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S M O'Hara

Publications and source records attributed to S M O'Hara.

At least 19 recordsLinked to original sources
PubMed2005

Preliminary study of immunomagnetic quantification of circulating tumor cells in patients with advanced disease.

OBJECTIVES: To enumerate the amount of circulating tumor cells (CTCs) in patients with advanced prostate cancer and to investigate the relationship between these numbers, prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) expression, and clinical parameters. METHODS: Whole blood was collected in proprietary CellSave tubes. Mononuclear cell fractions were isolated using epithelial cell antibody-coated magnetic nanoparticles. On one half of each immunomagnetically enriched cell fraction, automated fluorescent microscopy was used to identify the epithelial tumor cells. From the remainder of each sample, RNA extraction, cDNA synthesis, and polymerase chain reaction amplification of PSA and PSM were performed. RESULTS: Eighty-four patients with advanced prostate cancer submitted 130 samples for analysis. Intact CTCs were identified in 62% of samples; 83.3% of CTC-positive and 0% of CTC-negative samples were reverse transcriptase-polymerase chain reaction positive for PSA and PSM (P = 0.001). A significant positive correlation was found between the CTC number and PSA (r = 0.49), alkaline phosphatase (r = 0.47), and lactate dehydrogenase (r = 0.55) levels, and a significant negative correlation with hemoglobin (r = -0.35). The initial Gleason grade, prior therapy, current therapy, and type of metastasis (bone, soft tissue) did not correlate significantly with the CTC number. CONCLUSIONS: The presence of intact CTCs and the expression of PSA and PSM demonstrated robust agreement. The tumor cell numbers reflected current disease status and correlated significantly with the clinical disease indicators of PSA, hemoglobin, and liver function tests. These findings warrant further investigation of the diagnostic and prognostic value of enumerating intact CTCs.

Adult↗
PubMed2001

Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status.

OBJECTIVES: To investigate the diurnal variations in circulating tumor cells (CTCs) in metastatic carcinoma of the prostate (CAP) and to determine whether the change in CTCs correlated with disease progression. METHODS: Samples were prepared by immunomagnetic selection of cells from 7 mL of blood targeting the epithelial cell adhesion molecule and differential fluorescent labeling of the collected cells using a nucleic acid dye, antibodies directed against the common leukocyte (CD45), and cytokeratin antigens. Events that stained with the nucleic acid dye and expressed cytokeratin but lacked CD45 were defined as CTCs by multiparameter flow cytometry. RESULTS: Male controls (n = 22) exhibited 0.8 +/- 1.2 events per 7 mL blood compared with 5.9 +/- 4.7 in 10 samples from patients with localized CAP and 46.6 +/- 65.6 events in 10 samples from patients with metastatic CAP. Diurnal testing of 8 cases demonstrated stable levels of CTCs. Ten patients were serially analyzed during a 6-month period for serum prostate-specific antigen and CTCs. The correlation between the prostate-specific antigen level and CTC number was fair. Slow disease progression was found in 4 patients with low CTC numbers (3.0 +/- 3) but it was significantly higher than the control group (P <0.002). Rapid disease progression occurred in 6 patients who demonstrated high CTC numbers (68.5 +/- 71.9). Two patients received chemotherapy that caused substantial fluctuations in the CTCs with less pronounced changes in the prostate-specific antigen level. CONCLUSIONS: We conclude that the level of CTCs can be quantified in the circulation of patients with metastatic CAP and that the change in CTCs correlates with disease progression with no diurnal variations.

Aged↗
PubMed1999

Anterior chest wall: frequency of anatomic variations in children.

PURPOSE: To evaluate the frequency of anterior chest wall variations in children. MATERIALS AND METHODS: The computed tomographic (CT) images of 200 consecutive infants and children (114 boys and 86 girls; mean age, 10.5 years; age range, 3 months to 19 years) who underwent chest CT during a 20-month period were evaluated for chest wall variations. Children who had undergone chest wall surgery or were suspected of having a chest wall abnormality were excluded. The frequency of chest wall anomalies was compared with age and sex (Fisher exact test). RESULTS: The CT scans of 65 children (33%) depicted one or more variations in the anterior chest wall: titled sternum (n = 29), prominent convexity of anterior rib or costal cartilage (n = 19), prominent asymmetric costal cartilage (n = 20), well-defined paracostal subcutaneous nodule (n = 4), mild pectus excavatum (n = 4), or mild pectus carinatum (n = 4). The frequency of these findings did not vary significantly with age (P = .96) or sex (P = .36). CONCLUSION: Variations in the anterior chest wall are common, occurring in one-third of children, and should be considered normal. These asymptomatic variations should not be considered alarming when palpated at physical examination.

