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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 109 records · Page 6Linked to original sources

Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results.

OBJECTIVE: To investigate the contribution of meal and snack replacements for long-term weight maintenance and risk factor reduction in obese patients. RESEARCH METHODS AND PROCEDURES: Prospective, randomized, two-arm, parallel intervention for 12 weeks followed by a prospective single-arm 4-year trial in a University Hospital clinic. One hundred patients, >18 years old and with a body mass index > 25 and < or = 40 kg/m2, were prescribed a 1,200 to 1,500 kcal/d control diet (Group A) or an isoenergetic diet, including two meal and snack replacements (vitamin- and mineral-fortified shakes, soups, and bars) and one meal high in fruits and vegetables (Group B). Following a 3 months of weight loss, all patients were prescribed the same energy-restricted diet (1,200 to 1,500 kcal) with one meal and one snack replacement for an additional 4 years. RESULTS: All 100 patients were evaluated at 12 weeks. Mean percentage weight loss was 1.5 +/- 0.4% and 7.8 +/- 0.5% (mean +/- SEM) for Groups A and B, respectively. At 12 weeks systolic blood pressure, plasma triacylglycerol, glucose, and insulin concentrations were significantly reduced in Group B, whereas no changes occurred in Group A. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.2 +/- 0.8% for Group A and 8.4 +/- 0.8% (mean +/- SEM) for Group B. Both groups showed significant improvement in blood glucose and insulin (p < 0.001), but only Group B showed significant improvement in triacylglycerol and systolic blood pressure compared to baseline values (p < 0.001). DISCUSSION: Providing a structured meal plan via vitamin- and mineral-fortified liquid meal replacements is a safe and effective dietary strategy for obese patients. Long-term maintenance of weight loss with meal replacements can improve certain biomarkers of disease risk.

Adult↗

Commercial recombinant human beta-nerve growth factor and adult rat dorsal root ganglia contain an identical molecular species of nerve growth factor prohormone.

Examination of commercial recombinant human beta-nerve growth factor (rh-beta-NGF) preparations with polyclonal antibodies specific to 13-kDa NGF and pro-NGF-specific domains revealed the presence of high-molecular-mass immunoreactive proteins, including a 60-kDa NGF prohormone. On incubation with a mixture of N- and O-specific glycosidases, the 60-kDa NGF pro-hormone generated a 32-kDa protein corresponding to the molecular size of NGF precursor predicted by the cloned human NGF cDNA. Highly sensitive chemiluminescence immunoblot analysis of adult rat dorsal root ganglia, spinal cord, and colon tissues with NGF- and pro-NGF domain-specific antibodies also revealed the presence of high-molecular-mass proteins, including the 60-kDa NGF prohormone. Based on the presence of the 60-kDa NGF prohormone in dorsal root ganglia and its efferent tissues, we suggest that proteolytically unprocessed, glycosylated NGF prohormone may mediate interactions between neurons and the tissues they innervate.

Animals↗

Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta.

BACKGROUND & AIMS: Activation of NF-kappaB/Rel has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Various drugs used in the treatment of IBD, such as glucocorticoids, 5-aminosalicylic acid, and sulfasalazine, interfere with NF-kappaB/Rel signaling. The aim of this study was to define the molecular mechanism by which sulfasalazine inhibits NF-kappaB activation. METHODS: The effects of sulfasalazine and its moieties on NF-kappaB signaling were evaluated using electromobility shift, transfection, and immune complex kinase assays. The direct effect of sulfasalazine on IkappaB kinase (IKK) activity was investigated using purified recombinant IKK-alpha and -beta proteins. RESULTS: NF-kappaB/Rel activity induced by tumor necrosis factor alpha, 12-O-tetradecanoylphorbol-13-acetate, or overexpression of NF-kappaB-inducing kinase, IKK-alpha, IKK-beta, or constitutively active IKK-alpha and IKK-beta mutants was inhibited dose dependently by sulfasalazine. Sulfasalazine inhibited tumor necrosis factor alpha-induced activation of endogenous IKK in Jurkat T cells and SW620 colon cells, as well as the catalytic activity of purified IKK-alpha and IKK-beta in vitro. In contrast, the moieties of sulfasalazine, 5-aminosalicylic acid, and sulfapyridine or 4-aminosalicylic acid had no effect. Activation of extracellular signal-related kinase (ERK) 1 and 2, c-Jun-N-terminal kinase (JNK) 1, and p38 was unaffected by sulfasalazine. The decrease in substrate phosphorylation by IKK-alpha and -beta is associated with a decrease in autophosphorylation of IKKs and can be antagonized by excess adenosine triphosphate. CONCLUSIONS: These data identify sulfasalazine as a direct inhibitor of IKK-alpha and -beta by antagonizing adenosine triphosphate binding. The suppression of NF-kappaB activation by inhibition of the IKKs contributes to the well-known anti-inflammatory and immunosuppressive effects of sulfasalazine.

