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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 307 records · Page 17Linked to original sources

Experimental animal models of acute pancreatitis.

Experimental animal models have been employed to study pancreatitis for more than a century. Although not always related to the disease in humans, they have contributed greatly to our current understanding of the pathophysiology and cell biology of this disease. They have also become a standard tool for testing new and promising treatments against pancreatitis. The following article will review the most commonly used experimental models of pancreatitis and some of the lessons we have learned from them.

Acute Disease↗

Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis.

Chronic pancreatitis is characterized by proliferation of the extracellular matrix and by increased deposition of interstitial extracellular matrix proteins (collagens type I and III, fibronectin). In this study we analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix degrading metalloproteinases (MMP-1, -2 and -3) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in chronic pancreatitis (n = 8) and control pancreas (n = 7) by northern blot analysis. Transcripts for MMP-1 (interstitial collagenase), MMP-3 (stromelysin) and TIMP-1 were not detectable in chronic pancreatitis and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72 kDa collagenase IV) and TIMP-2 were enhanced in 7 out of 8 chronic pancreatitis tissue samples and showed a large degree of variation between individual patients. Transcript levels could not be correlated to the histologically detectable degree of inflammation and fibrosis or to the total amount of deposited collagen protein, which was high in all chronic pancreatitis tissue samples as determined by a standard colorimetric procedure. Increased steady state levels of transcripts encoding extracellular matrix proteins or extracellular matrix degrading proteases may thus reflect the activity of processes involved in the remodeling of the gland during chronic inflammation. The precise role of overexpression of MMP-2 and its inhibitor TIMP-2 will have to be elucidated in further studies.

Chronic Disease↗

Does adequate patient selection reduce the risk of gallstone recurrence after successful extracorporeal shockwave lithotripsy?

To determine the risk of gallbladder stone recurrence in these patients, 58 of the first consecutive 61 patients with solitary stones achieving complete stone clearance after ESWL and adjuvant bile acid therapy were included in a prospective study. All patients were observed for at least 12 months following discontinuation of oral bile acids. Twenty-one patients fulfilled our postulated ideal criteria (solitary radiolucent stones between 10-20 mm initial diameter, initial stone density < 50 HU, gallbladder ejection fraction > 70%). The remaining patients (n = 37) fulfilled the criteria of the Munich study group. In patients fulfilling our ideal criteria, stone recurrence was not observed in any patient, while in those fulfilling solely the criteria of the Munich group, five instances of stone recurrence were observed (13.5% [n = 37], p < 0.1). Initial stone count is only one factor influencing the probability of gallstone recurrence following ESWL and discontinuation of oral bile acids. Our data suggest that factors such as low initial stone density at gallbladder CT and good gallbladder function not only accelerate initial stone clearance but also reduce the risk of stone recurrence after ESWL once oral bile acids have been discontinued.

Adult↗

Pain perception threshold in major depression.

Somatosensory perception threshold (SPT) and pain perception threshold (PPT) were studied in 16 patients with major depression, compared to the findings in an age-matched and gender-matched control group and related to the psychopathological state evaluated by means of the Hamilton Depression Scale. Perception thresholds were assessed by means of a noninvasive high-frequency electric skin stimulation. Absolute perception thresholds were increased in the patients. However, the relative pain perception threshold (RPPT = PPT: SPT) was significantly reduced. RPPT was positively correlated with retardation. It was negatively correlated with anxiety, suggesting that a reduction of pain perception thresholds in depressive patients may be attributed to anxiety and impaired stress-coping.

Adult↗

Second messenger regulation of mRNA for corticotropin-releasing factor.

