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Biomedical subjects

A Berger

Publications and source records attributed to A Berger.

At least 37 records · Page 2Linked to original sources

Determination of cholesterol absorption in humans: from radiolabel to stable isotope studies.

Hypercholesterolemia is a major health risk. Dietary cholesterol absorption is one important factor affecting levels of plasma and tissue cholesterol. Considerable effort has thus been devoted to develop reliable in vivo clinical methodologies to determine dietary cholesterol absorption in humans. The present paper summarises radiolabelled experiments and major advances in stable isotope technologies to determine cholesterol absorption. Initially, direct methods employing gastro-intestinal intubation were developed. Later, indirect methods using oral-faecal cholesterol balance permitted calculation of cholesterol mass absorption. Once the use of radiolabelled [3H, 14C]cholesterol balance was developed in healthy humans, it was finally possible to distinguish exogenous and endogenous cholesterol. Non-invasive and safer stable isotope (2H, 13C, 18O) labelled cholesterol tracers then replaced radioisotopes for use in infants and adults. Stable isotopes and radioisotopes showed identical cholesterol kinetics. The most promising contemporary stable isotope assessment of cholesterol absorption is a dual stable isotope dual tracer approach based on simultaneous administration of oral and intravenous differentially labelled cholesterol tracers, followed by plasma sampling for 3-4 d. Online GC/Combustion/IRMS and GC/Pyrolysis/IRMS allow minimal amounts of dual stable isotope cholesterol tracers to be detected. Using the dual stable isotope dual tracer approach, the percent cholesterol absorption in adult volunteers has been determined to be 50-70%.

Absorption↗

Evaluation of a netilmicin-loading dose in very low birthweight infants.

BACKGROUND: The bactericidal efficacy of aminoglycosides is directly related to maximum serum concentrations, particularly the initial one. Therefore, several groups have recommended an aminoglycoside loading dose. Our goal was to develop a simplified dosage regimen for preterm infants which would result in therapeutic maximum serum concentrations early in the course of therapy. METHODS: Open, noncomparative study during November 2000 to April 2001. The modified netilmicin-dosing protocol included a loading dose of 5 mg/kg in the first week of life, followed by a maintenance regimen of 3.5 mg/kg every 24 h. After the first week of life the corresponding doses were 6 (loading) and 5 mg/kg (maintenance). A peak level was measured 30 min after the second dose, and a trough level immediately before the third dose. RESULTS: Thirty-five very low birthweight infants (mean birthweight 876 +/- 170, range 536-1,385 g; mean gestational age 26 +/- 1.8, range 23-30 weeks) who had 46 episodes of netilmicin treatment were included in the analysis. Mean netilmicin peak and trough values were 15.9 +/- 3.7 (range 8.9-28.9) and 3.4 +/- 1.3 (range 1.0-7.8) micromol/l, respectively. Ninety-one percent of all peak levels were within the targeted range of > or =10 micromol/l. Eleven trough values (24%) were > or =4 micromol/l: in 7 instances netilmicin was administered within the first week of life, 5 of these patients had concomitant indomethacin treatment. Only 1 of the 35 neonates had a rise in serum creatinine of > or =0.5 mg/dl during netilmicin therapy. Hearing evaluations were performed in 25 of the 29 surviving infants at discharge home, all of which gave normal results. CONCLUSIONS: The new netilmicin-dosing protocol yielded therapeutic maximum serum concentrations in 91% of cases after the second dose. However, a significant number of very low birthweight infants had elevated trough levels, particularly when netilmicin was administered in the first week of life with concomitant indomethacin treatment. We speculate that a longer interval between the loading dose and the first maintenance dose would result in fewer elevated trough levels with a similarly high number of therapeutic peak levels.

Anti-Bacterial Agents↗

Evaluation of living conditions of free-ranging animals by automated chronobiological analysis of behavior.

A biorhythmical method has been developed to assess behavior patterns and to evaluate the living conditions of animals that can be applied also to humans. All kinds of continuous and equidistant long-term recordings of behavior are suitable for this method. Time functions from an automatic telemetry system (ETHOSYS II) were analyzed macroscopically (comparison of daily levels) and microscopically (autocorrelation function and power spectral analysis). Degrees of functional coupling (DFCs) were calculated to identify and evaluate disturbances in behavior. Hierarchic frequency tuning of complex rhythmic functions of behaviors, leads primarily to period lengths that are synchronized with the 24-h period. DFCs, a measure of harmony between internal rhythms and the external 24-h period, were found to be high in well-adapted, healthy, and undisturbed individuals but were lowered during periods of adaptation, sickness, or social interaction. Specific stress conditions could be identified and evaluated in several species, under various conditions, using these biorhythmic analyses.

