Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease - United States.

The term "chronic Lyme disease" is used by some health care providers as a diagnosis for various constitutional, musculoskeletal, and neuropsychiatric symptoms (1,2). Patients with a diagnosis of chronic Lyme disease have been provided a wide range of medications as treatment, including long courses of intravenous (IV) antibiotics (3,4). Studies have not shown that such treatments lead to substantial long-term improvement for patients, and they can be harmful (1,5). This report describes cases of septic shock, osteomyelitis, Clostridium difficile colitis, and paraspinal abscess resulting from treatments for chronic Lyme disease. Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks.

Top 10 ideas to improve your bedside teaching in a busy emergency department.

Physicians are called upon to teach students, residents, patients and their families in the clinical environment every day as part of clinical care. A fast-paced emergency department offers a unique set of challenges that require the physician to be an effective communicator. We present a top 10 list of ideas selected from the literature for the busy clinician to use on that next shift to improve bedside teaching.

Recommendations for workforce development in regenerative medicine biomanufacturing.

In its 2019 report, The Skilled Technical Workforce: Crafting America's Science and Engineering Enterprise, the National Science Board recommended a national charge to create a skilled technical workforce (STW) driven by science and engineering. The RegenMed Development Organization (ReMDO), through its RegeneratOR Workforce Development Initiative, has taken on this challenge beginning with an assessment of regenerative medicine (RM) biomanufacturing knowledge, skills, and abilities (KSAs) needed for successful employment. While STW often refers only to associate degree or other prebaccalaureate prepared technicians, the RM biomanufacturing survey included responses related to baccalaureate prepared technicians. Three levels of preparation were articulated in the research: basic employability skills, core bioscience skills, and RM biomanufacturing technical skills. The first two of these skill levels have been defined by previous research and are generally accepted as foundational-the Common Employability Skills developed by the National Network of Business and Industry Associations and the Core Skill Standards for Bioscience Technicians developed by the National Center for the Biotechnology Workforce. Fifteen skill sets addressing the specialized needs of RM and related biotechnology sectors were identified in the ReMDO survey, defining a third level of KSAs needed for entry-level employment in RM biomanufacturing. The purpose of the article is to outline the KSAs necessary for RM biomanufacturing, quantify the skills gap that currently exists between skills required by employers and those acquired by employees and available in the labor market, and make recommendations for the application of these findings.

Cholecystokinin-58 and cholecystokinin-8 exhibit similar actions on calcium signaling, zymogen secretion, and cell fate in murine pancreatic acinar cells.

The gastrointestinal hormone CCK exists in various molecular forms, with differences in bioactivity between the well-characterized CCK-8 and larger CCK-58 previously reported. We have compared the effects of these peptides on cytosolic calcium concentration ([Ca(2+)](c)), mitochondrial metabolism, enzyme secretion, and cell fate in murine isolated pancreatic acinar cells using fluorescence confocal microscopy and patch-clamp electrophysiology. CCK-58 (1-10 pM) induced transient, oscillatory increases of [Ca(2+)](c), which showed apical to basolateral progression and were associated with a rise of mitochondrial NAD(P)H. CCK-58 (10 pM) induced zymogen exocytosis in isolated cells and amylase secretion from isolated cells and whole tissues. Hyperstimulation with supraphysiological CCK-58 (5 nM) induced a single large increase of [Ca(2+)](c) that declined to a plateau, which remained above the basal level 20 min after application and was dependent on external Ca(2+) entry. In cells dispersed from the same tissues, CCK-8 induced similar patterns of responses to those of CCK-58, with oscillatory increases of [Ca(2+)](c) at lower (pM) concentrations and sustained responses at 5 nM. CCK-58 and CCK-8 exhibited similar profiles of action on cell death, with increases in necrosis at high CCK-58 and CCK-8 (10 nM) that were not significantly different between peptides. The present experiments indicate that CCK-8 and CCK-58 have essentially identical actions on the acinar cell at high and low agonist concentrations, suggesting an action via the same receptor and that the differences observed in an intact rat model may result from indirect effects of the peptides. Our data strengthen the argument that CCK-58 is an important physiological form of this gastrointestinal hormone.

Direct activation of cytosolic Ca2+ signaling and enzyme secretion by cholecystokinin in human pancreatic acinar cells.

