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Biomedical subjects

T J Fahey

Publications and source records attributed to T J Fahey.

At least 19 recordsLinked to original sources

Laparoscopic distal pancreatectomy for inflammatory pseudotumor of the pancreas.

An 82-year-old woman presented with abdominal pain, nausea, emesis, and weight loss of ~25 lb over 6 months. A CT scan and MRI of the abdomen revealed a mass in the tail of the pancreas that was suspicious for malignancy. The patient underwent successful laparoscopic distal pancreatectomy and was discharged home on the 4th postoperative day after an uneventful course. Pathology revealed an inflammatory pseudotumor of the pancreas (IPT). Pancreatic IPT is a rare entity, and this case represents the first report of laparoscopic resection of this lesion. The presentation, diagnosis, histologic features, and therapy of IPT of the pancreas are reviewed.

Aged↗

Hand-assisted laparoscopic autoaugmentation gastrocystoplasty.

BACKGROUND: Autoaugmentation gastrocystoplasty has been previously performed successfully. This set of experiments was conducted to determine the feasibility of performing autoaugmentation gastrocystoplasty laparoscopically. METHODS: Hand-assisted laparoscopic autoaugmentation gastrocystoplasty was performed on 15 mongrel dogs. The surgery was carried out with two 10-mm trocars and a 6-cm Pfannenstiel incision. The gastric wedge, supplied by the right gastroepiploic artery, was resected with two applications of an endoscopic gastrointestinal anastomosis (GIA) stapler. The pedicle was demucosalized, and the anastomosis to the bladder was completed through the Pfannenstiel incision. RESULTS: All of the dogs were successfully treated laparoscopically and were eating at 48 h. There was no evidence of anastomotic leak dehiscence at the gastric resection staple line. CONCLUSION: Hand-assisted laparoscopic autoaugmentation gastrocystoplasty can be performed successfully in dogs. This operation may offer a superior alternative to standard bladder autoaugmentation procedures in children suffering from congenital bladder disorders.

Animals↗

Hand-assisted demucosalized gastrocystoplasty comparing different tissue closure methods.

OBJECTIVES: To perform experiments to determine whether a new tissue sealant (SynthaSeal) could be an alternative for suture closure in minimally invasive bladder autoaugmentation gastrocystoplasty using demucosalized stomach. Alternative methods to suture closure for tissue approximation such as laser tissue welding and fibrin glue have been reported. METHODS: Minimally invasive autoaugmentation gastrocystoplasty with demucosalized stomach was performed on 14 female mongrel dogs. Two dogs were used to refine the technique. The remaining dogs were assigned to a suture group (n = 6) or a SynthaSeal group (n = 6). Anastomoses were performed using either SynthaSeal or suture. The in vivo bladder volumes and pressures of the groups were measured before and after gastrocystoplasty. The animals were studied on day 14. Samples of the anastomotic area were taken to measure the tensile strength and stress. Histologic analysis was conducted to assess tissue healing. The anastomotic time was recorded for each group. RESULTS: The tensile strength of the anastomoses in the SynthaSeal group was significantly increased (9.99 +/- 1.14 Newtons) compared with the suture group (5.66 +/- 0.97 Newtons) (P <0.05). The breaking stress comparisons and anastomosis times were equivalent between the two groups. The histologic evaluation revealed minor tissue devitalization and a normal inflammatory response in both groups. CONCLUSIONS: Minimally invasive gastrocystoplasty using demucosalized stomach can be successfully performed with SynthaSeal tissue sealant. This may provide a reliable alternative to suture closure.

Anastomosis, Surgical↗

Characterisitcs of patients having thyroid surgery under regional anesthesia.

BACKGROUND: Recently local/regional anesthesia has been reintroduced as an alternative to general anesthesia for thyroidectomy. This study was undertaken to analyze characteristics and outcomes of patients who had thyroid surgery performed under regional anesthesia compared with those who had thyroidectomy under general anesthesia. STUDY DESIGN: One hundred seventy-five consecutive patients who underwent thyroid surgery under regional or general anesthesia during a 3-year period were analyzed. Fifty-eight operations were performed under regional anesthesia and 116 under general anesthesia. Patient characteristics analyzed included age, gender, obesity, anesthesia class, and tumor pathology. Postoperative complications, including nausea or vomiting, were compared. Additionally, operative times and length of stay in each group were compared. RESULTS: Patient characteristics including age, gender, tumor pathology, and anesthesia class were similar in both groups. But only 2% of patients treated under regional anesthesia were obese compared with 23% under general anesthesia. Although not significant, there was a trend toward decreased incidence of nausea and vomiting in the regional group. Other complications for the regional and general anesthesia groups were equal at 3%. Two patients required conversion to general anesthesia. Complications in the general anesthesia group included one episode of transient symptomatic hypocalcemia, two patients with transient vocal cord paralysis, and one episode of hematoma. Finally, there was a statistically significant increase in total operating room time and length of stay for the general anesthesia group. CONCLUSIONS: Regional anesthesia is a safe alternative to general anesthesia for patients undergoing thyroid surgery. Patients who cannot communicate verbally with the surgical team or who are obese may not be ideal candidates for regional anesthesia. The use of regional anesthesia results in a decreased length of stay and similar operative and operating room times.

