Molecular genetic rearrangements distinguish pre- and post-bone marrow transplantation lymphoproliferative processes

Chronic myelocytic leukemia (CML) may display a lymphoproliferative phase (lymphoid blast crisis) that is generally of B cell phenotype. Since lymphoproliferative disorders may occur following bone marrow transplantation (BMT), it may be difficult to distinguish posttransplant relapse of CML lymphoid blast crisis from de novo lymphoproliferation. Lymphoid blast crisis cells from a patient with CML displayed immunoglobulin heavy chain gene (C mu) rearrangement before BMT. Following BMT the patient developed a lymphoproliferative disorder involving multiple organs. Clonal rearrangement of C mu was demonstrated in several involved tissues. The rearranged C mu restriction fragment was distinct from that displayed before BMT. Additionally, rearrangement of the breakpoint cluster region (bcr) was demonstrated in the pretransplant blast crisis sample, but not in the posttransplant lymphoproliferation samples, thus confirming that these lymphoproliferative disorders were distinct. Molecular genetic techniques offer powerful diagnostic tools for monitoring the course of patients with CML undergoing BMT.     

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.     

Influence of age and dose on the end-organ responses to atrial natriuretic peptide in humans.

To test the hypothesis that age differentially affects the natriuretic, hemodynamic, and humoral response to exogenous ANP, we studied seven young (Y, 20 to 39 years) and five old (O, 65 to 83 years) healthy, normotensive, nonobese men during infusion of synthetic human ANP1,28 at two different rates: 1) 0.05 microgram/kg/min (high dose) for 1 h and 2) 0.005 microgram/kg/min (low dose) for 1 h. Compared to young, the old had higher basal ANP levels (O = 142 +/- 41 v Y = 29 +/- 4 pmol/L, P less than .025), achieved higher plasma levels with low-dose infusion (O = 327 +/- 24 v Y = 155 +/- 37 pmol/L, P less than .001) and had a longer ANP half-life (O = 7.8 +/- 0.6 v Y = 4.3 +/- 0.6 min, P less than .001), suggesting decreased catabolism in the old compared to the young. Despite these age-related differences in ANP levels, there was no difference in urinary sodium or cyclic GMP excretion. After termination of the low-dose infusion, plasma ANP and urinary cGMP promptly returned to baseline levels. Despite this, a sustained natriuresis (2-fold above control) was observed for 3 h in both groups. Low-dose infusion was associated with sustained suppression of aldosterone with minimal hemodynamic changes. During high-dose infusions there was no difference in natriuresis or peak ANP levels between the two groups (O = 1299 +/- 93 v Y = 1140 +/- 54 pmol/L). In contrast to the low-dose infusion, the high-dose infusion produced a transient natriuresis lasting only for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electronic clinical reminder and quality of primary diabetes care

Aims

To study the association of EMR’s clinical reminder use on a comprehensive set of diabetes quality metrics in U.S. office-based physicians and within solo- versus multi-physician practices. We conducted a retrospective cohort study on visits made by adults with diabetes identified from the National Ambulatory Medical Care Survey (2012–2014).

Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure

The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 +/- 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 +/- 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p less than 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p less than 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p less than 0.01), and LV systolic wall stress increased (p less than 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p less than 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 +/- 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 +/- 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, potentially related to subendocardial hypoperfusion.     

Malignant melanoma of the anus

The authors present a report of 12 patients with anal melanoma (AM) and review 255 cases reported since 1947. Combining these patients with those from the literature, the authors analyze several aspects of AM that are controversial or have not been studied in a systematic manner. The mean clinical tumor size was 4.1 cm. Seventy per cent were grossly pigmented, 63 per cent were polypoid, and 44 per cent were prolapsed. Two-thirds of AM were located in the proximal pecten, at or near the level of the anal valves. Microscopically, the most useful diagnostic criteria were melanin production, junctional change, and a nesting growth pattern. In four of the authors’ cases, atypical junctional change extended laterally from the overt invasive neoplasm for distances up to 1 cm. Approximately 60 per cent of patients had metastases at the time of diagnosis. There was no statistical difference in determinate survivals of patients treated for cure by local excision and abdominoperineal resection. Neither tumor size nor configuration affected survival. The choice of therapy was not influenced by tumor size. Read in part at the annual meeting of the International Academy of Pathology, Boston, Massachusetts, March 2, 1982. Dr. Mills is an American Cancer Society Junior Faculty Clinical Fellow.     

