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Biomedical subjects

G Cotsonis

Publications and source records attributed to G Cotsonis.

At least 19 recordsLinked to original sources
PubMed2002

Image cytometric bcl-2:bax and bcl-2:bcl-x ratios in invasive breast carcinoma: correlation with prognosis.

BACKGROUND: The bcl-2 family of proteins are important regulators of apoptosis. Some of the members, such as bcl-2 and bcl-x(L), inhibit cell death, whereas others, such as bax and bcl-x(S), promote cell death. We evaluated the ratios of bcl-2:bax and bcl-2:bcl-x expression by image cytometry in invasive breast carcinoma to determine prognostic significance. DESIGN: Five-micron sections of formalin-fixed, paraffin-embedded tissue from 88 invasive breast carcinomas were immunostained using steam antigen retrieval, an avidin biotin-complex technique with automated stainer and primary antibodies against bcl-2 (1/160; Dako, Carpenteria, CA), bax (1/1,500; PharMingen, San Diego, CA), and bcl-x (1/1,500; PharMingen). Positive controls were tonsil (bcl-2) and normal breast (bax and bcl-x) tissue samples. Immunostain was measured in 15 high power fields as percentage positive area (PPA) in nuclei and cytoplasm using the CAS 200 image analyzer (Becton Dickinson, San Jose, CA). RESULTS: Median follow-up was 105 months (range 11-130). Significantly improved disease-free survival was found in patients with a bcl-2:bcl-x ratio > or = 1 by univariate and multivariate analyses. The bcl-2:bax ratio was not predictive of overall or disease-free survival. A significant difference in overall and disease-free survival was found between carcinomas with positive and negative bcl-2 expression by univariate analysis; by multivariate analysis, bcl-2 expression was an independent prognostic factor for disease-free survival. The 5-year survival rates were 77% and 50% in patients with bcl-2-positive and bcl-2-negative carcinomas, respectively. CONCLUSION: A bcl-2:bcl-x ratio > or = 1, assessed by image cytometry, is significantly associated with improved disease-free survival in patients with invasive breast carcinoma. Significantly increased overall and disease-free survival is associated with positive bcl-2 expression.

Adult↗
PubMed2002

Hepatocellular carcinoma and markers of apoptosis (bcl-2, bax, bcl-x): prognostic significance.

Patients with tumors expressing promoters of apoptosis (bax) versus inhibitors of apoptosis (bcl-2, bcl-x) may have increased survival. The purpose of this study was to determine the frequency of expression of apoptotic markers in hepatocellular carcinoma (HCC) and their relationship with prognosis. Seventy HCC were immunostained for bcl-2, bax, and bcl-x. Staining intensity in tumor cells was graded 0 to 3+. Follow-up data were available for mean survival (57 cases) and death rates (58 cases). These values and clinical parameters were related to prognosis. Staining frequency for bcl-2, bax, and bcl-x was 20%, 66%, and 60%, respectively. Immunostaining intensity of bax correlated with overall survival and death rates: of 57 patients, the 37% with 0 to 1+ intensity had a median survival of 6.6 months, the 63% with 2 to 3+ intensity had a median survival of 31.9 months (P = 0.05); 86% of 19 patients with 0 to 1+ intensity died, and 50% of 36 patients with 2 to 3+ intensity died (P < 0.05). Intensity of bcl-x staining tended to correlate with survival: of the 57 patients with 0 to 1+, 42% had a median survival of 32.7 months compared with 5.8 months in the 58% with 2 to 3+ intensity (P = 0.06). By multivariate analysis, this relationship held for bax (P = 0.011) and bcl-x (P = 0.048). There was no correlation between bcl-2 expression, stage, or gender and prognosis. Patients with bax-expressing HCC experience improved survival compared with those with no or low bax expression, in uni- and multivariate models. Patients with no or low bcl-x tended toward improved survival compared with patients with more bcl-x in their HCC. bcl-2 expression did not correlate with prognosis.

