Diagnostic dilemmas in patients with cystic neoplasms of the pancreas

Summary Cystic neoplasms of the pancreas (CNP) are rare lesions that can be difficult to diagnose preoperatively. Twenty patients with cystic neoplasms of the pancreas including five microcystic adenomas, six benign mucinous cystic neoplasms, three malignant mucinous cystic neoplasms, two solid and papillary epithelial neoplasms, and four cystic neuroendocrine tumors were treated at a single institution between 1962 and 1987. The average duration of symptoms prior to diagnosis was 10 months. Five patients were asymptomatic. Forty percent of patients presented with an abdominal mass. Plain abdominal x-rays and UGI barium contrast studies were never diagnostic. Ultrasonography, computerized tomography (CT) and visceral angiography aided in the correct diagnosis in 28%, 36%, and 75% of patients studied, respectively. Overall a correct diagnosis was made preoperatively in only 35% of patients. Twelve of 13 patients were correctly diagnosed at laparotomy with intraoperative biopsy. Without biopsy the mass was misdiagnosed at laparotomy in five of six cases. CNP must be suspected inany patients who present with an upper abdominal mass with or without abdominal pain and no history of pancreatitis. CT may be diagnostic in up to one third of cases and should be obtained routinely to demonstrate the proximity of the lesion to other structures. Visceral angiography should also be obtained prior to operation. A generous incisional biopsy should be obtained of all pancreatic cysts that are not to be resected.     

Cost analysis of "bridging therapy" with low-molecular-weight heparin versus unfractionated heparin during temporary interruption of chronic anticoagulation

Patients on long-term anticoagulation who require interruption of therapy for surgery may receive "bridging therapy" with continuous-infusion unfractionated heparin or low-molecular-weight heparin (LMWH). We estimated the costs of bridging therapy with: (1) LMWH self-administered at home, (2) LMWH administered by a nurse to patients at home, and (3) continuous-infusion unfractionated heparin in the hospital. For surgeries requiring an overnight stay, bridging costs are estimated to be 672, 933, and 3,816 US dollars, respectively, for each of these strategies.     

Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death

OBJECTIVE: Autoantibodies to DNA topoisomerase I (topo I) are associated with diffuse systemic sclerosis (SSc), appear to be antigen driven, and may be triggered by cryptic epitopes exposed during in vivo topo I fragmentation. These autoantibodies recognize topo I and fragments of this autoantigen generated during apoptosis and necrosis. We undertook this study to determine whether lysosomal cathepsins are involved in topo I fragmentation during necrosis. METHODS: Topo I cleavage during necrosis was assessed by immunoblotting of lysates from L929 fibroblasts exposed to tumor necrosis factor alpha (TNFalpha) and the broad caspase inhibitor Z-VAD-FMK, and by immunoblotting of lysates from endothelial cells treated with HgCl2. Purified topo I and L929 nuclei were incubated with cathepsins B, D, G, H, and L, and topo I cleavage was detected by immunoblotting. The intracellular localization of cathepsin L activity and topo I in necrotic cells was examined using fluorescence microscopy. RESULTS: Treatment of L929 cells with TNFalpha and Z-VAD-FMK induced caspase-independent cell death with necrotic morphology. This cell death involved topo I cleavage into fragments of approximately 70 kd and 45 kd. This cleavage profile was reproduced in vitro by cathepsins L and H and was inhibited by the cathepsin L inhibitor Z-FY-CHO. During necrosis, cathepsin L activity diffused from lysosomes into the cytoplasm and nucleus, whereas topo I partially relocalized to the cytoplasm. Z-FY-CHO delayed necrosis and partially blocked topo I cleavage. The topo I cleavage fragments were also detected in necrotic endothelial cells and recognized by SSc sera containing anti-topo I antibodies. CONCLUSION: These results implicate cathepsins, particularly cathepsin L, in the cleavage of topo I during necrosis. This cleavage may generate potentially immunogenic fragments that could trigger anti-topo I immune responses in SSc.     

Myocardial glucose uptake is regulated by nitric oxide via endothelial nitric oxide synthase in Langendorff mouse heart