BACKGROUND & AIMS: Cholecystokinin (CCK) has been thought to act only indirectly on human pancreatic acinar cells via vagal nerve stimulation, rather than by direct CCK receptor activation as on rodent pancreatic acinar cells. We tested whether CCK (CCK-8 and human CCK-58) can act directly on human pancreatic acinar cells. METHODS: Human acinar cells were freshly isolated from pancreatic transection line samples, loaded with Fluo4-AM or quinacrine, and examined for Ca(2+), metabolic and secretory responses to CCK-8, human CCK-58, or acetylcholine with confocal microscopy. RESULTS: CCK-8 and human CCK-58 at physiologic concentrations (1-20 pmol/L) elicited rapid, robust, oscillatory increases of the cytosolic Ca(2+) ion concentration, showing apical to basal progression, in acinar cells from 14 patients with unobstructed pancreata. The cytosolic Ca(2+) ion concentration increases were followed by increases in mitochondrial adenosine triphosphate production and secretion. CCK-elicited Ca(2+) signals and exocytosis were not inhibited by atropine (1 mumol/L) or tetrodotoxin (100 nmol/L), showing that CCK was unlikely to have acted via neurotransmitter release. CCK-elicited Ca(2+) signals were inhibited reversibly by caffeine (5-20 mmol/L), indicating involvement of intracellular inositol trisphosphate receptor Ca(2+) release channels. Acetylcholine (50 nmol/L) elicited similar Ca(2+) signals. CONCLUSIONS: CCK at physiologic concentrations in the presence of atropine and tetrodotoxin elicits cytosolic Ca(2+) signaling, activates mitochondrial function, and stimulates enzyme secretion in isolated human pancreatic acinar cells. We conclude that CCK acts directly on acinar cells in the human pancreas.

Activation of submucosal but not myenteric plexus of the gastrointestinal tract accompanies reduction of food intake by camostat.

UNLABELLED: It has been shown in the rat that endogenous cholecystokinin (CCK), released in response to the non-nutrient trypsin inhibitor camostat, reduces food intake at meals and increases Fos-like immunoreactivity (Fos-LI; a marker for neuronal activation) in the dorsal vagal complex (DVC) of the hindbrain but not the myenteric plexus of the duodenum and jejunum. Experiment 1: We examined Fos-LI in the myenteric and the submucosal plexuses of the gut in response to orogastric gavage of camostat in rats. As we reported previously, camostat failed to increase Fos-LI in the myenteric plexus. We show here that camostat increased Fos-LI in the submucosal plexus of the duodenum and jejunum. Camostat also increased Fos-LI in the DVC. Experiment 2: Pretreatment with devazepide, a specific CCK(1) receptor antagonist abolished camostat-induced Fos-LI in the submucosal plexus and the DVC. Experiment 3: Bilateral subdiaphragmatic vagotomy reduced camostat-induced Fos-LI in the submucosal plexus approximately 40% and abolished it in the DVC. CONCLUSIONS: Activation of the submucosal plexus by cholecystokinin at the CCK(1) receptor accompanies stimulation of the dorsal vagal complex of the hindbrain and inhibition of food intake. Unlike the submucosal plexus, activation of the myenteric plexus is not necessary for cholecystokinin's influence on the dorsal vagal complex and food intake. The lack of activation in the myenteric plexus after camostat stimulation, in contrast to nutrient releasers of CCK such as oleate, suggests that intestinal stimulants can either release different amounts of CCK or cause release of CCK from I cells with different molecular forms of CCK. This would suggest that CCK-8 is released by camostat and is not able to travel to the myenteric plexus while a more stable form of CCK such as CCK-58 can travel to this site that is further away from the I cell.

Cholecystokinin-58 and cholecystokinin-8 produce similar but not identical activations of myenteric plexus and dorsal vagal complex.

