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Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

320 records · Page 18Linked to original sources

Self-efficacy and self-reported functional status in coronary heart disease: a six-month prospective study.

OBJECTIVE: We examine prospectively the role of specific forms of self-efficacy in the physical and role function for patients with coronary heart disease after controlling for the effects of anxiety and depression. METHODS: A 6-month prospective cohort study was conducted after cardiac catheterization of 198 HMO members, demonstrating clinically significant coronary disease. Coronary disease severity was assessed through cardiac catheterization; physical function, role function, anxiety, depression, and self-efficacy were assessed through questionnaires. RESULTS: The Cardiac Self-Efficacy Scale had two factors (maintain function and control symptoms) with high internal consistency and good convergent and discriminant validity. In multiple regression models, the self-efficacy scales significantly predicted physical function, social function, and family function after controlling for baseline function, baseline anxiety, and other significant correlates. CONCLUSIONS: Self-efficacy to maintain function and to control symptoms helps predict the physical function and role function, after accounting for coronary disease severity, anxiety, and depression in patients with clinically significant coronary disease. Interventions to improve self-efficacy may have a broader applicability in the heart disease population than previously appreciated.

Activities of Daily Living↗

Development of a brief diagnostic screen for panic disorder in primary care.

OBJECTIVE: The purpose of this study was to determine the utility of a brief screening tool for panic disorder in the primary care setting. METHODS: A total of 1476 primary care outpatients in three primary care medical clinics on the West Coast of the United States were studied. Patients completed a brief self-report measure, the five-item Autonomic Nervous System Questionnaire (ANS), while in the waiting room. The presence of DSM-IV panic disorder was subsequently determined in groups of "screen-positive" and "screen-negative" subjects using the Composite International Diagnostic Interview. A subset of patients (N = 511) also completed the 21-item Beck Anxiety Inventory. Indices of diagnostic utility were calculated using receiving operating characteristic analyses to guide the selection of optimal cutoff levels. RESULTS: The two-question version of the ANS had excellent sensitivity (range = 0.94-1.00 across the three clinic sites) and negative predictive value (0.94-1.00) but low specificity (0.25-0.59) and positive predictive value (range 0.18-0.40). The three- and five-question versions of the ANS had only modestly improved specificity, and this was achieved at the cost of reduced sensitivity and increased respondent burden to complete the questionnaire. The 21-item Beck Anxiety Inventory had maximal clinical utility at a cutoff level of > or =20, but sensitivity was lower than desirable for a screening instrument (0.67). CONCLUSIONS: The two-question version of the ANS shows promise as a screening instrument for panic disorder in the primary care setting.

Adult↗

Image analysis of Feulgen-stained c-H-ras-transformed NIH/3T3 cells.

Feulgen-DNA content, nuclear phenotypes, and levels of chromatin condensation were evaluated by image analysis in NIH/3T3 cells transformed with the c-H-ras oncogene of T24 cells. Three nuclear phenotypes, differing from those of untransformed control cells and defined in terms of patterns of chromatin condensation, were demonstrated microspectrophotometrically for the tumor cells. Polyploidy could only be observed in nuclei with extensive and deeply stained areas covered with condensed chromatin, i.e., only in a small fraction of the tumor cell nuclear population. The increased chromatin condensation that appeared with cell transformation affected the euchromatin zones. The image analysis provided data that, compared with those obtained in other situations involving cell transformation, could be relevant to the understanding of changes in chromatin supraorganization related to tumorigenesis and to tumor cell diagnosis.

Animals↗

Nucleus image properties and cell death in MCF-10F cells grown on slide substrates differing in nature and size.

The immortalized human breast epithelial cell line MCF-10F is an important tool for studies on experimental tumorigenesis induced by drugs, transfected Ha-ras oncogene, and hormones. Considering that many relevant data have thus far been established only for MCF-10F cells cultivated on glass, and that there are data showing different cell death ratios for tumorigenic cells obtained from benzo[a]pyrene (BP)-transformed MCF-10F cells cultivated on plastic compared with glass, nuclear parameters estimated by image analysis and cell death ratios were compared for cells grown on plastic and glass substrates differing in chamber surface sizes and working culture medium volumes. It was concluded that for slides with a growth size equal to 9.4 cm2, plastic substrate was more advantageous than glass for growing MCF-10F cells because although the apoptotic ratios (AR) for the cells grown on plastic are low as it would be expected for nontransformed cells, they are bigger than those reported for the BP-transformed MCF-10F cells cultivated on the same substrate but closer to those of the BP-transformed MCF-10F cells receiving a normal chromosome 17. In addition, the plastic substrate did not induce variable nuclear image results as those found in the latter. The 0.5-cm2-sized chambers on plastic slides proved to be inadequate for cell nuclear image analysis and cell death studies on account of the variable geometric, densitometric, and textural results and ARs produced and the unpublished consideration of a very slow growth rate generated under this growth condition.

