Flow cytometry: Potential utility in monitoring drug effects in breast cancer

Summary Flow cytometric analysis of DNA ploidy and S-phase fraction are well recognized prognostic indicators in breast cancer. The present paper deals with the widening of the applications of flow cytometry to monitoring the effectiveness of antiestrogen therapy, detecting clonal selection and emergence of drug resistance, and monitoring chemosensitizing properties of drugs. Antiestrogen activity can be studied by DNA flow cytometry to address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance. Patient plasma specimens containing various concentrations of triphenylethylenes can be monitored for drug-induced effects using cell cycle measurements and correlated toin vivo drug levels. DNA flow cytometry has also been instrumental in the study of the effects of prolonged low-dose (0.5 µM for > 100 days) tamoxifen treatment on human estrogen receptor negative MDA-MB-231 cells, where it was shown that tamoxifen may significantly alter cell cycle kinetics and tumorigenicity of these cells, selecting a new, more aggressive, and rapidly growing clone. Lastly, it has been shown that the chemosensitizing properties of another triphenylethylene antiestrogen, toremifene, on estrogen receptor negative, multidrug resistant MDA-MB-231-A1 human breast cancer cells can be studied using flow cytometric analysis. Toremifene (and its metabolites N-desmethyltoremifene and toremifene IV) are able to resensitize MDA-MB-231-A1 cells to vinblastine and doxorubicin, as reflected in a marked shift of cells to G₂/M phase of the cell cycle. Flow cytometry is a widely available technique that might be applied clinically to monitor, at the cellular level, drug effects on tumors, including the modulators of drug resistance.     

Assessment of myocardial viability by dynamic tomographic iodine 123 iodophenylpentadecanoic acid imaging: Comparison with rest-redistribution thallium 201 imaging

Background

This study examined the ability of dynamic ¹²³I-labeled iodophenylpentade-canoic acid (IPPA) imaging to detect myocardial viability in patients with left ventricular (LV) dysfunction caused by coronary artery disease.

Methods and Results

Serial 180-degree single-photon emission computed tomographic (SPECT) images (five sets, 8 minutes each) were obtained starting 4 minutes after injection of 2 to 6 mCi ¹²³I at rest in 21 patients with LV dysfunction (ejection fraction [EF] 34%±11%). The segmental uptake was compared with that of rest-redistribution ²⁰¹Tl images (20 segments/study). The number of perfusion defects (reversible and fixed) was similar by IPPA and thallium (11±5 vs 10±5 segments/patient; difference not significant). There was agreement between IPPA and thallium for presence or absence (κ=0.78±0.03) and nature (reversible, mild fixed, or severe fixed) of perfusion defects (κ=0.54±0.04). However, there were more reversible IPPA defects than reversible thallium defects (7±4 vs 3±4 segments/patient; p=0.001). In 14 patients the EF (by gated pool imaging) improved after coronary revascularization from 33%±11% to 39%±12% (p=0.002). The number of reversible IPPA defects was greater in the seven patients who had improvement in EF than in the patients without such improvement (10±4 vs 5±4 segments/patient; p=0.075).

Conclusions

¹²³I-labeled IPPA SPECT imaging is a promising new technique for assessment of viability. Reversible defects predict recovery of LV dysfunction after coronary revascularization.     

Coronary Health Issues for Lesbians

Since coronary heart disease (CHD) is the leading cause of death in American women it is therefore likely the leading cause of death among lesbians. Prevention of CHD is a major health issue for lesbians. Efforts must continue to empower all lesbians to take personal preventative action to prevent CHD. Women in general do not believe they are at risk for CHD. A common misperception is that CHD is a man's disease and the most likely threat to a woman's life is breast cancer. This misperception probably exists among lesbians as well. Over a lifetime, a woman is 10 times more likely to develop CHD than she is breast cancer. Breast cancer remains an important health concern for woman, but CHD risk must be addressed with potent educational and advocacy programs for the health of our communities. Prevention of the clinical manifestations of CHD hinges upon the prevention of plaque formation. It is an obligation of primary care providers to give advice regarding the prevention of plaque formation and therefore the prevention of subsequent CHD events and to collaborate with patients to address these issues in an individually tailored manner. This review addresses risk factors for CHD in lesbians to assist providers in achievement of that goal.     

Systematic Differences in Validity of Self-Reported Mammography Behavior: A Problem for Intergroup Comparisons?

Background. Prior studies of recall accuracy for screening mammogram behavior have examined relatively homogeneous groups. Data are limited on possible systematic group differences, so we evaluated women's recall accuracy in two separate care systems in one city.Methods. Women 50 to 70 years old with and without screening mammograms 10 to 14 months prior were identified from fiscal, clinic, and radiology records at a military care system (MCS) and a county-funded system (CFS) for indigents. Mammogram status was verified through radiology records. Women were excluded if mammograms were diagnostic, done for other than annual screening, or had abnormal results. Interview ers blinded to mammogram status surveyed randomly selected eligible women.Results. For 62 screened/31 unscreened MCS women and 78 screened/61 unscreened CFS women, specificity was similar, at 65 and 62%, respectively. In contrast, sensitivity varied significantly: 95% versus 79% (P = 0.011). Primary ethonocultural groups were Euro-American (MCS—60%) and Mexican American (CFS—85%). Although not different in specificity of recall (67% versus 61%), these major subgroups significantly differed in sensitivity (97% versus 80%, P = 0.017), proportion of true negatives due to never having a mammogram (35% versus 57%, P = 0.003), and proportion with ≥high school education (78% versus 19%, P < 0.00001).Conclusion. Systematic differences in recall validity may exist and compromise the accuracy of intergroup comparisons.     