The enteric nervous system (ENS: myenteric and submucosal plexuses) of the gastrointestinal tract may have a role in the reduction of food intake by cholecystokinin (CCK). Exogenous cholecystokinin-8 (CCK-8) activates the myenteric plexus and the feeding control areas of the dorsal vagal complex (DVC) of the brainstem. An increasing number of reports, however, have shown that CCK-58 is the sole or the major circulating form of CCK in rat, human and dog, and that it is qualitatively different from CCK-8 in evoking various gastrointestinal physiological responses (e.g., contraction of the gallbladder and exocrine pancreatic secretion). In the current report, we compared the abilities of exogenous CCK-58 to activate the myenteric plexus and the dorsal vagal complex with those of exogenous CCK-8 by quantifying Fos-like immunoreactivity (Fos-LI; a marker for neuronal activation). We report that CCK-58 (1, 3, and 5 nmol/kg) increased Fos-LI in the myenteric plexus (p<0.001) and in the DVC (p<0.001) compared to the saline vehicle. The highest dose of CCK-58 increased Fos-LI more than an equimolar dose of CCK-8 in the myenteric plexus and the area postrema. Thus, CCK-8 and CCK-58 produce the same qualitative pattern of activation of central and peripheral neurons, but do not provoke identical quantitative patterns at higher doses. The different patterns produced by the two peptides at higher doses, in areas open to the circulation (myenteric plexus and area postrema) may reflect endocrine actions not observed at lower doses.

Cholecystokinin-33 is more effective than cholecystokinin-8 in inhibiting food intake and in stimulating the myenteric plexus and dorsal vagal complex.

We compared the abilities of cholecystokinin-33 (CCK-33) and CCK-8 to reduce food intake and to activate feeding-related areas of the nervous system. (1) Overnight food-deprived rats were presented with a 10% sucrose solution, and intake was measured at 5-min intervals throughout a 90-min test beginning immediately after intraperitoneal injections of 1, 3, or 5 nMol/kg of CCK-33, CCK-8, or the vehicle control. In the initial 20 min (first meal), both peptides were equally effective, producing large reductions of food intake. Thereafter, however, CCK-33 was more effective than CCK-8, producing much more sustained reductions. Overall, both peptides reduced total food intake, but CCK-33 was more effective than CCK-8. (2) Possible roles for the myenteric plexus of the duodenum and the dorsal vagal complex (DVC) of the brainstem in the differential satiety effects of CCK-33 and CCK-8 were examined by quantifying CCK-33- and CCK-8-stimulated Fos-like immunoreactivity (Fos-LI) in each site. Consistent with the greater ability of CCK-33 to produce sustained inhibitions of food intake, CCK-33 produced more Fos-LI than CCK-8 in nearly every section of the sampled sites. The results demonstrate: (1) Different forms of CCK have different efficacies in reducing food intake; (2) CCK-33 produces a much more prolonged satiety action than CCK-8; and (3) the myenteric plexus and DVC may play roles in these differential satiety actions.

Progressive ORF virus infection in a patient with lymphoma: successful treatment using imiquimod.

Orf virus is a parapoxvirus that infects small ruminants worldwide. We present the case report of a 73-year-old woman with non-Hodgkins lymphoma who developed progressive orf virus lesions that were unresponsive to surgical debridement and to cidofovir therapy. The patient's orf virus infection was successfully treated with topical imiquimod despite progression of her malignancy.

Surgical outcomes in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy.

HYPOTHESIS: Matched patients who test positive or negative for human immunodeficiency virus (HIV) who are undergoing comparable operations have similar complication rates and outcomes. DESIGN: A retrospective study of surgical outcomes in HIV-infected and matched HIV-noninfected patients. Baseline information including HIV-related laboratory results, complications, and mortality was collected from printed and electronic records through 12 postoperative months. SETTING: Kaiser Permanente Medical Care Program-Northern California, an integrated health organization with more than 3 million members, including more than 5000 HIV-infected members. PATIENTS: From July 1,1997, through June 30, 2002, HIV-infected members undergoing surgical procedures were matched 1:1 with HIV-noninfected patients undergoing surgical procedures by type, location, and year of surgery as well as by sex and age. Surgical procedures studied included appendectomy, arthrotomy or arthroscopy, bowel resection, cholecystectomy, cardiothoracic procedures, hernia repair, hysterectomy, hip or knee replacement, laparoscopy or laparotomy, and mammoplasty. MAIN OUTCOME MEASURES: Complications and mortality through 12 postoperative months, comparisons between HIV-infected and HIV-noninfected patients using matched-pair analyses, and HIV-infected cohort data were analyzed using the Fisher exact test and logistic regression. RESULTS: Of 332 HIV-infected-HIV-noninfected pairs (mean age, 46.7 years; male sex, 91%), more than 95.0% were followed up through 12 postoperative months or until their deaths. Pairs had similar comorbidities, length of hospital stay, and number of postoperative surgical visits (P>.05, all variables). Among HIV-infected patients, the median years with HIV infection was 8.4 years; median CD4 T-cell count was 379/microL; 61.5% of these patients had an HIV RNA level less than 500 copies per milliliter; and 68% were receiving highly active antiretroviral therapy. Various complications were no more frequent among HIV-infected than in HIV-noninfected patients (11.1% vs 10.2%; P = .79), except for pneumonia (P = .04). There were more deaths within the 12 postoperative months in HIV-infected patients (10/332 vs 2/332; P = .02); 2 patients died 30 days or less after being operated on. Among HIV-infected patients, viral load of 30 000 copies per milliliter or more was associated with increased complications (adjusted odds ratio, 2.95; P = .007), but a CD4 cell count less than 200/muL was not associated with poorer outcomes. CONCLUSIONS: The HIV-infected patients had more incidences of postoperative pneumonia and higher 12-month mortality, although other operative outcomes were comparable for HIV-infected and HIV-noninfected patients. Viral suppression to fewer than 30 000 copies per milliliter reduced surgical complications.

