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Biomedical subjects

N R Thomford

Publications and source records attributed to N R Thomford.

At least 19 recordsLinked to original sources

Papillary cystic and solid tumors of the pancreas: a pancreatic embryonic tumor? Studies of three cases and cumulative review of the world's literature.

BACKGROUND: The papillary cystic and solid tumor of the pancreas is rare. It occurs predominantly in young women, and most present a benign behavior. The pathogenesis of this tumor has attracted a number of investigations but remains unclear. METHODS: We present three patients with this tumor and a review of 289 others from the world's literature, a total of 292 cases. On the basis of the analyses of the clinical and pathologic features from the reported cases, the pathogenesis of this unusual tumor has been further explored. RESULTS: Ninety percent of the patients were female, with a mean age of 23.9 years. The tumors were usually quite large with a mean diameter of 10.3 cm. Ninety-two percent of these tumors were totally or partially cystic. Rupture of the capsule resulted in hemoperitoneum in eight cases, five of which were without any identifiable cause. Forty-three tumors (14.7%) have been recognized as malignant. The overall prognosis has been excellent and an aggressive approach to resection is indicated. CONCLUSIONS: The results of immunohistochemical staining and electromicroscopy were rather diverse, but most, including the current cases, support the hypothesis that the tumor originates from pleuripotential embryonic stem cells. Thus the term pancreatic embryonic tumors seems preferable to papillary cystic and solid tumor of the pancreas to delineate the origin of the tumor and to reflect some of its biologic characteristics.

Adolescent

Estrogen receptor in carcinoma in situ of the cervix.

The lining epithelium of the human cervix uteri is an estrogen dependent tissue containing specific intracellular receptors for this hormone. However, the influence of estrogen on an early neoplastic lesion arising from this epithelium, such as carcinoma in situ of the cervix, has not been determined. We evaluated 24 formalin fixed paraffin embedded tissue specimens of cervical carcinoma in situ for the presence of estrogen receptor by the immunoperoxidase technique. The antigenic sites of estrogen receptor were exposed by DNAse treatment followed by peroxidase-antiperoxidase (PAP) staining with monoclonal antibody against estrogen receptor. Parallel negative controls were run using negative control antibody and rat serum. Quality control for positive staining was performed using breast cancer tissue sections from specimens with known estrogen receptor detected by the radioreceptor method. Strongly positive staining was observed in all specimens in the nuclei of glandular epithelium, stromal cells, and basal and parabasal cells. However, nuclei within carcinoma in situ of the cervix showed no evidence of positive staining. Due to lack of specific intracellular receptor for estrogen, it appears that carcinoma in situ of the cervix will not be under direct influence of estrogen.

Adult

Palmitic acid kinetics in fasting, traumatized patients.

The contribution of free fatty acid oxidation to the elevation in energy expenditure after trauma has not been well characterized. Six control subjects and six traumatized patients were fasted for 48 hours and given a primed continuous infusion of (1-14C)palmitate to measure plasma palmitate and total free fatty acid kinetics. Traumatized patients had greater urinary nitrogen losses (20.8 vs. 9.3 g N per day) and a significantly greater ratio of measured to predicted resting energy expenditure (+36% vs. -6%) compared with controls. Individual and total plasma free fatty acid concentrations were similar for the two groups. The turnover and oxidation of plasma palmitate and total free fatty acids were not changed by multiple trauma. These results demonstrated that plasma free fatty acids and palmitate do not contribute to increased energy expenditure following trauma.

Adult

Palmitate and stearate kinetics in the rat during sepsis and trauma.

Kinetics of plasma free palmitate and stearate were measured in control and septic-traumatized rats to determine the contribution plasma free fatty acids make to increased resting energy expenditure. Measurements were made at 24 hr after insult using a primed, 4-hr continuous infusion of selected (1-14C) fatty acid. The plasma concentration of palmitate was increased and stearate was decreased in sepsis-trauma rats compared to plasma concentrations in healthy control rats. Fatty acid turnover rates during sepsis-trauma were changed from control turnover rates in the same direction as plasma concentrations. Oxidation rates for palmitate and stearate at 24 hr after induction of sepsis-trauma were not different from oxidation rates in control rats. Plasma free fatty acids were concluded not to exhibit increased oxidation after sepsis-trauma and not to contribute extra energy during hypercatabolism. This finding contrasts with glucose and amino acids which have an increased oxidation rate during hypercatabolism.

Animals

Pharmacokinetics and toxicity of isolated perfusion of lung with doxorubicin.

The treatment of pulmonary metastases from soft tissue sarcomas with chemotherapy has an overall response rate of less than 30%, and the majority of these responses are short lived. It is postulated that increased drug delivery to the pulmonary metastases may improve the outcome of these patients. An isolated perfusion system would have the ability of delivering increased levels of drug to target tissue without the systemic toxic effect of the drug. The purpose of this study was to establish the pharmacokinetics of doxorubicin delivery, lung toxicity, and the ideal dose for clinical application in an in vivo isolated perfusion model. Our results suggest that normothermic isolated perfusion of the lung with doxorubicin using a dose level up to 6 micrograms/ml in the perfusate can be accomplished without histologic lung injury, systemic toxicity, or adverse clinical outcome. Perfusate concentration of greater than 7 micrograms/ml caused significant histologic injury and adverse clinical outcome without systemic toxicity. The technique may be utilized in selective settings to improve treatment in mesenchymal tumors metastatic to the lung.

