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R J Nauta

Publications and source records attributed to R J Nauta.

At least 37 records · Page 2Linked to original sources

Antitumour activity of 5-fluorouracil, verapamil and hyperthermia against human gastric adenocarcinoma cell (AGS) in vitro.

The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of 5-fluorouracil (5-FU), used at different concentrations, in inhibiting the growth of gastric adenocarcinoma cells. Combined verapamil and hyperthermia treatment showed a significant decrease in cell count when compared to control (72.2%), hyperthermia alone (68.4%), or verapamil alone (65%). At a high concentration of 5-FU (50 micrograms/ml), verapamil and hyperthermia had an additive growth inhibitory effect over a 4-day period when compared to control. A combination of 5-FU at low concentration (0.5 microgram/ml) with verapamil significantly suppressed growth by 31.2% in comparison to control--with this effect being independent of the duration of treatment. The modalities analysed in this study require further investigation and have potential for clinical applicability to gastric cancer therapy in the future.

Adenocarcinoma↗

The clinical impact of risk factor analysis and prophylaxis on pulmonary embolism.

Pulmonary emboli cause 50,000 deaths annually despite recognized risk factors and methods of prophylaxis. To determine the impact of risk factor analysis and the use of prophylaxis, a retrospective chart review of patients suffering pulmonary embolism (PE) at Georgetown University Hospital was performed. During a fifty-month period, 25,000 surgical and 36,000 nonsurgical admissions included 171 cases of PE. The incidence of PE among surgical patients was 0.24% (n = 61) and was 0.30% (n = 110) among nonsurgical patients as confirmed in 82% by pulmonary angiography or high-probability ventilation/perfusion scans. PE prophylaxis included pneumatic stockings, low-dose heparin, combination low-dose heparin/stockings, and coumarin. However, prophylactic measures were absent in 23% of the surgical and in all the nonsurgical patients suffering PE. On the basis of established criteria (SVS/ISCVS), 57% of surgical patients suffering PE were considered at high risk as compared with 13% of nonsurgical patients. Conversely, 54% of nonsurgical patients suffering a PE were considered to be at low risk. Standard treatment modalities were instituted after nonfatal PE: anticoagulation (61%), inferior vena cava filter (14%), and anticoagulation/filter (6%). While risk factor analysis identifies high-risk surgical patients, it may be less effective in identifying nonsurgical patients at increased risk for PE.

Adult↗

Three-dimensional models of the abdominal vasculature based on helical CT: usefulness in patients with pancreatic neoplasms.

Three-dimensional (3D) rendering of helical (spiral) CT data is used increasingly to show abnormalities of the vascular system [1]. Abdominal applications have focused mainly on the arterial system, but the portal venous system also can be depicted effectively with this technique. In patients with pancreaticobiliary neoplasms, axial display of helical CT images generally allows accurate staging of the lesion [2, 3]. Many surgeons, however, continue to request arteriography to specifically look for evidence of vascular encasement that would preclude surgery or vascular anomalies that would alter the surgical approach [4, 5]. The purpose of this essay is to illustrate the value of 3D rendering of CT data in providing useful information for surgical planning and showing the extent of vascular involvement by tumor.

Abdomen↗

Pre-existing liver disease in the trauma patient.

Interest in the importance of pre-existing disease as an outcome predictor in trauma patients has begun to receive attention only recently. Data relating specifically to pre-existing liver disease remains scant. With an overall prevalence of 0.5% among all trauma patients, pre-existing liver disease has been shown to increase mean duration of hospital stay by up to 36% and mortality by a factor of five (Table 9). This data appears to support the recommendation of the American College of Surgeons Committee on Trauma in their most recent bulletin, "Resources for the Optimal Care of the Injured Patient," that a history of cirrhosis in an injured patient should alert prehospital providers to contact medical control and consider transport to a trauma center. The majority of the data on the pathophysiologic and clinical responses and management of the patient with pre-existing liver disease have been extrapolated from literature on liver disease in the surgical patient and in sepsis. Few specific data on the management of the trauma patient with pre-existing liver disease and its effects on morbidity and mortality are available. We hope this review stimulates further research, particularly on the pathophysiologic and clinical responses to trauma exhibited by patients with liver disease.

Critical Care↗

1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition.

The antiproliferative action of 1,25-dihydroxyvitamin D3 in osteosarcoma, breast carcinoma, and colon carcinoma cell lines has been described. In this study, the level of vitamin D receptor was analyzed in a panel of colon adenoma and adenocarcinoma cell lines and the receptor level was correlated with the response to treatment with 1,25-dihydroxyvitamin D3. Ribonuclease protection and ligand-binding assays quantitated the level of vitamin D receptor mRNA expression and the level of functional receptors, respectively. The more well-differentiated cell lines, such as VACO 330, showed higher levels of vitamin D receptor than less-differentiated cell lines, such as SW620. Proliferation assay, clonogenic assay, and growth curve study in HT29 and SW620 cell lines assessed the antiproliferative effect of 1,25-dihydroxyvitamin D3 at concentrations ranging from 10(-11) to 10(-6) M. HT29 showed significant (P < 0.05) growth inhibition at 10(-9) to 10(-6) M concentrations, but growth of SW620 remained unchanged. The amount of vitamin D receptor in 12 malignant colonic tumors was compared with that of adjacent normal tissue, and in 9 cases, the tumor expressed a lower vitamin D receptor level. Our results suggest that the level of vitamin D receptor correlates with the degree of differentiation in human colon cancer cell lines and may serve as a useful biological marker in predicting clinical outcome in patients.

Adenoma↗

Intraoperative high-dose rate interstitial irradiation of hepatic metastases from colorectal carcinoma. Results of a phase I-II trial.

BACKGROUND: Resection of liver metastases from colorectal carcinoma can be curative. Unresectable but liver-confined metastases might be ablated by high-dose radiation with a similar curative result. METHODS: At Georgetown University Hospital, 22 patients with unresectable hepatic metastases from colorectal carcinoma underwent 24 interstitial irradiation procedures at laparotomy in a Phase I-II study. A single dose was administered with a high-dose rate iridium-192 afterloader. Dose to the tumor periphery was 20 Gy, 25 Gy, and 30 Gy in 13, 9, and 2 procedures, respectively. RESULTS: No acute or chronic radiation toxicity has occurred at a median follow-up of 11 months. Median actuarial local control at irradiated sites was 8 months, with 26% actuarial local control at 26 months by computed tomography (CT) or magnetic resonance imaging (MRI) scanning. In the two patients undergoing two procedures each, a second biopsy of previously irradiated areas demonstrated tumor eradication. CONCLUSIONS: This innovative, radical approach to unresectable colorectal hepatic metastases proved safe. Additional study is needed to determine whether interstitial irradiation is as effective as surgical resection, or whether it alters the natural history of the disease or longevity.

Adult↗

Interleukin-1 receptor antibody (IL-1rab) protection and treatment against lethal endotoxemia in mice.

Interleukin-1 (IL-1) is a mediator of endotoxin shock and IL-1 receptor blockade has been shown to have therapeutic efficacy against endotoxic shock and sepsis in laboratory models. The current studies were designed to characterize the efficacy of a murine monoclonal IL-1 receptor antibody (IL-1rab) against endotoxin (LPS) lethality and to investigate whether combined anticytokine therapy using the IL-1rab and a highly specific polyclonal rabbit anti-mouse TNF antibody (TNF Ab) could provide additive or synergistic efficacy against LPS lethality in C57B1/6 female mice. A single intraperitoneal (ip) dose of IL-1rab, 0.1 or 0.2 mg, significantly reduced lethality from LPS, 30 to 40 mg/kg ip, compared to nonimmune IgG, 0.1 or 0.2 mg, in control mice (P2 < 0.05). Treatment with IL-1rab was effective when administered from 6 hr before to 1 hr after LPS. After LPS, circulating levels of IL-6 were significantly lower in IL-1rab-treated mice [IL-6 (ng/ml) 2 h after LPS: IgG, 100 +/- 25, IL-1rab, 41 +/- 8; 4 h after LPS: IgG, 46 +/- 13, IL-1rab, 8 +/- 1; P2 < 0.05 and 0.03, respectively]. Northern blot analysis showed that IL-1rab markedly lowered IL-6 gene expression after LPS. Combined treatment with IL-1rab and TNF Ab did not result in any improvement in survival after LPS compared to either agent alone. These results indicate that an IL-1 receptor antibody has therapeutic efficacy against LPS and significantly decreases IL-6 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An unusual case of intermittent venous obstruction of the upper extremity.

