Intracellular coexpression of epidermal growth factor receptor, Her-2/neu, and p21ras in human breast cancers: evidence for the existence of distinctive patterns of genetic evolution that are common to tumors from different patients.

Multiparameter flow cytometry studies were performed on cells from the primary tumors of 94 patients with breast cancer. Correlated cellular measurements of cell DNA content, Her-2/neu, epidermal growth factor receptor (EGFR), and p21ras levels were performed on each of 5,000 to 100,000 cells from each tumor. When criteria for positivity were matched with those in common use for immunohistochemical studies, 28 of 94 (30%) breast cancers were classified as positive for Her-2/neu overexpression. When similar criteria were applied to the EGFR measurements, 23 of 94 (24%) cases were classified as positive for EGFR overexpression. Similarly, 23 of 94 (24%) cases were classified as positive for p21ras overexpression. By conventional flow cytometric criteria for DNA ploidy, 24 cases were diploid, 28 were tetraploid, and 42 were aneuploid. When the measurements were treated as separate sets of data, the only statistically significant correlations noted were the high frequency of diploid tumors, which did not overexpress any of the three oncogenes studied (P < 0.05), and an association between Her-2/neu overexpression and aneuploidy (P < 0.03). When the data were treated as correlated intracellular measurements, 90 of the 94 tumors studied contained a population of cells in which the intracellular levels of Her-2/neu expression were directly correlated with the levels of EGFR expression in the same cells. The ratio of Her-2/neu molecules to EGFR molecules in the same cells exceeded 1 in the majority of tetraploid and aneuploid cases and was close to or less than 1 in the majority of diploid cases. In nearly all tumors, p21ras overexpression was observed only in cells that overexpressed Her-2/neu, EGFR, or both, and p21ras levels per cell were more closely correlated with levels of EGFR per cell in the same cells than with Her-2/neu levels per cell. The data are consistent with a model in which heterodimerization of Her-2/neu and EGFR in individual cells is achieved by one of several genetic evolutionary pathways, all of which commonly lead to p21ras overexpression. The two major genetic evolutionary pathways identified in this study are an aneuploid, Her-2/neu overexpression-driven pathway seen in 59 of 94 tumors, and a diploid, EGFR overexpression-driven pathway seen in 19 of 94 tumors. All tumors with Her-2/neu:EGFR ratios greater than 2 contained an infiltrating ductal carcinoma component, whereas all infiltrating pure lobular carcinomas had Her-2/ neu:EGFR ratios that were less than 2. All of the genetic evolutionary pathways identified in this study were represented among the 11 tumors from patients who experienced early tumor recurrences.

Comparison of central venous catheter dressings in bone marrow transplant recipients.

PURPOSE/OBJECTIVES: To determine the effect of two central venous catheter (CVC) dressing protocols on catheter-related infections in hospitalized patients with long-term tunneled catheters undergoing an autologous bone marrow transplant (BMT), to determine the prevalence of long-term CVC-related infections in this population, and to identify other factors in the study sample related to long-term CVC infection. DESIGN: Experimental. SETTING: BMT unit of a regional oncology center in a tertiary care hospital. SAMPLE: The sample consisted of 101 adult patients with cancer with long-term, tunneled CVCs inserted in the operating room on admission for autologous BMT. METHODS: Patients randomly were assigned to one of two dressing-change procedure groups. The control group received the current standard of care for patients receiving BMT--a dry, sterile gauze dressing (DSGD) changed every 24 hours. The experimental group received Opsite 3000TM (Smith + Nephew Ltd., Massilon, OH) transparent moisture vapor permeable dressings (MVPD) changed weekly. MAIN RESEARCH VARIABLES: CVC infection rates, frequency of IV tubing changes, immune status, duration of catheter use, occurrence and outcome of catheter occlusion, and use of a catheter for total parenteral nutrition. FINDINGS: Researchers determined the difference in CVC-related infections between the two groups and the impact of select variables on CVC-related infection. When all categories of CVC-related infection (i.e., suspected, sepsis, tunnel) were considered, no statistical difference was found in the likelihood of the groups remaining infection-free (p = 0.76) over time. CVC sepsis occurred in one patient in the DSGD group and five patients in the MVPD group; however, this difference was not statistically significant over time (p = 0.067). CONCLUSIONS: Development of CVC sepsis or tunnel infection in close proximity to the time of CVC surgical placement suggests that factors other than the assigned dressing were associated with the occurrence of CVC-related infection in three cases. Although the MVPD group required dressing changes more frequently than every seven days (as specified by the protocol) because of exit-site drainage and nonocclusiveness, transparent dressings were more cost-effective than daily gauze dressings in this population. IMPLICATIONS FOR NURSING PRACTICE: For adults undergoing autologous BMT, either DSGD or transparent CVC dressing can be used safely based on patient preference and skin tolerance to the dressing material.

Assessing sequential oncogene amplification in human breast cancer.

Studies of amplification and/or overexpression of c-myc, HER-2/neu, and H-ras in breast cancer have shown that each is associated with a poor prognosis. The purpose of this study was to explore the possibility that there is a preferred sequence of amplification of these oncogenes in breast cancer. The frequencies of amplification and patterns of co-amplification of c-myc, HER-2/neu, and H-ras were studied in a group of 84 breast cancers. The data suggested a preferred sequence of amplification that consisted of c-myc amplification-HER-2/neu amplification-H-ras amplification. This model was supported by loglinear analysis. In addition, the levels of amplification of JC-A, a DNA fragment newly isolated from a patient with advanced breast cancer, were studied in 61 of these cases. The data suggested that JC-A amplification occurred early. Loglinear analysis supported a model in which JC-A amplification occurred either before or after c-myc amplification but was unrelated to Her-2/neu or ras amplification.