Animals

Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature.

Mesothelioma of the peritoneum is a rare malignant neoplasm easily mistaken by both surgeon and pathologist for one of the more common neoplasms of the abdomen. Review of our records from metropolitan-area hospitals for the past 15 years identified seven patients with primary peritoneal mesotheliomas. Their diagnosis, management, and survival is analyzed. We report a case of an extended survivor (7 years) and one of a long-term survivor (15 years), as well as what we believe to be the only case in the literature presenting with a coexistent malignant neoplasm. Prevention of this commonly fatal neoplasm is linked to avoiding occupational exposure to asbestos; long-term survival for a few patients may be achieved with correct identification of the neoplasm and aggressive management. This report includes a review of the literature.

Adult

Influence of clerkship structure and timing on individual student performance.

Student oral and written surgical clerkship performances may be related to the clerkship structure and the time of year the students rotate through the clerkship. The influence of calendar block, hospital site (university hospital, affiliated private tertiary-care hospital, and rural preceptor experience), and the mix of general surgical versus subspeciality rotations on oral and written student surgery clerkship scores was analyzed. Multivariate analysis of variance revealed significant differences in score for calendar block (p = 0.02) only; this difference resided in the written examination. The various combinations of rotations were not different from one another in terms of measured outcome.

Clinical Clerkship

Isolated perfusion of pancreas with mitomycin C.

The current treatment of pancreatic cancer with resection and/or radiation is considered unsatisfactory because of a high incidence of failure and a moderate incidence of complications. A sizable number of these patients present with localized or regional disease. Regional high-dose chemotherapy, such as with isolated perfusion, may offer an alternative therapy with low treatment-related morbidity and mortality and better end results in this group of patients. In an effort to develop such a treatment modality, we evaluated the pharmacokinetics and toxicity of mitomycin C (MMC) during isolated perfusion of pancreas in a canine model. From this study, it appears that a dose of 0.25 mg MMC/kg body weight is most suitable for isolated perfusion of pancreas at 39 degrees C, maintaining flow rate and pressure within physiologic range. Isolated perfusion with a dose of 0.25 mg/kg body weight has very mild short- and long-term toxicities and markedly increases drug delivery to the pancreas, duodenum, and peripancreatic lymph nodes, making it the most suitable dose for possible clinical application.

Amylases

CT of the abdomen after the Whipple procedure: value in depicting postoperative anatomy, surgical complications, and tumor recurrence.

We performed a retrospective study of CT scans in 29 patients who had undergone the Whipple procedure (radical pancreaticoduodenectomy) to study the CT appearance of the postsurgical anatomy and assess the use of CT in the evaluation of early postoperative complications and recurrent tumor. In the postoperative period, the scans from 15 patients revealed seven transient fluid collections; four deep abscesses, three of which were successfully drained under CT guidance; three superficial abscesses; and five cases of ascites. In 19 patients, CT scans were obtained up to 4 years after surgery to search for recurrent tumor. The most frequent site of recurrence was the liver. CT correctly identified liver metastases in six of seven patients and was falsely positive in one. Recurrence also was found twice in retroperitoneal lymph nodes; one time each in the mesenteric root, spleen, and lung base; and twice causing afferent loop blockage. Surgical proof of recurrence was obtained in eight cases. Our experience suggests that an understanding of the normal postoperative anatomy following the Whipple procedure is essential in evaluating postoperative CT scans. Scans obtained for detection of tumor recurrence should be optimized for imaging the liver because this was the most frequent site of recurrence.

Adult

Carney's triad with recurrent gastric leiomyoblastoma.

The triad of gastric leiomyoblastoma, extra-adrenal paraganglioma, and pulmonary chondroma was first described by Carney in 1977. Fewer than 30 patients with this syndrome have since been reported. In most patients the initial lesion has been a gastric leiomyoblastoma. The patient we describe had recurrences of a gastric leiomyoblastoma 15 and 17 years, respectively, after the initial gastric resection. Subsequently, multiple pulmonary lesions were excised and confirmed to be chondromas, but no evidence of a paraganglioma has yet been identified. Gastric leiomyoblastomas in patients with Carney's triad frequently recur; however, the prognosis is quite favorable in contrast to that of sporadic cases. Whenever a patient with one of the classical lesions of Carney's triad is encountered, the possibility of this unusual syndrome should be considered. The evaluation and follow-up of these patients should include a search for the other two components.

Adult

Estrogen receptors in ductal carcinoma in situ of breast.

