forskolin. There was no effect of this concentration of TMB-8 on the sustained phase of these agonists. These studies suggest that, in lower concentrations, TMB-8 inhibits the mobilization of iCa2+, which is important for the interaction of Gs with the catalytic unit of adenylyl cyclase and the initial increase in AVP-stimulated Pf. In higher concentrations, TMB-8 inhibits adenylyl cyclase activity directly.     

Lack of Polarized Type 1 or Type 2 Cytokine Profile in Asymptomatic HIV-1-Infected Patients During a Two-Year Bimonthly Follow-Up

The production of type 1 (interferon or IFN-γ) and type 2 (interleukin or IL-4 and IL-10) cytokines by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic human immunodeficiency virus-seropositive (HIV⁺) patients untreated with any antiviral, antibacterial or antimycotic drugs, and from healthy individuals, was evaluated by quantitative ELISA. Patients who were HIV⁺ were characterized by the absence of abnormal cytokine production. The level of each cytokine differed among individuals in the same group with intersubject variations greater for HIV⁺ patients than for healthy individuals. The longitudinal evaluation of IFN-γ, IL-4 and IL-10 production showed intrasubject variations which were particularly marked in HIV⁺ patients. Accordingly, HIV⁺ patients and, to a lesser extent, healthy individuals were characterized by a wide spectrum of possible profiles, which were confined to type 0 phenotype. In HIV⁺ patients no correlation was found between each cytokine level and the number of CD4⁺ T cells, not even in those with a falling CD4⁺ T-cell count and clinical symptoms.     

Contribution of CD4+, CD8+CD28+, and CD8+CD28- T cells to CD3+ lymphocyte homeostasis during the natural course of HIV-1 infection.

The relationship between the number of circulating CD4+ T cells and the presence of particular CD8+ T cell subsets was analyzed by flow cytometry on PBL from asymptomatic HIV-1-infected patients whose specimens were collected every 2 mo for a total period of 32 mo. Only slight variations were detected in the absolute number of lymphocytes and percentage of CD3+ lymphocytes, whereas both CD4+ and CD8+ T cell subsets showed wide intrapatient variation. Variations in the number of CD8+CD28+ cells paralleled those of the CD4+ T cell subset in each patient tested, while the presence of CD8+CD28- T cells correlated inversely with CD4+ and CD8+CD28+ T cells. These data show that changes in the number of circulating CD4+-and CD8+CD28+ T cells are strongly related to the presence of CD8+CD28- T cells in these patients. Insight into the significance of CD8+CD28- T cell expansion will allow us to understand the mechanisms and significance of the HIV-1- driven change in CD4+CD8+ T cell homeostasis and the basic immunopathology of HIV disease.     

Calcium transport in the rabbit superficial proximal convoluted tubule.

Calcium transport was studied in isolated S2 segments of rabbit superficial proximal convoluted tubules. 45Ca was added to the perfusate for measurement of lumen-to-bath flux (JlbCa), to the bath for bath-to-lumen flux (JblCa), and to both perfusate and bath for net flux (JnetCa). In these studies, the perfusate consisted of an equilibrium solution that was designed to minimize water flux or electrochemical potential differences (PD). Under these conditions, JlbCa (9.1 +/- 1.0 peq/mm X min) was not different from JblCa (7.3 +/- 1.3 peq/mm X min), and JnetCa was not different from zero, which suggests that calcium transport in the superficial proximal convoluted tubule is due primarily to passive transport. The efflux coefficient was 9.5 +/- 1.2 X 10(-5) cm/s, which was not significantly different from the influx coefficient, 7.0 +/- 1.3 X 10(-5) cm/s. When the PD was made positive or negative with use of different perfusates, net calcium absorption or secretion was demonstrated, respectively, which supports a major role for passive transport. These results indicate that in the superficial proximal convoluted tubule of the rabbit, passive driving forces are the major determinants of calcium transport.     

Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma

The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies – include growth curves, cell death, migration assays and in vivo studies – verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.     

Diabetes in Italy: a public health problem]

BACKGROUND: Type 2 diabetes is the most frequent form of diabetes in the adult population and is associated with an increasing risk of cardiovascular diseases. The objective of this study was to describe the prevalence and the state of control in an Italian population sample examined within the Osservatorio Epidemiologico Cardiovascolare study. METHODS: The sample of this study consisted in 8972 subjects, men and women aged 35-74 years. A fasting capillary blood glucose > or = 126 mg/dl or being on antidiabetic treatment were the criteria used to define diabetes, while a fasting capillary blood glucose < 140 mg/dl was considered to represent effective treatment (controlled diabetes) in treated patients. RESULTS: Diabetes was present in 8.4% of men and 6% in women. The prevalence of glucose intolerance was 8.2% in men and 4.3% in women. Only 50.7% of diabetic men and 56.5% of diabetic women knew about their disease; among these people, 21% was on treatment with oral antidiabetics and/or insulin. Such a therapy was effective in 39.5% of the treated cases. CONCLUSIONS: The prevalence of diabetes as well as glucose intolerance was greater in men and in the regions of the Center and South of Italy. The state of control of diabetes cannot be considered satisfactory; women and older age groups, when prevention strategies are less important, appear to be under better care.     

Initial survival data of kidney transplant patients with pre-transplant monoclonal gammopathy

Soltero L, Carbajal H, Xu J, McCarthy J, Suki WN, Gaber AO, Adrogué HE. Initial survival data of kidney transplant patients with pre‐transplant monoclonal gammopathy.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01539.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: Monoclonal gammopathy of undetermined significance (MGUS) is the presence of a serum monoclonal protein at a concentration of <3 g/dL without evidence of lymphoproliferative disease or organ damage. The prevalence of MGUS in kidney transplantation (KT) candidates is unknown. The present is a retrospective report of patients who underwent evaluation for a KT and were found to have MGUS at our center. Methods: All transplant candidates found to have MGUS between the years 2000 and 2007 were included. Variables were collected. Patients with MGUS that received a KT were compared with patients with MGUS that were not transplanted. Results: Of a total of 1215 KT candidates, 34 were found to have MGUS during the KT evaluation. Nine patients with MGUS were transplanted. Myeloma or lymphoproliferative disease was not observed. Following transplantation, the MGUS group had a lower survival than the non‐transplanted group. However, survival from the time of MGUS diagnosis was not different between the transplanted and non‐transplanted MGUS groups. Conclusions: In this group, transplantation did not confer a survival benefit. It is our hope that these initial data will serve as a platform for future studies. We suggest MGUS screening in all patients older than 50 yr of age undergoing evaluation for transplantation.     

Retrograde intubation during laryngeal cleft repair on cardiopulmonary bypass

Retrograde intubation is part of the difficult airway algorithm in the American Society of Anesthesiologists, but its usage is rare in small pediatric patients with the advent of new intubation techniques. We present our experience of retrograde intubation for a 4-month-old patient who presented for laryngeal cleft repair on cardiopulmonary bypass. This case highlights the unique place for retrograde intubation in small patients in the current era.