Hormonal receptors in mammary carcinoma: comparison between quantitative and qualitative methods

Alternatives to the traditional hormone receptor dosages for prognostic evaluation and clinical approach to breast cancer have been proposed for immunohistochemical determinations. For correlation purposes, such procedures were compared in 37 patients presenting 5 to 15 years of survival. Considering 30 fm/mg as the positivity index, the disagreement between both methods reached 35.1% with estrogen and 48.5% with progesterone receptors. When the positiveness level was changed to 20 fm/mg, the discrepancies were reduced to 32% with ER and increased to 57% with PgR. This study leads us to not recommend the immunohistochemical method applied to paraffin sections as an alternative procedure to the dextran-charcoal dosage for prognosis and therapeutic management of mammary carcinoma.     

Variance components analysis of carotid and femoral intima-media thickness measurements. REGRESS Study Group, Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study

B-mode ultrasound intima-media thickness (IMT) measurements of carotid and femoral arterial walls are used in atherosclerosis studies. In this study, the components contributing to IMT measurement variability in males with coronary artery disease were investigated by means of repeated B-mode ultrasound scans and repeated off-line video image analyses. For statistical analysis, a mixed-model analysis of variance was used. From sonographer data, it was shown that human subjects and their arterial wall segments contributed 75% of the total IMT measurement variability in this population. Inter-sonographer variance contributed 25%. The intra-sonographer variance was negligible (<1%). In off-line image analysis, variance components due to subjects and segments, inter-analyst variance, and residual fluctuation were 88%, < 1% and 11%, respectively. Intra-analyst variance was negligible (<1%). The major source of B-mode ultrasound IMT measurement variability finds its origin in subjects and their arterial walls. Although sonographers proved a lesser source of variability, in comparative studies they should enter a study well trained and should be randomly assigned to subjects. Follow-up examinations should preferably be done by the same sonographer. Off-line image analysis contributed little to IMT measurement variability.     

Epidural anesthesia impairs both central and peripheral thermoregulatory control during general anesthesia

BACKGROUND: The authors tested the hypotheses that: (1) the vasoconstriction threshold during combined epidural/general anesthesia is less than that during general anesthesia alone; and (2) after vasoconstriction, core cooling rates during combined epidural/general anesthesia are greater than those during general anesthesia alone. Vasoconstriction thresholds and heat balance were evaluated under controlled circumstances in volunteers, whereas the clinical importance of intraoperative thermoregulatory vasoconstriction was evaluated in patients. METHODS: Five volunteers were each evaluated twice. On one of the randomly ordered days, epidural anesthesia (approximately T9 dermatomal level) was induced and maintained with 2-chloroprocaine. On both study days, general anesthesia was induced and maintained with isoflurane (0.7% end-tidal concentration), and core hypothermia was induced by surface cooling and continued for at least 1 h after fingertip vasoconstriction was observed. Patients undergoing colorectal surgery were randomly assigned to combined epidural/enflurane anesthesia (n = 13) or enflurane alone (n = 13). In appropriate patients, epidural anesthesia was maintained by an infusion of bupivacaine. The core temperature that triggered fingertip vasoconstriction identified the threshold. RESULTS: In the volunteers, the vasoconstriction threshold was 36.0 +/- 0.2 degrees C during isoflurane anesthesia alone, but significantly less, 35.1 +/- 0.7 degrees C, during combined epidural/isoflurane anesthesia. Cutaneous heat loss and the rates of core cooling were similar 30 min before vasoconstriction with and without epidural anesthesia. In the 30 min after vasoconstriction, heat loss decreased 33 +/- 13 W when the volunteers were given isoflurane alone, but only 8 +/- 16 W during combined epidural/isoflurane anesthesia. Similarly, the core cooling rates in the 30 min after vasoconstriction were significantly greater during combined epidural/isoflurane anesthesia (0.8 +/- 0.2 degrees C/h) than during isoflurane alone (0.2 +/- 0.1 degrees C/h). In the patients, end-tidal enflurane concentrations were slightly, but significantly, less in the patients given combined epidural/enflurane anesthesia (0.6 +/- 0.2% vs. 0.8 +/- 0.2%). Nonetheless, the vasoconstriction threshold was 34.5 +/- 0.6 degrees C in the epidural/enflurane group, which was significantly less than that in the other patients, 35.6 +/- 0.8 degrees C. When the study ended after 3 h of anesthesia, patients given combined epidural/enflurane anesthesia were 1.2 degrees C more hypothermic than those given general anesthesia alone. The rate of core cooling during the last hour of the study was 0.4 +/- 0.2 degrees C/h during combined epidural/enflurane anesthesia, but only 0.1 +/- 0.3 degrees C/h during enflurane alone. CONCLUSIONS: These data indicate that epidural anesthesia reduces the vasoconstriction threshold during general anesthesia. Furthermore, the markedly reduced rate of core cooling during general anesthesia alone illustrates the importance of leg vasoconstriction in maintaining core temperature.     

