Health law: medical record implications of the Safe Medical Devices Act of 1990

Health information management professionals have involuntarily been placed by Congress and the FDA not only in the important position of being able to assist their employers in complying with the SMDA, but also at the cutting edge in the development of new and more pervasive techniques of healthcare regulation. The implementation of the SMDA in the near term and over the next 48 months promises to have substantial implications for those charged with responsibility for medical record information.     

Autobiographical memory in diabetes mellitus patients

Objective: Although current theorizing proposes that adjustment to insulin-dependent diabetes mellitus (IDDM) is influenced by appraisals of past health, there is little research into the role of autobiographical recall in patients with this condition. Autobiographical memory patterns were investigated in patients with IDDM and controls. Method: Fifteen patients with IDDM and 15 control participants were administered the Autobiographical Memory Test, the Beck Depression Inventory (BDI), and the Multidimensional Health Locus of Control Survey (MHLCS). Results: Patients with IDDM displayed impaired access to specific positive memories and took longer to retrieve memories than controls. Impaired retrieval in patients with IDDM was associated with higher scores on the MHLCS-Powerful Others scale. Conclusions: Findings suggest that impaired recall of positive experiences is associated with poor adjustment to IDDM.     

Predictors of blood transfusions in spinal instrumentation and fusion surgery

STUDY DESIGN: A retrospective review of 244 adult spine instrumentation and fusion surgery cases (1994-1995) from one institution. OBJECTIVES: To ascertain the predictors of blood transfusions for adult patients undergoing different types of multilevel spine surgery. SUMMARY OF BACKGROUND DATA: Blood loss and transfusion requirements during and after multilevel spine surgeries have always been perceived as great. Identifying the predictors of blood transfusion with this type of surgery may aid in reducing the amount of blood loss and the transfusion requirements. METHODS: The charts of 244 adult patients who underwent multilevel spine surgery from January 1994 to July 1995 were retrospectively reviewed. RESULTS: A large percentage of patients required blood transfusion. The significant determinants for increased amounts of allogeneic red blood cell units transfused on the day of surgery using linear multiple regression modeling were low preoperative hemoglobin concentration, tumor surgery, increased number of posterior levels surgically fused, history of pulmonary disease, decreased amount of autologous blood available, and no use of the Jackson table (R2 = 0. 63). The significant determinants for an increased amount of autologous red blood cell units transfused on the day of surgery using linear multiple regression modeling were increased autologous red blood cells available, low preoperative hemoglobin concentration, and increased number of posterior levels surgically fused (R2 = 0. 60). CONCLUSION: The need for transfusion is associated with multiple factors, suggesting that a multifaceted, integrated approach may be necessary to reduce this risk.     

Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer.

PURPOSE: The human epidermal growth factor receptor (EGFR) plays an oncogenic role in solid cancer, including brain cancer. The present study was designed to prolong survival in mice with intracranial human brain cancer with the weekly i.v. injection of nonviral gene therapy causing RNA interference (RNAi) of EGFR gene expression. EXPERIMENTAL DESIGN: Human U87 gliomas were implanted in the brain of adult scid mice, and weekly i.v. gene therapy was started at day 5 after implantation of 500000 cells. An expression plasmid encoding a short hairpin RNA directed at nucleotides 2529-2557 within the human EGFR mRNA was encapsulated in pegylated immunoliposomes. The pegylated immunoliposome was targeted to brain cancer with 2 receptor-specific monoclonal antibodies (MAb), the murine 83-14 MAb to the human insulin receptor and the rat 8D3 MAb to the mouse transferrin receptor. RESULTS: In cultured glioma cells, the delivery of the RNAi expression plasmid resulted in a 95% suppression of EGFR function, based on measurement of thymidine incorporation or intracellular calcium signaling. Weekly i.v. RNAi gene therapy caused reduced tumor expression of immunoreactive EGFR and an 88% increase in survival time of mice with advanced intracranial brain cancer. CONCLUSIONS: Weekly i.v. nonviral RNAi gene therapy directed against the human EGFR is a new therapeutic approach to silencing oncogenic genes in solid cancers. This is enabled with a nonviral gene transfer technology that delivers liposome-encapsulated plasmid DNA across cellular barriers with receptor-specific targeting ligands.     

Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis

Infiltrating pleomorphic lobular carcinoma (PLC) is an aggressive variant of infiltrating lobular carcinoma. Recently, in situ changes identical to PLC (PLCIS) have been described. The role of prognostic markers and their correlation with therapeutics, clinical outcome, and genetic changes is not well established in PLC. The authors examined 38 cases of this entity to understand better this tumor's biology. Immunohistochemical (IHC) analysis was performed in 21 specimens for estrogen and progesterone steroid receptors, p53, Her 2 (p185), and GCDFP-15. Genomic deoxyribonucleic acid was obtained from microdissected tumor as well as normal control cells, and loss of heterozygosity was investigated at the ESR (16q24), p53 (TP53 17p), Her 2 (17q 11-12), and BRCA 1 (17q12-25) loci. In this series, the average patient age was 57.5 years (age range, 24-92 years). Twenty-seven women were postmenopausal. Tumor size ranged from 1.2 to 25 cm. Six patients were a pathologic stage I; 19, stage II; 12, stage III; and one, stage IV. Histologically, multifocal nodular aggregates of discohesive pleomorphic tumor cells were seen interspersed in dense and fibrotic breast parenchyma. Twenty-nine percent of the specimens demonstrated associated signet ring cells. The remainder had dishesive, globoid, plasmacytoid cells with high-grade nuclear features. PLCIS was identified in 17 of 38 patients (45%), and lobular carcinoma in situ (LCIS) was noted in 8 patients (21%). IHC analysis showed estrogen immunoreactivity in 81%, progesterone in 67%, GCDFP-15 in 71%, and Her 2 in 81% (2+ to 3+ membranous staining) of specimens. Antibodies to p53 stained the tumor cell nuclei in 48% of the tumors. Loss of heterozygosity was identified in 52% of the specimens at the p53 locus, 18% at the ESR locus, 19% to 24% at the Her 2 loci, and 27% to 32% at the BRCA 1 locus. Follow-up was available in 19 patients and ranged from 12 months to 15 years (mean, 73 months). Seven patients had no evidence of disease at last examination (range, 1-15 years), three patients were alive with disease (range, 2-14 years), and nine patients were dead of disease (range, 2 months-9 years). Six patients had subsequent diagnoses of tumor in the contralateral breast. Analysis shows that PLC tends to appear in older postmenopausal women who present with locally advanced disease. PLCIS was found to be associated with PLC 45% of the time. The aggressive clinical course of patients with PLC is supported by tumor immunoreactivity with unfavorable markers Her 2 and p53. Overexpression of Her 2 in PLC may be therapeutically relevant, enabling the use of novel chemotherapeutic drugs like Herceptin. Interestingly, tumors that were Her 2 immunoreactive also maintained estrogen hormone immunoreactivity.     

Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma.

The nonrandom recurrent nature of chromosome abnormalities in myeloma suggests a role for them in disease pathogenesis. We performed a careful cytogenetic analysis of patients with abnormal karyotypes (n = 254), to discern patterns of association, search for novel abnormalities and elucidate clinical implications. Patients with karyotypic abnormalities suggestive of myelodysplasia/acute leukemia were excluded. In this study we compared survival by abnormality only between patients with abnormal karyotypes. Patients with abnormalities were more likely to have features of aggressive disease as compared to all other patients without abnormalities entered into the myeloma database (lower hemoglobin, higher beta(2)-microglobulin, labeling-index and plasmocytosis; all P < 0.0001). Several groups of patients could be readily identified; hypodiploid (22%), pseudodiploid (36%), hyperdiploid (31%) and near-tetraploid (11%). Clustering associations were seen among several trisomies and monosomy of chromosome 13 and 14. Several monosomies (-2, -3, -13, -14 and -19), 1p translocations/ deletions, and hypodiploidy were associated with a significantly shorter survival. Trisomy of chromosome 13 was rare ( <2%). Even among patients with abnormal karyotypes, specific chromosome abnormalities can impart biologic variability in myeloma, including several monosomies, hypodiploidy and abnormalities of 1p.     

Do placental sections accurately reflect umbilical cord nucleated red blood cell and white blood cell differential counts?

OBJECTIVE: Elevated levels of umbilical cord nucleated red blood cells (nRBCs) have been used to assess in utero hypoxia. Although the umbilical nRBC value has been the 'gold standard', umbilical blood may not be obtained at delivery. We determined if the levels of nRBCs and white blood cell (WBC) counts in fixed placental sections might serve as a proxy for cord blood values. STUDY DESIGN: Umbilical blood and placenta were collected from 25 deliveries at Harbor-UCLA Medical Center. Umbilical blood and placental sections were analyzed for nRBCs (per 100 WBC) and WBC differential, and compared with the t-test or the Mann-Whitney rank sum test. RESULTS: nRBC counts were equivalent in umbilical cord and placental sections (5 vs. 4/100 WBC). Umbilical lymphocyte and polymorphonuclear leukocyte (PMN) counts were normally distributed, averaging 35 +/- 9 and 56 +/- 2/100 WBC, respectively. Placental lymphocyte (33 +/- 2/100 WBC) and PMN (60 +/- 2/100 WBC) counts were equivalent to cord blood values. CONCLUSION: WBC differentials and nRBC counts are equivalent in umbilical cord blood and processed placental pathology sections. For infants in whom cord blood cell counts are desired though umbilical cord samples are unavailable, fixed placental sections may serve as a proxy.     

Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding

BACKGROUND: Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy. METHODS: In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group). RESULTS: There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia. CONCLUSIONS: The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.     

Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31.

PURPOSE: Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) -positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. PATIENTS AND METHODS: National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. RESULTS: Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for > or = 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. CONCLUSION: Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy.