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Biomedical subjects

T O'Leary

Publications and source records attributed to T O'Leary.

At least 19 recordsLinked to original sources

Pap smear screening in an equal-access health care system. Yield of screening and predictors of squamous intraepithelial lesions and atypical squamous cells of undetermined significance.

PURPOSE: The purpose of this study was to examine predictors of squamous intraepithelial lesions (SIL) and atypical squamous cells of undetermined significance (ASCUS) in an equal access health care setting.METHODS: A cohort of 10,713 active-duty United States Air Force women who provided one cervical/vaginal smear (CVS) as part of routine medical care between January 1, 1994 and December 31, 1996 were selected for this study. Each of the specimens was characterized by a "Bethesda System" diagnosis: within normal limits, repair/reactive, ASCUS, low grade SIL, high grade SIL, invasive carcinoma, infectious disease or unsatisfactory.RESULTS: Significant disease was associated with age younger than 30 years, enlisted rank, Hispanic ethnicity and the presence of genital warts on examination. SIL was associated with age 21-25 and Hispanic ethnicity in the logistic regression model. A diagnosis of ASCUS was associated with age younger than 30, marital status as single/never married, presence of genital warts on physical examination, and a history of previous abnormal CVS since entering military service. Age younger than 30, a marital status of single/never married and a previous abnormal CVS were associated with ASCUS in the logistic regression model.CONCLUSIONS: The disparity noted between women of low and high socioeconomic status was not seen here; those with the lowest income and education were not significantly more likely to have SIL or ASCUS when age was considered in the model. The significant association between Hispanic ethnicity and SIL, which should be further explored, may indicate the need for increased screening in this population.

Journal Article↗

The environmental response of Middle Ordovician large organic walled microfossils from the Goldwyer and Nita Formations, Canning Basin, Western Australia.

Middle Ordovician large organic walled microfossils (chitinozoans, scolecodonts, hydrozoans and foraminiferal linings) were recovered from the upper Goldwyer and lower Nita formations, Canning Basin, Western Australia, from three cores (WMC Santalum 1A, Kunzea 1 and Acacia 2). Petrophysical logs of these cores reveal an overall upward shallowing supersequence, overprinted by numerous transgression/regression couplets that can be correlated over 100km.Analysis of the abundance of the microfossils with respect to the gamma log signatures reveals that both chitinozoan abundance and diversity decrease as water depth shallows; however, the opposite is not always true and other factors probably intervene. Scolecodonts show an increase in abundance in transgressions, while hydrozoans and foraminiferal linings show no consistent response to trangressive or regressive phases. Cyathochitina hunderumensis tends to dominate chitinozoan assemblages where there is a transgression, while species of Belonechitina replace Cy. hunderumensis in regressive phases.

Journal Article↗

Loss of heterozygosity at 1p36 predicts poor prognosis in gastrointestinal stromal/smooth muscle tumors.

Gastrointestinal stromal/smooth muscle tumors are uncommon neoplasms for which current criteria for diagnosing malignancy (size and mitotic index) sometimes fail to predict outcome. Cytogenetic studies reveal frequent chromosome 1 abnormalities in these tumors, but significant underlying molecular changes have not been elucidated, and their significance is unknown. DNA was obtained from the formalin-fixed, paraffin-embedded tissue of 80 gastrointestinal stromal/smooth muscle tumors. Tumors were topographically microdissected from surrounding normal tissue; microsatellite markers from tumor and normal tissue were amplified by PCR in the regions of chromosome 1p36 (D1S199, D1S228, D1S450, D1S214, D1S243), 1p12 (D1S418),1p13 (D1S252, D1S514), and 1q32(D1S103). The presence or absence of heterozygosity for each case was mapped at each informative marker. Relationships among loss of heterozygosity (LOH), tumor size, mitotic index, and survival were investigated using correlation analysis, Kaplan-Meier plots, and the Cox model. LOH at 1p36 was found in 24 of 80 cases, suggesting the possibility of a tumor suppressor gene at 1 p36 near the site of a suspected neuroblastoma tumor suppressor gene. Patients whose tumors demonstrated LOH at 1 p36 had significantly shorter survival (p = 0.017) than those whose tumors did not. LOH at 1 p36 retained independent prognostic significance in a multivariate model that included KIT mutation status and tumor size; the mitotic index, however, did not retain independent significance in such a model. LOH was observed at 1 p12-1p13 (most frequently at 1p13.3) in 19 of 80 cases, but loss of heterozygosity at this site did not influence survival. No LOH was observed near 1q32. These findings provide strong evidence for a prognostically significant tumor suppressor gene in the region of chromosome 1p36.3.