Adult↗
PubMed2001

Differential expression of active mitogen-activated protein kinase in cutaneous endothelial neoplasms: implications for biologic behavior and response to therapy.

BACKGROUND: Tumors of endothelium range from benign hemangiomas of infancy to highly malignant angiosarcomas of the elderly. Hemangiomas are the most common tumors in infants and may affect up to 10% of all children. The biologic behavior of these lesions ranges from self-resolving, in the case of hemangiomas and pyogenic granulomas, to lethal metastatic neoplasms in the case of angiosarcoma. Although the clinical outcomes of these diseases are easily distinguished, the biologic basis for these differences is not well understood. Activation of mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that may predict response of a tumor to chemotherapy. OBJECTIVE: Our purpose was to examine expression of phosphorylated (activated) MAPK in hemangiomas of infancy, pyogenic granulomas, hemangioendotheliomas, and angiosarcomas to determine whether phosphorylated MAPK was expressed in endothelial tumors. In addition, we examined endothelial tumors of infectious origin, Kaposi's sarcoma, and verruga peruana. METHODS: Skin sections from benign and malignant endothelial tumors, including hemangioma of infancy, angiosarcoma, and infectious endothelial lesions (Kaposi's sarcoma, verruga peruana) were stained with an antibody specific for phosphorylated MAPK. RESULTS: We demonstrated strong expression of phosphorylated MAPK in benign endothelial tumors, including capillary hemangioma of infancy and pyogenic granuloma, and greatly decreased expression in angiosarcoma. In addition, infectious endothelial tumors stained strongly with this antibody, similar to benign tumors. The presence of immunoreactive phosphorylated MAPK appears to be inversely correlated with degree of malignancy. CONCLUSION: We demonstrate that the use of antibodies specific for signal transduction pathways is feasible in paraffin-fixed tissue. Thus the activity of a given signal transduction pathway can be ascertained in a biopsy specimen. Immunohistochemistry for phosphorylated MAPK may help the pathologist distinguish benign from malignant endothelial processes and thus guide therapy.

Granuloma, Pyogenic↗
PubMed2001

Progesterone receptor immunohistochemical quantitation compared with cytosolic assay: correlation with prognosis in breast cancer.

Quantitation of estrogen and progesterone receptors (PR) represents the standard of care in the treatment of patients with breast cancer. Historically this was performed by cytosolic assay; current methods utilize immunohistochemical staining, which may be quantitated visually or by image cytometry. Formalin-fixed paraffin embedded sections from 95 breast carcinomas were immunostained with an avidin-biotin complex technique. steam antigen retrieval, and a monoclonal PR antibody (1/40 Biogenex). Nuclear immunostain was quantitated visually as the percentage of immunopositive nuclei, scored as 0 to 4. By image cytometry, the percentage of positively staining nuclear area (PPNA) was determined in 15 hpf using the CAS 200 Image Analyzer. Dextran-coated charcoal (DCC) ligand binding assay data were divided into negative (<10 fmol), low positive (10-50), or positive (>50). A statistically significant correlation was found between stage (P = 0.0001), the presence of nodal metastases (P = 0.0001), cytosolic assay (P = 0.036), image cytometry (P = 0.01), and disease-free survival. Only stage (P = 0.0001) and PR quantitation per cytosolic assay (P = 0.0001) correlated with overall survival. The method of choice for the assessment of PR hormone status in breast carcinomas is the DCC ligand binding assay. This method correlates with both survival and disease-free survival. Image cytometric quantitation of PR immunohistochemical staining correlates only with disease-free survival. The commonly used method of visual quantitation of PR immunostaining fails to relate either to survival or disease-free survival.

Breast Neoplasms↗
PubMed1999

Analysis of cyclin dependent kinase inhibitors in malignant astrocytomas.