The axillary vein can be subject to intermittent obstruction from numerous anatomic structures such as the pectoralis minor and the scalenus anterior muscles. The diagnosis can be readily made on history and physical examination of the upper extremity, but it can be difficult to confirm by routine venogram done with the arm in the standard position at the side with full extension at the antecubital fossa. Positional venography with the arm fully abducted and flexion of that antecubital fossa allows for better definition of this extrinsic compression. In the case presented, a fascial band arising from the medial head of the biceps was compressing the axillary vein and was suspected on history and physical examination; it was confirmed with positional venography as noted. As in this case, it is important to make the diagnosis early, before thrombosis of the vein occurs, to minimize the associated morbidity. Transaxillary exploration was performed with excision of the band and complete resolution of the symptoms. Subsequent noninvasive studies were performed that showed complete resolution of the extrinsic axillary vein compression. Having a high suspicion of intermittent venous obstruction with early diagnosis and surgical correction of any extrinsic compression are the keys to a successful outcome in these patients.

Adult↗

The role of calcium ions and calcium channel entry blockers in experimental ischemia-reperfusion-induced liver injury.

Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model. The possible activation of proteases converting the xanthine dehydrogenase to xanthine oxidase, the significant mitochondrial calcium loading during the ischemic period, and the potentiation of calcium and oxygen-derived free radicals to promote injury to mitochondria are mechanisms supported by this study, based on both histologic observations and on the pattern of enzyme leak after the acute ischemic event.

Alanine Transaminase↗

Resection of a granular cell tumor at the hepatic confluence. A precarious location for a benign tumor.

Granular cell tumors are lesions that account for less than 10 per cent of benign biliary tumors and only 1 per cent occur in the biliary tract. Since the first description, 45 other cases have been described to which we add a case. In reviewing the literature, a striking predominance in black females is evident. The most frequent location of these tumors in the biliary tree appears to be the common bile duct (50%), followed by the cystic duct (37%), the hepatic ducts (15%), and the gallbladder (4%). Most patients have been treated with resection followed by restoration of biliary continuity using biliary enteric diversion. In the case presented, the tumor was located at the hepatic confluence with extension into the hepatic substance requiring segmental duct cholangiojejunostomy after resection. This resulted in fulminant sepsis and death despite adequate preoperative biliary decompression and the lack of signs or symptoms of infected bile. Alternative forms of management in the treatment of this benign condition at this location are discussed.

Adult↗

The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity.

The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases.

Adolescent↗

Solid and papillary epithelial neoplasm of the pancreas: clinical findings of a rare tumor.

A young woman presented with a large pancreatic mass that was found to be a solid and papillary epithelial neoplasm. The endoscopic, radiologic, and gross appearance of this tumor is described. The origin of the tumor is probably from a multipotential stem cell of the pancreas. Surgical resection is usually curative, although radiotherapy and chemotherapy have been successfully used. This unusual tumor should be considered in the differential diagnosis of a young female with a pancreatic mass.

Adult↗

Primary hepatocellular carcinoma: hospital based epidemiologic study.