Animal Migration↗

[MR imaging of ano-perineal suppurations].

A good digital examination is usually sufficient for the diagnosis and the treatment planning of anal fistulae. Cross-sectional imaging techniques, however, can accurately identify deep abscesses and characterize complex fistulae. MRI is well suited for this examination, with almost no motion artifact, excellent contrast between muscles and fatty spaces, and multiplanar acquisition. A fistula starts from an internal opening in the digestive tube and can end in an abscess cavity or open at the skin at an external opening. The cryptoglandular anal fistulae (fistula-in-ano) are non-specific in origin and are usually simple, whereas specific fistulae are due to many diseases such as Crohn's disease, tuberculosis, trauma, radiation, colloid carcinoma, hidradenitis suppurative, actinomycosis or lymphoma and are often complex. MRI appears useful in the cases with recurrent fistulae, Crohn's disease, when the secondary orifice is atypically placed, during a multistep treatment for complex fistulae, or when an anal stenosis forbids a clinical or ultrasound examination. A good knowledge of the perineum anatomy is required for analysing the fistula tracts. The muscle planes separate fatty spaces which have an important role in the spread of the disease: sub-mucosal space, marginal space, intersphincteric space, postanal space of Courtney, supralevator space, and the two ischioanal spaces on both sides of the anal canal. The anal canal is surrounded by the ring-like internal sphincter, which continues the internal muscularis propria of the rectum, and the external sphincter, which is intermingled with the puborectalis muscle. We perform our MRI examination with an external phased array coil, and we place a cannula to identify the anal canal. The T2W sequences give the more interesting information, but the sequences with fat-suppression and gadolinium chelate injection are also very useful. The MRI examination allows the analysis of: 1) the location of the fistula tracts according to Park's classification, 2) the location of the internal opening, 3) the locations of the external opening(s), 4) the location of deep abscesses, 5) the long distance extensions, 6) the state of the ano-rectal wall and the perirectal spaces, 6) the damages of the anal sphincter.

Abscess↗

The two-stage concept with temporary subcutaneous implantation of a vacuum sealing system: an alternative surgical approach in infected partial abdominal defects after lapratomy or abdominoplasty.

BACKGROUND: Infected abdominal defects after laparatomy or abdominoplasty may present serious complications. The management of a progressive infection in the abdominal region with partial necrosis -without peritoneal irritation - is treated variously. Multiple revisions due to re-infection or seroma are often necessary. The different surgical treatment options almost always necessitate an extended immobilisation and hospitalisation of the patient. PATIENTS AND METHODS: In five patients with infected partial abdominal defects after abdominoplasty (n = 3) or laparatomy (n = 2) successful management of infection was achieved in a two stages with temporary subcutaneous implantation of a polyurethane foam, combined with a vacuum assisted wound closure device, followed by secondary wound closure. In the first step a debridement, subcutaneous implantation of the foam, combined with intermittent subathmospheric pressure through a V.A.C. device was performed. In the second step an explantation of the foam, re-debridement and secondary wound closure was possible over 2 - 4 drains. RESULTS: In all patients - after a temporary immobilisation of 5 days, and systemic antibiotic administration - wound healing was achieved. In one diabetic patient another single revision was necessary, because of the necrosis of a distal wound edge. The mean hospitalisation after application of these procedures was 15 days (12 - 19). CONCLUSIONS: The surgical treatment of infected partial abdominal defects after laparatomy or abdominoplasty - performed in a two-stage procedure with temporary subcutaneous implantation of a V.A.C.-system, and secondary wound closure, offers a high level of safety, and presents an useful alternative tool in the difficult management of these patients.

Abdominal Muscles↗

Effects of non-esterified stanols in a liquid emulsion on cholesterol absorption and synthesis in hypercholesterolemic men.