An understanding of how second messengers and their ligands are coupled to CRF gene activation is necessary if we are to understand the regulation of the CRF gene in physiological and pathological states. The protein kinase A, protein kinase C and glucocorticoid second messenger systems mediate most of the regulation of the CRF gene. In in vitro systems, CRF gene expression is stimulated 20-30-fold by activation of either the protein kinase A or the protein kinase C system. Glucocorticoid is able to inhibit stimulation via both pathways, but appears to be more effective in repressing activation mediated by protein kinase C. Glucocorticoid negative regulation requires the presence of glucocorticoid receptor possessing an intact DNA-binding domain, suggesting that this effect involves binding of the receptor to the CRF promoter. These in vitro studies should serve to guide investigators towards the possible mechanisms underlying CRF gene regulation in vivo.

Animals↗

Henoch-Schönlein purpura with ileitis terminalis.

Gastrointestinal manifestations of Henoch-Schönlein purpura commonly include abdominal pain and gastrointestinal bleeding as well as extraintestinal signs and symptoms. We report here on a 24-year-old man with gastrointestinal pain in whom the classical features of Henoch-Schönlein purpura appeared only 6 days after acute abdominal symptoms. At endoscopic investigation inflammation with aphthous lesions was detected at the terminal ileum, which is a common feature of Crohn's disease. The observation that vasculitic disorders such as Henoch-Schönlein purpura can present with inflammatory lesions at the terminal ileum which are indistinguishable from those of Crohn's disease underlines the potential vasculitic basis of the latter condition.

Adult↗

Auditory evoked potentials in schizophrenic patients before and during neuroleptic treatment. Relationship to psychopathological state.

The auditory evoked potential (AEP) components N1 and P2 were investigated under a no-task condition in a group of 14 acutely ill unmedicated schizophrenic patients and compared with the findings in an age- and sex-matched control group. In the patients, N1 latency was significantly increased, P2 latency and N1-P2 interpeak latency were reduced. There were significant relationships between AEP parameters and the psychopathological state evaluated by means of the brief psychiatric ratings scale (BPRS). The N1 and P2 latencies were negatively correlated with the BPRS subscore "anergia" and positively correlated with "agitation". In 8 of the patients, a standardized neuroleptic treatment was started with 10 mg haloperidol/day. After 2 weeks of treatment, BPRS scores and N1 amplitude had significantly decreased. However, there was no relationship between BPRS improvement and N1 amplitude reduction. N1 latency in the unmedicated state was negatively correlated with subsequent therapeutic response measured as proportional improvement of the BPRS score within 2 weeks. Thus, N1 latency may be seen as a psychophysiological measure with prognostic applications.

Adult↗

Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group.

BACKGROUND: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. METHODS: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. RESULTS: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placebo and gabexate mesilate groups. CONCLUSIONS: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

Acute Disease↗

Vasoactive intestinal peptide (VIP) stimulates androstenedione release in isolated perfused pig adrenals.

The effect of the vasoactive intestinal peptide (VIP) on adrenal androstenedione release was investigated in isolated perfused pig adrenals. Our system allowed a direct comparison with the effect of ACTH, gonadotropins and proopiomelanocortin 79-96, which has been suggested to be the specific cortical androgen stimulating hormone (CASH). VIP 10(-8) M provoked a threefold increase of androstenedione release which was similar to the effect of ACTH at a physiological concentration of 10(-10) M. Gonadotropins at a perfusate concentration of 0.5 I.U. weakly but significantly increased androstenedione output, the response amounting to 32% of that elicited by ACTH or VIP. Perfusion of the adrenals with CASH at concentrations of 10(-11) to 10(-8) M did not affect the release of adrenal androstenedione. VIP appears to be a modulator of adrenal androgen release which might be involved in a local neuroendocrine control of adrenal androgen secretion.

Adrenal Glands↗

Institutional respite care: benefits and risks for dementia patients and caregivers.

Thirty-seven dementia patients and their caregivers were studied before and after a two-week in-hospital respite stay. Institutional respite care did not alter behavior problems in dementia patients, nor did changes in performance of activities of daily living (ADLs) by Alzheimer's disease (AD) patients exceed those expected from disease progression. Caregivers exhibited an improvement in burden and depression during the respite study, but levels returned to baseline following the patient's return home.