Base Sequence↗

Sensitivity of cross-reacting antihuman antibodies in formalin-fixed porcine skin: including antibodies to proliferation antigens and cytokeratins with specificity in the skin.

Although no animal is a perfect skin model for the study of toxicological and therapeutic agents, structurally the pig may be superior to even non-human primates. Because our work involves effects of toxicological and therapeutic agents on the skin, we wanted to identify stains which may prove useful as well as determine cross-reactivity of some newer antihuman antibodies. We performed a battery of formalin-fixed skin from weanling pigs and minipigs. The battery of antibodies included LCA, CD3, OPD-4, CD34, UCHL-1, L-26, KP-1, MAC-387, Factor XIIIa, Leu-7, S-100 protein, HMB-45, GFAP, synaptophysin, neurofilament protein, ubiquitin, vimentin, type IV collagen, laminin, fibronectin, Factor VIII related antigen, Desmin-M, smooth muscle actin, cytokeratin 7, cytokeratin 20, AEI/AE3, CAM 5.2, EMA, GCDFP, Ki-67, and PCNA. Immunohistochemical stains for CD3, Leu-7, S-100 protein, type IV collagen, laminin, Factor VIII related antigen, GFAP, synaptophysin, neurofilament protein, ubiquitin, smooth muscle actin, vimentin, Desmin-M, cytokeratin 7, cytokeratin 20, AE1/AE3, CAM 5.2, Ki-67 and PCNA showed consistent cross-reactivity. In formalin-fixed tissue, only antibodies to lymphoreticular cells showed poor cross-reactivity. A high percentage of the remaining antibodies did show good cross-reactivity but with some interesting similarities and differences in specificity.

Animals↗

Evaluation of cross-reacting anti-human antibodies in the euthymic hairless guinea pig model (HGP) suggests that the HGP may be a model for the study of proliferative skin disease.

Animal models have an important role in cutaneous research. The guinea pig has proven to be a useful model in a wide spectrum of these cutaneous studies; however, its usefulness is often compromised by the need for depilation. A euthymic hairless guinea pig (HGP) model avoids the problems associated with depilation. Morphologically, as in human skin, these animals have a multi-cell-layer epidermis. Proliferation kinetic studies, as well as documentation of the degree of immunologic cross-reactivity between available antibodies to human cutaneous antigens, could extend the usefulness of this animal model. We performed a battery of anti-human antibodies on formalin fixed tissue, to a variety of antigens present within the skin and on inflammatory cells. These included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin, collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of antibodies is limited, the markedly increased staining of Ki-67 and PCNA within keratinocytes in the epidermis as compared to normal human skin reflects a high proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may be useful in studying effects on cell cycle kinetics and apoptosis.

Actins↗

Pulmonary blastomas.