Adenosine Triphosphate↗

Protective role of neurotrophins in experimental inflammation of the rat gut.

BACKGROUND & AIMS: Sensory neuropeptides modulate the mucosal response to inflammation in experimental colitis. Because nerve growth factor (NGF) regulates the expression of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) and is implicated as a link between the nervous system and the immune system in the inflammatory process, we investigated the functional role of NGF and neurotrophin-3 during experimental colitis. METHODS: Immunoneutralizing antibodies specific for NGF and neurotrophin (NT)-3 were used to block their endogenous activity. Mild trinitrobenzene sulfonic acid (TNBS) colitis was induced, and damage scores were assessed after 1 week. Neuropeptide content in the colon and NT messenger RNA (mRNA) expression were determined. RESULTS: The pretreatment with anti-NGF or anti-NT-3 caused a significant 2-3-fold increase in the severity of the experimental inflammation as assessed by a macroscopic damage score, histologic ulceration score, and myeloperoxidase activity in the tissue. CGRP, but not substance P, contents in the colon were significantly reduced by NGF immunoneutralization. NGF mRNA was slightly up-regulated after NGF immunoneutralization, but NT-3 mRNA was unchanged by NT-3 immunoneutralization. CGRP mRNA was not significantly changed after 1 week of colitis by NGF or NT-3 immunoneutralization, whereas beta-preprotachykinin mRNA was up-regulated after immunoneutralization. CONCLUSIONS: These findings suggest a regulatory role for NGF and NT-3 in experimental inflammation of the gut. This effect may be partly caused by the reduction of mucosal CGRP content caused by the NGF blockade.

Animals↗

[Anxiety as a concomitant symptom of depression in the elderly].

Anxiety is a symptom frequently encountered in elderly depressed patients. It is supposed to have an unfavourable prognostic impact. We studied the frequency of psychic anxiety and its relationship to demographic, social and clinical variables in a group of 54 elderly depressed patients admitted to a gerontopsychiatric day-clinic. Severity of depression, cognitive performance, functional level, social situation and life satisfaction were studied by means of standardized instruments. In about half of the patients studied, we found significant psychic anxiety. Compared to the other depressed patients, patients with anxiety suffered more frequently from cognitive impairment and were more dissatisfied with the acceptance of their disease by other persons. They more frequently lived together with other persons in one household. When leaving psychic anxiety out of consideration as a depressive symptom, the severity of depression was not different in patients with and without anxiety. Anxious patients were equally responsive to day-clinic treatment as non-anxious patients. However, duration of treatment was considerably increased. Thus, elderly depressed patients with anxiety show particular psychosocial and clinical features and require special attention in diagnostics and treatment.

Activities of Daily Living↗

[The EEG as an indicator of cholinergic deficit in Alzheimer's disease].

There are tight relationships between the EEG and the activity of the cholinergic system. The excitability of cortical neurons is increased by the ascending cholinergic projections of the nucleus basalis of Meynert. Cholinergic deafferentiation of the cortex leads to an increase of slow-wave EEG activity. Cholinergic deficit is a typical feature of Alzheimer's disease. It is goes along with characteristic EEG alterations, mainly increased activity in the slow frequency bands. The amount of EEG alterations increases as the disease progresses. It is correlated with the severity of symptoms, neuropsychological performance, cerebral perfusion, cerebral glucose utilization and the extent of histopathological changes. EEG alterations are a valuable diagnostic tool in Alzheimer's disease. They may be suited for early diagnosis and may allow the prediction of the therapeutic response to cholinergic drugs.

Alzheimer Disease↗

Sonographic measurement of thickened bowel wall segments as a quantitative parameter for activity in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with morphological changes of the bowel wall that can be visualized by abdominal ultrasound (US). This method is a tool to detect the extent of bowel wall thickening and the length of involved segments. The purpose of this study was to determine the value of sonographic measurement of inflamed bowel wall segments as a quantitative parameter for disease activity. 137 patients with Crohn's disease (CD) and 32 patients with ulcerative colitis (UC) were included in the present study. A total 356 US examinations were performed within a one-year period. In a segment-by-segment analysis we determined the "volume of inflamed bowel wall" (VIB) by measuring wall thickness and longitudinal extent of pathologically altered bowel segments. VIB was used as a quantitative parameter for disease activity based on sonomorphological findings. At the same time the following parameters were also determined: CD activity index (CDAI) in patients with CD, clinical activity index (CAI) in patients with UC, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). We found no relevant correlation between VIB and biochemical indices of inflammation (ESR, CRP) and between VIB and clinical activity of IBD (CDAI, CAI). All correlation coefficients were below 0.5. It can be concluded that the extent of inflammatory changes of the bowel wall detected by US is not strictly associated with clinical activity and laboratory parameters of inflammation.