Adolescent↗
PubMed1999

Gastric retention of zinc-based pennies: radiographic appearance and hazards.

PURPOSE: To determine the radiographic appearance and features of corrosion in U.S. coins exposed to gastric acid. MATERIALS AND METHODS: Six U.S. copper-based pre-1982 pennies, 12 zinc-based post-1982 pennies, a quarter, a nickel, and a dime were exposed to postprandial concentrations of gastric acid (0.15N HCl) for 7 days, and radiographs were obtained daily. Half the zinc-based coins were scraped to disrupt their copper coating. Coins were weighed at the start and completion of the study. RESULTS: Post-1982 zinc-based pennies developed radiolucent corrosive changes within 24 hours. Erosions on the coins became more apparent over time. Frank holes were present on day 2. The weights of these coins decreased 5%-8% during the study. Pre-1982 copper pennies and "silver-colored" coins showed no change on radiographs over 7 days. CONCLUSION: Unexpected radiolucent corrosions may develop in post-1982 zinc alloy pennies when retained in the stomach. Coins have long been considered innocuous foreign bodies in the gastrointestinal tracts of children. However, because of the potential for ulceration and zinc-related morbidity, closer clinical and radiographic observation is warranted. Coins with scalloped edges or holes should be endoscopically removed, as they have likely been retained longer than 1 or 2 days.

Child, Preschool↗
PubMed1999

Renal effects of uroguanylin and guanylin in vivo.

Uroguanylin and guanylin are newly discovered endogenous heat-stable peptides that bind to and activate a membrane bound guanylyl cyclase signaling receptor (termed guanylyl cyclase C; GC-C). These peptides are not only found in blood but are secreted into the lumen of the intestine and effect a net secretion of electrolytes (Na+, K+, Cl-, HCO3-) and fluid into the intestine via a cyclic guanosine-3', 5'-monophosphate (cGMP) mechanism. GC-C is also the receptor for Escherichia coli heat-stable enterotoxin (STa) and activation by STa results in a diarrheal illness. Employing mouse renal in vivo models, we have demonstrated that uroguanylin, guanylin, and STa elicit natriuretic, kaliuretic, and diuretic effects. These biological responses are time- and dose-dependent. Maximum natriuretic and kaliuretic effects are observed within 30-40 min following infusion with pharmacological doses of the peptides in a sealed-urethra mouse model. Our mouse renal clearance model confirms these results and shows significant natriuresis following a constant infusion of uroguanylin for 30 min, while the glomerular filtration rate, plasma creatinine, urine osmolality, heart rate, and blood pressure remain constant. These data suggest the peptides act through tubular transport mechanisms. Consistent with a tubular mechanism, messenger RNA-differential display PCR of kidney RNA extracted from vehicle- and uroguanylin-treated mice show the message for the Na+/K+ ATPase gamma-subunit is down-regulated. Interestingly, GC-C knockout mice (Gucy2c -/-) also exhibit significant uroguanylin-induced natriuresis and kaliuresis in vivo, suggesting the presence of an alternate receptor signaling mechanism in the kidney. Thus, uroguanylin and guanylin seem to serve as intestinal and renal natriuretic peptide-hormones influencing salt and water transport in the kidney through GC-C dependent and independent pathways. Furthermore, our recent clinical probe study has revealed a 70-fold increase in levels of urinary uroguanylin in patients with congestive heart failure. In conclusion, our studies support the concept that uroguanylin and guanylin are endogenous effector peptides involved in regulating body salt and water homeostasis.

Animals↗
PubMed1999

Intense contrast enhancement of the adrenal glands: another abdominal CT finding associated with hypoperfusion complex in children.

OBJECTIVE: A constellation of CT findings has been associated with posttraumatic shock in children. Findings include fluid-filled, dilated bowel; intense enhancement of bowel wall, mesentery, pancreas, kidneys, aorta, and inferior vena cava; and small caliber of aorta and inferior vena cava. The objective of this study is to describe an additional CT finding in the hypoperfusion complex: symmetric, intense contrast enhancement of the adrenal glands. CONCLUSION: Intense enhancement (as great as that of adjacent vascular structures) of normal-shaped adrenal glands occurs in association with hemodynamic instability in children. The presence of intense adrenal enhancement may provide additional evidence of hemodynamic instability and help differentiate it from direct bowel injury.

Adrenal Glands↗
PubMed1998

Necrotizing myofasciitis: an atypical cause of "acute abdomen" in an immunocompromised child.

We report the case of an immunocompromised 15-year-old boy who presented with symptoms mimicking an "acute abdomen" related to necrotizing myofasciitis of the anterior abdominal wall. CT demonstrated the abdominal wall process as the cause of the patient's symptoms and sonographically guided aspiration confirmed the diagnosis. Despite prompt diagnosis and aggressive surgical debridement, the infection continued to progress and the patient died within 24 h of presentation.