Synthesis of biologically active canine CCK-58.

The carboxyl terminal octapeptide of cholecystokinin (CCK-8) has been hypothesized to account for the bioactivity of all the molecular forms of cholecystokinin. However, the physiological relevance of CCK-58 has not been rigorously examined because of the lack of sufficient amounts of the peptide and concerns about inactivation of natural peptides during their purification. Therefore, canine-sulfated CCK-58 was synthesized and conditions determined for its unblocking and purification that preserved the sulfated tyrosine. Synthetic CCK-58 was indistinguishable from natural CCK-58 by amino acid analysis and by mass spectrometry. Synthetic CCK-58 and CCK-8 have different patterns of pancreatic stimulation: both caused a dose-related increase in amylase release, while only CCK-58 stimulated bile-pancreatic output volume. Thus, CCK-58 and CCK-8 are biased agonists at the CCK-A receptor (they have distinct patterns of action mediated by the same receptor). Previous work has demonstrated that the identical carboxyl termini of CCK-8 and CCK-58 have different solution conformations. Taken together, the physiological and structural results support the hypothesis that different carboxyl terminal conformations of CCK-58 and CCK-8 alter the expression of their biological activity.

Unique activities of cholecystokinin-58; physiological and pathological relevance.

PURPOSE OF REVIEW: Cholecystokinin, a regulatory peptide found in multiple molecular forms in brain and small intestine, is responsible for integration of functions associated with the intake, digestion and absorption of food. Whether the different molecular forms have identical biological activities is controversial. New information suggests that CCK58, the largest form of cholecystokinin detected in blood and tissue, has unique functions compared with other forms, and may be the predominant, perhaps only, circulating form in mammals. RECENT FINDINGS: CCK58 has highly distinctive actions compared with shorter forms, most notably the strong stimulation of water secretion from the pancreas, and the lack of induction of pancreatitis by supramaximal doses of the peptide. Because CCK58 may be the main endogenous form of cholecystokinin, these recent findings have far reaching implications because almost all studies carried out with cholecystokinin have been done with shorter forms, predominately CCK8. Conclusions of studies using CCK8 or other shorter forms of cholecystokinin, therefore, may need to be reevaluated. SUMMARY: There is a compelling reason to reevaluate the role of cholecystokinin in health and disease because the predominant form of cholecystokinin, CCK58, has unique biological activities compared with forms of cholecystokinin used in previous basic and clinical studies.

Supramaximal CCK-58 does not induce pancreatitis in the rat: role of pancreatic water secretion.