Apoptosis↗

The pathology of breast cancer: staging and prognostic indicators.

The natural history of breast cancer is complex and the treatment modalities need to be adjusted to this heterogeneous disease. Several prognostic indicators have been described for breast cancer, including the extent of axillary nodal metastasis, the size of the primary tumor mass, various histopathologic characteristics, estrogen and progesterone receptor content, tumor proliferation index, detection of oncogenes, tumor suppressor genes, loss of heterozygosity, and growth factors. Although no single parameter or combination of parameters can definitively predict the outcome of the disease, combined criteria such as tumor estrogen receptor content, cell proliferative index, and lymph node status are relevant for identifying subsets of breast cancer patients that may require different therapeutic modalities. Detection of oncogenes, tumor suppressor genes, and growth factors need further evaluation to determine their usefulness as prognostic factors.

Breast Neoplasms↗

Hormone prevention of mammary carcinogenesis: a new approach in anticancer research.

The observation that chemically induced breast cancer is prevented when the mammary gland is completely differentiated by a full term pregnancy prior to exposure to a carcinogen, led us to test the hypothesis that synthetic ovarian hormones commonly used for the purpose of contraception might drive mammary gland differentiation enough to be protective from carcinogen--induced neoplastic transformation. This hypothesis was only partially proven, due to the unexpected finding that a high dose of the progestagenic agent medroxyprogesterone acetate (MPA), increased tumor incidence, whereas a similar dose of the mostly estrogenic norethynodrel--mestranol (NM) was protective. An additional finding was the fact that these two agents exerted a different action on thoracic than on abdominal mammary glands. MPA inhibited differentiation of TEBs in the former, but stimulated lobule development in the latter. This difference in response seemed to be associated to the asynchronous development of the mammary glands located in different topographic regions. These observations indicated that the response of the mammary gland epithelium with either differentiation or cell proliferation is in great part modulated by the condition of the target organ. Although the concept of hormone prevention of breast cancer promises to be an achievable goal, there are still basic fundamental questions that need to be answered. First, how do estrogens and progesterone act on the mammary epithelium, second, what is the sequence in which they act on the mammary gland in order to induce differentiation of the organ, third, why the same homonal milieu in a single animal results in asynchronous development of glands located in thoracic versus those in the abdominal region.

9,10-Dimethyl-1,2-benzanthracene↗

Comparative review of two new wide-spectrum penicillins: mezlocillin and piperacillin.

The antimicrobial spectra, pharmacokinetics, tissue penetration, side effects, clinical trials and indications, dosage, and cost of mezlocillin (Mezlin) and piperacillin (Pipracil), two new semisynthetic beta-lactam penicillins, are reviewed. Both mezlocillin and piperacillin are active against a wider range of bacteria than previously available penicillins, but their spectra are not identical. Piperacillin is more active than mezlocillin against Pseudomonas aeruginosa; their activities against Klebsiella pneumoniae, Streptococcus faecalis, and Bacteroides fragilis are similar to one another. Neither drug is absorbed orally; both are well absorbed (60-70%) after i.m. injection. Following i.v. infusion or injection, both drugs distribute rapidly (distribution half-life = 10-20 min); neither is protein bound substantially. Both drugs are primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Elimination half-lives of both drugs are slightly prolonged in renal-failure patients. However, the half-life of mezlocillin in renal failure is longer then the half-life of piperacillin because of dose-dependent kinetics of mezlocillin at low glomecular filtration rates. Probenecid alters the disposition of both drugs. Both drugs are widely distributed throughout the body. Reported side effects are similar to those of other penicillins. Mezlocillin and piperacillin may be used to treat susceptible organisms causing the following conditions: complicated and uncomplicated urinary-tract infections, septicemia, uncomplicated gonococcal urethritis, and lower respiratory-tract, intra-abdominal, gynecologic, skin, and skin-structure infections. Piperacillin is also effective for bone and joint infections. Dosages of both antibiotics should be adjusted based on patients' clinical condition and renal status. Both agents are relatively expensive in comparison with older penicillins and cephalosporins; their daily costs are similar to third-generation cephalosporins, carbenicillin, and ticarcillin. The potential benefits of mezlocillin and piperacillin are in their extended in vitro spectra of activity and minimal toxicities. More comparative clinical trials are needed to support any claims of clinical superiority of these drugs over older, less expensive regimens.