From 1968-1985 a series of thirty-seven patients with primary hepatocellular carcinoma was collected from the tumor registry of the Fairfax County Hospital, in the metropolitan Washington, D.C. area. These patients were found to have a mean age at diagnosis of sixty-two (males) to sixty-six (females). Thirty per cent of patients were previously cirrhotic and nineteen per cent had a history of viral hepatitis. There were no patients with documented birth control pill or steroid use. The most common presenting symptoms were anorexia and right upper quadrant pain. Liver-spleen scan was the most commonly used diagnostic study, but by the 1980's CT scanning was usually diagnostic. Both alkaline phosphatase and serum glutamyloxalotransferase were reliably elevated in twenty-six of twenty-eight and twenty-one of twenty-four patients respectively. Forty-eight per cent of patients with tumor histology reported had multicentric tumors, thirty-eight per cent had nodular tumors, and fourteen per cent had diffuse disease. Survival was as dismal in this as in other studies with a mean of seventy-nine days. No significant difference was noted between cirrhotic and non-cirrhotic patients. Chemotherapy and radiation therapy did not significantly impact upon survival. Finally, a cohort analysis was done and a possibly significant peak in incidence of primary hepatocellular carcinoma was seen in men born from about 1911 through 1920. The authors noted that these males were in the group of draft eligible persons for World War II and questioned a link between veteran status and later development of HCC.

Adult↗

A radical approach to bacterial panniculitis of the abdominal wall in the morbidly obese.

The morbidly obese patient, although at risk for many perioperative complications of radical surgery, paradoxically presents the opportunity for wide excision of abdominal soft-tissue infections. This report describes the successful radical surgical management of bacterial panniculitis of the abdominal wall occasioned by a variety of extrafascial and intraperitoneal sources in 13 patients. All patients were followed up for a minimum of 2 years, except for one patient who died 2 months after hospital discharge. The remainder are alive with intact fascial closure and no pannicular infection. A radical approach to the infected abdominal wall, incorporating wide en-bloc excision of skin, subcutaneous tissue, muscle, and strangulated intestine, facilitates successful fascial and skin closure in a noninfected field in the morbidly obese.

Abdominal Muscles↗

Duodenojejunostomy as an alternative to anastomosis of the small intestine at the ligament of Treitz.

Side to side duodenojejunostomy is a reasonable alternative to other methods of reconstitution of the continuity of the upper portion of the GI tract in selected circumstances. It is not necessary to use duodenojejunostomy in resections distal to the ligament of Treitz because an end to end anastomosis may be readily accomplished. The described technique, however, provides a convenient means of reconstruction for the upper portion of the GI. tract when resection of the small intestine is necessary at the ligament of Treitz or in close proximity to the origin of the mesenteric vasculature. Thus, adequate resection at the ligament of Treitz may be performed when necessary, and the need to subsequently visualize or mobilize the transected duodenal stump to construct an anastomosis in that region is obviated.

Adult↗

Oxygen-derived free radicals in hepatic ischemia and reperfusion injury in the rat.

We have previously described a chronic, in vivo biochemical and histologic model of ischemia and reperfusion injury and wished to test the ability of superoxide dismutase, catalase and allopurinol to protect against the hepatocellular injury demonstrated by this model. Xanthine oxidase inhibitors given preoperatively produced a significant hepatocellular protective effect when compared with a comparable insult delivered to a cohort of control rats. The protection given seemed greater than that produced by pretreatment with free radical scavengers. Possible mechanisms for this observation are discussed. Investigations combining free radical scavengers with xanthine oxidase inhibitors may further define protection for warm hepatic ischemia and reperfusion injury.

Allopurinol↗

Cholangitis, hemobilia, and cholangiocarcinoma. Management of a fistula between an obstructed right hepatic duct and the portal vein.

Cholangitis is the most common cause of sepsis in patients with obstructing carcinomas of the biliary tree. Catheter and stent placement may relieve or exacerbate the septic course. Transhepatic stent placement produced a cholangioportal fistula and hemobilia in a patient with cholangiocarcinoma. The described technique of retrograde operative decompression and clot evacuation may be used in patients in whom portal dissection is hazardous or in whom preservation of an existing cholangiojejunostomy in the portal region is desired.

Adenoma, Bile Duct↗