The cyclin-dependent kinase inhibitors p16, p21, and p27 in human brain, and brain tumors were examined to explore clinicopathologic correlations. Western analysis and immunohistochemistry was performed and correlated retrospectively with the patients clinical characteristics. A trend was found between increased progression-free survival and p27 expression. There was no correlation between p27 expression and age or gender. The expression of p27 in malignant gliomas may have prognostic value. In addition, an investigation of the therapeutic benefit of overexpression of this cyclin-dependent kinase inhibitor is warranted given reports of diminished malignant potential of tumors expressing p27.

Adolescent↗
PubMed1998

T1-selective diffusion weighted fMRI at 1.5T.

Apparent diffusion coefficients (ADC) of protons contributing to the functional signal can be determined from diffusion weighted functional magnetic resonance imaging (MRI) studies. An earlier study indicated that ADCs calculated from the functional signal of an activated primary sensorimotor cortex are large, and consistent with a CSF or intravascular contribution to the functional signal. We have added inversion recovery pulses to isotropic diffusion weighted imaging to null CSF protons selectively within the imaging slice, or to null the outer volume blood flowing into the imaging slice. With the use of gradient recalled diffusion weighted echo-planar imaging at low gradient b factors, and without the use of inversion pulses, the ADCs x 10(3) in mm2/s (+/- SD) from the functional signal were 6.81 +/- 1.19. These ADCs were significantly higher than resting primary sensorimotor cortex ADCs of 2.26 +/- 1.49, measured at the same b factors. When CSF nulling was applied, the functional signal ADCs remained high. Application of inflow nulling decreased the functional signal to such a small value, that ADCs estimated from these functional signals were not assessed. The results are consistent with an intravascular contribution to the functional signal and to its large ADC.

Adult↗
PubMed1998

Thymic dysfunction and time of infection predict mortality in human immunodeficiency virus-infected infants. CDC Perinatal AIDS Collaborative Transmission Study Group.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

CD4 Lymphocyte Count↗
PubMed1998

Gene amplification as a prognostic factor in primary brain tumors.

The most reliable prognostic factors for patients with primary malignant brain tumors remain histology, age, and functional status. Management of these individuals might be improved by quantifying pertinent molecular markers. We have measured the gene dosage of the epidermal growth factor receptor (EGFR), mouse double minute 2 (MDM2), and cyclin-dependent kinase 4 (CDK4) genes in a series of brain tumor specimens and correlated their amplification status with standard prognostic factors and survival. Individual tumor DNA was successively hybridized with probes for EGFR, MDM2, and CDK4. The signal was quantified by densitometry, and amplification was defined as gene signal > or = 2 times normal. Survival, age, Karnofsky performance status, and histology were correlated with gene amplification. Nineteen astrocytomas, 20 anaplastic astrocytomas, and 70 glioblastomas had complete data available. Median survival with and without any form of gene amplification was 70.7 and 88.6 weeks, respectively (P = 0.0369). For the EGFR gene alone, those with and without amplification had a median survival of 58.9 and 88.6 weeks, respectively (P = 0.0104). By Cox analysis, only tumor histology (P = 0.04) and Karnofsky performance status (P = 0.0157) were significant independent predictors of survival. Gene amplification by itself was not predictive of survival, even for glioblastomas (P = 0.8249). The lack of correlation between gene amplification and survival for patients with primary malignant brain tumors may be because EGFR, MDM2, and CDK4 are only portions of larger signaling systems. Therefore, the lack of a direct correlation between a single gene and outcome is not entirely unexpected.

Adult↗
PubMed1997

Experimental peri-implantitis in consecutively placed, loaded root-form and plate-form implants in adult Macaca mulatta monkeys.

This study is part of an on-going project describing the character of round- and plate-form implants placed in a primate model. In this paper 20 loaded plate-form and 23 root-form implants were connected to prostheses and experimental peri-implantitis was induced by ceasing scaling procedures and placing braided silk ligature around the implants. Twenty-four prostheses utilizing natural teeth were studied for comparison. Clinical measurements were carried out monthly for 6 months and radiographic measurements at 3 and 6 months post-ligature placement and cessation of scaling. Both root-form implants and plate-form implants showed a significant loss of crestal bone height at 3 and 6 months after ligature placement (P < .001 after 6 months). The difference in bone loss between plate- and root-form implants, however, was not significant.

Alveolar Bone Loss↗
PubMed1997

A prospective characterization of upper gastrointestinal hemorrhage presenting with hematochezia.

BACKGROUND: Although hematochezia is well recognized to occur in patients with upper GI hemorrhage (UGIH), its prevalence, clinical presentation, causes, and outcome in these patients are not well defined. METHODS: Consecutive patients evaluated for UGIH by the gastroenterology service at a large inner city hospital from August 1, 1990, through September 31, 1994, were prospectively identified. Vital signs and stool color were recorded on admission to the emergency department. Endoscopy was performed in all patients, usually within 48 h of admission. The cause of bleeding was determined by endoscopy, surgery, or autopsy. RESULTS: Over the 50-month study period, 727 patients with UGIH meeting the inclusion criteria were evaluated, with 104 (14%) presenting with hematochezia (18 with bright red blood and 86 with maroon blood). The most common causes of bleeding were duodenal ulcer (44%) and gastric ulcer (20%). In comparison with patients with melena (N = 441), patients with hematochezia were older (55 vs 50 yr, p < 0.01) and more likely to present with duodenal ulcer bleeding (43 vs 25%, p < 0.01); no differences in vital signs, including prevalence of shock, or admission Hb concentration were found. However, transfusion requirements (5.4 vs 4.0 units, p = 0.01), need for surgery (11.7 vs 5.7%, p = 0.03), and mortality (13.6 vs 7.5%, p = 0.05) were significantly higher in patients with hematochezia than in those with melena, suggesting more severe bleeding and a worse outcome. CONCLUSIONS: Hematochezia is common in patients with UGIH, and the presenting features are similar to those of patients with melena. Duodenal ulcer is the most common cause of bleeding associated with hematochezia. Patients with UGIH and hematochezia seem to have a worse prognosis.

Adolescent↗
PubMed1996

Chronic unexplained diarrhea in human immunodeficiency virus infection: determination of the best diagnostic approach.

BACKGROUND & AIMS: Chronic unexplained diarrhea is a common complication of human immunodeficiency virus infection, although the best diagnostic approach is unknown. The purpose of our study was to evaluate the clinical use of endoscopy for the evaluation of this problem. METHODS: Patients infected with human immunodeficiency virus with chronic unexplained diarrhea underwent upper endoscopy to the jejunum followed by colonoscopy. RESULTS: Forty-eight patients were evaluated. A potential cause of diarrhea was found in 21 patients (44%; 95% confidence interval, 30%-58%). Colonoscopy with biopsy identified an etiology in 13 patients, including cytomegalovirus colitis alone in 9. In all but 1 patient with colonic disease, the diagnosis was made by biopsy of the rectosigmoid colon. Upper endoscopy with biopsy identified microsporidiosis in 7 patients and cryptosporidiosis in 2 patients. Logistic regression analysis identified weight loss and duration of diarrhea (P < 0.001) as the only independent predictors for diagnosis. No patient without weight loss and a CD4 lymphocyte count of > 100/mm3 had a diagnosis established. Of the 25 patients without a diagnosis in whom long-term follow-up was available, improvement or spontaneous resolution of diarrhea occurred in 9 (38%). CONCLUSIONS: Clinical parameters are helpful in predicting which patients may benefit from endoscopic examination.

Adult↗
PubMed1996

Analysis of consecutively placed loaded root-form and plate-form implants in adult Macaca mulatta monkeys.

