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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 487 records · Page 27Linked to original sources
PubMedDate not supplied

Hepatic and pancreatic metabolism and biliary excretion of the protease inhibitor camostat mesilate.

The hepatic metabolism and biliary and pancreatic excretion of the serine protease inhibitor camostat mesilate and its metabolites FOY-251 and GBA were studied in rats in vivo and in in sutu liver-perfusion experiments. After oral feeding (100 mg/kg) and iv infusion (5 mg/kg.h) of camostat mesilate, the original compound and both metabolites appeared in bile, but could not be detected in pancreatic juice. In plasma, only FOY-251 and GBA were detected. In the perfused rat liver, camostat mesilate (10 microM) was eliminated by 33.8% and its molar rate of degradation to FOY-251 was 25.1%. During the study period about 0.1% of camostat mesilate and FOY-251 appeared in bile. The liver perfusion of FOY-251 or GBA revealed very low hepatic extraction rates of 10.3 and 2.4%, respectively. In conclusion, the low hepatic extraction rate of camostat mesilate and its metabolites leads to high concentrations of the active metabolite FOY-251 in plasma. Camostat mesilate and its metabolites are effectively excreted into bile, but not in rat pancreatic juice.

Administration, Oral↗
PubMedDate not supplied

Bak expression and cell death occur in peritumorous tissue but not in pancreatic cancer cells.

Bak is a pro-apoptotic member of the Bcl-2 family whose genes are involved in regulation of programmed cell death. Using in situ hybridization, immunohistochemistry, and Northern blot analysis, we studied the expression of Bak in specimens from 12 normal pancreata and 26 primary pancreatic cancers, and correlated the findings with the clinical and histopathologic data of the patients. By comparison with normal pancreas, Northern blot analysis demonstrated a 2.5-fold increase of Bak messenger RNA expression in the tumor samples (P <0. 001). Elevated levels were found in 15 of the 26 pancreatic cancer tissue specimens. In these samples Bak expression was increased 4.3 fold (P <0.001). No association was detected between Bak expression and tumor stage. In situ hybridization and immunohistochemistry revealed that the tumor cells themselves and the stroma cells expressed only low levels of Bak. In contrast, in regions adjacent to the tumor, which showed chronic inflammation, there was always high expression in the acinar and inflammatory cells, explaining the increased Bak levels found in the tumor samples by means of Northern blot analysis. In the normal pancreas the expression of Bak was generally moderate in the acinar cells and low in the ductal and islet cells. In situ analysis using the terminal deoxynucleotidyl transferase method further showed that there was extensive cell death in the peritumorous areas with chronic inflammation. Taken together, these results suggest that in pancreatic cancer Bak expression and programmed cell death are present in cells that are localized in regions of chronic inflammation surrounding the pancreatic cancer cells but not in the tumor cells themselves, a situation that may facilitate tumor growth and spread.

Adolescent↗
PubMedDate not supplied

Effects of felodipine, a new dihydropyridine vasodilator, on regional myocardial blood flow during acute coronary occlusion in the pig.

We studied the effects of felodipine [4-(2,3-dichlorophenyl)-1,4-dihydropyridine-2,6-dimethyl 3,5-dicarboxylic 3-ethylester and 5-methylester] on the coronary vascular bed of pig hearts with an ischemic region in the left ventricle following ligation of the left anterior descending coronary artery. At an infusion rate of 0.12 nmol X kg-1 X min-1, felodipine caused a slight reduction in mean arterial blood pressure and a decrease in coronary vascular resistance in both normal myocardium and partly ischemic myocardium of the border zone. In another series of experiments, felodipine was infused at a higher rate (0.38 nmol X kg-1 X min-1). The resultant decrease in mean arterial blood pressure, which was about 30%, was counterbalanced by inflation of an aortic balloon to keep the afterload and the coronary perfusion pressure constant. In this situation, felodipine caused a pronounced increase in blood flow to all parts of the heart except the central ischemic zone, where blood flow was extremely low. We conclude that felodipine has a coronary vasodilator action which is at least of the same magnitude as its peripheral vasodilator action, and that it markedly increases coronary blood flow in the border zone of an ischemic area.

Animals↗
PubMedDate not supplied

Effects of tropisetron, a 5-HT3 receptor antagonist, on proximal gastric motor and sensory function in nonulcer dyspepsia.