Abdomen, Acute↗
PubMed1998

Sonographic appearance of the bladder after endoscopic incision of ureteroceles.

OBJECTIVE: Our intent was to describe the range of postoperative sonographic appearances of the bladder after endoscopic incision of ureteroceles. CONCLUSION: Preoperative and postoperative sonographic examinations of the bladder were reviewed in 14 patients (15 ureteroceles) who underwent endoscopic ureterocele incision. Five different appearances of the ureterovesical junction after endoscopic incision were found: a pseudomass (5/15), focal mucosal thickening (3/15), residual ureterocele with decrease in size (3/15), persistent unchanged ureterocele (1/15), and no residual abnormality (3/15). The most common postoperative sonographic appearance associated with development of vesicoureteral reflux was a mucosal pseudomass (4/6). The other bladder sonographic appearances had no correlation with development of reflux, degree of hydronephrosis, or success of the surgery.

Child↗
PubMed1997

Transrectal ultrasound-guided biopsy causes hematogenous dissemination of prostate cells as determined by RT-PCR.

OBJECTIVES: To determine if transrectal ultrasound-guided (TRUS) prostate biopsy causes dissemination of prostate cells into the circulation as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) targeted against prostate-specific antigen (PSA) mRNA. METHODS: RT-PCR PSA analysis was performed before and after prostatic invasive manipulations in 50 men. The cases consisted of 47 patients with TRUS and 3 with transurethral resection of the prostate (TURP). Peripheral venous blood (8 mL) was drawn before and within 60 minutes after the procedure. Total RNA was extracted from fractionated blood, and RNA/cDNA quality was assured and normalized with beta-actin RT-PCR analysis. The PSA primers hybridize exons 3 and 5, yielding a 254-basepair PCR product. The assay detects one LNCaP cell in a background of 100 million lymphoid cells and a single copy of PSA cDNA on an ethidium bromide gel. RESULTS: Among the 47 TRUS cases, 43 specimens were evaluable. Forty-two cases were negative before biopsy; among these patients, 4 cases (9.5%) converted to a positive RT-PCR PSA result. Both benign and malignant TRUS biopsies were capable of producing a positive RT-PCR PSA signal implicating iatrogenic dissemination of cells. All three TURP cases converted from a negative to a highly intense positive signal. CONCLUSIONS: We conclude that a positive RT-PCR PSA signal may result from release of prostate cells into the peripheral circulation after a TRUS biopsy and TURP. TURP causes greater dissemination than TRUS. Based on these preliminary data, we recommend that future molecular staging studies should be based on blood specimens drawn before performance of TRUS biopsy. This may be an important mechanism of prostate cancer dissemination meriting further investigations.

Aged↗
PubMed1997

Development of monoclonal antibodies to the malondialdehyde-deoxyguanosine adduct, pyrimidopurinone.

Malondialdehyde (MDA), an endogenous product of lipid peroxidation and prostaglandin biosynthesis, is mutagenic in bacterial and mammalian cells and carcinogenic in rats. In order to determine whether MDA-modified bases are formed in nucleic acids in vivo, sensitive immunoassays to detect MDA-DNA and MDA-RNA adducts are being developed in our laboratory. Murine monoclonal antibodies reactive with the MDA-deoxyguanosine adduct 3-beta-D-erythro-pentofuranosylpyrimido[1,2-alpha]purin-10(3H)-one (M1G-R) were prepared and characterized. Several MDA-modified nucleosides and deoxynucleosides and structural analogs were synthesized and characterized and were compared as competitive inhibitors in enzyme-linked immunosorbent assays (ELISAs). Less than 5 fmol of M1G in MDA-modified DNA was detected in a direct ELISA, and antibody binding to the modified DNA was competitively inhibited by free M1G-dR. DNA from Salmonella typhimurium treated with concentrations of MDA that induce reversion to histidine prototrophy was enzymatically digested, and M1G-dR was quantitated by competitive ELISA. Over a range of MDA concentrations from 10 to 40 mM, the level of M1G residues in bacterial DNA increased from 0.2 to 2.5/10(6) base pairs.

Acrolein↗
PubMed1997

Acute gastrointestinal bleeding.

Diagnosis and intervention in pediatric GI bleeding is the shared responsibility of pediatric endoscopists, radiologists, and surgeons. Brisk hemorrhage, though alarming, is most often self-limited; few cases require urgent surgery before diagnostic evaluation is accomplished. The choice between endoscopic and radiographic evaluation varies with the differential diagnoses being considered and with local referral patterns. Many imaging options exist for assessing GI bleeding in children, but these options are generally narrowed by clinical history and age-appropriate differential possibilities.

Acute Disease↗