Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.

Retroodontoid Pseudotumor Related to Development of Myelopathy Secondary to Atlantoaxial Instability on Os Odontoideum.

Retroodontoid pseudotumor (ROP) is a nonneoplasic lesion of unknown etiology, commonly associated with inflammatory conditions, and the term of pannus is usually used. Less frequently, ROP formation can develop with other noninflammatory entities, with atlantoaxial instability as most accepted pathophysiological mechanism for posttraumatic or degenerative ROP. As it can clinically and radiologically mimic a malignant tumor, it is paramount for the radiologist to know this entity. Magnetic resonance imaging is the modality of choice to reveal the possible severe complication of ROP in the form of a compressive myelopathy of the upper cervical cord. The purpose of the surgical treatment is the regression or complete disappearance of ROP, with posterior decompression by laminectomy and posterior C1-C2 or occipitocervical fixation. We present the case of an elderly patient with retroodontoid soft tissue mass secondary to a chronic atlantoaxial instability on os odontoideum, an extremely rare cause of ROP. The patient developed a posttraumatic cervical myelopathy related to the decompensation of this C1-C2 instability responsible for the formation of a compressive ROP. We will overview the retroodontoid pseudotumor and its differential diagnosis.

Cancer incidence in the Mexican-American.

Lower incidence rates of cancer for all anatomic sites combined were found in male and female Spanish-surnamed residents of Los Angeles County when compared to other whites. These Mexican-Americans were at lower risk for cancer of the buccal cavity, colon, rectum, larynx, lung, breast, bladder, prostate, and testis, and were at higher risk for cancer of the stomach, gallbladder, liver, and cervix. Immigrant Mexican-Americans had incidence rates most divergent from other whites, whereas indigenous Mexican-Americans had rates between the other two groups. The cancer pattern in Mexican-Americans was generally similar to that in American Indians. These data were most consistent with environmental variations in cause.

'Diaphragmlike' stricture and ulcer of the colon during diclofenac treatment.

Diclofenac sodium is a widely used enteric-coated nonsteroidal anti-inflammatory drug. We describe a woman with Hemoccult-positive stools and iron deficiency anemia who developed both a colonic ulcer and a "diaphragm-like" colonic stricture while taking enteric-coated diclofenac. These lesions were evident on colonoscopy but not on barium studies. Biopsy specimens of the ulcer and stricture revealed particulate matter that was indistinguishable from diclofenac pill fragments by electron microscopy. Discontinuation of diclofenac therapy resulted in resolution of anemia and Hemoccult-positive stools. We conclude that (1) enteric-coated diclofenac is associated with both colonic ulcers and diaphragm-like colonic strictures; (2) the pathophysiologic mechanism for the development of both ulcers and strictures may involve a direct action of diclofenac within these lesions; (3) colonoscopy may be superior to barium studies in evaluating patients receiving diclofenac who have iron deficiency anemia and/or Hemoccult-positive stools.

HIV-1 western blot assay: What determines an indeterminate status?

BACKGROUND: The Western blot assay is the gold standard for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1). However, indeterminate Western blot reactivity to HIV-1 proteins may occur in individuals, who may not be infected with HIV. AIM: This retrospective study was aimed to determine the diagnostic value of the interpretation criteria in relation to commercial kits for HIV-1 diagnosis. METHODS AND MATERIALS: A total of 556 serum/plasma specimens collected from high-risk population attending our HIV clinic from 2000-2004 were tested by three different western blot kits: NEW LAV BLOT I (n=244), HIV BLOT 2.2; (n=112), Genetic Systems HIV-1 (n=237). And the results of western blot strips were analyzed using the various interpretation criteria: WHO/NACO, CDC/ ASTPHLD, ARC, FDA, CRSS and JHU. Some specimens were run on more than one kit. RT-PCR assay was performed on 5 specimens, which were indeterminate with LAV BLOT I. RESULTS: The discrepancy in LAV BLOT I positive results were between 157(64)-176(72), and indeterminate results were between 44(18) to 63(25). No such variations were observed in genetic systems. There are some HIV negative (by PCR) specimens were indeterminate in LAV BLOT I revealing the kit more sensitive and less effective for diagnostic purpose. CONCLUSION: The genetic systems kit is superior to other kits we analyzed and its results are concordant with HIV-1 PCR results. To report, the choice of western blot commercial kit is paramount important than the use of particular interpretation criteria for the diagnosis of HIV-1.