Pulmonary blastoma is a rare lung tumor composed of immature mesenchyme and/or epithelium that morphologically mimics embryonal pulmonary structure. The prognosis of these tumors is poor, and the clinical course is not readily predicted from histologic appearance. In this report, the clinical, gross, microscopic, and immunopathologic features of 52 cases are described, and prognostically important correlates are determined. Twenty-eight patients were women, and 24 were men. There was a unimodal age peak in the fourth decade; only two patients were younger than 10 years old, and both had biphasic blastomas. Forty-one percent of patients were asymptomatic. Chest radiography typically showed a peripheral or midlung mass without predilection for any lobe. Microscopically, tumors could be divided into two classes: those composed solely of malignant glands of embryonal appearance (well-differentiated fetal adenocarcinomas [WDFA], 28 cases) and those with a biphasic appearance (24 cases). The malignant epithelium contained cytokeratin, carcinoembryonic antigen, milk fat globulin, and often chromogranin; vimentin, actin, and less frequently desmin and myoglobin were present in malignant stromal cells. More often WDFA was a smaller tumor (less than 5 cm) than biphasic tumors (P less than or equal to 0.001). It was more likely to be asymptomatic (P less than or equal to 0.001), and it was less likely to show pleural effusion by chest radiography (P less than or equal to 0.01) or giant or bizarre tumor cells (P less than or equal to 0.001) or frequent (greater than or equal to 30 mitoses/10 high-power fields) mitoses in the microscopic sections (P less than or equal to 0.01). Only 14% of patients with WDFA died of their tumor; 52% of patients with biphasic tumors died (mean follow-up, 97 months and 49 months, respectively). For patients with WDFA, the presence of thoracic adenopathy by chest radiography (P less than or equal to 0.001) and metastasis at initial presentation (P less than or equal to 0.001), followed by tumor recurrence (P less than or equal to 0.01), were the factors most highly correlated with poor prognosis. For patients with biphasic tumors, tumor recurrence (P less than or equal to 0.001) was the most significant indicator of poor prognosis, followed by metastasis at initial presentation (P less than or equal to 0.05) and gross size of the tumor (greater than or equal to 5 cm) (P less than or equal to 0.05). These findings support the idea that histologic class and gross and clinical findings can be of prognostic value in pulmonary blastoma.

Actuarial Analysis↗

The relationship between psychosocial factors and breast cancer: some unexpected results.

A growing body of research suggests a link between psychosocial factors and breast cancer. Research in this area often contains methodological problems, however, such as small sample size, inadequate comparison groups, omission of important control variables, inclusion of only a few psychosocial variables, and failure to analyze moderating effects. To overcome these problems, the present study examined the link between breast cancer and multiple psychosocial variables (life events, coping, Type A behavior pattern, availability of social support) among 1,052 women with and without breast cancer. After controlling for history of breast cancer and age, we found very few significant relationships between psychosocial variables and breast cancer. Furthermore, the relationship between life events and breast cancer was not moderated by coping, Type A, or availability of social support. Methodological and substantive reasons for these findings are discussed.

Adaptation, Psychological↗

Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome.

The prevalence of myocarditis was retrospectively evaluated in 71 consecutive necropsy patients who died from acquired immunodeficiency syndrome (AIDS) between 1982 and 1986. Myocarditis was found in 37 cases (52%). Biventricular dilation at necropsy was present in seven cases (10%) and was accompanied by myocarditis in each case; fatal congestive heart failure occurred in four of these seven cases. Although viral, protozoan, bacterial, fungal and mycobacterial opportunistic pathogens were present in myocardial sections of 7 of 37 myocarditis cases, the etiology of myocarditis in the majority of these patients with AIDS remained idiopathic. Thus, myocarditis is a frequent finding at necropsy in patients with AIDS and may contribute to the development of biventricular dilation.

Acquired Immunodeficiency Syndrome↗

Evaluation of single-drug and combination antifungal therapy in an experimental model of candidiasis in rabbits with prolonged neutropenia.

We developed an experimental model of candidiasis in rabbits with prolonged neutropenia. Rabbits were made neutropenic with cytosine arabinoside (Ara-C) administered through an indwelling silastic catheter that had been surgically implanted in the external jugular vein. Neutropenia was sustained with intravenous Ara-C, and bacterial complications were prevented with parenteral ceftazidime plus ampicillin. Candidiasis was established by intravenously administering Candida albicans or Candida tropicalis (1-2 x 10(5) colony-forming units) and resulted in hepatic and splenic lesions that mimicked those associated with hepatosplenic candidiasis in humans. The kidney proved to be the site most refractory to eradication of Candida spp. and offered a target organ for assessing antifungal therapy. We evaluated amphotericin B, 5-flucytosine, ketoconazole, and rifampin, alone and in combination. Although each agent reduced the colony counts of Candida in the liver, spleen, and lung, the combination of amphotericin B and 5-flucytosine was the only regimen effective in eradicating renal candidiasis.

Agranulocytosis↗

Hepatosplenic candidiasis: wheels within wheels.

