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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 19 recordsLinked to original sources

Action spectroscopy of H3+ and D2H+ using overtone excitation.

The H3+ ion and its deuterated isotopologues H2D+, D2H+ and D3+ play an important role in astrophysical and laboratory plasmas. The main challenge for understanding these ions and their interaction at low temperatures are state-specific experiments. This requires manipulation and a simple but efficient in situ characterization of their low-lying rotational states. In this contribution we report measurements of near infrared (NIR) absorption spectra. Required high sensitivity is achieved by combining liquid nitrogen cooled plasma with the technique of NIR cavity ringdown absorption spectroscopy. The measured transition frequencies are then used for exciting cold ions stored in a low-temperature 22-pole radiofrequency ion trap. Absorption of a photon by the stored ion is detected by using the laser-induced reactions technique. As a monitor reaction, the endothermic proton (or deuteron) transfer to Ar is used in our studies. Since the formed ArH+ (or ArD+) ions are detected with near unit efficiency, the stored ions can be characterized very efficiently, even if there are just a few of them.

Journal Article↗

Common familial influences on clustering of metabolic syndrome traits with central obesity and insulin resistance: the Kiel obesity prevention study.

OBJECTIVE: The phenotypic heterogeneity of metabolic syndrome (MSX) suggests heterogeneity of the underlying genotype. The aim of the present study was to examine the common genetic background that contributes to the clustering between the two main features (insulin resistance, central obesity) and different MSX component traits. METHODS: In all, 492 individuals from 90 families were investigated in a three-generation family path study as part of the Kiel Obesity Prevention Study (KOPS, 162 grandparents, 66.1+/-6.7 years, 173 parents, 41.3+/-5.4 years and 157 children, 10.8+/-3.4 years). Overall heritability was estimated and common familial (genetic and environmental) influences on insulin resistance (HOMA-IR) or central obesity (elevated waist circumference, WC), respectively, and different MSX traits were compared in a bivariate cross-trait correlation model. RESULTS: Prevalence of MSX (according to NCEP criteria) was 27.2% (f) and 27.8% (m) in adults and 3.5% (f) and 8.5% (m) in children and adolescents, respectively. MSX phenotype was found to be highly variable, comprising 16 subtypes of component trait combinations. Within-trait heritability was 38.5% for HOMA-IR and 53.5% for WC, cross-trait heritability was 53.4%. As much as 6-18% and 3-10% of the shared variance between different MSX component traits (lipid profile, blood pressure) and WC or HOMA-IR, respectively, may be genetic. With the exception of HDL-C, the shared genetic variance between MSX component traits and WC was higher than the genetic variance shared with HOMA-IR. CONCLUSION: A common genetic background contributes to the clustering of different MSX component traits and central obesity or insulin resistance. Common genetic influences favour central obesity as a major characteristic linking these traits.

Adult↗

[Clinical aspects of retinopathy of prematurity. Results following diode laser coagulation].

Retinopathy of prematurity (ROP) represents a disease of the immature retina of preterm infants due to irregular vascularisation. The present article gives information about different parameters of the newborns (gestational age, birth weight, need of oxygen, stage of ROP) and shows the results concerning anatomical and functional aspects following diode laser treatment in 61 prematurely born babies, diagnosed and treated in a period of 5S years in the Hospital of the Ludwig Maximilians University. The mean +/- SD gestational age was 24.9 (+/- 1.59) weeks, the mean +/- SD birth weight was 683 (+/- 174) grams. Diode laser treatment was performed at a mean +/- SD age of 36.14 (+/- 2.04) weeks. Stage 3 retinopathy with "plus disease" was diagnosed in 95.5 % of the infants. In comparison to term born babies or preterm infants without ROP, the diode laser-treated newborns showed a higher incidence of myopia (59 %). An unfavourable outcome in term of the anatomic situation was seen in 9.8 % of these babies.

Child, Preschool↗

High-resolution dissociative recombination of cold H3+and first evidence for nuclear spin effects.

The energy-resolved rate coefficient for the dissociative recombination (DR) of H(3)(+) with slow electrons has been measured by the storage-ring method using an ion beam produced from a radiofrequency multipole ion trap, employing buffer-gas cooling at 13 K. The electron energy spread of the merged-beams measurement is reduced to 500 microeV by using a cryogenic GaAs photocathode. This and a previous cold- measurement jointly confirm the capability of ion storage rings, with suitable ion sources, to store and investigate H(3)(+) in the two lowest, (J,G) = (1,1) and (1,0) rotational states prevailing also in cold interstellar matter. The use of para-H(2) in the ion source, expected to enhance para-H(3)(+) in the stored ion beam, is found to increase the DR rate coefficient at meV electron energies.