Adolescent↗

[The research situation in abdominal sonography in the gastroenterology departments of university hospitals in the Federal Republic of Germany].

Objective of the present study is to provide a current overview of the present state of research in abdominal ultrasound in the gastroenterological departments of university hospitals in Germany. We conducted a survey assessing the number of research projects in progress, sources of financial support, sponsorship by the private sector and publications generated. Reports from 28 of 35 gastroenterological departments responding to the survey indicated that a total of 124 research projects were in progress during the survey period, for an average of 3.5 projects per department. Clinical issues were addressed in 78 studies, technical questions in 33 studies and other questions in 13 studies. Of the 117 publications generated, 50 appeared in German-language journals and 67 in English-language journals. At present, neither the German Research Association (DFG) or the European Union (EU) is financially underwriting an ultrasound research project in the gastroenterological department of any German university hospital. Ultrasound remains the most frequently applied diagnostic imaging technique in gastroenterology. In order to convert the enormous technological progress into improved diagnostic capabilities, there must be a significant expansion in research support for gastrointestinal ultrasound.

Abdomen↗

Does maternal smoking hinder mother-child transmission of Helicobacter pylori infection?

Evidence for early childhood as the critical period of Helicobacter pylori infection and for clustering of the infection within families suggests a major role of intrafamilial transmission. In a previous study, we found a strong inverse relation between maternal smoking and H. pylori infection among preschool children, suggesting the possibility that mother-child transmission of the infection may be less efficient if the mother smokes. To evaluate this hypothesis further, we carried out a subsequent population-based study in which H. pylori infection was measured by 13C-urea breath test in 947 preschool children and their mothers. We obtained detailed information on potential risk factors for infection, including maternal smoking, by standardized questionnaires. Overall, 9.8% (93 of 947) of the children and 34.7% (329 of 947) of the mothers were infected. Prevalence of infection was much lower among children of uninfected mothers (1.9%) than among children of infected mothers (24.7%). There was a strong inverse relation of children's infection with maternal smoking (adjusted odds ratio = 0.24; 95% confidence interval = 0.12-0.49) among children of infected mothers, but not among children of uninfected mothers. These results support the hypothesis of a predominant role for mother-child transmission of H. pylori infection, which may be less efficient if the mother smokes.

Breath Tests↗

Increase of bone mineral density with sodium fluoride in patients with Crohn's disease.

BACKGROUND AND AIMS: Low bone density with an increased risk of vertebral fractures is a frequent complication in inflammatory bowel disease. Since the aetiology of osteopathia in these patients is different compared to postmenopausal or steroid-induced osteoporosis, no treatment strategy is established. Supplementation of calcium and vitamin D has been shown to prevent further bone loss, but no data are available showing the anabolic effect of sodium fluoride in Crohn's disease. METHODS: We carried out a one-year prospective clinical trial in 33 patients with chronic active Crohn's disease who were randomly assigned to receive either calcium (500 mg b.i.d.) and 1000 IU vitamin D3 only, or retarded-release sodium fluoride (25 mg t.i.d.) additionally. The diagnosis of Crohn's disease had been made at least two years ago, and all patients had received systemic high-dose steroid therapy during the previous year. Eleven of 15 patients who received calcium/vitamin D and 15 of 18 patients who additionally received sodium fluoride completed the study. The primary endpoint of the study was the increase of bone mineral density, measured by dual energy X-ray absorptiometry (DXA) after one year of treatment. Bone-specific alkaline phosphatase and osteocalcin were used as markers for bone turnover. RESULTS: In the calcium/vitamin D only group, bone density was not significantly changed after one year of treatment, whereas in the calcium/vitamin D/fluoride group, bone density of the lumbar spine increased from -1.39+/-0.3 (Z-score, mean +/- SEM) to -0.65+/-0.3 (P<0.05) after one year of treatment. Increase of bone density was positively correlated to the osteoblastic markers bone-specific alkaline phosphatase (r = 0.53) and osteocalcin (r = 0.43). CONCLUSIONS: Sodium fluoride in combination with vitamin D and calcium is an effective, well-tolerated and inexpensive treatment to increase lumbar bone density in patients with chronic active Crohn's disease and osteoporosis.