Although the role of nitric oxide (NO) in the modulation of vascular tone has been studied and well understood, its potential role in the control of myocardial metabolism is only recently evident. Several lines of evidence indicate that NO regulates myocardial glucose metabolism; however, the details and mechanisms responsible are still unknown. The aim of this study was to further define the role of NO in the control of myocardial glucose metabolism and the nitric oxide synthase (NOS) isoform responsible using transgenic animals lacking endothelial NOS (ecNOS). In the present study, we examined the regulation of myocardial glucose uptake using isometrically contracting Langendorff-perfused hearts from normal mice (C57BL/6J), mice with defects in the expression of ecNOS [ecNOS (-/-)], and its heterozygote [ecNOS (+/-)], and wild-type mice [ecNOS (+/+)] (n=6, respectively). In hearts from normal mice, little myocardial glucose uptake was observed. This myocardial glucose uptake increased significantly in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME). Similarly, in the hearts from ecNOS (-/-), glucose uptake was much greater than in normal mice, whereas myocardial glucose uptake of ecNOS (+/-) and ecNOS (+/+) mice was not different from normal mice. In addition, myocardial glucose uptake of ecNOS (+/-) and ecNOS (+/+) mice increased significantly in the presence of L-NAME. At a workload of 800 g. beats/min, L-NAME increased glucose uptake from 0.1+/-0.1 to 3+/-0.4 microg/min x mg in ecNOS (+/-) mice and from 0.2+/-0.1 to 2.7+/-0.7 microg/min x mg in ecNOS (+/+) mice. Furthermore, in the hearts from ecNOS (-/-) mice, 8-bromoguanosine 3':5'-cyclic monophosphate (8-Br-cGMP), a cGMP analog or S-nitroso-N-acetylpenicillamine (SNAP), a NO donor essentially shut off glucose uptake, and in hearts from ecNOS (+/-) mice, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), an inhibitor of cGMP, increased the glucose uptake significantly. These results indicate clearly that cardiac NO production regulates myocardial glucose uptake via a cGMP-dependent mechanism and strongly suggest that ecNOS plays a pivotal role in this regulation. These findings may be important in the understanding of the pathogenesis of the diseases such as ischemic heart disease, heart failure, diabetes mellitus, hypertension, and hypercholesterolemia, in which NO synthesis is altered and substrate utilization by the heart changes.     

Slow release theophylline in patients with airways obstruction with particular reference to the effects of food upon serum levels

Eighteen patients with airways obstruction were given slow release theophylline and were then investigated to determine the influence of a standard meal upon the serum levels achieved over the ensuing 12-hour period. After food the peak to trough differences were decreased and the serum levels were significantly lower over the first 6 hours. In this study, the patients were given 10 mg/kg/day of slow release theophylline and none subsequently was found to have toxic levels, therefore this was considered to be a reasonable dose with which to initiate therapy in adults with uncomplicated airflow limitation. However even under the strictly controlled conditions of the study there were wide variations between individuals in the blood levels achieved and serum monitoring is necessary to use theophylline in an optimal fashion.     

Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis

The role of tumor necrosis factor-alpha (TNF alpha) in the lethal consequences of intravascular lipopolysaccharide (LPS) or Escherichia coli sepsis was compared with that in bacterial peritonitis. Intravenous administration of E. coli LPS or E. coli (live or dead) resulted in large transient increases in serum TNF alpha levels, peaking at 90 min at 10,000-30,000 units/ml. In contrast, the serum TNF alpha response following the induction of bacterial peritonitis was substantially less, peaking at 200-500 units/ml. Sterile peritonitis (essentially nonlethal) and bacterial peritonitis (greater than 60% lethal) elevated TNF alpha levels to 1000-2000 units/lavage within the peritoneal cavity 2 h after challenge. Passive immunization with neutralizing goat anti-TNF alpha IgG improved survival from 8% to 75% in rats administered LPS intravenously but was completely ineffective in protecting rats from lethal E. coli peritonitis. Thus significant differences exist in the role TNF alpha plays in systemic intravascular models of sepsis and bacterial peritonitis.     

Selection of patients for bile diversion surgery: use of bile acid measurement in fasting gastric aspirates

Eighteen patients with dyspepsia and vomiting which followed surgery for peptic ulcer have completed a study to examine the role of diverting bile from the stomach by a Roux-en-Y procedure. Bile regurgitation and mild epigastric pain relieved by vomiting were abolished. Measurements of bile acids in the fasting gastric aspirate were useful in predicting the outcome of surgery; good results were obtained when initially there was reflex into the stomach of more than 120 mumol/hour of bile acids. A wider group of patients than those selected in previous series may benefit from this operation, as good results can be obtained in patients with dyspepsia relieved by alkali and without achlorhydria or gastritis. Endoscopy was repeated one year after Roux-en-Y operation. Erythema of the mucosa was improved, but gastritis did not improve.     

Irritant induced cough as a model of intrapulmonary airway reactivity

Theophylline, papaverine and isoprenaline produced dose-related inhibition of citric acid induced cough. In addition, cough susceptibility correlated well with the susceptibility of intrapulmonary airways to constrict whether aerosolised citric acid or intravenous histamine were used as the agonists. The anti tussive activity of isoprenaline could be inhibited with propranolol whereas that of theophylline was unaffected. Atropine and propranolol alone failed to modify citric acid induced cough. We suggest that the reactivity of intrapulmonary airway smooth muscle dictates the cough response following inhalation of a citric acid mist.