Activities of Daily Living↗

New methods for assessment of enzyme activity: do they help to optimize enzyme treatment?

Several factors related to the patient and the pancreatin formulation influence the efficacy of enzyme supplementation. Up to now, only few tests exist to judge the efficacy of enzyme replacement therapy in pancreatic insufficiency. Tube tests and fecal fat excretion studies are cumbersome, time-consuming and unpleasant. Recently, several breath tests for the detection of pancreatic insufficiency have been developed. The cholesteryl octanoate breath test differentiated between healthy controls and patients with pancreatic insufficiency already after a 30-min collection period. Using this test, it was demonstrated that a pancreatin preparation containing small microspheres (1.0-1.2 mm) induces high duodenal lipolytic activity parallel to gastric emptying of food. In contrast, the gastric emptying of large microspheres (1.8-2.0 mm) is significantly delayed. The cholesteryl octanoate breath test detects pancreatic insufficiency within 30-60 min and offers the possibility of monitoring the in vivo release of pancreatin preparations.

Amylases↗

The psychotherapy of core borderline psychopathology.

A psychodynamic formulation of borderline psychopathology includes the understanding of the borderline patient's aloneness problems, need-fear dilemma issues, and difficulties with primitive guilt. The aloneness problems are at the core of the disorder, and involve an inability to maintain an evocative memory, and holding and soothing introjects of significant people when under stress of separation. The possible childhood origins of these difficulties are explored and related to the ways these issues emerge in psychotherapy. The psychodynamic formulation is crucial in the psychotherapeutic approach to the aloneness problems. It helps the therapist work with the aloneness difficulties and understand the options as the therapy continues. Since rapid therapeutic decisions are often necessary with borderline patients, the formulation provides the necessary framework, and helps the therapist process and utilize countertransference feelings. Projective identification is an important concept that helps explain the complex transference/countertransference experiences, and is used in defining the resolution of the aloneness problems of borderline patients. Finally, limit-setting and the use of transitional objects are explored, utilizing the psychodynamic framework that has been defined.

Adult↗

Social work practitioners as researchers: is it possible?

Social workers are encouraged and often expected to conduct research in addition to their clinical duties. Unfortunately, few practitioners seem interested and there is usually a lack of tangible supports in most practice settings. To counter this, a support group of non-supervisory clinical social workers in a Department of Veterans Affairs Medical Center met regularly with a social work educator-consultant in order to strengthen research skills, maintain motivation, and promote publication. This group successfully published seven articles with an additional five in process. In contrast, a second research group at the same facility foundered after eight months. Similarities and differences between the two groups are discussed. Recommendations are made about how agencies might encourage and sustain practitioners in the development and publication of clinical research.

Curriculum↗

Pathophysiology of acute pancreatitis.

The pathophysiology of acute pancreatitis is characterized by a loss of intracellular and extracellular compartmentation, by an obstruction of pancreatic secretory transport and by an activation of pancreatic enzymes. In biliary acute pancreatitis, outflow obstruction with pancreatic duct hypertension and a toxic effect of bile salts contribute to disruption of pancreatic ductules, with subsequent loss of extracellular compartmentation. Alcohol induces functional alterations of plasma membranes and alters the balance between proteolytic enzymes and protease inhibitors, thus triggering enzyme activation, autodigestion and cell destruction. Once the disease has been initiated, the appearance of interstitial edema and inflammatory infiltration are the basic features of acute pancreatitis. The accumulation of polymorphonuclear granulocytes in pancreatic and extrapancreatic tissue, and the release of leukocyte enzymes play an essential role in the further progression of the disease and in the development of systemic complications. Activation of different cascade systems by proteolytic activity, and consumption of alpha 2-macroglobulin further characterize the severe clinical course of acute pancreatitis.

Acute Disease↗