Workup of a patient with familial pancreatic cancer.
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Biomedical subjects
Publications and source records attributed to W M Steinberg.
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By the application of RT-PCR, we have demonstrated that in the human endometrium mRNAs for insulin-like growth factors, IGF-I and II, and their receptors are expressed not only in the intact endometrium, but also in the freshly isolated stromal and epithelial cells. The expression of multiple transcript forms of the IGF-I and II at various phases of the menstrual cycle, occurs by differential use of all four IGF-I transcriptional start sites, and two of the four known promoter sites of the IGF-II gene. The complete spectrum of transcripts is displayed by the proliferative phase and the menstrual phase endometrium. During the secretory phase, the exon 1 upstream start site of the IGF-I gene and the P2 promoter of the IGF-II gene are not used. Irrespective of the phase of the menstrual cycle, the stromal cells always display the same transcriptional patterns of both growth factor genes as those of the intact endometrium. In contrast, the epithelial cells do not express IGF-I transcript originating from the exon 2 upstream initiation site. These results indicate that the expressions of the IGF-I and II genes in the intact endometrium and stromal and epithelial cells are modulated at the transcriptional level during the menstrual cycle by differential usage of promoters and start sites.
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It has recently been shown that the infusion of oleic acid into the rat pancreaticobiliary duct causes a reproducible and long-lasting atrophy of the exocrine pancreas. The effects of this pancreatic atrophy on non-invasive pancreatic function tests have not been fully characterized. This study was undertaken to determine which pancreatic function test was most useful in determining pancreatic insufficiency in this model. Pancreatic insufficiency (PI) was induced in male Wistar rats by oleic acid infusion and three pancreatic function tests were compared in these animals and saline controls. The coefficient of fat absorption on a 5 or 45% fat diet and bentiromide testing could not differentiate animals with or without PI, but fecal chymotrypsin levels were excellent discriminators. All animals with PI had fecal chymotrypsin levels below 67 U/g feces whereas all saline controls were above this level. We conclude that, in this model of PI, the fecal chymotrypsin concentration is the best non-invasive test to determine pancreatic insufficiency.
To characterize the CEA in colonic effluent, anti-CEA monoclonal antibody COL-4 was used in a qualitative radioimmunoassay in both fractionated and unfractionated colonic effluent. Both effluent samples and tissue extracts, were subjected to Western blotting and tissue sections to immunohistochemistry. Quantitative levels of colonic effluent CEA were determined by a kit (Abbott-EIA). Higher mean values of COL-4 binding activity were seen only in patients with a past history of polyps (P < 0.01). Quantitated CEA correlated with the presence of colorectal cancer (CRC) as compared to normal subjects, (1133 +/- 875 vs. 459 ng/ml +/- 602, P < 0.05) but not when standardized for protein content. COL-4 reacted with an 180,000 M(r) CEA in the effluent and activity was associated with membrane fraction of the effluent, but bore no relation to the immunohistological staining. We conclude that CEA is detectable in colonic effluent and is membrane associated, but the overlapping values in effluent samples do not make this a useful test in the diagnosis of CRC.
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We report three patients with diabetic ketoacidosis (DKA) who presented with striking elevations of serum lipase levels and less striking elevations of amylase and trypsinogen. All three had nausea and vomiting, but none had objective evidence of abdominal pain, and computed tomography scans of the pancreas were unremarkable. These cases suggest the association of asymptomatic enzyme elevations with DKA. We review the literature on this subject.
"Hypertext" applications have become an important educational resource for medical teaching. ToolBook version 1.5 allows the import of SVGA 256 color, 640 x 480 pixel images. We developed a program for the review of Gastroenterology by Subspecialty Board applicants which included digitized pathology, endoscopy, dermatology, and radiology images interfaced with textual description. 5 cases were presented with 6 questions per case to test the user's comprehension of the material. A scoring function was included to give feedback to the users. An evaluation questionnaire was also completed to survey user satisfaction with the program. A similar "shell" could be applied to other teaching programs.
The authors retrospectively describe the computed tomographic (CT) findings in 35 patients with peptic ulcer disease. Three of eight patients with gastritis or duodenitis had bowel-wall thickening. Ten of the remaining 27 patients had CT evidence of ulcer perforation (n = 2) or penetration (n = 8), four cases of which were unsuspected clinically. Both patients with acute free perforation had pneumoperitoneum, and one showed free extravasation of orally administered contrast material. The precise site of perforation could not be established in either case with CT. The eight patients with ulcer penetration had CT evidence of bowel-wall thickening (n = 3) and inflammatory changes in adjacent soft tissues and organs (n = 8), including the pancreas (n = 4), liver (n = 1), and lesser omentum (n = 1). Ulcer craters were seen in only two. The CT findings of penetration can mimic other disease processes. CT was not useful in detecting uncomplicated peptic ulcer disease.