In contrast to supramaximal CCK-8 or caerulein, acute or prolonged supraphysiological levels of endogenous CCK-58 do not cause pancreatitis. Compared with CCK-8, CCK-58 is a much stronger stimulant of pancreatic chloride and water secretion, equivalent to maximally effective secretin, but with a chloride-to-bicarbonate ratio characteristic of acinar fluid. Because supraphysiological endogenous CCK does not cause pancreatitis and because coadministration of secretin ameliorated caerulein- or CCK-8-induced pancreatitis, coincident with restoring pancreatic water secretion, we hypothesized that supramaximal CCK-58 would not induce pancreatitis. Conscious rats were infused intravenously with 2 or 4 nmol x kg(-1) x h(-1) of CCK-8 or synthetic rat CCK-58 for 6 h, and pancreases were examined for morphological and biochemical indexes of acute pancreatitis. A second group was treated as above while monitoring pancreatic protein and water secretion. CCK-8 at 2 nmol x kg(-1) x h(-1) caused severe edematous pancreatitis as evidenced by morphological and biochemical criteria. CCK-58 at this dose had minimal or no effect on these indexes. CCK-58 at 4 nmol x kg(-1) x h(-1) increased some indexes of pancreatic damage but less than either the 2 or 4 nmol x kg(-1) x h(-1) dose of CCK-8. Pancreatic water and protein secretion were nearly or completely abolished within 3 h of onset of CCK-8 infusion, whereas water and protein secretion were maintained near basal levels in CCK-58-treated rats. We hypothesize that supramaximal CCK-58 does not induce pancreatitis because it maintains pancreatic acinar chloride and water secretion, which are essential for exocytosis of activated zymogens. We conclude that CCK-58 may be a valuable tool for investigating events that trigger pancreatitis.

Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat.

We hypothesized that endogenous CCK reduces food intake by activating the dorsal vagal complex (DVC) and the myenteric neurons of the gut. To test this hypothesis, adult rats were given camostat mesilate; a nonnutrient releaser of endogenous CCK, by orogastric gavage, and Fos-like immunoreactivity (Fos-LI) was quantified in the DVC and the myenteric plexus. The results for endogenous CCK were compared with those for exogenous CCK-8. Exogenous CCK-8 reduced food intake and stimulated Fos-LI in the DVC and in myenteric neurons of the duodenum and jejunum. In comparison, endogenous CCK reduced food intake and increased DVC Fos-LI but did not increase Fos-LI in the myenteric plexus. Similar to CCK-8, devazepide, a specific CCK(1) receptor antagonist, and not L365,260, a specific CCK(2) receptor antagonist, attenuated the reduction of food intake by camostat. In addition, Fos-LI in the DVC in response to both exogenous CCK-8 and camostat administration was significantly attenuated by vagotomy, as well as by blocking CCK(1) receptors. These results demonstrate for the first time that reduction of food intake in adult rats by endogenous CCK released by a nonnutrient mechanism requires CCK(1) receptors, the vagus nerve, and activation of the DVC, but not the myenteric plexus.

Circulating ethanol does not stimulate pancreatic secretion in conscious rats.

The purpose of this study was to test the hypothesis that circulating ethanol at concentrations of approximately 0.1 mg% stimulates pancreatic secretion. Awake rats recovered from surgery were used in these experiments. Intravenous infusion protocols were established that produced blood ethanol concentrations 0.1 mg% for over an hour. Maintenance of 0.1 mg% blood ethanol concentration or transient concentrations as high as 0.17 mg% did not cause significant increases in pancreatic protein or fluid secretion. To test whether elevated blood ethanol would augment stimulated pancreatic secretion, the trypsin inhibitor camostat was infused intraduodenally at doses of 0.05, 0.2, and 0.5 mg/hr, each dose level infused for 2 hours. Elevated blood ethanol concentrations (0.1 mg%) did not significantly affect camostat-stimulated pancreatic protein or fluid secretion. In contrast to intravenous infusion, intraduodenal infusion of ethanol significantly stimulated pancreatic protein and fluid secretion, which was associated with blood ethanol concentrations of > or =0.19 mg%. The increases in pancreatic secretion were completely blocked by intravenous infusion of the cholecystokinin (CCK) receptor antagonist CR1409. We conclude that circulating ethanol does not stimulate pancreatic secretion in awake, recovered rats and that intraduodenal ethanol-stimulated pancreatic secretion is mediated by CCK.

Quinolones: a comprehensive review.

With the recent introduction of agents such as gatifloxacin and moxifloxacin, the traditional gram-negative coverage of fluoroquinolones has been expanded to include specific gram-positive organisms. Clinical applications beyond genitourinary tract infections include upper and lower respiratory infections, gastrointestinal infections, gynecologic infections, sexually transmitted diseases, and some skin and soft tissue infections. Most quinolones have excellent oral bioavailability, with serum drug concentrations equivalent to intravenous administration. Quinolones have few adverse effects, most notably nausea, headache, dizziness, and confusion. Less common but more serious adverse events include prolongation of the corrected QT interval, phototoxicity, liver enzyme abnormalities, arthropathy, and cartilage and tendon abnormalities. The new fluoroquinolones are rarely first-line agents and should be employed judiciously. Inappropriate use of agents from this important class of antibiotics will likely worsen current problems with antibiotic resistance. Applications of fluoroquinolones in biologic warfare are also discussed.