BACKGROUND: Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). In a double-blind crossover study, we evaluated the effects of tropisetron, a 5-HT3 receptor antagonist, on gastric accommodation, reflex relaxation, and sensitivity in NUD patients. METHODS: Eight patients and 10 healthy controls received placebo or 5 mg tropisetron on separate days. On each day, gastric accommodation and relaxation were investigated using a gastric barostat. The perception during gastric distension and relaxation was scored by a verbal perception score. RESULTS: Under both medications, gastric accommodation and postprandial gastric reflex relaxation were not impaired in the NUD patients. The visceral perception was increased in the NUD patients and not substantially influenced by tropisetron. CONCLUSIONS: Tropisetron does not influence gastric accommodation, reflex relaxation, or gastric sensitivity in NUD patients and healthy controls.

Adult↗
PubMedDate not supplied

Genomic imprinting of IGF-II and H19 in adult human pancreatic tissues.

BACKGROUND/AIM: Genomic imprinting is a chromosomal modification causing differential expression of maternal and paternal alleles. Loss of imprinting (LOI) of IGF-II and H19 has been suggested to be an early oncogenic event in cancerogenesis. Aim of the present study was to describe the status of IGF-II and H19 imprinting in adult human pancreatic tissues. METHODS: Allele-specific gene expression was studied using RNA and DNA from human pancreatic cancer, chronic pancreatitis, and normal pancreas tissues heterozygous for ApaI (IGF-II) or RsaI (H19) restriction fragment length polymorphism. Reverse-transcriptase polymerase chain reaction products were digested with either ApaI or RsaI and analyzed on agarose gels to study the status of allelic expression. The expression level of H19 and IGF-II was studied on Northern blots or by polymerase chain reaction. RESULTS: H19 was imprinted in normal pancreas and in chronic pancreatitis. H19 LOI was observed in 1 of 4 informative cancer tissues and was not associated with increased H19 transcript levels. Biallelic expression of IGF-II was found in 6 of 10 informative cancer tissues and in 6 of 9 informative normal tissues. In chronic pancreatitis, the IGF-II gene was imprinted in all informative samples. IGF-II mRNA was not overexpressed in the tissues showing LOI. CONCLUSION: Low frequencies of H19 LOI and the lack of correlation between biallelic expression and overexpression observed for both H19 and IGF-II suggest that LOI of H19 and IGF-II is not a relevant oncogenic factor during human exocrine pancreatic cancerogenesis.

Adenocarcinoma↗
PubMedDate not supplied

Gallstones and acute pancreatitis--mechanisms and mechanics.

The observation that necrotizing pancreatitis and gallstones can be associated is more than 300 years old [1]. Since the beginning of our century, numerous investigations have addressed the question as to how gallstones cause pancreatitis. Despite this effort and many excellent clinical and experimental studies, few pathophysiological issues in gastroenterology have remained so controversial and even fewer have found advocates with such incompatible views and uncompromising convictions. We will review the past and present theories regarding the pathophysiology of gallstone-induced pancreatitis and outline the therapeutic consequences implied by these concepts.

Acute Disease↗
PubMedDate not supplied

Transference, countertransference, and abuse in psychotherapy.

The complex factors that can lead to either creative or destructive experiences in psychotherapy for both patients and therapists are explored with reference to the treatment of patients with a history of abuse. Particular emphasis is placed upon the formation of an intermediate space, in which a safe therapeutic environment is established, allowing for the creative interplay of past and present. The concepts of the transitional object, transitional phenomena, and projective identification are defined and amplified in explaining how they help to determine whether a safe therapeutic space is achieved, or whether destructive, abusive experiences are re-created, for both patient and therapist. In addition, the importance of the therapist's capacity to tolerate the ambiguity and uncertainty of psychotherapy is elaborated. The relationship between these formulations and the therapist's countertransference is emphasized. Also described is the importance of supervision in helping therapists--during training and throughout professional life--to discuss shame-arousing experiences with their patients.

Borderline Personality Disorder↗
PubMedDate not supplied

When your star performer can't manage.

Vic, the CEO of a sporting goods company in this fictional case study, is pleased with the numbers. For several years now, they've gone steadily in one direction: up. But there's trouble in paradise Hidden from the public's view of industry-dominating winners--from the coolest snowboards to the hottest in-line skates--lies a product development department that may be ready to shatter like cheap fiberglass. There's one reason in particular for the dark rumblings that periodically reach Vic, and his name is Linus Carver. Carver, the company's chief of product development, is the workaholic mad genius who is responsible for most--he might say all--of the company's successful products. At the same time, he has managed to alienate the rest of his staff, including the two whizkid Generation Xers he brought in. He has been charged with everything from stealing ideas to squashing the initiative of the rest of the team. From his perch as CEO, Vic preaches "team". And he's even made a few stabs at reining Carver in--his latest move has been to recommend that his mercurial star get some coaching. But Vic also knows who butters his bread. In short, he's bewildered. Four commentators suggest how Vic can keep the company's product-development group intact and it sales growth strong.