Journal Article↗

Prevalidation of a new in vitro reconstituted human cornea model to assess the eye irritating potential of chemicals.

This multicentre study aimed at evaluating the reliability (reproducibility) and relevance (predictivity) of a new commercially available human corneal epithelial (HCE) model (SkinEthic Laboratories, Nice, France) to assess acute ocular irritation. A prevalidation approach (protocol optimisation, transfer and performance) was followed and at each of the four participating laboratories, 20 coded reference chemicals, covering the whole range of irritancy, were tested. The compounds were applied topically to the HCE cultures and the level of cytotoxicity (tissue viability and histological analysis) was determined. Once a standardised protocol was established, a high level of reproducibility between the laboratories was observed. In order to assess the capability of the HCE model to discriminate between irritants (I) and non-irritants (NI), a classification prediction model (PM) was defined based on a viability cut-off value of 60%. The obtained in vitro classifications were compared with different in vivo classifications (e.g. Globally Harmonised System) which were calculated from individual rabbit data described in the ECETOC data bank. Although an overall concordance of 80% was obtained (sensitivity = 100% and specificity = 56%), the predictivity of the HCE model substantially increased when other sources of in vivo and in vitro data were taken into account.

Cornea↗

The value of endoscopic diagnosis and the treatment of pancreas injuries following blunt abdominal trauma.

BACKGROUND: Injuries to the pancreas following blunt abdominal trauma are rare due to its protected retroperitoneal position. Many pancreatic lesions remain unnoticed at first and only become apparent when complications arise or during treatment of other injuries. The mortality rate is between 12 and 30%, and if treatment is delayed it is as high as 60%. METHODS: Using medical records over the past 5 years, we investigated when and in what circumstances endoscopic retrograde cholangiopancreaticography (ERCP) was used in the diagnosis and treatment of pancreas injuries after blunt abdominal trauma. Penetrating injuries were not taken into consideration. RESULTS: An ERCP was performed on a total of five patients with suspected injuries to the pancreas after blunt abdominal trauma. No duct participation could be determined in three of the patients with a first degree pancreatic lesion. A 44-year-old woman sustained severe internal and external injuries after a traffic accident. Because of the nature of her injuries, pancreatic left resection with splenectomy was necessary. After the operation, a pancreatic fistula diagnosed. The ductus pancreaticus (DP) was successfully treated by stenting with the use of endoscopic retrograde pancreaticography. A 24-year old woman was kicked in the epigastrium by a horse. On the day after the incident, she complained of increasing pain in the upper abdomen, and she had elevated amylase and lipase levels. Computed tomography scan showed free fluid. Less than 48 h after the accident, ERCP was performed and a leakage in the DP in the head-body region (fourth degree) was identified. We placed a stent, and during the subsequent laparoscopy the omental bursa was flushed out and a drainage laid. After 14 days, the patient was sent home. We removed the drainage 4 weeks after the accident, and the stent after 12 weeks. CONCLUSION: The major advantage of the prompt retrograde discription of the pancreatobiliary system after an accident in which pancreas involvement is suspected is the more precise assessment of the extent of the injuries. If a stent is placed in the same session, it is possible to carry out definitive and interventional treatment.

Abdominal Injuries↗

[What is anti-aging medicine?].

The apparent demographic changes in our society with a substantial increase of elderly people threatened by restrictions due to diseases, invalidity, and disability call for new forms of "active prevention," namely anti-aging medicine. This kind of medical intervention is not intended to stop or reverse the aging process, but to recognize and decrease the risks of developing chronic diseases provoked by genetic disposition, lifestyle, and biochemical changes and to initiate preventive strategies. These medical interventions are based on knowledge about biological organ functions during the course of a lifetime that proceed according to a general time frame: increase of function from birth to the age 15-28, followed by a continuous decrease until the "disability threshold" is reached, with decompensation of organic function, leading to disease and possibly to death. In light of this background, a modular system of prevention was generated for practical medicine, including risk calculators for detection of the individual health risk and diagnosis of premature loss of organic function using specific vitality tests. Finally, a concept of preventive methods was elaborated based on scientific and clinical evidence.

Aged↗

Efficient and fast targeted production of murine models based on ENU mutagenesis.