Adolescent↗

p44/p42-MAP kinase expression in papillary thyroid carcinomas.

BACKGROUND: Recent studies suggest that mitogen-activated protein (MAP) kinase contributes to the growth and tumorigenesis of human epithelial cancers. Furthermore, blockade of this pathway may inhibit the growth of epithelial cancers. To determine whether MAP kinase is activated in human papillary thyroid carcinomas (PTCs), we analyzed the presence of native MAP kinase (MAPK) and activated phosphorylated MAP kinase (pMAPK) in papillary thyroid cancers and thyroid carcinoma cell lines. METHODS: Protein from paired specimens of 10 patients with PTC was analyzed by immunoblot for MAPK and pMAPK. In addition, MAPK protein expression and cell growth were analyzed in 3 thyroid tumor cell lines treated with a mitogen extracellular kinase inhibitor, U0126. RESULTS: All 10 PTCs had equal expression of MAPK in the tumors and adjacent normal tissue. Six of the 10 tumors demonstrated increased expression of the pMAPK in the tumor specimen compared to the adjacent normal tissue. Interestingly, 3 of 4 patients without differential expression had multifocal PTC. The pMAPK was expressed constitutively in 3 thyroid cancer cell lines. The MAPK inhibitor treatment decreased pMAPK expression and decreased serum-induced growth in all 3 cell lines. CONCLUSIONS: MAP kinase activation is common in PTCs and may offer a potential target for growth inhibition of PTCs.

Blotting, Western↗

Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer.

A large body of evidence suggests that cyclooxygenase-2 (COX-2) is important in gastrointestinal cancer. The purpose of this study was to determine whether COX-2 was expressed in adenocarcinoma of the human pancreas. Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in pancreatic tissue. Levels of COX-2 mRNA were increased by >60-fold in pancreatic cancer compared to adjacent nontumorous tissue. COX-2 protein was present in 9 of 10 cases of adenocarcinoma of the pancreas but was undetectable in nontumorous pancreatic tissue. Immunohistochemical analysis showed that COX-2 was expressed in malignant epithelial cells. In cultured human pancreatic cancer cells, levels of COX-2 mRNA and protein were induced by treatment with tumor-promoting phorbol esters. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of pancreatic cancer.

Adenocarcinoma↗

Detection of telomerase activity in breast masses by fine-needle aspiration.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that compensates for the telomere shortening that occurs in its absence. Reactivation of telomerase is thought to be an important step in cellular immortalization, and recent studies have indicated that telomerase activity is often detected in primary human malignancies. The clinical implications of telomerase activity in human tumors are currently under investigation. METHODS: Eighty-nine samples (46 FNAs and 43 gross tissue biopsies) from 44 patients with breast masses were analyzed prospectively for the presence of telomerase activity by a modification of the telomere repeat amplification protocol (TRAP). All samples were obtained directly from the excised mass at the time of specimen removal in the operating room. RESULTS: Telomerase activity was detected in 17 of 19 (90%) FNA samples and 15 of 18 (83%) invasive breast cancer tissue biopsies. Telomerase was also detected in 9 of 16 (56%) FNAs and 8 of 15 (53%) tissue biopsies from 16 fibroadenomas. Other benign proliferative lesions (n = 5) did not have detectable telomerase activity in either FNA or tissue specimens. FNA-TRAP results correlated with the gross tissue specimen TRAP results in 95% of all cases. CONCLUSION: The FNA-TRAP assay for telomerase detection is a highly sensitive and accurate method for the detection of telomerase activity in breast masses. Future application of these techniques should facilitate evaluation of telomerase as a tumor marker in the clinical management of breast and other solid malignancies.

Adolescent↗

Telomerase activity in the differentiation of benign and malignant adrenal tumors.

BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that extends the ends of chromosomes by synthesizing the 6 oligonucleotide repeat TTAGGG and thus serves as a marker for cellular immortality. Although absent in most adult somatic tissues, telomerase activity is present in stem cells and is reactivated in nearly all primary human malignancies. In this study we sought to determine whether tumors of the adrenal glands contain telomerase activity and whether telomerase activity can be used to differentiate benign and malignant tumors of the adrenal glands. METHODS: Tissue was obtained from 23 specimens at adrenalectomy. Adjacent normal adrenal tissue was obtained for control. All specimens were rapidly frozen and stored at -80 degrees C until assay. Telomerase activity was determined by the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was present in 5 of 23 (22%) of the adrenal tumors. All 3 malignant tumors were strongly TRAP positive. There was a single cortical adenoma that had very weak telomerase activity. The single TRAP-positive tumor of the adrenal medulla was a ganglioneuroma. CONCLUSIONS: Benign adrenal tumors infrequently contain telomerase activity, whereas telomerase reactivation appears to be common in malignant tumors of the adrenal glands. These data suggest that determination of telomerase activity may offer a novel way to facilitate the differentiation of benign and malignant adrenal tumors.

Adrenal Gland Neoplasms↗

Telomerase activity in benign and malignant thyroid diseases.

BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the excitation of proliferative stem cells, male germ cells, and activated lymphocytes. The measurement of telomerase activity in clinically obtained tissue samples may provide useful information as both a diagnostic and prognostic marker. In this study, we sought to determine whether telomerase activity might prove helpful in the assessment of benign and malignant thyroid tumors. METHODS: A modified, semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol assay was used for detection of telomerase activity in 59 samples obtained at thyroidectomy, including 15 thyroid cancers, 22 benign thyroid diseases, and 22 adjacent normal thyroid tissues. RESULTS: Four of 13 differentiated thyroid carcinomas (30%) and 2 of 2 medullary carcinomas (100%) expressed telomerase activity. Unexpectedly, we also detected activity in 3 of 22 (14%) adjacent normal thyroid tissues and 6 of 22 (28%) benign thyroid diseases. Pathologic review of the telomerase-positive benign specimens revealed that many contained extensive lymphoid infiltrates with germinal centers (six of nine, 67%), as did two of four telomerase-positive papillary carcinomas. CONCLUSIONS: In contradistinction to other epithelial carcinomas, telomerase does not appear to be frequently reactivated in differentiated thyroid carcinomas.

Adult↗

Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration.

BACKGROUND: The association between nonsteroidal antiinflammatory drug (NSAID) intake and gastroduodenal peptic ulceration is well recognized. Recent experimental data implicate NSAIDs in the development of a similar spectrum of pathologic lesions of the small bowel. However, clinically significant NSAID-induced small bowel ulcerations have been reported infrequently. This study sought to examine small bowel complications of NSAID use requiring surgical intervention. STUDY DESIGN: A retrospective study of all patients (n = 283) who underwent small bowel resection on the general surgery services at the University of Texas Southwestern Medical Center during a 3-year period from 1991 to 1994 was conducted. Patients who had a history of chronic NSAID use, no other predisposing risk factors for gastrointestinal bleeding, and pathologically confirmed small bowel ulcerations complicated by hemorrhage, perforation, or obstruction were included in this study. RESULTS: Eleven patients with 12 surgical complications of NSAID-induced small bowel ulcerations were identified. These 11 patients all underwent emergent laparotomies with small bowel resection (one patient had two separate operations, 8 months apart). Small bowel ulcerations were noted to occur in the jejunum (4) and the ileum (8) and were multiple in half of the cases. Complications included bleeding (50%), perforation (33%), and obstruction (17%). CONCLUSIONS: This report is the first examining a series of surgical complications of NSAID-associated small bowel ulcerations. Our data suggest that small bowel complications of NSAID use requiring surgical intervention may occur more frequently than is currently recognized and, like peptic ulcer disease attributed to NSAIDs, result in significant morbidity and mortality.

Aged↗

Seasonal air and soil temperature effects on photosynthesis in red spruce (Picea rubens) saplings.

Net photosynthesis and stomatal conductance were measured in ten red spruce (Picea rubens Sarg.) saplings, growing near Ithaca, New York, throughout the early spring and late-fall growing periods. Gas exchange and daily minimum and maximum soil and air temperatures were also measured. Linear regression analysis showed that rates of net photosynthesis were positively correlated with both minimum daily soil and air temperatures but that minimum soil temperature was a better predictor of net photosynthesis. Moreover, net photosynthesis was more sensitive to changes in soil temperature than to changes in air temperature, and photosynthesis was approximately twice as sensitive to temperature changes during the fall than during the spring.

Journal Article↗

Rapid, nonradioactive screening for mutations in exons 10, 11, and 16 of the RET protooncogene associated with inherited medullary thyroid carcinoma.