Eight immunocompromised cancer patients with tissue-proved candidiasis underwent serial abdominal ultrasound (US) and computed tomography (CT). At US, four patterns of hepatic and splenic candidiasis were recognized, one of which the authors call a "wheels-within-wheels" pattern. In addition, periportal linear areas of increased attenuation, possibly calcified, were identified at follow-up, nonenhanced CT. Some abscesses were better seen on nonenhanced CT scans, while others became visible only with enhancement. Although lesions not seen at US were often seen at CT, the opposite was also true. In two cases, pathologic proof of candidiasis was established even when all imaging studies were normal. For maximum imaging sensitivity, patients should be studied with US and nonenhanced and enhanced CT. Even when both US and CT scans are negative, if there is a strong clinical suggestion of candidiasis, open biopsy is recommended.

Abscess↗

Hepatic candidiasis in cancer patients: the evolving picture of the syndrome.

Focal hepatosplenic candidiasis has been recognized with increasing frequency in recent years. We reviewed the cases of eight patients seen between 1982 and 1985, and information on 60 patients whose cases have been reported in the world literature. The characteristics of focal hepatosplenic candidiasis include persistent fever in a neutropenic patient whose leukocyte count is returning to normal, often coupled with abdominal pain; an elevated alkaline phosphatase level; and less commonly, rebound leukocytosis. The characteristic "bull's eye" lesions seen with hepatic ultrasound examination or computed tomography generally are not detectable until neutrophil recovery has occurred. Diagnosis can be established only by biopsy evidence of yeasts or pseudohyphae in the granulomatous lesions. Cultures are frequently negative, however, especially in patients who have been pretreated with antifungal agents. We review the evolving nature of hepatosplenic candidiasis, focusing on diagnosis and treatment.

Adolescent↗

Synthesis and evaluation of a miniature organic model of chymotrypsin.

An artificial chymotrypsin, with all the features of the real chymotrypsin, namely a binding site (from cyclodextrin) attached to a catalytic site containing an imidazolyl group, a carboxylate group and a hydroxyl group, has been synthesized. This artificial chymotrypsin has a molecular weight of only 1,365 while the real enzyme has a molecular weight of 24,800. However, from preliminary measurements, both the real and artificial enzymes have approximately the same catalytic activity (both rate and binding constants).

Chymotrypsin↗

Experimental evaluation of five liver-spleen specific CT contrast agents.

We tested five experimental liver-spleen specific computed tomography (CT) contrast agents, all of which are aqueous emulsions of iodinated vegetable oils. These compounds were compared with ethiodized oil emulsion 13 (EOE-13) and with a 5% dextrose in water control. We evaluated three animal/dose level models with both histology and CT to determine the best screening method for compounds of this type. We compared a rat/high dose model, a rat/medium dose model, and a rabbit/low dose model; the best discrimination was seen with the rabbit/low dose model. Histology of liver, spleen, and lung did not correlate with the attenuation values obtained from CT. We conclude that use of CT and a rabbit/low dose model is superior for screening compounds of this type. Of the compounds tested, only one, an emulsion of ethyl monoiodostearate (compound 208E), approached the effectiveness of EOE-13.

Animals↗

Liposarcoma of the lower extremity.

Twenty patients with primary liposarcoma of the lower extremity were treated over a 25-year period. The adequacy of the initial surgical procedure and histological grade of malignancy both influenced survival rates. In addition local recurrence was noted only in patients who had undergone "inadequate" initial excision. Inguinal lymph nodes were uninvolved by tumor in all cases. In general, patients with liposarcomas of myxoid and/or round cell type survived for long periods of time. However, even patients with myxoid lesions occasionally exhibited evidence of early blood-borne metastases. This study suggests an important relationship between an inadequate primary resection, local recurrence, and eventual retroperitoneal spread. In the majority of cases, this may have resulted from failure to control the primary distal extremity tumor, with subsequent contiguous spread of metastases into the ipsilateral retroperitoneal space. If feasible, radical soft part resection should be performed as the primary surgical therapy of these neoplasms. Tumors contiguous to the knee or ankle joint should be treated by primary amputation. Failure to control local disease may result in blood-borne dissemination or local spread along musculoaponeurotic planes to involve proximal groin or retroperitoneal space.

Histiocytoma, Benign Fibrous↗