Mice with targeted genetic alterations are the most effective tools for deciphering organismal gene function. We generated an ENU-based parallel C3HeB/FeJ sperm and DNA archive characterized by a high probability to identify allelic variants of target genes as well as high efficiencies in allele retrieval and model revitalization. Our archive size of over 17,000 samples contains approximately 340,000 independent alleles (20 functional mutations per individual sample). Based on an estimated number of approximately 30,000 mouse genes, the parallel sperm/DNA archive should permit the identification and recovery of ten or more alleles per average target gene which translates to a calculated 99% success rate in the discovery of five allelic variants for any given average gene. The low rate of unrelated ENU-induced passenger mutations has no practical impact on the analysis of the allele-specific phenotype at the G3 generation because of dilution and free segregation of such unrelated passenger mutations. To date 39 mouse models representing 33 different genes have been recovered from our archive using in vitro fertilization techniques. The generation time for a murine model heterozygous for a mutation in a gene of interest is less than 2 months, i.e., three to four times faster compared with current embryonic stem-cell-based technologies. We conclude that ENU-based targeted mutagenesis is a powerful tool for the fast and high-throughput production of murine gene-specific models for biomedical research.

Alleles↗

Cost-effectiveness of orlistat for the treatment of overweight and obese patients in Ireland.

OBJECTIVE: To assess the cost-effectiveness of orlistat plus a calorie-controlled diet compared with a calorie-controlled diet alone for the treatment of overweight and obese patients in Ireland. DESIGN: Economic modelling techniques using published international efficacy data and Irish cost data were used to estimate the cost-effectiveness of orlistat in obese patients when only responders to treatment (ie achieve 5% weight loss after 3 months of treatment) continue orlistat after 3 months. The model incorporated known relationships between weight loss and quality of life (utility) gain, and weight loss and reduction in risk of type 2 diabetes (T2DM) to predict the impact of weight loss on quality-adjusted-life-years (QALYs) gained and on the onset of T2DM. The costs associated with each treatment arm included the acquisition cost of orlistat, cost of a calorie-controlled dietary programme and monitoring and treatment costs associated with T2DM. An Irish health-care perspective was taken for the analysis, based on 2003 costs. SUBJECTS: Weight loss data on 1386 patients from five pivotal orlistat clinical trials with at least 12 months duration were pooled (two American and three primarily European studies). All the studies were randomized, placebo-controlled, multicentre trials with a similar design. The inclusion criteria were BMI > or =28 kg / m(2), age > or =18 y, no diagnosed T2DM and the ability to lose 2.5 kg in weight during the introductory period. MEASUREMENTS: Cost effectiveness was modelled from these data and presented as incremental cost per QALY. RESULTS: When orlistat treatment plus a calorie-controlled diet was compared with a calorie-controlled diet alone, the incremental cost per year was euro 478. The number needed to treat (NNT) to gain one QALY was estimated to be 35. The incremental cost per QALY gained was within the range considered cost-effective at euro 16,954. Sensitivity analysis demonstrated an incremental cost per QALY of euro 11,000-35,000 under a variety of assumptions. CONCLUSIONS: Our model suggests that orlistat is effective and cost-effective in obese patients, if after 3 months of treatment, only treatment responders continue treatment.

Adult↗

Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management.

There is evidence for a close interrelation between the adrenomedullary and adrenocortical tissues, and there are well-characterized models of their paracrine interaction. To contribute to the studies of systemic interactions between these tissues, we studied a 52-year-old female patient with a pheochromocytoma and a contralateral cortisol-producing adenoma. Due to a misunderstanding, she presented to her family doctor to have an inherited kidney disease ruled out. An adrenal mass was discovered incidentally by ultrasound. A computerized tomography of the abdomen revealed bilateral adrenal masses. Due to excess catecholamine secretion, bilateral pheochromocytomas based on multiple endocrine neoplasia syndrome were suspected. Laboratory work-up, selective adrenal venous sampling and magnetic resonance imaging studies established the diagnosis of a pheochromocytoma in the right-hand adrenal gland and a cortisol-producing adenoma on the left. Simultaneous bilateral laparoscopic subtotal adrenalectomy was performed. Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right-hand adrenal gland, while the left was negative; the left-hand adrenal gland stained positive against the ACTH receptor (MC2R) while the right was negative. Genetically, the patient was negative for MEN2, von Hippel-Lindau disease, and mutations in subunits B, C, and D of the succinate dehydrogenase gene. Although presence of bilateral adrenal adenomas or bilateral adrenal pheochromocytomas in certain inherited disorders are possible, this rare case of an adrenal pheochromocytoma combined with a contralateral cortisol-producing adrenal adenoma may further underline the wide range of complex interactions between the two endocrine systems.