Germline mutations in exons 10, 11, and 16 of the RET protooncogene are associated with the heritable cancer syndromes multiple endocrine neoplasia (MEN) type 2A, familial medullary thyroid carcinoma (FMTC), and MEN type 2B. Nonradioactive mutation analysis with nondenaturing Phastgels and the Phast System was performed on DNA amplified by the polymerase chain reaction from exons 10, 11, and 16 of the RET protooncogene from patients with MEN 2A, MEN 2B, or FMTC. The analysis requires approximately 45-90 min for electrophoresis and 35 min for staining. This assay detected 20 of 21 different mutations that represented approximately 90% of all known mutations associated with these lesions. A rare silent polymorphism within exon 10 was also detected. This form of mutation analysis provides simple, rapid, and highly sensitive nonradioactive detection of mutations known to be associated with MEN 2A, FMTC, and MEN 2B.

Carcinoma, Medullary↗

The role of tumor necrosis factor and nitric oxide in the acute cardiovascular response to endotoxin.

OBJECTIVE: This study was designed to examine the differential effects of tumor necrosis factor (TNF) and nitric oxide on the acute cardiovascular changes that occur in response to endotoxemia. SUMMARY BACKGROUND DATA: Recent studies have suggested that some, if not all, of the cardiovascular effects of TNF are mediated through release of nitric oxide. However, the mechanisms through which TNF and nitric oxide induce hypotension and shock in vivo in response to systemic endotoxemia remain poorly characterized, despite current interest in the use of nitric oxide antagonists to ameliorate septic shock. METHODS: A reproducible model of endotoxemia was established in adult Sprague-Dawley rats. The acute cardiovascular changes that occur after bolus infusion of endotoxin was then determined in rats treated with either TNF antibody, N-methyl arginine, or both. RESULTS: Inhibition of either TNF or nitric oxide restores mean arterial blood pressure to normal after endotoxemia (p < 0.05). However, nitric oxide exerts its effects principally on the peripheral vasculature, whereas TNF appears to act on the myocardium. A combination of TNF antiserum pretreatment and N-methyl arginine administration is necessary to return mean arterial blood pressure to normal 60 minutes after endotoxin infusion. CONCLUSION: Tumor necrosis factor and nitric oxide mediate the acute cardiovascular effects of endotoxemia through distinct mechanisms. Nitric oxide is released as a result of both TNF-dependent and TNF-independent mechanisms, whereas the cardiovascular effects of TNF are only partially mediated through nitric oxide.

Animals↗

Increasing incidence and changing presentation of thyroid cancer over a 30-year period.

During a 30-year period 8561 thyroidectomies were performed and 660 new patients presented with thyroid cancer. The number of thyroidectomies performed annually remained relatively constant for the past 20 years but the annual incidence of thyroid cancer increased from two patients in 1963 to 60 in 1992. Possible contributing factors include: altered referral patterns as a result of the introduction of fine-needle aspiration biopsy; an increase in the incidence of occult papillary cancer as a result of performing total thyroidectomy for multinodular goitre; and a background increase of thyroid cancer in the population. Data from the New South Wales State Cancer Registry implicate a background increase in the incidence of thyroid cancer in the population as a major contributing factor.

Humans↗

Differential TNF secretion by wound fibroblasts compared to normal fibroblasts in response to LPS.

Fibroblasts cultured from wound sites have been shown to have an altered phenotype compared to normal dermal fibroblasts and are generally regarded as target cells of the cytokine response at sites of injury. This study was undertaken to determine whether wound fibroblasts can contribute to proinflammatory cytokine production in wounds and, in particular, whether they are capable of secreting TNF. Wound fibroblasts were cultured from polyvinyl alcohol sponges implanted subcutaneously for 2 weeks in Balb/c mice. Fibroblasts harvested from the skin and subcutaneous tissue of untreated mice served as a control population of cells. All cells were passaged at least twice and then stimulated with a dose range of LPS. Supernatants were harvested 8 hr following stimulation and TNF was assayed using a standard L929 cell-killing assay. There was a significant TNF response to LPS by wound fibroblasts, evident as early as 4 hr following exposure to LPS and associated with an upregulation of TNF mRNA. Normal dermal fibroblasts did not secrete any measurable amounts of TNF in response to LPS. The results indicate that wound fibroblasts generate a brisk TNF response to stimulation with LPS, in contrast to normal subcutaneous fibroblasts. These data reveal an additional unique property of wound-harvested fibroblasts and suggest a possible contributing mechanism to disordered wound healing in the face of infection or conditions characterized by excessive fibrosis.

Animals↗

Giant double parathyroid adenoma presenting as a hypercalcaemic crisis.

The largest documented case of a double parathyroid adenoma is reported. The patient presented in hypercalcaemic crisis with a large intrathoracic mass. After removal of a massive cystic parathyroid adenoma from the right superior mediastinum, a second very large parathyroid adenoma was found on the contralateral side adjacent to the left thyroid lobe. This case illustrates the importance of the cervical approach, as well as routine bilateral neck exploration, for all cases of primary hyperparathyroidism.

Adenoma↗