Partial characterization of antigens from M. leprae evoking IgG and IgM antibodies in armadillos

Armadillo IgG and IgM antibody responses to Mycobacterium leprae were analyzed using isotypic-specific antisera by means of immunoblotting. Blots developed for IgG antibodies to M. leprae showed multiple protein antigens (Mr = 12-90 K) in some heavily infected armadillos. In contrast, blots developed for IgM antibodies to M. leprae showed a single, broad, diffuse band of immunoreactivity at approximately 33 kDa. The 33-kDa immunogen was detectable with silver stain modified for carbohydrate reactivity, suggesting the presence of a polysaccharide component. In addition, binding of 125I-concanavalin A to the 33-kDa component demonstrated the presence of mannose and/or glucose residues.     

Durable hematologic complete response and suppression of HTLV-1 viral load following alemtuzumab in zidovudine/IFN-{alpha}-refractory adult T-cell leukemia

Adult T-cell leukemia (ATL) is a highly chemoresistant and usually fatal T-cell malignancy due to the human T-cell lymphotropic virus-1 (HTLV-1). After chemotherapy failure, antiretrovirals and interferon-alpha (IFN-alpha) produce brief responses followed by progression and death. More effective agents and new approaches to detect and treat minimal residual disease are needed. ATL cells express CD52, the target of the antibody alemtuzumab, which is active in a preclinical model of ATL and is cytotoxic for p53-deficient cells. A patient with refractory chronic ATL in transformation achieved longer than a 1-year complete hematologic response following 12 weeks of outpatient subcutaneous alemtuzumab. Persistent suppression of HTLV-1 viral load, even at recovery of T cells, after alemtuzumab and efficient in vitro complement-mediated cytotoxicity of primary ATL cells with mutated TP53 were observed. The unprecedented response and the profound suppression of HTLV-1 viral load observed in this patient suggest that further clinical investigation of alemtuzumab in ATL is warranted.     

Immunoassay analysis of proteins in gingival crevicular fluid samples from resorbing teeth

Objective:To carry out an immunoassay analysis of biomarkers expressed in gingival crevicular fluid (GCF) with the main goal of finding a useful diagnostic pattern to distinguish between resorbing deciduous teeth and nonresorbing controls.Materials and Methods:A split-mouth design was used in this study with a total of 22 GCF samples collected from 11 patients in the mixed dentition. For each child, one deciduous molar with radiographic evidence of root resorption was used as the test tooth whereas the contralateral first permanent molar with formed roots was used as the control tooth. Samples were processed with immunoassays using a panel of selected biomarkers including interleukin-1 beta (IL-1b), interleukin-1 receptor antagonist (IL-1RA), nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase-9 (MMP-9), and dentin sialoprotein (DSP).Results:There were no statistically significant differences in levels of IL-1b, OPG, and MMP-9 between test and control sites (P > .05). IL-1RA was the only biomarker to show a significant down-regulation (P  =  .04) in GCF samples collected from resorbing teeth. RANKL data showed a heavily skewed distribution and was deemed unreliable. Only one deciduous GCF sample had detectable levels of DSP; therefore, no further statistical calculation was applicable because of the limited amount of data for this biomarker.Conclusions:This study indicated that IL1-RA is down-regulated in GCF from resorbing primary molars, thus suggesting this cytokine as a potential analyte to be included in a panel that can discriminate between resorbing and nonresorbing teeth.