Adrenal Cortex Neoplasms↗

Synchronous occurrence of a follicular, papillary and medullary thyroid carcinoma in a recurrent goiter.

The simultaneous occurrence of different types of thyroid carcinoma in a single patient is an unusual event. We report the case of a 52-year-old man with the history of two previous thyroid operations for benign goiters, who developed a recurrent goiter. The patient was referred to our department for thyroidectomy. In the pathohistological examination the specimen showed a 5 cm follicular carcinoma and a 0.3 cm papillary microcarcinoma in the right lobe as well as a 1.5 cm medullary carcinoma in the left lobe. All tumors were clearly separated from each other, representing the pure entity of each type. Postoperatively, RET germline mutation was ruled out by sequence analysis of peripheral blood leucocytes. Postoperative I-131-radioiodine scan showed multiple lung and liver metastases, while calcitonin was negative. There is no known common cause of these three different tumor types and they developed most independently from each other. The personal history of our patient was interesting in two aspects: (1) he suffered a period of severe staphylococcal sepsis with temporal immunosuppression and (2) he worked for long years as a coremaker in a foundry. This work represented possible long term exposure to inhalative carcinogenous toxins like hydrazine, which caused thyroid parafollicular cell adenomas in an animal model.

Adenocarcinoma, Follicular↗

Action spectroscopy and temperature diagnostics of H+ 3 by chemical probing.

Infrared absorption spectroscopy of few hundred H+(3) ions trapped in a 22-pole ion trap is presented using chemical probing as a sensitive detection technique down to the single ion level. By exciting selected overtone transitions of the (v(1)=0,v(2) (l)=3(1))<--(0,0(0)) vibrational band using an external cavity diode laser an accurate diagnostics measurement of the effective translational and rotational temperatures of the trapped ions was performed. The absolute accuracy of the measured transition frequencies was improved by a factor of four compared to previous plasma spectroscopy measurements using velocity modulation [Ventrudo et al., J. Chem. Phys. 100, 6263 (1994)]. The observed buffer gas cooling conditions in the ion trap indicate how to cool trapped H+(3) ions into the lowest ortho and para rotational states. Future experiments will utilize such an internally cold ion ensemble for state-selected dissociative recombination experiments at the heavy ion storage ring Test Storage Ring (TSR).

Journal Article↗

Size-dependent electron-impact detachment of internally cold Cn- and Aln- clusters.

The cross sections for electron detachment of internally cold Cn- and Aln- clusters were measured using an electrostatic ion beam trap fitted with an internal electron target. The measured electron-impact detachment cross sections for the Cn- (n = 1-9) clusters exhibit even-odd oscillations reflecting the binding energy trend, namely, higher cross sections for weaker binding. Surprisingly, however, these cross sections increase on the average with cluster size, n, in spite of the increase in electron binding. In contrast, the Aln- (n = 2-5) clusters follow the known scaling laws for electron detachment. We suggest that the size-dependent polarizability of these clusters is responsible for the observed behavior.

Journal Article↗

Exclusion of an extracolonic disease modifier locus on chromosome 1p33-36 in a large Swiss familial adenomatous polyposis kindred.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited colorectal cancer predisposition syndrome, displays considerable inter- and intrafamilial phenotypic heterogeneity, which represents a major problem in genetic counselling of APC mutation carriers. The Min mouse model indicated a putative disease modifier locus on chromosome 4, which is syntenic to human chromosome 1p35-36. This finding was subsequently supported by parametric and nonparametric linkage analyses in FAP families, however, without identifying functional variants in candidate genes. Recently, germline mutations in the base-excision repair gene MYH (1p33-34) have been described in patients with multiple adenomas, pointing to a possible role as disease modifier in FAP. Here, we present critical reassessment of one of the largest FAP kindreds published, which was previously used in linkage mapping of 1p35-36. In this family, all affected members harbour the same APC germline mutation (5945delA), but display marked phenotypic variability, in particular regarding the occurrence of extracolonic disease that segregates in several branches of the family tree. Using updated clinical information, additional mutation carriers and polymorphic markers, fine mapping of the critical region as well as mutation analysis of the MYH gene were performed. These investigations allowed us to significantly exclude (i) the 1p33-36 region as a modifier locus and (ii) MYH as a modifier gene for extracolonic disease in this FAP kindred. Our results do not eliminate 1p33-36 from suspicion in other families, but clearly indicate that in our family linkage analysis of further putative candidate regions is necessary to identify a disease modifier locus in FAP.