Body-size corrections for in vivo neutron activation analysis

Differences in body size and shape can cause large variances in the results of in vivo neutron activation analysis. Preliminary body-size correction data were obtained for the delayed-gamma neutron activation facility (DGNA) at Brookhaven National Laboratory (BNL), based on phantom standards of different sizes, used in combination with computer simulations on the effect of different body sizes.     

Gene-for-gene disease resistance without the hypersensitive response in Arabidopsis dnd1 mutant

The cell death response known as the hypersensitive response (HR) is a central feature of gene-for-gene plant disease resistance. A mutant line of Arabidopsis thaliana was identified in which effective gene-for-gene resistance occurs despite the virtual absence of HR cell death. Plants mutated at the DND1 locus are defective in HR cell death but retain characteristic responses to avirulent Pseudomonas syringae such as induction of pathogenesis-related gene expression and strong restriction of pathogen growth. Mutant dnd1 plants also exhibit enhanced resistance against a broad spectrum of virulent fungal, bacterial, and viral pathogens. The resistance against virulent pathogens in dnd1 plants is quantitatively less strong and is differentiable from the gene-for-gene resistance mediated by resistance genes RPS2 and RPM1. Levels of salicylic acid compounds and mRNAs for pathogenesis-related genes are elevated constitutively in dnd1 plants. This constitutive induction of systemic acquired resistance may substitute for HR cell death in potentiating the stronger gene-for-gene defense response. Although cell death may contribute to defense signal transduction in wild-type plants, the dnd1 mutant demonstrates that strong restriction of pathogen growth can occur in the absence of extensive HR cell death in the gene-for-gene resistance response of Arabidopsis against P. syringae.     

Difference between the measured and ordered dose of catecholamine infusions

OBJECTIVE: To measure the actual concentrations of dopamine, dobutamine, and epinephrine in infusates prepared for patients, and to compare these concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl infusates that had been prescribed to evaluate drug preparation accuracy. DESIGN: Prospective, unblind study. SETTING: Pediatric intensive care unit in a tertiary-care teaching hospital. PARTICIPANTS: All dopamine, dobutamine, and epinephrine infusions ordered for patients during the 2-month study period were eligible for inclusion in the study. MEASUREMENTS: Daily samples of dopamine, dobutamine, and epinephrine infusates that were prepared for 41 pediatric patients were obtained; the infusate catecholamine concentration was measured by HPLC and compared with the ordered concentration. The concentration than was multiplied by the rate of infusion to determine the catecholamine dose. MAIN RESULTS: There were significant differences between the measured doses of dopamine, dobutamine, and epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p = 0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of preparation inaccuracies. Failure to account for the HCl salt in the stock drug accounted for some, but not all, of the inaccuracy of the dopamine HCl and epinephrine HCl infusates. There was a wide interday variability in the measured catecholamine dosage in patients receiving the same dose for 3 days or more. CONCLUSIONS: There are daily fluctuations in the preparation of dopamine, dobutamine, and epinephrine infusates that could alter the amount of drug actually delivered to critically ill patients and potentially contribute to their hemodynamic instability.     