A number of investigators have suggested treatment of precursor lesions for invasive breast cancer such as ductal carcinoma in situ with antiestrogen. However, very little information is available on the incidence of estrogen receptor in such lesions and the probability of treatment success. Fourteen formalin-fixed tissue specimens of intraductal carcinoma in situ from 14 female patients aged 40 to 66 years were evaluated for the presence of estrogen receptor by immunoperoxidase technique using estrogen receptor antibody. Eight of the 14 lesions (57%) were positive for estrogen receptor. The incidence of estrogen receptor in intraductal carcinoma in situ is very similar to that of invasive carcinoma of breast, leading to the speculation that ER-positive invasive carcinoma originates from ER-positive precursor lesions. Since only 70 per cent of positive receptor lesions are expected to respond to antiestrogens, it appears that only 40 per cent of patients with ductal carcinoma in situ of breast will benefit from endocrine therapy.

Adult

Interaction of ketosis and liver regeneration in the rat.

Monoacetoacetin, the monoglyceride of acetoacetate, was investigated as a nutritional support for the regenerating liver. Following partial hepatectomy, rats were either fed an oral diet ad libitum or administered by total parenteral feeding glucose alone, monoacetoacetin-glucose mixture, or lipid emulsion-glucose for the nonprotein calories. Five rats from each treatment were killed at 6-hr intervals beginning 12 hr after partial hepatectomy and ending at 72 hr. The number of cells synthesizing DNA and the number of cells in mitosis were compared. Rats fed orally or infused with glucose alone or with lipid emulsion had similar parameters throughout. Rats infused with monoacetoacetin had approximately double the number of cells in mitosis and DNA synthesis compared to the other treatments. This stimulation by monoacetoacetin persisted 72 hr. It was concluded from the data that acetoacetate was the agent responsible for increased DNA synthesis and mitosis, but the mechanism for the stimulation was not identified.

3-Hydroxybutyric Acid

Pharmacokinetics and tissue uptake of mitomycin C in isolated perfusion of pancreas.

Isolated perfusion of organs or anatomic sites with chemotherapeutic agents offers a pharmacokinetic advantage of increasing drug bioavailability to target tissues which may result in a greater magnitude of biologic effect (pharmacologic or toxic) without systemic toxicity. Using a previously developed animal model, isolated perfusion (IP) of the canine pancreas-duodenum with incremental doses of mitomycin C (MMC) had shown a dose of 0.25 mg/kg body weight to be the maximum tolerable dose. The current study was designed to compare the pharmacologic advantage of drug delivery by IP by directly measuring tissue drug levels of radiolabeled MMC and comparing them with tissue levels attained by selective intraarterial (IA) and intravenous (IV) routes using identical doses of drug (n = 4 each). IP of pancreas-duodenum was performed for 45 min with a perfusate-to-systemic drug leak rate of less than 5%. IP was accomplished by using extracorporeal pump oxygenator at 39 degrees C and flow initiated at 110-120 ml/min, with a mean pressure of 90 mm Hg. Vascular inflow and outflow was isolated to the cannulated superior pancreaticoduodenal artery and vein. In the IA group drug was infused over 45 min through same artery as IP. IV group underwent identical dosing through the jugular vein. Direct measurement of drug in harvested pancreas and duodenum for each individual was done by tissue solubilization and scintillation assay. A 6-fold greater tissue level of drug in IP over IA and a 15-fold increase in IP over IV methods of delivery were found (P less than 0.01).

Animals

Idiopathic benign stricture of the common bile duct.

An unusual case of idiopathic benign stricture of the intrapancreatic portion of the common bile duct is described. Because of the absence of a history of pancreatitis or an operation upon the biliary tract, the obstruction was thought to be due to malignancy. However, histologic studies of tissues removed by pancreaticoduodenectomy established that the lesion was a benign stricture.

Aged

Anatomicosurgical segments of the human pancreas.

Two anatomicosurgical segments of the human pancreas were recognized in 30 corrosion casts after injection of the pancreatic arteries thus confirming prior anatomico-surgical studies. The right (cephalocervical) and the left (corporocaudate) segments of the pancreas are separated by a paucivascular area. They are linked by the pancreatic duct and often by a single, small artery, which may be a branch of the gastroduodenal, gastroepiploic (gastromental), or dorsal pancreatic artery. Both segments are suitable for segmental pancreas transplantation.

Aged

Evaluation of free fatty acid kinetics during TPN feeding of healthy rats.

Free fatty acid (FFA) kinetics were evaluated in TPN-fed healthy rats using a single fatty acid tracer. Rats were divided into three groups according to the nonprotein energetic substrate infused: glucose (A), monoacetoacetin-glucose (B), and lipid emulsion-glucose (C). Fat kinetics were measured by continuous infusion of [1-14C]palmitate. Total FFA and individual FFA concentrations were measured and turnover and oxidation were determined for the total pool of FFA and for palmitate. Groups A and B were similar in all parameters. Group C had increased total and individual FFA concentrations. Group C appeared to have decreased total plasma FFA turnover and unchanged oxidation compared to groups A and B. Palmitate appeared to have a 400% increase in oxidation and a 50% increase in turnover for rats in Group C when compared to Groups A and B. It is concluded that a single tracer does not accurately reflect plasma FFA during TPN using lipid emulsion.

Animals