Nonreamed nailing of tibial diaphyseal fractures in blunt polytrauma patients.

The efficacy of nonreamed nailing as the treatment of choice of unstable blunt tibial diaphyseal fractures was studied. From March 1, 1990, through August 31, 1991, 72 patients with 74 fractures that required fixation were treated. One patient died and six were lost to follow-up, leaving 65 patients with 67 fractures. Follow-up averaged 21 months (range 5-43). Fisher's exact and logistic regression analyses were used to compare grades of open fractures, comminution as classified by Winquist, and dynamic and static nailings. The failure rates of 51 titanium and 16 stainless steel nails were compared. Times to union were compared by the log rank statistic method. The average time to union was 32 weeks with 26 (39%) additional operations required to achieve union; 13 dynamizations (12 successful), 12 exchange nailings (11 successful), and one plate and bone graft. The rate of reconstructive procedures to achieve union was a more sensitive indicator of difficulties achieving union than was time to union. Reoperation rates were 33% for closed or grade I and II fractures compared with 46% for grade III fractures (NS). Among closed grade I and II static versus dynamic nailing, times to union were 36 versus 25 weeks (p < 0.01), and the reoperation rates were 44% versus 13% (p < 0.04). Winquist I and II fractures required a 24% reoperation rate versus 53% for grade III and IV and segmental fractures (p < 0.01). Static locked fractures required a 48% reoperation rate versus 12% for dynamic locked fractures (p < 0.01). A logistic regression analysis demonstrated that locking mode was the most important factor in determining reoperation rates. Fifteen additional reoperations for infection, broken or painful implants, or to remodel bones that united with an incomplete circumference of cortex were performed. With an additional 12 elective nail removals, the total reoperations numbered 53 (79%). Titanium alloy nails had a 2% failure rate versus 25% for stainless steel nails (p < 0.01). Two of 28 (7%) grade III fractures became infected. All fractures united within 10 degrees of normal alignment and 1 cm of length. Nine (13%) united with an incomplete cortical circumference, refractory to dynamization and full weight bearing. Thirteen of the 58 (22%) fractures available for an evaluation of ankle motion were symptomatic, with < 10 degrees of dorsiflexion.(ABSTRACT TRUNCATED AT 400 WORDS)

Maternal predictors of fetal demise in trauma during pregnancy.

Trauma complicates 6 to 7 per cent of all pregnancies, but fetal demise secondary to maternal trauma occurs much less frequently. This study was done to analyze the incidence of fetal demise as a function of 21 maternal characteristics determined within the first 24 hours after trauma. Nine instances of fetal demise were identified from 73 pregnant patients with trauma admitted to four Level I trauma centers from a combined data base of 30,000 patients. Maternal factors examined by logistic regression were Injury Severity Score (ISS), Trauma Score (TS), Abbreviated Injury Scale (AIS), fluid requirements in the initial 24 hours, systolic blood pressure (SBP), heart rate (HR), hemoglobin, hematocrit and arterial blood gas analysis. Fetal demise was found to be associated with increasing ISS, increasing face and abdominal AIS, increasing fluid requirements, maternal acidosis and maternal hypoxia. Standard maternal laboratory and physiologic parameters, such as hemoglobin and hematocrit, oxygen and hemoglobin saturation, partial pressure of carbon dioxide, SBP and HR were not predictive. The TS was also found to be nonpredictive.

Collateral compensation of severe carotid stenosis.

In 516 patients who had endarterectomies for unilateral severe carotid stenoses, arteriography demonstrated no contralateral severe stenoses or occlusions. Pre and postoperative ocular pneumoplethysmography (OPG-Gee) measured simultaneous bilateral ophthalmic systolic pressures (OSP). Immediately after each OPG test a brachial systolic pressure (BSP) was measured with a stethoscope, cuff and manometer. Bilateral ophthalmobrachial systolic pressure (OBSP) indices were calculated from the three pressures measured with the combined testing. Analysis of these OBSP data indicates that the severe stenoses were relatively well compensated in 314 of the 516 patients (61%) whereas there was limited collateral compensation in the remaining 202 patients (39%). The data also suggest that the latter group incurs a greater element of compensatory central hypertension, which is reversed by carotid endarterectomy.

Reappraisal of ocular pneumoplethysmography after carotid endarterectomy.

An initial report documented a 3-year experience (1978 through 1980) with ocular pneumoplethysmography (OPG-Gee) done in the recovery room after carotid endarterectomy. The present report analyzes a similar 4-year experience (1981 through 1984) on 864 carotid endarterectomies performed by 20 surgeons in which the results of OPG tests done in the recovery room suggested carotid endarterectomy thromboses in 33 of the 864 patients (3.8%). All patients underwent immediate reoperation, and thromboses were confirmed in 26 of the 33 patients (79%). In the seven patients without thromboses, findings at reoperation accounted for the abnormal physiology in six of the seven patients. Overall, in 32 of the 33 patients (97%) the recovery room OPG tests accurately reflected a source of hemodynamic compromise. The application of the special OPG-Gee criteria in this report will minimize needless reoperation after carotid endarterectomy.