Chronic expression of P-selectin on endothelial cells stimulated by the T-cell cytokine, interleukin-3

P-selectin expressed on the surface of endothelium mediates leukocyte adhesion in vitro and rolling in vivo. Several inducers of cell-surface P-selectin expression on endothelial cells (EC) have previously been identified, all of which yield transient cell-surface expression of P-selectin lasting minutes to a few hours. We now show that a T-lymphocyte product, interleukin-3 (IL-3), stimulates the long-term endothelial cells (HUVEC). IL-3 induced cell-surface P-selectin expression in two phases. An initial peak at 10 minutes was followed by a prolonged upregulation beginning 16 hours after IL-3 addition and lasting at least 4 days. The level of P-selectin expression induced by IL-3 added for 48 hours was similar to that induced by treatment of HUVEC for 10 minutes with thrombin, and the effect of adding IL-3 for 48 hours followed by thrombin for 10 minutes was additive. Induction of cell-surface P-selectin expression by IL-3 was blocked by pretreatment of EC with a blocking monoclonal antibody against the IL-3 receptor alpha-chain. Lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) and a mutant form of IL-3 with decreased potency did not induce cell-surface P-selectin expression after 48 hours' incubation with HUVEC, suggesting that the effect was specific to IL-3. The increase in cell-surface P-selectin expression occurring after 16 hours of incubation with IL-3 was accompanied by a similar prolonged increase in the steady-state mRNA level that was not observed at 10 minutes after IL-3 addition. As T-lymphocyte infiltration is a hallmark of chronic inflammation, our observations suggest that the secretion of IL-3 by T lymphocytes may serve to maintain the inflammatory state during chronic inflammation.     

The role of scintigraphy in the evaluation of fever of unknown origin

Nuclear medicine imaging techniques are an important adjunct to other currently used modalities in the evaluation of patients with fever of unknown origin. Bone scanning performed with technetium-labeled phosphonate agents may identify osteomyelitis when plain radiography fails and may disclose sites of joint inflammation or unsuspected osseous tumor metastasis. Indium-labeled autologous leukocytes localize at sites of inflammation in the same manner as unlabeled leukocytes. Gallium citrate accumulates in areas of inflammation and in some tumors, most notably lymphomas. In most cases, scintigraphy is best used to determine the location of a lesion rather than to specifically identify the pathologic process.     

Total-body and regional bone mineral content and areal bone mineral density in children aged 8-18 y: the Fels Longitudinal Study

We used a modification of the isolated perfused rat heart, in which coronary effluent and interstitial transudate were separately collected, to investigate the localization and production of angiotensin II (Ang II) in the heart. During combined renin (0.7 to 1.5 pmol Ang I/mL per minute) and angiotensinogen (6 to 12 pmol/mL) perfusion (4 to 8 mL/min) for 60 minutes (n=3), the steady-state levels of Ang II in interstitial transudate in two consecutive 10-minute periods were 4.3+/-1.5 and 3.6+/-1.5 fmol/mL compared with 1.1+/-0.4 and 1.1+/-0.6 fmol/mL in coronary effluent (mean+/-half range). During perfusion with Ang II (n=5), steady-state Ang II in interstitial transudate was 32+/-19% of arterial Ang II compared with 65+/-16% in coronary effluent (mean+/-SD, P<.02). During perfusion with Ang I (n=5), Ang II in interstitial transudate was 5.1+/-0.6% of arterial Ang I compared with 2.2+/-0.3% in coronary effluent (P<.05). The tissue concentration of Ang II in the combined renin/angiotensinogen perfusions (per gram) was as high as the concentration in interstitial transudate (per milliliter). Addition of losartan (10(-6) mol/L) to the renin/angiotensinogen perfusion (n=3) had no significant effect on the tissue level of Ang II, whereas losartan in the perfusions with Ang I (n=5) or Ang II (n=5) decreased tissue Ang II to undetectably low levels. The results indicate that the heart is capable of producing Ang II and that this can lead to higher levels in tissue than in blood plasma. Cardiac Ang II does not appear to be restricted to the extracellular fluid. This is in part due to AT1-receptor-mediated cellular uptake of extracellular Ang II, but our results also raise the possibility of intracellular Ang II production.