A unique 7p/12q chromosomal abnormality associated with recurrent abortion and hypofibrinogenemia

Recurrent first trimester abortions led to evaluation of a 25-year-old woman. Studies revealed she had hypofibrinogenemia (68 mg/dL) without evidence of dysfibrinogenemia or increased fibrinogen turnover. She was also found to have a unique 46,XX, t(7;12) (p 15.2;q24.31) karyotype. Hypofibrinogenemia and identical chromosomal abnormalities were found in other members of her kindred. Southern blots of genomic DNA from the patient, her mother, and her daughter hybridized to human fibrinogen probes showed alpha, beta, and gamma fibrinogen genes to be present and without structural alterations when compared to normal controls. We conclude that the chromosomal abnormality and the hypofibrinogenemia are related but in an unclear manner. Because fibrinogen infusion in the proposita was associated with successful gestation, we also concluded that the chromosomal abnormality itself was not responsible for the repeated abortions but that fibrinogen concentration may be critical in securing implantation.     

JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor

Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF- stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway.     

Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia

The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (lung-resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.     

Eradication of polymerase chain reaction detectable immunoglobulin gene rearrangement in non-Hodgkin's lymphoma is associated with decreased relapse after autologous bone marrow transplantation

In B-cell non-Hodgkin's lymphoma (NHL), as in other B-cell malignancies, clonal rearrangement of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain gene (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To determine the clinical utility of IgH polymerase chain reaction (PCR), we analyzed peripheral blood (PB) and bone marrow (BM) samples from 25 patients with NHL with no PCR detectable chromosomal rearrangement who have undergone autologous bone marrow transplantation (ABMT). Patients with histologic bone marrow infiltration at the time of bone marrow harvest were selected for study since this provided us with diagnostic tissue samples. As an initial strategy DNA was amplified using consensus variable (VH) and joining (JH) region primers. In those cases failing to amplify using consensus region primers, PCR was performed using a panel of VH family-specific framework region 1 (FR1) primers. The clonal products were directly sequenced. From the V-N-D region nucleotide sequences, clone specific probes were constructed and used for subsequent detection of MRD. A clonal PCR product could be PCR amplified and directly sequenced in 18 (72%, 90% confidence intervals 54%-86%) of these 25 patients, 8 with diffuse and 10 with follicular NHL. Eight of these 18 patients have relapsed after ABMT. All had detectable lymphoma cells before relapse and the sequence of the CDR III region at the time of relapse was identical to that obtained at the time of ABMT. All 10 patients who remain in complete remission from 18 to 36 months after ABMT had eradication of PCR detectable lymphoma cells after ABMT, although in three patients PCR detectable MRD was detected early after ABMT. We conclude that sequencing and the use of patient specific IgH CDR III oligonucleotides probes provides a simple and highly reliable method to determine the specificity of the IgH PCR technique. The clinical utility of this technique is demonstrated by the finding that eradication of PCR detectable lymphoma cells in these patients is associated with decreased relapse after ABMT (P = .0002).     

Dependent ‐care by battered women: Protecting their children

The phenomenon of battered women's dependent‐care (Orem, 1991), that is, their efforts to prevent hazards to the life, health, and well‐being of their children, was examined. Open‐ended, semi‐structured interviews were conducted with mothers (N = 50) at battered women's shelters in a metropolitan area in the Midwest. The women demonstrated deliberate, creative, and diverse dependent‐care. Caring action and timing provided the basis for patterns of dependent‐care. Health care providers need to recognize these caring actions and consider their value from the perspective of battered women.     

The process of embarking on a weight control program

The purpose of this study was to describe the process of embarking on a weight control program, to understand more about the decision to seek treatment for obesity, a chronic health problem. Obese women were interviewed using field methods. The grounded theory approach was utilized to analyze the data. Loss and isolation were predominant themes and stages through which women progressed before entering treatment. The entering of treatment was viewed as a way of adapting to sex role norms, or what was expected of women by society. Body image concerns‐the loss of attractiveness—was an overriding theme. Physical health played a minor role in this decision to seek treatment for obesity. This investigation generated hypotheses for further study related to the importance of body image versus physical health as a motivator for weight control.     

Diagnosis of acute surgical abdomen – The best diagnostic tool to reach a final diagnosiscin

ObjectiveTo evaluate the best diagnostic tool (clinical, radiological, laboratory, or endoscopy) used to reach a final diagnosis of four most common presentations of acute abdomen to the surgical unit in the Limerick University Hospital, Limerick, Ireland.MethodsData was analyzed retrospectively of prospective collected data of all patients who had been admitted at a single academic institution from July 2011 till September 2011. Radiology, operating theatre and histopathology, haematology and endoscopy databases were searched from the Hospital Inpatient Enquiry (HIPE) department for patients who had presented with acute abdominal pain. Patients' charts were searched manually and final diagnosis of each patient was recorded.ResultsOut of 30 confirmed final diagnosis of appendicitis or appendicular mass, 9/30 (30.0%) were diagnosed with radiological (either on ultrasonography or CT scan). The remaining 21 cases (70.0%) were diagnosed clinically. Majority cases of diverticulitis 16/22 (72.7%) was diagnosed radiologically compared to only 6/22 (27.3%) of those confirmed by endoscopy. All diagnosis of gallstone-related diseases (cholecytitis, biliary colic, or cholelithiasis and/or choledocholithiasis) and bowel obstruction were confirmed by radiological investigation.ConclusionsAppendicitis can be accurately diagnosed clinically based on history and clinical examination alone. Diagnosis of diverticular disease, gallstone disease, and bowel obstruction further requires radiology intervention to confirm the provisional diagnosis.