The present paper describes 36 consecutively treated non-human primates (Macaca mulatta) as part of a balanced block design study to examine osseointegration in root- and plate-form implants prepared by atraumatic preparation of bone. Clinical measurements around selected teeth and digital radiology were utilized to monitor periodontal disease and bone loss around root- and plate-form implants which were loaded with a fixed prosthesis. Results indicate that once monthly regimen of scaling and root planing can prevent attachment loss in natural teeth, serving as abutments of loaded bridges. Root-form implants exhibited a significant loss of crestal bone height during the first year (P < 0.03) while plate-form implants showed less loss in bone height. There was an increase in bone mass over time for root-form or plate-form implants. Both root-form and plate-form implants provided radiographic evidence of osseointegration in loaded bridges.

Alveolar Bone Loss↗
PubMed1996

Upper gastrointestinal bleeding in patients with chronic renal failure: role of vascular ectasia.

OBJECTIVES: The role of vascular ectasia (VE) as a cause of bleeding in the upper GI tract (UGIB) in patients with chronic renal failure (CRF) is controversial. We evaluated the prevalence VE as a cause of UGIB in patients with CRF and examined factors associated with its presence. METHODS: Over a 50-month period (from August 1, 1990, to September 30, 1994) all patients with UGIB evaluated by our gastroenterology consultative service at a large inner city hospital were prospectively identified. CRF was defined as a serum creatinine concentration > or = 2 mg/dl for the 6 months before and after the bleeding episode. Endoscopy was performed in all patients, usually within 48 h of admission. VE was considered causative if the typical endoscopic features were observed in the absence of other potential bleeding sources. RESULTS: Of the 727 patients with UGIB undergoing endoscopy, 60 (8%) had CRF. The mean age of these patients was 61 +/- 15 yr, and the mean serum creatinine concentration was 5.6 mg/dl (range, 2-29.4 mg/dl). Hypertension and diabetes mellitus were the most common causes of renal failure. Gastric ulcer (37%) and duodenal (23%) ulcer were the most frequently identified causes of UGIB, followed by VE in eight patients (13%). VE was significantly more common in patients with CRF (13 vs 1.3%, p < 0.01). The prevalence of VE as a cause of UGIB was related to duration of renal failure (p = 0.004) and need for hemodialysis (p < 0.0001). VE was also the most frequent cause of recurrent bleeding in these patients. CONCLUSIONS: The most common cause of UGIB in patients with CRF is peptic ulcer disease. VE is more frequent in patients with CRF than in those with normal renal function, and its prevalence seems to be related to the duration and severity of renal disease.

Angiodysplasia↗
PubMed1994

Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease.

A prospective, randomized, controlled clinical trial in patients with coronary artery disease (CAD) and a concurrent physical disability evaluated the effects of a home exercise training program on cardiovascular function and blood lipids. Eighty-eight men between the ages of 42 and 72 years (mean 62) with documented CAD and a physical disability with functional use of > or = 2 extremities including 1 arm were randomized to either a 6-month home exercise training program using wheelchair ergometry or to a control group that received usual and customary care. Both groups received dietary instructions and were requested to follow a fat-controlled diet. Exercise test variables with echocardiography and blood lipids were measured at baseline and at 6 months. The home exercise training group significantly improved both peak exercise left ventricular ejection fraction (p = 0.007) and fractional shortening (p = 0.01) between baseline to 6 months, whereas the control group showed no significant changes. Exercise training effects of decreased resting heart rate (p = 0.03) and decreased peak rate pressure product (p = 0.03) were also found in the treatment group. No exercise-related cardiac complications occurred. Both groups significantly (p < or = 0.01) increased high-density lipoprotein cholesterol levels. These results indicate that physically disabled men with CAD can safely participate in a home exercise training program which may result in intrinsic cardiac benefits. The metabolic cost of activities of daily living imposed on this disabled population may also have a positive effect on high-density lipoprotein cholesterol levels.