UNLABELLED: BACKGROUND Numerous studies have shown that dietary plant sterols (phytosterols and phytostanols) and their esters can decrease cholesterol absorption. However, few researchers have examined the effects of plant sterols on cholesterol absorption and synthesis using stable isotope tracers, instead of relying on endogenous pathway precursors. Further, we have worked with non-esterified lecithin-solubilized stanols as opposed to the more frequently studied esterified sterols and stanols. The vehicle was an oil-in-water liquid emulsion rather than the more common spread vehicle typically employed. AIM OF THE STUDY: To determine the effects of relatively low doses of lecithin-solubilized non-esterified stanols in liquid emulsions on cholesterol absorption and synthesis in mildly hypercholesterolemic subjects. METHODS: In a randomized, double blind crossover design, 12 mildly hypercholesterolemic men received either a free phytostanol supplement (3 g/d in 3 servings) or a control treatment for 3 days. Cholesterol endogenous synthesis rate was determined using the rate of incorporation of deuterium from body water into newly formed cholesterol molecules. Cholesterol absorption at the intestinal level was determined using the dual isotope method using 13C cholesterol injected intravenously and 180 cholesterol given orally. RESULTS: Cholesterol absorption was 55.7 +/- 6.5 % for the control and 33.5 +/- 5.3% for the phytostanol treatment. This massive reduction of the cholesterol absorption did not induce, on average, a difference in cholesterol endogenous synthesis which was measured at 0.074 +/- 0.0015 pool/d for plant sterols and 0.0736 +/- 0.0015 pool/d for controls (p > 0.05). CONCLUSIONS: The results demonstrated that lecithin-solubilized stanols administrated during a short period of time (3 days) in an oil-in-water emulsion can dramatically decrease cholesterol absorption, without a consistent, concomitant increase in synthesis, which is highly suggestive of effective LDL cholesterol lowering. The effects of synthesis should be verified in a longer study with more subjects.

Adult↗

Effects of insulin-like growth factor I on growth and polyamine metabolism in various organs in rats.

BACKGROUND/AIM: Human insulin-like growth factor I (IGF-I) is known to be the mediator of growth hormone dependent proliferation and is responsible for growth-promoting effects in the gastrointestinal tract. Polyamines play an essential role in cell growth and differentiation. The aim of the present study was to investigate the growth-promoting potency of IGF-I in various organ systems simultaneously in rats and the potential role of the polyamine metabolism during IGF-I-induced gastrointestinal growth. METHODS: Based on results of initial dose-response studies, male Wistar rats (150 g) were either treated by subcutaneous injections with (1) IGF-I (1 x 1,000 microg/kg/24 h); (2) IGF-I plus alpha-difluoromethylornithine (3 x 300 mg i.p./kg/24 h plus 2% in drinking water), a specific inhibitor of intracellular polyamine de novo synthesis, or (3) saline (controls). 9-10 animals per group were sacrificed after 5 days of treatment. RESULTS: IGF-I caused a significant (p < 0.005) increase in the weight of small intestine and spleen due to hyperplasia in the small intestine and hypertrophy and hyperplasia in the spleen, while no trophic effects could be observed in stomach or pancreas. The amylase concentration in the pancreas was increased. Simultaneously administered alpha-difluoromethylornithine significantly (p < 0.005) abolished the IGF-I-induced trophic effects in small intestine and spleen. CONCLUSIONS: These data reveal different trophic effects of IGF-I in various organ systems: while significant growth stimulation was found in small intestine and spleen, no proliferation was seen in pancreas and stomach. Polyamines obviously play an important role in IGF-I-mediated gastrointestinal growth.

Animals↗

[Out of hours coronary angiography: changing indications].

The authors have recently demonstrated that 13% of indications for cardiac catheterisation performed "after hours" (week ends, holidays or from 6 pm to 7 am) are Class III of the AHA/ACC recommendations (i.e. indications not based on recognised medical evidence). In order to limit procedures performed for these unrecognised indications, a consensus of experts has defined a number of local recommendations. The aim of this paper was to study the impact of these recommendations on the indications of "out of hours" cardiac catheterisation. Two patient populations were identified and compared with respect to these recommendations. The first group comprised 157 consecutive patients treated between 1993 and 1994 (average age 58 +/- 13 years; 35% females) and the second one of 148 consecutive patients treated from 1998 to 1999 (average age 57 +/- 13 years; 25% females). The local recommendations were respected in 61% of cases and not applied in 39% of cases. This was a satisfactory result in view of the fact that the local recommendations are more restrictive than international guidelines as they cover emergency indications. In the second group of patients, there were no AHA/ACC Class III indications (30% Class I, 6% Class IIa and 3% Class IIb). There was a significant increase in the number of primary angioplasties for acute myocardial infarction (27 vs 2%; p < 0.001) and an expected reduction in salvage angioplasties (17 vs 7%; p < 0.01). There was no significant change in the indications in patients with unstable angina, the European and American guidelines having been published at the end of data collection. Therefore, the introduction of recommendations for out of hours cardiac catheterisation has limited the number performed for unrecognised indications in favour of evidence based procedures.