Adult↗

Characteristic distribution pattern of Helicobacter pylori in dental plaque and saliva detected with nested PCR.

The precise mode of transmission and the natural reservoir for Helicobacter pylori are unknown. PCR assays have proved to be highly sensitive and specific and are regarded as the method of choice for detecting H. pylori DNA in the oral cavity. The aim of this study was to investigate the prevalence and distribution of H. pylori in the oral cavity. Forty-two patients undergoing gastroscopy were investigated for the presence of H. pylori in dental plaque and saliva by nested PCR, and in the stomach by the 13C-urea breath test. Samples tested comprised dental plaque from molars, premolars and incisors and saliva. Two sets of primers homologous to the 860-bp fragment of H. pylori DNA, which have been shown previously to be highly sensitive and specific, were used for nested PCR. Eleven patients (26.2%) were infected with H. pylori in the stomach. H. pylori DNA was identified in dental plaque samples from 41 patients (97%) and in 23 saliva samples (55%). The prevalence in dental plaque from molars, premolars and incisors was 82%, 64% and 59%, with an odds ratio of 3.18, 1.24 and 1 (reference), respectively. In conclusion, H. pylori was present in the oral cavity of 97% of tested patients, with a characteristic distribution that was independent of the infection status of the stomach. Thus H. pylori may belong to the normal oral microflora.

Adult↗

Quantitation of Helicobacter pylori in dental plaque samples by competitive polymerase chain reaction.

AIM: To establish a competitive PCR (cPCR) assay for quantitation of H pylori organisms in dental plaque samples. METHODS: The cPCR co-amplified target H pylori DNA and a known amount of internal standard template in the same tube with the same primers directed to 0.86 kb DNA of H pylori. The internal standard was a synthesised DNA bearing the same primer recognition sites at two ends and a non-homologous core sequence as the target DNA fragment. Quantitation was based on determination of the relative, not absolute, amounts of the differently sized and [32P]-dCTP labelled products derived from H pylori DNA and the competitive internal standard after gel electrophoresis separation. RESULTS: A significant correlation between known amounts of H pylori added to dental plaque samples and the results of the cPCR was found, and a standard line was developed which allowed quantitation of H pylori in the plaque samples. cPCR was performed on supragingival plaque samples from 10 adult patients with H pylori infection in the stomach, and from five adults and six children without H pylori infection in the stomach. The ranges of H pylori numbers were 1-213 (median 25), 6-76 (10), and 4-94 (14) cells/mg of dental plaque in the three groups, respectively. CONCLUSIONS: cPCR is useful for quantitation of H pylori in supragingival dental plaque samples; however, the number of the organisms in dental plaque samples seems very low.

Adolescent↗

Regulation of adherens junction protein p120(ctn) by 10 nM CCK precedes actin breakdown in rat pancreatic acini.

The initial pathophysiological events that characterize CCK-hyperstimulation pancreatitis include the breakdown of the actin filament system and disruption of cadherin-catenin protein complexes. Cadherins and catenins are part of adherens junctions, which may act as anchor for the cellular actin filament system. We examined the composition and regulation of adherens junctions during CCK-induced acinar cell damage. Freshly isolated CCK-stimulated rat pancreatic acini were examined for actin filaments and functional adherens junctions by immunocytology and laser confocal scanning microscopy or by coprecipitation and immunoblotting for E-cadherin, beta- and alpha-catenin, p120(ctn), and phosphotyrosine. In addition to E-cadherin and beta-catenin, acinar cells express the cadherin-regulatory protein p120(ctn) and the attachment protein alpha-catenin. Both colocalize and coimmunoprecipitate with E-cadherin in one complex, and all colocalize with the terminal actin web. Supramaximal secretory CCK concentrations (10 nM) initiated tyrosine phosphorylation of p120(ctn) but not of beta-catenin within 2 min, preceding the breakdown of the terminal actin web by several minutes. Under these conditions, the cadherin-catenin association within the adherens junction complex remained intact. We describe for the first time supramaximal CCK-dependent tyrosine phosphorylation of the adherens junction protein p120(ctn) and demonstrate the presence of an intact adherens junction protein complex in acinar cells. p120(ctn) may participate in the actin filament breakdown during experimental conditions mimicking pancreatitis.