Hereditary pancreatitis and pancreatic carcinoma.

Few risk factors for pancreatic cancer have emerged except for chronic pancreatitis. Recently, hereditary pancreatitis was estimated to carry a standardized incidence ratio of 53, a risk about 25 times higher than smoking. A review of the ongoing hereditary pancreatitis study of the Midwest Multicenter Pancreatic Study Group suggests that the risk of pancreatic cancer is related to long-standing pancreatitis rather than to the cationic trypsinogen mutations. No recommendations can be made on screening patients with hereditary pancreatitis for pancreatic cancer at this time. However, prospective data, serum, and pancreatic juice should be collected and banked on consenting patients at risk as part of prospective, multicenter trials so that evidence-based recommendations for hereditary pancreatitis and other types of chronic pancreatitis can be made in the future.

Use of omeprazole in the management of giant duodenal ulcer: results of a prospective study.

BACKGROUND: Giant duodenal ulcer (GDU) is generally thought to require surgical intervention. Proton pump inhibitors have beneficial effects in peptic ulcer disease, but their role in GDU disease is unknown. We examined the use of omeprazole in GDU management. METHODS: Twenty-eight patients were diagnosed with GDU. One patient required immediate operative intervention. The remaining 27 were placed on omeprazole (40 mg daily). When ulcer healing was documented by endoscopy, the patients were placed on oral histamine-2 receptor antagonist therapy. RESULTS: Of the 28 study patients, 20 (71.4%) did not require operative intervention, and 8 (28.6%) required operation for ulcer complications. Of the 15 patients with adherent clot or a visible vessel at initial endoscopy, 7 (46.7%) required operative intervention, as compared with 1 (7.7%) of the 13 patients without a visible vessel or adherent clot. This difference was statistically significant (P < .05). Twenty-three patients underwent antral biopsy and/or enzyme-linked immunosorbent assay for Helicobacter pylori, and 9 (39.1%) had a positive result. CONCLUSIONS: Omeprazole is effective in the treatment of GDU disease. An adherent clot or a visible vessel at endoscopy indicates a higher likelihood of complications requiring operation. The relatively low H pylori infection rate, as compared with other peptic ulcer disease, may indicate a different pathophysiology in GDU.

Optimisation of the enzyme-based determination of hydrogen peroxide using the quartz crystal microbalance.

The benzidines, 3,3'-diaminobenzidine (DAB), 3,3'-dimethoxybenzidine (DMOB) and 3,3',5,5'-tetramethylbenzidine (TMB) were enzymatically oxidised to detect hydrogen peroxide, using the quartz crystal. The oxidised product mainly remains in suspension, resulting in a limited quartz sensor signal. We have used two non-ionic surfactants, Tween 80 and Triton X-100 to interact with the oxidised amphiphilic products to increase their solubility and surface activity, and their ability to adsorb to the crystal surface. Tween 80 exhibits optimised response effects for DAB, DMOB and TMB at 0.012, 0.005, and 0.002% (v/v), respectively, whereas Triton X-100 is optimum at 0.1, 0.2, and 0.006% (v/v), respectively. As a result, we have improved the quartz crystal sensor sensitivity to peroxide. The use of Triton X-100 gave an improved response time.

Pancreatic cancer surveillance in a high-risk cohort. Is it worth the cost?