Adult↗

Microarray data analysis: a practical approach for selecting differentially expressed genes.

BACKGROUND: The biomedical community is rapidly developing new methods of data analysis for microarray experiments, with the goal of establishing new standards to objectively process the massive datasets produced from functional genomic experiments. Each microarray experiment measures thousands of genes simultaneously producing an unprecedented amount of biological information across increasingly numerous experiments; however, in general, only a very small percentage of the genes present on any given array are identified as differentially regulated. The challenge then is to process this information objectively and efficiently in order to obtain knowledge of the biological system under study and by which to compare information gained across multiple experiments. In this context, systematic and objective mathematical approaches, which are simple to apply across a large number of experimental designs, become fundamental to correctly handle the mass of data and to understand the true complexity of the biological systems under study. RESULTS: The present report develops a method of extracting differentially expressed genes across any number of experimental samples by first evaluating the maximum fold change (FC) across all experimental parameters and across the entire range of absolute expression levels. The model developed works by first evaluating the FC across the entire range of absolute expression levels in any number of experimental conditions. The selection of those genes within the top X% of highest FCs observed within absolute expression bins was evaluated both with and without the use of replicates. Lastly, the FC model was validated by both real time polymerase chain reaction (RT-PCR) and variance data. Semi-quantitative RT-PCR analysis demonstrated 73% concordance with the microarray data from Mu11K Affymetrix GeneChips. Furthermore, 94.1% of those genes selected by the 5% FC model were found to lie above measurement variability using a SDwithin confidence level of 99.9%. CONCLUSION: As evidenced by the high rate of validation, the FC model has the potential to minimize the number of required replicates in expensive microarray experiments by extracting information on gene expression patterns (e.g. characterizing biological and/or measurement variance) within an experiment. The simplicity of the overall process allows the analyst to easily select model limits which best describe the data. The genes selected by this process can be compared between experiments and are shown to objectively extract information which is biologically & statistically significant.

Animals↗

Posthemorrhagic hydrocephalus in preterm infants: long-term follow-up and shunt-related complications.

INTRODUCTION: A retrospective analysis of 42 preterm infants with intraventricular hemorrhage was performed in order to evaluate shunt-related problems in neonates with posthemorrhagic hydrocephalus. PATIENTS AND METHODS: Within the last 15 years, 76 infants with intraventricular hemorrhage were treated primarily by external ventricular drainage, and 42 needed permanent shunting. Shunting was performed 28-101 days after the patients' birth, ventriculoatrial shunts being placed in 10 patients and ventriculoperitoneal shunts in 32. RESULTS: The mean number of shunt revisions per patient was 1.57. The main reasons for shunt revision were infection (7.1%) and blockage (45.2%). Primary ventriculoperitoneal and ventriculoatrial shunts differed only insignificantly in revision rate and length of shunt survival, whereas ventriculoperitoneal shunts used in shunt revisions required significantly fewer further revisions. CONCLUSIONS: The neurological outcome was not related to the necessity for or to complications of a shunt. Programmable valve systems and neuroendoscopy appear to be helpful in the overall management and in the treatment of complications.

Brain Damage, Chronic↗

Immunocytochemical detection of bone marrow micrometastases in colorectal carcinoma patients, using a monoclonal antibody to villin.

The search continues to find methods to more effectively distinguish colorectal carcinoma patients who could be separated into high-risk and low-risk categories. Investigators have reported on the detection of occult micrometastases in bone marrow using antibodies to cytokeratin, which is a marker of epithelial cells but which has no tissue specificity, as opposed to villin, a cytoskeletal protein that is specifically involved in the formation of brush-border microvilli in the small intestine and colon epithelium. Specificity and sensitivity of antibody to villin (ID2C3) and antibody to cytokeratin (A45-B/B3) were first studied in normal bone marrow and in a test system in which cancer cell lines were mixed in normal bone marrow. In a preliminary study including 16 colorectal carcinoma patients, we compared the number of villin-positive cells with cytokeratin-presenting cells. As A45-B/B3, ID2C3 was determined to be sensitive enough to detect one cancer cell in 10(6) hematopoietic cells. Staining of hematopoietic cells with irrelevant antibody and a light staining of megakaryocytes with ID2C3 limited the specificity of the method. In colorectal carcinoma patients, correlation between ID2C3 and A45-B/B3 was 94%. Sensitivity and specificity of ID2C3 antibody to villin were satisfactory. Its clinical relevance must be investigated in further studies.