Bacteria↗

Zinc deficiency dermatitis accompanying parenteral nutrition supplemented with trace elements.

Zinc deficiency dermatitis in a patient on long-term total parenteral nutrition (TPN) with trace-element supplementation is reported, and the therapeutic aspects of zinc deficiency are reviewed. A 36-year-old white man was hospitalized and found to have a small-bowel perforation secondary to internal herniation. Small-bowel resection with end-to-end anastomosis was performed, and TPN supplemented with folic acid, multivitamins, trace elements (including elemental zinc 2 mg/day), and fat was begun. Four months later, the patient developed a moist, erythematous, painful groin rash that did not respond to one month of topical antifungal and topical and intravenous antibacterial treatment. At five months after admission, zinc deficiency was suspected; serum zinc concentration was 85 micrograms/dl (normal = 55-150 micrograms/dl). The total daily zinc dose was increased to 60 mg, and within two days the patient's lesions began to improve. The rash healed within two weeks. Six days after increased zinc therapy was begun, lab tests showed: hair zinc content, 185 micrograms/g (normal = 163 micrograms/g); serum zinc content, 90 micrograms/dl; and erythrocyte zinc content, 1058 micrograms/dl (normal = 1100-1400 micrograms/dl). Signs and symptoms of zinc deficiency, zinc disposition in man, predisposing factors to zinc deficiency, laboratory analysis of zinc nutriture, zinc therapy, and zinc toxicity are discussed. Knowledge of drug use, diet, geographic location, underlying disease, and other patient-specific factors is important in recognizing the patient at risk of developing zinc deficiency. Several tests should be performed to document zinc deficiency. Zinc replacement guidelines are outlined.

Adult↗

Architectural pattern of the normal and cancerous breast under the influence of parity.

Epidemiological and clinical observations indicate that breast cancer incidence is greater in nulliparous women, whereas early parity confers protection. Since the initiation of breast cancer is related to the degree of development of the organ, this study was designed with the purpose of determining what basic differences exist between the parous and the nulliparous women's breast, and whether these differences correlated with the presence or absence of malignancies. For this purpose, the architecture of the mammary gland of parous and nulliparous women with breast cancer was compared with that of women free of mammary pathology. The women ranged in an age from 20 to 63 years. Normal whole breasts obtained at autopsy or cancer-bearing breasts surgically removed by modified radical mastectomy were studied in whole mount preparations in which the number and relative proportion of normal structures, i.e., lobules type 1, 2, and 3 (Lob 1, 2, and 3), were determined. In the breast of nulliparous women, the predominant structure present was the Lob 1; the presence of cancer did not modify the basic architectural pattern of the breast, which contained a higher proportion of Lob 1, as well. In parous women free of cancer, the breast contained a greater percentage of Lob 3 and a moderately increased number of Lob 2, with a concomitant reduction in Lob 1. Parous women with breast cancer, on the other hand, exhibited a different architecture in the mammary gland, which had a greater percentage of Lob 1 and a lower of Lob 3 than the noncancerous group, approaching the percentages found in nulliparous women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Roscovitine inhibits the proliferative activity of immortal and neoplastic human breast epithelial cells.

[2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylp urine] (roscovitine) is a potent and selective inhibitor of cyclin-dependent kinases cdc2 and cdk2. In this study, we evaluated the potential involvement of this novel cyclin-dependent kinase inhibitor in the proliferative activity of malignant and non-malignant human breast epithelial cells in vitro. Estrogen receptor-positive MCF-7 breast carcinoma cells, immortalized estrogen receptor-negative breast epithelial cells and highly malignant estrogen receptor-negative MDA-MB-231 breast epithelial cells, were incubated with different concentrations of roscovitine ranging from 1 to 40 micrograms/ml, and cell numbers were measured with the WST-1 colorimetric assay after 24, 48, 72, 96, 120, and 144 hours of treatment. Our results demonstrated that roscovitine inhibited the proliferation of human breast epithelial cells in a dose- and time-dependent manner. Roscovitine treatment decreased the number of viable cells and prevented the exponential growth of all the cell lines examined. The antiproliferative effect of this potent cdk inhibitor was independent of the estrogen receptor status of the cells. These data suggest that roscovitine is a potential antiproliferative drug for the treatment and/or prevention of both estrogen responsive and non-responsive breast cancers.

