A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Chronic hepatitis C in patients with persistently normal alanine transaminase levels.

BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.     

Transplacental IgG Subclass Concentrations in Pregnancies at Risk of Haemolytic Disease of the Newborn

The relationship of haemolytic disease of the newborn (HDN) to the transplacental passage of the four IgG subclasses was assessed at varous gestational ages by comparing the maternal and fetal IgG subclass concentrations in 34 pregnancies at risk of HDN with those in 30 pregnancies not at risk. Higher maternal and fetal IgG1 levels were attained in pregnancies at risk of HDN than in pregnancies not at risk. In contrast, a slight decrease in maternal IgG2 and IgG4 levels occurred in pregnancies at risk of HDN, as compared with a slight rise in maternal IgG2 and IgG4 levels in pregnancies not at risk of HDN. Changes in fetal IgG2 and 4 concentrations in either type of pregnancy were very similar, showing only slight increases between the 19th and 34th week of gestation. A slight decrease in maternal IgG3 occurred in both types of pregnancy. In contrast, higher and fairly steady levels of fetal IgG3 were observed in fetuses not at risk of HDN throughout gestation, when compared with those in 'at risk' pregnancies. However, the statistical reliability of these results is not clear since only small numbers of samples were tested and because wide variations in IgG concentrations were observed. The IgG subclass concentrations in 50 paired maternal and cord blood samples were also measured and revealed that IgG1 levels were substantially higher in cord rather than maternal blood; cord and maternal IgG2, 3 and 4 levels, on the other hand, were fairly similar.     

Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.     

The predictive value of specific immunoglobulin E levels for the first diagnosis of cow''s milk allergy. A critical analysis of pediatric literature

Investigators have tried to identify a level of seric specific immunoglobulin E (IgE) that had a sufficient predictive value to diagnose a food allergy without having will resort to the food challenge. To search in literature, all the studies that have estimated the possibility to identify a level of seric specific cow milk IgE with a positive predictive value (PPV) of 95% for the first diagnosis of cow's milk allergy (CMA) in pediatric age. We have identified six studies, nearly all studies suffer from relevant methodological bias. Proposed cut-off are all different. The studied pediatric populations were highly selected. Also neglecting the methodological bias of the studies and the great difference of value between the proposed cut-off, it always remains to consider that the pre-test probability of having a CMA between the children enrolled in the six studies included in this review is particularly high. The likelihood ratio helps to transfer the results of a study on a diagnostic test just to our population, and it is more realistic rather than to entrust itself to the PPV or the negative predictive value, that are much influenced from the prevalence of the disease in the studied population.     

Comparing different methods for homocysteine determination.

Slightly elevated values of homocysteine are commonly associated with thromboembolic diseases, while high values can be found in patients with congenital metabolic defects or nutritional problems. The clinical use of homocysteine as an independent marker of cardiovascular disease was limited in the past by technical problems with its measurement, the instrumentation (HPLC, radioenzymatic assays, gas chromatography-mass spectrometry, etc.) and the necessary skills required. Commercially available immunoassays now permit a simpler and more rapid measurement of homocysteine, that is more suitable for routine clinical laboratories; in this paper we analyze the results obtained by using three fully automated methods for homocysteine determination (Abbott IMx immunoassay, Abbott AxSYM immunoassay and Immulite 2000 homocysteine immunoassay) and their correlation with the widely used HPLC method. The results clearly indicate that all three automated immunochemical methods correlate well with the HPLC method (slope 0.97-1.03; intercept 0.95-1.91 with a recovery above 95% for all three methods).     

A technique to reposition sinotubular junction in aortic valve reimplantation procedures with the De Paulis Valsalva graft.

Sinotubular junction reconstruction in reimplantation type of valve-sparing aortic procedure can present some problem when a Valsalva graft is used. Since in the Valsalva graft the sinotubular junction height is predetermined, correct matching with native commissures height can be difficult. We propose a method by which it is possible to create a new sinotubular junction in Valsalva graft without altering its original configuration.