Aged↗

Plastic surgical management in tissue extravasation of cytotoxic agents in the upper extremity.

Extravasation injuries in subcutaneous tissues during peripheral intravenous administration can result in extensive soft-tissue defects. Early treatment (surgical removal of the extravasated material within 24 h) and late treatment (debridement and coverage) are two possible approaches for this kind of injury. Eighteen patients who suffered a significant extravasation injury were treated surgically between 1/1996 and 5/2001. All patients were referred late (mean 22 days after the event) to our clinic with soft-tissue defects or skin necrosis and were accordingly only amenable to late treatment. The patients with defects over the dorsum of the hand, forearm or cubital fossa area underwent debridement, temporary wound coverage and skin grafting or coverage with a local flap. Spotted infiltrating lesions and necrosis are typical histologic features of a cytotoxic agent extravasation. A safe margin of resection is only achievable with a wide three dimensional excision. The healing time of defects was a mean of 15 days after either skin grafting or flap coverage with no significant difference between the two differing treatment groups. Early referral of patients with extravasation injuries to a specialized department for plastic and hand surgery may in future enable earlier surgical treatment, reduce time of illness and costs.

Antineoplastic Agents↗

Depression and risk of heart failure among older persons with isolated systolic hypertension.

BACKGROUND: Investigators have shown that depression is associated with an increased risk of coronary heart disease in general and myocardial infarction in particular. However, it is unknown whether depression, independent of its association with myocardial infarction, is a risk factor for heart failure. METHODS: This study examined whether depression was a predictor of incident heart failure among 4538 persons aged 60 years and older with isolated systolic hypertension who were enrolled in the Systolic Hypertension in the Elderly Program (SHEP). Depression was defined as a score of 16 or more at baseline on the Center for Epidemiological Studies Depression Scale (CES-D). The relationship between depression and heart failure was assessed using Cox proportional hazards regression. RESULTS: The average follow-up was 4.5 years. Heart failure developed in 138 (3.2%) of 4317 nondepressed persons and in 18 (8.1%) of 221 depressed persons. After controlling for age; sex; race; history of myocardial infarction, diabetes, or angina; blood pressure; cholesterol levels; electrocardiographic abnormalities; smoking; disability; and SHEP treatment group, depressed persons had more than a 2-fold higher risk of developing heart failure compared with nondepressed persons (hazard ratio, 2.59; 95% confidence interval, 1.57-4.27; P<.001). After additional adjustment for the occurrence of myocardial infarction during follow-up, depressed persons remained at elevated risk of heart failure (hazard ratio, 2.82; 95% confidence interval, 1.71-4.67; P<.001). CONCLUSIONS: Depression is independently associated with a substantial increase in the risk of heart failure among older persons with isolated systolic hypertension. This association does not appear to be mediated by myocardial infarction.

Aged↗

Biphasic response to human galanin of extracellular acidification in human Bowes melanoma cells.

The metabolic response of galanin GAL1 receptor subtype, endogenously expressed in human Bowes melanoma (HBM) cells, was investigated. Cytosensor microphysiometry was used to determine the extracellular acidification rate. A biphasic response, consisting of a rapid increase in the extracellular acidification rate followed by a decrease below the basal level, was observed after perfusion with human galanin. The magnitude and the rate of onset of both phases were dependent on the galanin concentration. The increase in the extracellular acidification rate (maximum of 25% of basal level; -log(EC(50))=7.23+/-0.14) was transient, whereas the following decrease (maximum of 40% of basal level; -log(EC(50))=7.77+/-0.23) was sustained. The EC(50) values for the increase and decrease were in a similar range. After consecutive galanin administration, the magnitude of the response was the same as for the unexposed cells, indicating the absence of galanin receptor desensitization or internalization in HBM cells. Responses were blocked by pretreatment with pertussis toxin and phorbol-12-myristate-13-acetate (PMA), indicating a G-protein/protein kinase C signalling pathway. Our microphysiometry results show a biphasic response of the extracellular acidification rate mediated by the galanin receptor expressed in HBM cells which has not been described previously for any other endogenously expressed neuropeptide receptor.

1-Methyl-3-isobutylxanthine↗