Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia

BACKGROUND AND OBJECTIVES: A female patient presented with splenomegaly and lymphocytosis with atypical lymphoid cell morphology. We identified t(2;7)(p12;q21) prompting studies of the translocation breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG k genes in the t(2;7) leading to over-expression of CDK6 protein. DESIGN AND METHODS: A variety of clinical and laboratory techniques including cell marker, cytogenetic and histologic studies were applied in order to establish the diagnosis. Fluorescence in situ hybridization (FISH) and Southern blotting were used for mapping the translocation breakpoint and Western blotting for assessing protein expression. RESULTS: Immunophenotyping showed the presence of a B-cell population with strong expression of FMC7, CD22, CD79b, CD5 and k restricted surface immunoglobulins. Based on morphology and immunophenotypic markers the diagnosis of B-cell non-Hodgkin's lymphoma was made. Karyotyping revealed a clone with t(2;7)(p12;q21-22). Evidence for clonal evolution with additional abnormalities including a deletion of the TP53 was present. We established by FISH and Southern blotting that the breakpoint on 7q21-22 fell in a region 66kb telomeric to the previously reported breakpoint for the t(2;7) and was the same as that observed in a t(7;21). CDK6 protein was over-expressed. The patient received alkylating agents and splenectomy and is alive but the lymphocytosis persists with evidence of disease progression. INTERPRETATIONS AND CONCLUSIONS: We have demonstrated that CDK6 expression is dysregulated even when the breakpoint on 7q21-22 is located 66kb upstream from the coding region. Interestingly, the precise assignment of the lymphoma type in our case was not possible even when the splenic histology was analyzed.     

The consciousness rainbow: an explication of Rogerian field pattern manifestations.

The consciousness rainbow is a heuristic designed to be used in nursing practice in conjunction with the personalized nursing practice model based on Rogers' science of unitary human beings (Rogers, 1970, 1990). The first phase in practicing nursing is pattern manifestation appraisal, followed by deliberative mutual patterning. This article presents pattern manifestation appraisal by describing patterns associated with "being," "well-being," and "not being." Clients who enter well-being via another dimension are encouraged to experience "being" in the present as a step toward genuine well-being.     

Acute myeloid leukaemia expressing the leucocyte integrin CD11b — a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis

While assessing the prognostic implications of immunophenotyping in 382 patients enrolled in treatment protocols of the Eastern Cooperative Oncology Group (ECOG) for de novo adult acute myeloid leukaemia, we identified 95 patients with a unique antigen profile characterized by high expression of the leucocyte integrin CD11b (CD11b⁺ AML). High expression of CD11b was defined as 32% positive blasts based on the retrospectively established prognostic cut-off point for this antigen. Although CD11b is normally expressed by mature monocytes, natural killer cells and granulocytes, leukaemic blasts in CD11b⁺ AML lacked other immunologic monocytic features (e.g. CD14 and CD122, the interleukin-2 receptor β chain) and demonstrated a high degree of immaturity, as reflected by a high incidence of blasts expressing the stem cell factor receptor, CD117, and few blasts positive for the myeloid differentiation antigen CD15. Furthermore, by FAB criteria, only 41% of CD11b⁺ AML cases were classified as M4/M5. Patients with CD11b⁺ AML had a low response rate (54%) when compared with acute monocytic leukaemia (AMOL; 82%, P  = 0.006) or AML overall (68%, P  = 0.031), independent of age, cytogenetic abnormalities and P-glycoprotein expression. Because of its poor prognosis, recognition of CD11b⁺ AML is clinically warranted and, given its morphologic and cytogenetic ambiguity, must be based on the unique antigen profile.     

A clinical and socio-medical investigation of patients 5 years after surgical treatment for duodenal ulcer. II. Association of social and psychological factors with surgical outcome

Within the framework of the Aarhus County Vagotomy Trial a socio-medical investigation was performed. Eighty-eight patients were interviewed. Data were collected concerning the patients' own assessments and several psychological symptoms. The interview also comprised questions about education, career, and personal and family problems. The surgeon's assessment, expressed by the Visick classification, was significantly correlated with the patients' assessments. In the analysis of predictors for surgical failure expressed by the Visick classification, age was the only significant predictor. Indicators of social or psychological stress showed a tendency towards association with an unfavourable outcome. No associations were found between the selected predictors and surgical failure expressed as recurrent ulcer. Patients classified as Visick III or IV had an accumulation of non-specific psychological symptoms indicating psychological impairment. It is suggested that evaluations of surgical outcome for duodenal ulcer consider both a specific surgical dimension and a subjective dimension expressed by the patients' judgements and/or expression of their health status.     

Phenotype Presentation of Hypophosphatemic Rickets in Adults

Hypophosphatemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting. The purpose of this cross-sectional study of 38 HR patients was to characterize the phenotype of adult HR patients. Moreover, skeletal and endodontic severity scores were defined to assess possible gender differences in disease severity in patients with genetically verified X-linked HR. Compared to normal reference data, i.e., z = 0, HR patients had significantly lower final height, with a mean difference in z-score of ?1.9 (95% CI ?2.4 to ?1.4, P < 0.001). Compared to paired z-scores of final height, z-scores of leg length were significantly lower and those of sitting height were significantly higher (P < 0.001), resulting in disproportion as indicated by the significantly elevated sitting height ratio, mean difference in z-score of 2.6 (95% CI 2.1–3.1, P < 0.001). Z-scores of head circumference (median 1.4, range ?0.4 to 5.5, P < 0.001) and z-scores of bone mineral density (BMD) of the lumbar spine (median 1.9, range ?1.5 to 8.6, P < 0.001) were significantly elevated compared to normal reference data. The relative risk (RR) of fracture was reduced (RR = 0.34, 95% CI 0.20–0.57, P < 0.001). The skeletal severity score tended to be higher in males compared to females (P = 0.07), and no gender difference in endodontic severity was found. In conclusion, adult HR patients were characterized by short stature and were disproportioned. They had elevated BMD of the lumbar spine and a reduced risk of fractures. We found a tendency for males to be more severely affected than females.     

In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym?: a mechanistic, mathematical model of DILI

Drug-induced liver injury (DILI) is not only a major concern for all patients requiring drug therapy, but also for the pharmaceutical industry. Many new in vitro assays and pre-clinical animal models are being developed to help screen compounds for the potential to cause DILI. This study demonstrates that mechanistic, mathematical modeling offers a method for interpreting and extrapolating results. The DILIsym? model (version 1A), a mathematical representation of DILI, was combined with in vitro data for the model hepatotoxicant methapyrilene (MP) to carry out an in vitro to in vivo extrapolation. In addition, simulations comparing DILI responses across species illustrated how modeling can aid in selecting the most appropriate pre-clinical species for safety testing results relevant to humans. The parameter inputs used to predict DILI for MP were restricted to in vitro inputs solely related to ADME (absorption, distribution, metabolism, elimination) processes. MP toxicity was correctly predicted to occur in rats, but was not apparent in the simulations for humans and mice (consistent with literature). When the hepatotoxicity of MP and acetaminophen (APAP) was compared across rats, mice, and humans at an equivalent dose, the species most susceptible to APAP was not susceptible to MP, and vice versa. Furthermore, consideration of variability in simulated population samples (SimPops?) provided confidence in the predictions and allowed examination of the biological parameters most predictive of outcome. Differences in model sensitivity to the parameters were related to species differences, but the severity of DILI for each drug/species combination was also an important factor.