We wished to determine whether DNA flow cytometric analysis could detect DNA abnormalities in normal-appearing mucosa of patients with colonic neoplasia. Eighty-five patients were studied either at colonoscopy or at surgical resection. Forty-five had macroscopically normal colonoscopy; 13 had adenomatous polyps, and 27 had colorectal carcinoma. Biopsies were obtained from the cancer and from normal-appearing mucosa 5 cm from the lesion. The patients who had normal colonoscopy had rectal biopsies. The samples were prepared for analysis on a Coulter EPICS C flow cytometer. Cells were analyzed for presence of aneuploidy (%AN), percent in DNA synthetic phase (%S), and percent growth fraction (%GF = %S + %G2M). Aneuploidy was present in 12 of 27 carcinomas (44%), but in none of the samples from polyps or normal-appearing colorectal mucosa adjacent to cancers. The %S from cancers was greater than those from polyps (9.6 +/- 6.3 vs. 5.1 +/- 1.8, p less than 0.005). However, %S from specimens arising from normal-appearing mucosa 5 cm distant from cancer could not be differentiated from the rectal mucosa of macroscopically normal colons (5.9 +/- 2.5 vs. 5.2 +/- 2.7). The %GF of cancer specimens was greater than those from adenomas (26.0 +/- 11.0 vs. 10.8 +/- 3.7, p less than 0.005). However, the %GF of normal-appearing mucosa 5 cm distant from the cancer was similar to the findings from mucosa arising from macroscopically normal colons (10.5 +/- 3.3 vs. 11.0 +/- 3.4). In conclusion, DNA flow cytometric analysis of normal-appearing colonic mucosa from patients with colonic carcinoma does not demonstrate abnormalities of DNA content or cell cycle kinetics, and therefore, cannot predict the presence of colonic neoplasia.
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We compared the diagnostic sensitivities of serum amylase, lipase (assayed enzymatically and immunologically), trypsinogen and elastase-1, the 2-h-timed urine amylase excretion and the ratio of amylase and creatinine clearances in the recognition of acute pancreatitis. Serial serum and urine findings from 39 patients with acute pancreatitis, and from 42 patients with non-pancreatic causes of abdominal pain (controls), as well as findings from 24 healthy subjects (normals) were studied. Decision thresholds were established for each parameter using either the control or the normal population, and the resulting diagnostic sensitivities determined. On hospital admission, all serum assays were equally sensitive, but on subsequent days lipase, trypsinogen and elastase-1 assays all significantly surpassed the sensitivity of the serum amylase assay. On the second and subsequent hospitalization days, determination of timed urine amylase excretion offered no advantage over the serum amylase, and the ratio of amylase and creatinine clearances lacked discrimination altogether.
A 28-year-old woman with nausea, vomiting, and abdominal pain had been hospitalized elsewhere on 13 separate occasions over the year before this admission for similar episodes thought to be secondary to acute pancreatitis. She had undergone repeated work-ups including endoscopic retrograde cholangiopancreatography, computed tomographic scan, and exploratory laparotomy. There was a discrepancy between her unremarkable physical examination and extremely elevated amylase (3,210 U/L) which suggested nonpancreatic hyperamylasemia; normal serum pancreatic isoamylase, trypsinogen, and lipase confirmed this suspicion. The patient was noted to have self-induced vomiting in the hospital which she admitted was frequent behavior. her psychiatric disturbance was characterized as an atypical eating disorder. This case illustrates that hyperamylasemia in association with abdominal pain, nausea, and vomiting may not be secondary to pancreatitis and that use of a second serum marker (such as trypsinogen, lipase, or isoamylase) helps to establish a definitive diagnosis.
This article summarizes the sensitivities, specificities, and predictive values of five types of predictors of severity of acute pancreatitis: the clinician's assessment, Ranson and modified Glasgow criteria, peritoneal tap, computed tomographic scan, and individual laboratory tests.
Data on the risks and benefits of using the oral contraceptive continue to accumulate. Because of continuing changes in the formulation and dosage of both the estrogens and progestins, the medical community must constantly re-evaluate all older data when considering current risk/benefit ratios. The changes in pill formulation have led to increased acceptability with a reduction of both nuisance and serious long-term side effects. The risks must be balanced against the major contraceptive and non-contraceptive benefits that are provided by the pill. Although both the benefits and risks have been documented in the literature, both the physician and the patient are being overwhelmed by press reports stressing mainly the negative aspects of the pill. It is incumbent on all physicians to periodically review the sources and validity of all medical reports on the pill. While the benefits of the pill outweigh the risks, the physician must be constantly aware of the changing world literature in order to optimize his/her prescribing patterns.
The optimal strategy for the diagnosis of acute pancreatitis with enzyme assay results as indicators was evaluated in 67 emergency cases in whom this condition was suspected. We measured urine amylase expressed as activity concentration (U/L), timed excretion (U/h), and amylase/creatinine clearance ratio, and also serum amylase, elastase, lipase, and trypsinogen, at admission and repeatedly during hospitalization. The receiver-operator characteristic function was used to evaluate the diagnostic discrimination of each variable among initial findings and among the highest individual findings established retrospectively. We applied the same treatment to multiple univariate discrimination, using the six possible pairs and the four possible triplets of serum indicators. The results suggest that such urine assays should be abandoned, that all individual serum assays combine about 0.9 sensitivity with 0.9 specificity, that pairing of two assays does not clearly enhance discrimination, and that triplets of tests may degrade discrimination. The trade-off between sensitivity and specificity is a function not only of the chosen decision threshold but also of the sampling strategy (initial vs highest values) and of the interpretation rule (Boolean "and" vs "or" strategy).