Administrative Personnel↗
PubMedDate not supplied

TGFbeta and the extracellular matrix in pancreatitis.

Regeneration from cerulein-induced pancreatitis is accompanied by a transient synthesis and deposition of extracellular matrix components in the rat pancreas. To study the involvement of transforming growth factor beta1 (TGFbeta1), one of the most potent modulators of the extracellular matrix, in the process of pancreatic regeneration we examined the expression of this gene on the transcript and protein level in pancreata of rats sacrificed 0 hours, 24 hours, 2, 3, 5, 7 days after a 12 hour infusion of maximal doses of cerulein (10 microg kg(-1) h(-1)). TGFbeta1 protein increased twofold after 24 hours and 48 hours and returned to control values 7 days after induction of pancreatitis, while TGFbeta1-mRNA reached maximal values (3-fold over controls) after 2 days. The largest amount of TGFbeta1 mRNA was found in pancreatic acinar cells and in stromal cells. To verify the functional implication of TGFbeta overexpression in regulating extracellular matrix remodeling during regeneration from acute pancreatitis, rats were treated with 3 injections of neutralizing antibody against TGFbeta1 given 30 min before, and 24 hours and 48 hours after the start of infusion. In rats treated with maximal doses of cerulein and TGFbeta antibodies, pancreatic hydroxyproline content and expression of collagens I and III and of TGFbeta1 were significantly reduced. These results provide evidence that transforming growth factor beta1 among other cytokines is involved in the regulation of extracellular matrix remodeling in the rat pancreas during regeneration from cerulein-induced acute pancreatitis. In addition, there is evidence in the literature that application of recombinant TGFbeta after recurrent episodes of acute cerulein-induced pancreatitis promotes pancreatic fibrosis (3). Thus, TGFbeta is a regulator of extracellular matrix remodeling in the pancreas, and may be an important promoting factor in the pathogenesis of chronic pancreatitis. This hypothesis is supported by data in the literature showing enhanced TGFbeta expression in human chronic pancreatitis (2) and development of fibrosis and inflammation in pancreata of transgenic mice overexpressing TGFbeta1 (3).

Acute Disease↗
PubMedDate not supplied

Planar vector projection of short-latency median nerve somatosensory evoked potentials.

A planar vector projection of short-latency somatosensory evoked potentials (SEP) following stimulation of the median nerve was obtained by recording SEP over Fpz-Oz and T3-T4 and plotting the amplitudes on both channels at corresponding time points against each other. The resulting curve showed three successive loops pointing ipsilateral occipital (N1), contralateral occipital (N2) and ipsilateral frontal (N3) to the stimulated side. Normal values for latency, amplitude and direction of these loops were obtained from 10 normal adults. N1 can be attributed to the cuneate nucleus and medial lemniscus, N2 to the primary somatosensory cortex and N3 to the frontal cortex.

Adolescent↗
PubMedDate not supplied

Definitive treatment of the borderline personality.

A discussion of "Notes on the Potential Differentiation of Borderline Conditions," by W.W. Meissner, M.D. Through psychotherapy, borderline personalities can develop a mature level of emotional autonomy. Their fundamental psychopathology involves annihilation anxiety consequent on inadequacy and instability of holding-soothing introjects. Psychological corollaries of this deficit render them unable to effect the internalization of real caring relationships that is necessary for development of effective holding introjects. Ideally, psychotherapy proceeds in three phases. Phase I is devoted to amelioration of the pathological impediments to using relationships with the therapist and others as resources for a holding-soothing form of emotional security. The outcome is development of a relatively stable idealized self-object transference in terms of holding-soothing, along with formation of relatively stable idealized holding-soothing introjects. Phase II of treatment involves optimal disillusionment in relation to idealization of the therapist as holding-soother; this results in gradual acceptance of the realistic use of external objects along with modification of holding-soothing introjects to correspond more nearly with reality. Stable autonomy in the area of self-security is fully attained in Phase III, in which the relationship with the therapist provides the context for the patient's developing capacities by means of identification to care for, esteem, love, and trust himself or herself. Psychotherapy of narcissistic issues is also important, but special precautions must be observed.

Adult↗
PubMedDate not supplied

Solitary versus multiple gallstones: the importance of total biliary protein concentration and other factors.