Antineoplastic Agents↗

A preliminary report: frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy.

PURPOSE: To investigate whether a significant proportion of prostate cancer patients who have late sequelae after high-dose external-beam conformal radiation therapy are radio-sensitive because they are carriers of ataxia-telangiectasia, that is, are heterozygous for mutations in the ATM gene. PATIENTS AND METHODS: A group of prostate cancer patients were selected who experienced severe late sequelae, specifically proctitis or cystitis, after high-dose external-beam conformal radiation therapy, together with a control group of patients treated in the same way but who did not have severe late effects. Blood samples were taken from these patients, genomic DNA extracted, and mutations sought in the ATM gene. RESULTS: Of 17 late-effect patients in whom most or all of the ATM gene has been examined, significant mutations (17.6%) were identified in three. No significant mutations were found in the control group. The incidence of ataxia- telangiectasia heterozygotes in the United States population is 1% to 2%. DISCUSSION: These preliminary data suggest that a disproportionate number, but by no means all, of prostate cancer radiotherapy patients who experience severe late effects are ataxia-telangiectasia heterozygotes. If this conclusion is confirmed, these individuals could be identified prospectively and, with dose de-escalation, spared a great deal of discomfort and suffering. As a corollary, if most of the small late-effects population were prospectively identifiable, the dose to the remaining population could potentially be escalated. Present methods of identifying mutations in a large gene, such as ATM, are cumbersome and expensive, but the technology is evolving rapidly, so that rapid screening of the ATM gene is imminent.

Ataxia Telangiectasia↗

Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells.

The glycoprotein hormone, human chorionic gonadotropin (hCG) inhibits mammary tumorigenesis through induction of differentiation, and inhibits the proliferation of human breast epithelial cells (HBEC) in vitro. The present study was designed to determine whether the inhibitory effects of hCG was associated with the modulation of apoptotic gene expression. MCF-10F, a normal immortalized HBEC, BP1-E, a benzo(a)pyrene (BP) transformed cell line, and the urothelial cell line T24, were treated with 100 IU/ml of a commercially available preparation of hCG. Cell growth analysis and RNA extraction for determination of apoptotic gene expression were performed at 24 and 120 hrs of hCG treatment. Both hCG-treated and control cells grew at similar rates for the first 24 hours. A significant reduction in the number of viable MCF-10F and BP1-E cells occurred by 120 hours of treatment, whereas the number of both hCG treated and control T24 cells were similar. Northern blot analysis revealed that the 24 hour-hCG treatment induced an elevation in the expression of the apoptotic genes TRPM2, ICE, TGF-beta, p53, bax, and p21WAF1/CIP1 in MCF-10F cells. By 120 hours of treatment MCF-10F cells maintained the same level of gene expression observed at 24 hours, except for a reduction in c-myc and bax. Control cells exhibited an elevation in the expression of TRPM2, TGF-beta, p53, bax, and p21WAF1/CIP1, whose levels became similar to those observed in hCG-treated cells. The 24 hour-treated BP1-E cells showed activation of ICE, bax and p21WAF1/CIP1. However, TRPM2 expression was moderately activated. By 120 hours TRPM2, ICE, TGF-beta, c-myc and p21WAF1/CIP1 were elevated in both treated and control cells except bax which was slightly down-regulated. The levels of bc12 were significantly decreased by hCG treatment. Gene expression was not modified by hCG treatment in T24 cells. Our findings suggest that hCG induced an acceleration in the expression of apoptotic genes, which became evident before detection of cell growth inhibition. Gene activation differed among immortalized, and chemically transformed cells, suggesting that hCG might utilize both p53 dependent and p53 independent pathways for inhibiting cell cycle progression. The importance of these findings lies in the potential use of agents like hCG for the chemoprevention and chemotherapy of breast cancer.

Apoptosis↗