Actins↗

Prospective comparison of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in the preoperative assessment of masses in the pancreatic head.

AIMS: To compare the diagnostic value of endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in the differentiation of malignant from benign masses in the pancreatic head. METHODS: Within 14 months 95 prospective patients with masses in the pancreatic head were assigned for preoperative EUS and ERCP. Both procedures were performed and recorded according to a standardized protocol. Based on intraoperative findings and histology, 50 patients (53%) suffered from malignant and 45 patients (47%) from benign (inflammatory) tumors. RESULTS: Success rates were 96% for EUS and 95% for ERCP. The overall results for EUS and ERCP to predict malignant masses were, respectively: sensitivity 78 and 81%, specificity 93 and 88%, positive predictive value 93 and 89%, negative predictive value 78 and 80%, and diagnostic accuracy 85 and 84%. When EUS and ERCP were taken together, the sensitivity was 92% (specificity 85%), but the diagnostic accuracy (89%) was not significantly enhanced. The results for EUS to diagnose lymph node metastases preoperatively were: sensitivity 55%, specificity 91%, positive predictive value 69%, negative predictive value 84%, and accuracy 81%. CONCLUSIONS: EUS and ERCP have similar diagnostic accuracies to separate malignant from benign masses in the pancreatic head. Combination of both procedures is not superior to the use of one modality alone. Abnormal lymph nodes visualized on EUS in patients with inflammatory masses in the pancreatic head due to chronic pancreatitis should be interpreted cautiously.

Adult↗

Helicobacter pylori infection, intake of analgesics or anti-inflammatory medication, and personal factors in relation to dyspeptic symptoms in patients of a general practitioner.

BACKGROUND: Several studies have assessed the relationship between Helicobacter pylori infection and dyspeptic symptoms in highly selected patient populations and they have yielded inconsistent results. AIM: To investigate the relationship between current H. pylori infection, intake of analgesics or anti-inflammatory medication, and personal factors with dyspeptic symptoms in a large, unselected patient population of a general practitioner (GP). METHOD: Consecutive patients of a GP were invited to participate in a cross-sectional study regardless of the reason for their visit. Active infection with H. pylori was measured using the 13C-urea breath test (13C-UBT). A standardised questionnaire covering demographic, socioeconomic and lifestyle factors, and dyspeptic symptoms was completed by the patients. The number and severity of dyspeptic symptoms were quantified using a symptom score. RESULTS: Five hundred and one out of 531 eligible patients returned their questionnaires; a response rate of 94.4%. The prevalence of H. pylori infection, as indicated by a positive 13C-UBT, was 21.1% and was unrelated to dyspeptic symptoms. After adjustment for potential confounders by multiple logistic regression, a symptom score in the upper quartile of the symptom score distribution was significantly associated with female sex (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1 to 3.0) and intake of analgesics or anti-inflammatory drugs other than non-steroidal anti-inflammatory drugs (NSAIDs) (OR = 2.3, 95% CI = 1.1 to 4.7). Older age (60 to 79 years) was associated with fewer symptoms (OR = 0.4, 95% CI = 0.2 to 0.9) when compared with the youngest age group (15 to 39 years). CONCLUSION: Female sex, younger age, and intake of analgesics or anti-inflammatory drugs other than NSAIDs, but not H. pylori infection, were independently associated with dyspeptic symptoms in this population.

Adolescent↗

[Evaluation of gene expression for cag A in strains of Helicobacter pylori colonizing gastric mucosa].

Recent studies indicate that infection with H. pylori strains expressing cytotoxic proteins such as cag A or vac A is an important risk factor for the development of chronic atrophic gastritis, gastric cancer, or MALT-type lymphoma. The aims of this study were: 1) to develop an RT-PCR assay for the analysis of cag A gene expression in H. pylori present in gastric mucosa specimens obtained during gastroendoscopy; 2) to examine with this method the correlation between the presence of cag A gene and its expression. The study was performed in 82 patients (40 females and 42 males). cag A DNA was detected in gastric mucosa in 42 patients, among them in 17 out of 35 with dyspepsia, in 14 out of 25 with peptic ulcer disease, in 2 out of 10 with gastric cancer and in 8 out of 11 with a family history of gastric cancer (Tab. 1). cag A gene expression could not be confirmed in only two cases positive for cag A DNA (both patients had a family history of gastric cancer, Fig. 1). The results of this study indicate that the RT-PCR assay is a useful tool for the molecular diagnostics of H. pylori infection. Further studies are needed to explain the role of cag A gene in the pathogenesis of peptic ulcer and gastric tumors.

Adult↗