Selective impairment in the recognition of anger induced by diazepam

Rationale: Facial expressions appear to be processed by at least partially separable neuro-cognitive systems. Given this functional specialisation of expression processing, it is plausible that these neurocognitive systems may also be dissociable pharmacologically. Objective: The present study therefore compared the effects of diazepam (15 mg) with placebo upon the ability to recognise emotional expressions. Methods: A double blind, independent group design was used to compare the effects of diazepam and matched placebo in32 healthy volunteers. Participants were presented morphed facial expression stimuli following a paradigm developed for use with patients with brain damage and asked to name one of the six basic emotions (sadness, happiness, anger, disgust, fear and surprise). Results: Diazepam selectively impaired subjects’ ability to recognise angry expressions but did not affect recognition of any other emotional expression. Conclusions: The findings are interpreted as providing further support for the suggestion that there are dissociable systems responsible for processing emotional expressions. It is suggested that these findings may have implications for understanding paradoxical aggression sometimes elicited by benzodiazepines. Received: 27 May 1999 / Accepted: 7 July 1999     

The anaesthetic management of a patient with Emery-Dreifuss muscular dystrophy

Purpose

This case report presents a patient with Emery-Dreifuss Muscular Dystrophy and describes the anaesthetic considerations.

Clinical features

The features of Emery-Dreifuss Muscular Dystrophy are contractures, humeroperoneal muscle weakness and cardiomyopathy. The anaesthetic considerations for this syndrome are difficult tracheal intubation, difficult spinal anaesthetic, heart block, gastric reflux, rhabdomyolysis, and unproved malignant hyperthermia susceptibility.

Conclusion

The major anaesthetic problem for the patient with Emery-Dreifuss Muscular Dystrophy could be a life-threatening cardiomyopathy.     

Appendicitis: Higher risk in Mexican Americans?

Objectives. Mexican Americans (MAs), compared to white non‐Hispanics (WNHs), have higher rates of biliary disease, noninsulin dependent diabetes, and endstage renal disease but lower rates of lung cancer, hip fractures, and mortality from coronary heart disease. Relatively little research has been done to identify other ethnic differences in disease incidence. We used surgical procedure rates to confirm known ethnic differences and to explore our clinical suspicion that MAs have higher rates of appendectomy than WNHs.

Methods. We used a registry of surgical procedures at two teaching hospitals in South Texas to calculate proportional operation ratios (PORs) for MAs versus WNHs. These two hospitals are the primary source of acute hospital care for the indigent in the area. The POR is arithmetically identical to proportional incidence and mortality ratios.

Results. MAs underwent appendectomy proportionally more often than WNHs at both hospitals (POR = 1.41 and 1.75, p < 0.0001). Other significant PORs were consistent with known ethnic disease differences in biliary tract operations, vascular access for chronic hemodialysis, lung cancer, and coronary artery bypass.

Conclusions. These findings support the hypothesis that MAs may undergo appendectomy more often than WNHs and so may be at higher risk of appendicitis.     

Evidence for preferential repair of 3-carbethoxypsoralen plus UVA induced DNA lesions in the active MAT{alpha} locus in Saccharomyces cerevisiae using the UvrABC assay

The occurrence of preferential repair in Saccharomyces cerevisiaeof the active MAT locus compared with the inactive HML locuswas confirmed after 254 nm UV irradiation. Experiments carriedout using the UvrABC excinuclease assay with the monofunctionalfurocoumarin 3-carbethoxypsoralen (3-CPs) plus UVA radiationwhich induce mainly monoadducts in DNA demonstrated preferentialrepair of the active MAT locus compared with the inactive HMLlocus in a SIR⁺ strain. However, as after 254 nm UV irradiation,no difference in the rate of removal of 3-CPs plus UVA inducedlesions was observed between the two loci in the sir-3 mutantin which both loci are active. Thus, it appears that 3-CPs plusUVA induced monoadducts as well as pyrimidine dinners a e subjectto preferential repair. ³To whom correspondence should be addressed     

Stability of the intra-operative arterial to end-tidal carbon dioxide partial pressure difference in children with congenital heart disease

The purpose of this study was to evaluate the stability of the arterial PCO2 (PaCO2) to end-tidal PCO2 (PETCO2) partial pressure difference (Pa-ETCO2) during surgery using PETCO2 monitoring, in children with congenital heart disease (CHD). Forty children with CHD were studied: ten children with no interchamber communication and normal pulmonary blood flow (PBF) (normal group); ten acyanotic children with increased PBF (acyanotic-shunting group); ten cyanotic children with mixing type lesions and normal or increased PBF (mixing group), and ten cyanotic children with right-to-left intracardiac shunts demonstrating decreased and variable PBF (cyanotic-shunting group). Simultaneous PaCO2 recordings and PETCO2 measurements were obtained for each patient during five intraoperative events: (1) control time, arterial line placement under anaesthesia; (2) time 1, patient preparation; (3) time 2, immediately after sternotomy; (4) time 3, after heparin administration; and (5) time 4, immediately after aortic cannulation. Initially, cyanotic children demonstrated a greater Pa-ETCO2 compared with acyanotic children (P less than 0.05). There was no difference in the Pa-ETCO2 over time in the control, acyanotic-shunting, or mixing groups. The Pa-ETCO2 in the children with cyanotic-shunting lesions at times 2 and 3 was greater (P less than 0.05) than at their control times. We conclude that the Pa-ETCO2 of children with acyanotic-shunting and mixing congenital heart lesions is stable intraoperatively, although patients with mixing congenital heart lesions may demonstrate large individual variations. In children with cyanotic-shunting congenital heart lesions, the Pa-ETCO2 is not stable. The PETCO2 cannot be used during surgery to estimate reliably the PaCO2 in children with cyanotic CHD.