CCK-58 is the only detectable endocrine form of cholecystokinin in rat.

CCK-58 differs from CCK-8 in patterns of expression of pancreatic secretion of fluid and amylase and gallbladder contraction. These differences have physiological relevance only if CCK-58 release is stimulated by nutrients entering the intestine and if CCK-58 circulates in sizeable amounts. In this study, we report that when radiolabeled CCK-58 is added to rat blood and plasma is formed, there is extensive loss and degradation of the radioactive peptide. Therefore, a new method was developed to minimize loss and degradation of this label. This method recovered >85% of the label with no detectable degradation. Furthermore, the optimized method recovered all unlabeled exogenous cholecystokinin molecular forms in >80% yields. Blood from fasted rats and rats in which cholecystokinin release was stimulated by the trypsin inhibitor camostat contained only CCK-58 (3.5 +/- 0.5 and 17 +/- 1.5 fmol/ml, respectively). Because CCK-58 predominates in the blood, this molecular form should be used in studies on the physiology and pathophysiology of cholecystokinin.

Luminal CCK-releasing factor stimulates CCK release from human intestinal endocrine and STC-1 cells.

CCK is secreted into the blood from intestinal endocrine cells following ingestion of a meal. Recently, it has been demonstrated that the ability of certain foods to stimulate CCK release is mediated by endogenously produced CCK-releasing factors. A newly discovered luminal CCK-releasing factor (LCRF) is secreted into the intestine, where it stimulates CCK secretion. However, the mechanism whereby LCRF affects intestinal epithelial cells is unknown. The current study was designed to determine whether LCRF has a direct effect on CCK cells to stimulate hormone secretion. In dispersed human intestinal mucosal cells, LCRF (5-200 nM) significantly stimulated CCK release in a concentration-dependent manner. This stimulatory effect was absent in calcium-free media and was inhibited by the L-type calcium-channel blockers diltiazem and nifedipine. To examine direct cellular effects of LCRF on CCK cells, further studies were conducted in the CCK-containing enteroendocrine cell line STC-1. As in native cells, LCRF significantly stimulated CCK release from STC-1 cells in a calcium-dependent manner. In cells loaded with a calcium-sensitive dye, LCRF stimulation produced a rapid increase in intracellular calcium. To examine the electrophysiological basis for this stimulation, whole cell recordings were made from STC-1 cells. Whole cell calcium currents were identified under basal conditions; moreover, calcium-channel activity was increased by LCRF. These studies demonstrate that 1) LCRF has a direct effect on human intestinal cells to stimulate CCK secretion, 2) stimulated hormone release is calcium dependent, and 3) LCRF activates calcium currents in CCK cells, which leads to CCK secretion.

Differential bile-pancreatic secretory effects of CCK-58 and CCK-8.

In this work, we 1) synthesized rat CCK-58, 2) determined the amounts and forms of rat CCK in whole blood after stimulation of its release by casein, 3) determined the potency of CCK-8 and CCK-58 peptides to displace labeled CCK-8 from CCK(A) and CCK(B) receptors transfected into Chinese hamster ovary (CHO) cells, and 4) examined the biological actions of CCK-8 and rat CCK-58 in an anesthetized rat model. CCK-58 was the only detected endocrine form of CCK in rat blood. Synthetic rat CCK-58 was less potent than CCK-8 for displacing the label from CCK(A) and CCK(B) receptors in transfected CHO cells. However, rat CCK-58 was more potent than CCK-8 for stimulation of pancreatic protein secretion in the anesthetized rat. In addition, CCK-58 but not CCK-8 stimulated fluid secretion in this anesthetized rat model. These data suggest that regions outside the COOH terminus of rat CCK-58 influence the expression of CCK biological activity. The presence of only CCK-58 in the circulation and the fact that its biological activity differs from CCK-8 suggests that CCK-58 deserves scrutiny in other physiological models of CCK activity.