Adenomatous Polyposis Coli↗

Pheochromocytoma during pregnancy: laparoscopic and conventional surgical treatment of two cases.

Pheochromocytoma is a rare entity. When it presents during pregnancy, rapid recognition and diagnosis are crucial in order to avoid the maternal and fetal morbidity and mortality associated with severe, uncontrolled hypertension. Difficulties arise from the differential diagnosis of pre-eclampsia. We report two patients operated on for pheochromocytoma during pregnancy. The first patient developed new-onset hypertension in early pregnancy. Prior to presentation, there had been non-specific signs of endocrine disorder, namely a mild diabetes, but no hypertension requiring medication. The second patient sought medical care for irregular heartbeat, shortness of breath, and fatigue during the 6th week of pregnancy. She was found to be hypertensive; diagnostic evaluation revealed substantially increased catecholamine levels. The diagnosis was made by elevated urinary catecholamines and by MRI scan as well as ultrasonography, both of which demonstrated an adrenal mass. Both patients underwent surgical extirpation of the affected adrenal gland. The procedure was performed laparoscopically in the case of the second patient. Pre-operatively, both patients were pre-treated with alpha-blockade followed by secondary beta-blockade. Patient two also received methyldopa for control of hypertension. Both patients were readily weaned from antihypertensive medications post-operatively, with complete resolution of hypertension within a few hours. Each pregnancy progressed normally to term.

Adrenal Gland Neoplasms↗

In vitro investigation of marginal accuracy of implant-supported screw-retained partial dentures.

Mismatch occurring during the fabrication of implant-supported dentures may induce stress to the peri-implant bone. The purpose of this study was to investigate the influence of two different alloys and the fabrication method on the marginal accuracy of cast partial dentures. Two laboratory implants were bonded into an aluminium block so that the distance between their longitudinal axes was 21 mm. Frameworks designed for screw-retained partial dentures were cast either with pure titanium (rematitan) or with a CoCr-alloy (remanium CD). Two groups of 10 frameworks were cast in a single piece. The first group was made of pure titanium, and the second group of a CoCr-alloy (remanium CD). A third group of 10 was cast in two pieces and then laser-welded onto a soldering model. This latter group was also made of the CoCr-alloy. All the frameworks were screwed to the original model with defined torque. Using light microscopy, marginal accuracy was determined by measuring vertical gaps at eight defined points around each implant. Titanium frameworks cast in a single piece demonstrated mean vertical gaps of 40 microm (s.d. = 11 microm) compared with 72 microm (s.d. = 40 microm) for CoCr-frameworks. These differences were not significant (U-test, P = 0.124) because of a considerable variation of the values for CoCr-frameworks (minimum: 8 microm and maximum: 216 microm). However, frameworks cast in two pieces and mated with a laser showed significantly better accuracy in comparison with the other experimental groups (mean: 17 microm +/- 6; P < 0.01). (i) The fit of implant-supported partial dentures cast with pure titanium in a single piece is preferable to that of those made with the CoCr-alloy and (ii) the highest accuracy can be achieved by using a two-piece casting technique combined with laser welding. Manufacturing the framework pieces separately and then welding them together provides the best marginal fit.

Bone Screws↗

Laryngeal electromyography: technical features.

Laryngeal Electromyography (LEMG) is an auxiliary diagnostic method used for the comprehension and diagnosis of different neurological diseases that compromise laryngeal function. The most common LEMG technique is the percutaneous insertion of needle electrodes guided by surface anatomical references. We describe techniques for inserting needle electrodes into the tireoaritenoideus (TA), cricotireoideus (CT), cricoaritenoideus lateralis (CAL) and cricoaritenoideus posterioris (CAP) muscles; these are used at UNICAMP laryngology ambulatory, we discuss difficulties found and their proposed solutions. All patients were submitted to otorhinolaryngological, phonoaudiological and laryngeal endoscopy before LEMG. The CAP approach, by digital rotation of the thyroid cartilage was found to be the most difficult, followed by the CAL approach. TA and CT approaches gave no major problems, except with some older and obese patients. A significant complication of the TA approach via thyroid cartilage was a hematoma in one patient which partially obstructed the laryngeal lumen.

Adolescent↗