Adult↗
PubMed1994

Striking prevalence of over-the-counter nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a well-established cause of gastrointestinal disease. There appears to be an association with peptic ulcer disease complications, specifically ulcer-related bleeding. Studies addressing this relationship have primarily evaluated prescription use of these agents. There has been little study of over-the-counter NSAID use in patients with either ulcer or nonulcer-related upper gastrointestinal hemorrhage. METHODS: Consecutive patients with upper gastrointestinal hemorrhage evaluated by a gastroenterology consultative service at a large inner-city hospital from August 1, 1990 to July 31, 1992 were identified. The use of any prescription or over-the-counter NSAID during the week before admission was prospectively assessed. Computerized pharmacy records were available for confirmation of prescription drug use. RESULTS: During the 2-year period of study, 421 patients were evaluated for upper gastrointestinal hemorrhage. The mean age of the patients was 50 years and the majority were male and black. The most common cause of bleeding was peptic ulcer disease, identified in over 50% of patients. Use of an over-the-counter aspirin or nonaspirin NSAID was reported in 145 patients (35%) and 36 patients (9%), respectively, during the week before admission. Prescription use of a nonaspirin NSAID or aspirin was reported in 56 patients (14%) and 27 patients (6%), respectively. The overall prevalence of NSAID use during the week before admission was 56% (95% confidence interval, 51.2% to 60.8%). The use of any NSAID was significantly associated with gastric compared with duodenal ulcer hemorrhage, and ulcer-related bleeding compared with variceal hemorrhage. CONCLUSIONS: Over-the-counter NSAID use is frequent in our patient population and exceeds prescription use. Although ulcer-related bleeding was significantly associated with use of these drugs, NSAIDs were commonly used in patients with nonulcer-related upper gastrointestinal hemorrhage as well. Over-the-counter NSAID use may represent a more important cause of peptic ulcer disease and ulcer-related hemorrhage than previously appreciated.

Adult↗
PubMed1994

A multi-center analysis of the use of enalapril and lisinopril in elderly hypertensive patients.

OBJECTIVE: To evaluate the clinical use and adverse effects of enalapril and lisinopril in elderly hypertensive subjects. DESIGN: A multi-center, retrospective, drug use evaluation survey. SETTING: Ambulatory care clinics at 14 VA and 14 academic medical centers. PATIENTS: 422 elderly (> 60 years of age) patients with hypertension and no clinical evidence of congestive heart failure. INTERVENTION: At least 3 consecutive months of anti-hypertensive therapy with either enalapril or lisinopril. MEASUREMENTS: Blood pressure, serum creatinine, serum potassium, concomitant disease states, concurrent medications, and documentation of any adverse event that might be related to ACE inhibitor therapy. RESULTS: There were no significant differences in systolic and diastolic blood pressures, serum creatinine, or serum potassium between enalapril- and lisinopril-treated patients at baseline and after 3 months of therapy. Both treatments resulted in a significant reduction in diastolic blood pressure. There was no significant difference in the incidence of adverse effects between the two treatments. Significantly more patients were dosed on a twice daily regimen of enalapril than lisinopril. CONCLUSION: The data from this retrospective study confirm the safe and effective use of enalapril and lisinopril, two long-acting ACE inhibitors, in elderly hypertensive patients.

Age Factors↗
PubMed1991

The incidence of meconium-stained amniotic fluid from 1980 through 1986, by year and gestational age.

The annual incidence of meconium-stained amniotic fluid was analyzed for changes in a total obstetric sample of 45,115 singleton, vertex, liveborn infants over a 7-year study period. The incidence of meconium-stained amniotic fluid for the total obstetric population was calculated for each year of the study period. The sample was then stratified by estimated gestational age, and the incidence of meconium-stained amniotic fluid was calculated for each gestational age group. The incidence of meconium-stained amniotic fluid increased 40.9% over the study period, from 18.8% in 1980 to 26.5% in 1986 (P less than .001). This increase was found to be in a consistent linear trend (P less than .05). The incidence of meconium-stained amniotic fluid was also found to increase significantly in a linear trend as gestational age of the fetus increased. These findings lend support to both the maturational theory and the stress theory of meconium passage in utero.

Amniotic Fluid↗