BACKGROUND: Nucleating and antinucleating factors play an important role in the pathogenesis of cholesterol crystal nucleation. PATIENTS AND METHODS: In 88 gallstone patients (59 female, 29 male) bile was examined for total biliary protein and glycoprotein concentration, nucleation time and cholesterol saturation index. Gallstone density was measured by in vivo computed tomography. RESULTS: Total biliary protein concentration was positively correlated with the number of gallstones (r = 0.84, p < 0.01) and higher in radiologically detectable isodense gallstones as compared to non-isodense stones (p < 0.01). A negative correlation between total biliary protein concentration, glycoprotein concentration and nucleation time was observed (r = -0.45, p < 0.01 and r = -0.49, p < 0.05). Nucleation time was significantly shorter in the case of multiple versus solitary stones (2.6 +/- 1.3 versus 8.5 +/- 3.0 days, p < 0.01). Cholesterol saturation index and biliary cholesterol concentration were similar in both cases, however a negative correlation between cholesterol saturation index and stone density (r = -0.79, p < 0.01) was found. No correlation was found between cholesterol saturation index and nucleation time (r = -0.04, p > 0.1), independent of gallstone number. None of the examined parameters was related to sex, age, weight or gallbladder function. CONCLUSIONS: Multiple gallbladder stones seem to be associated with shorter nucleation time and higher biliary concentrations of total protein and glycoprotein than solitary stones.

Bile↗
PubMedDate not supplied

Difficult bile duct stone recurrence after endoscopy and extracorporeal shockwave lithotripsy.

BACKGROUND/AIMS: In a prospective study, we investigated stone recurrence in high risk patients with difficult common bile duct stones treated with extracorporeal shockwave lithotripsy (ESWL) after futile endoscopic attempts at stone extraction with sphincterotomy. METHODOLOGY: Endoscopic stone extraction proved unsuccessful in 35 of 659 patients presenting with common bile duct stones (5.5%, 11 males and 24 females: mean age 71.0+/-10.0 yrs; BMI 25.8+/-3.9; ASA-Classification 2.63+/-0.65), due to large stone size (10 patients), incarcerated stones (15 patients), stones inaccessible to the Dormia basket (7 patients) or an impacted Dormia basket (3 patients). The stones were localized radiologically. ESWL was performed using the HM3 lithotripter (Dornier, Munich/FRG). RESULTS: Immediately following ESWL, 17.1% of the patients treated showed complete stone clearance. In an additional 57.1%, further endoscopic stone extraction was required to achieve complete stone clearance, while 20.0% were discharged with small residual stone fragments. The remaining 2 patients (5.7%) required surgical intervention. Thirty four of 35 patients (97.1%) were followed-up for an average of 27+/-11 months. Five patients (14.3%) experienced stone recurrence at an average of 13.8+/-5.7 months post ESWL. CONCLUSIONS: ESWL is a useful and safe adjunct to endoscopic management of difficult common bile duct stones in older, high-risk patients. The stone recurrence rate was about 14% after one year. All recurrent stones were treatable by endoscopy.

Aged↗
PubMedDate not supplied

Comparison of different endocrine stimulation tests in nondiabetic patients with chronic pancreatitis.

BACKGROUND/AIMS: The purpose of this study was to evaluate endocrine functional impairment in nondiabetic patients with chronic pancreatitis and to determine its reliability in the staging of this disease. METHODOLOGY: Eighteen patients with chronic pancreatitis and fasting normoglycemia (fasting blood glucose level < 100 mg/dl) and 10 healthy subjects underwent an oral glucose tolerance test (OGTT), an intravenous glucose test (IGT) and an arginine stimulation test (AST). Blood glucose and serum concentrations of insulin, C-peptide and glucagon were measured before and after stimulation. Exocrine pancreatic function was assessed by the pancreolauryl serum test (PLT), and morphological changes were staged by endoscopic retrograde pancreaticography (ERP), which were rated as I (mild), II (moderate) or III (severe). RESULTS: Glucagon and C-peptide secretions after arginine stimulation were reduced in patients with moderate and severe chronic pancreatitis while no parameter was able to show impaired endocrine function in the early stage (ERP I) of the disease. Serum insulin concentrations proved to be of no use in the diagnosis of pathological B-cell function, since even patients with severe chronic pancreatitis and fasting normoglycemia demonstrated normal insulin secretion. CONCLUSIONS: We conclude that there is a close correlation between morphological changes of the pancreas and functional endocrine reserve capacity, whereas endocrine stimulation tests were not shown to be helpful in the clinical assessment of nondiabetic patients with chronic pancreatitis.

Adolescent↗