Pancreatic adenocarcinoma is the 10th most common malignancy and 4th largest cancer killer in adults. Earlier tumor detection through screening of high risk groups, presumably to increase the percentage of cases resectable for cure in these cohorts, has emerged as a prominent strategy to combat this disease. This article examines the feasibility of this strategy in patients with hereditary pancreatic cancer (HPC) and hereditary pancreatitis (HP). Because of a variety of factors, specific cost projections for screening with HPC kindreds are problematic at best. Patients with HP exhibit a 53-fold increased risk of pancreatic cancer, with a cumulative risk of 40% by age 70. The authors discuss the modalities available to screen this cohort and subsequently perform a theoretical cost analysis. The authors' findings suggest that screening has the potential to be cost-effective only in hereditary pancreatitis patients = 50 years-of-age. The most cost-effective option will likely combine an initial serologic test with high sensitivity and a subsequent serologic or pancreatic juice test with sufficient specificity to act as a "gatekeeper" to imaging with endoscopic ultrasound (EUS). Banking of blood and pancreatic juice samples should be mandatory in any screening protocol. The lower tumor yield in other high-risk groups (e.g., non-hereditary chronic pancreatitis) will effectively preclude the use of such screening protocols. The vast majority of patients will continue to present with unresectable disease.

Peripherally inserted central catheters revisited.

BACKGROUND: This study compares central venous catheters (CVC) and peripherally inserted central catheters (PICC) for indications for insertion, complications, and economic impact. METHODS: A retrospective review of 838 (283 CVC, 555 PICC) consecutively placed venous catheters reflected 49,365 CVC and 11,814 PICC days. RESULTS: There were 57 (20%) complications in the CVC group, 197 (35%) complications in the PICC group. PICC were associated with a statistically significant increase in the incidence of catheter malfunction (P = 0.0005), arm vein phlebitis (P = 0.0004), and overall complications (P = 0.00001). A higher complication rate was noted in PICC inserted for chemotherapy (P = 0.00001) and parenteral hyperalimentation administration (P = 0.04). Charges for inpatient insertion of PICC and CVC were $500 and $2,500, respectively. CONCLUSIONS: PICC have a significantly higher complication rate than CVC. PICC provide cost-effective central access of 2 to 3 weeks' duration, reserving operatively placed CVC for longer access requirements.

Effects of dominance rank on d-amphetamine-induced increases in aggression.

Previous research has suggested that certain social factors, e.g., dominance rank, can determine the behavioral effects of drugs in individual members of a social group. In the present experiment, the effects of d-amphetamine were studied in two adult male monkeys with dominance rankings that changed during a reorganization of the social hierarchy in a captive group of stumptail macaques (Macaca arctoides). A range of doses of d-amphetamine was administered to each subject, and dose-effect curves were determined before and after group reorganization and stabilization. The data revealed drug effects which were dependent upon dose and the social rank of the animals. When either subject occupied the highest ranking or alpha position within the dominance hierarchy, rate of aggressive behavior initiated by the subject was several times greater than when that monkey occupied a lower position within the dominance hierarchy. Moreover, for either subject, the dose-effect curve was shifted to the right when the monkey was highest in the dominance hierarchy. Finally, aggression initiated by the drug-treated subject was directed more frequently toward adult members of the group when the subject was highest in the hierarchy and toward nonadult animals when the subject was lower in the hierarchy. These data support the hypothesis that the dominance position of an animal in a group can be a determinant of the behavioral effect of certain drugs.

An areawide cancer reporting network.

A cancer Surveillance Program was formed in 1970 to provide a mechanism for the early identification of some 22,000 cancer cases that are diagnosed annually among the large and varied population of Los Angeles County. The program's rapid reporting procedures facilitate early access to patients for interviewing and specimen collection. Routine review of all reports of microscopically diagnosed malignancies in hospitals throughout the county and screening of all of the county's death certificates provide virtually complete data on cancer incidence in the county. Case reports include information on age, ethnic group, birthplace, residence, religion, marital status, occupation, and industry. Continuing analysis of this information has led to the development of epidemiologic studies of several factors which may have an etiological relationship to human cancer. Among these factors are genetic susceptibility, exposure to air pollutants and industrial carcinogens and possible viral transmission.

Pancreatic disease in the elderly.

This article reviews age-related alterations in pancreatic structure and function and provides an update of advances in clinical understanding of the epidemiology, pathogenesis, and pathophysiology of acute pancreatitis, chronic pancreatitis, and pancreatic adenocarcinoma. This article also provides guidelines for the integration of recent radiologic, endoscopic, surgical, and oncologic advances in these areas into the current clinical practice of the gerontologist and gastroenterologist.