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Biomedical subjects

A Weber

Publications and source records attributed to A Weber.

At least 181 records · Page 10Linked to original sources

Exclusion of the adrenocorticotropin (ACTH) receptor (MC2R) locus in some families with ACTH resistance but no mutations of the MC2R coding sequence (familial glucocorticoid deficiency type 2).

Several mutations in the coding exon of the ACTH receptor (MC2R) gene have been reported in cases of familial glucocorticoid deficiency or FGD. However, many patients with a similar syndrome do not present any mutation in the coding region of this gene. This is the case in 11 families we have investigated. Patients in these families present the typical clinical features of FGD, but no mutation was found in the coding exon of the ACTH receptor. To determine whether mutations on MC2R gene, but outside the coding region, may be involved in FGD in these families, we have performed a linkage analysis. Using three markers flanking MC2R gene on chromosome 18, we were able to exclude linkage in a region of 12 centimorgans around the gene. This result clearly indicates that FGD is genetically heterogeneous. Defects in gene(s) different from MC2R gene are implicated in this syndrome.

Adrenocorticotropic Hormone↗

Effects of repetitive use and cleaning techniques of disposable jet nebulizers on aerosol generation.

STUDY OBJECTIVE: Patients with cystic fibrosis use disposable jet nebulizers for the self-administration of antibiotics, DNase, and bronchodilators several times per day. Most patients elect to reuse their disposable nebulizers. The purpose of this study was to determine if significant changes in particle size distribution or output (mL/min) occurred with reuse. DESIGN: In vitro studies were performed using four disposable models and one durable jet nebulizer for up to 100 runs; measurements of particle size and output were obtained at 10 run intervals, using saline solution alone, tobramycin, gentamicin, or a mixture of albuterol and cromolyn. Particle size determinations were made with a laser diffraction analyzer. RESULTS: There was no significant difference between the baseline performance of the four disposable models and the durable Pari LC, when measuring particle size distribution of the aerosol; the Pari LC had an output rate two to three times higher than the four disposable models. For each of the four solutes tested, there was no clinically significant change in performance for up to 100 cycles, when the nebulizers were properly cleaned between uses. Unwashed units containing tobramycin started to fail by 40 runs. CONCLUSIONS: When properly maintained, there was no trend of deterioration of performance with repeated use of disposable nebulizers. Microbial contamination was not addressed in this study and must be considered prior to recommendations for the reuse of disposable nebulizers.

Administration, Inhalation↗

[Significance of social medicine in the medical contract office].

In the German statutory social security system, the necessity of long-term care for chronically ill persons with multi-morbidity and reduced performance has made the socio-medical management of illness and its consequences an important characteristic of primary medical activity. In routine practice a discrepancy between the practical demands and social-medical insights has often been observed. With this in mind, the aim of our pilot study was to systematically collect data on the state of the art and attitudes towards the relevant spheres of work in a defined group of physicians and analyse this data. The study was carried out in the form of a voluntary questionnaire within the medical association (Arztlicher Kreisverband-AKV) in the area of Erlangen-Hochstadt. The database was a computer-processible, anonymous questionnaire with which first of all general socio-demographic and activity-related data was collected. The following 10 questions included, in addition to an estimation of the participants' own socio-medical knowledge, questions on the general status of socio-medical knowledge and how the individual gained this knowledge and the importance of socio-medical themes in routine practice. The data was evaluated using descriptive statistics in the form of exploratory data analysis. Of the 320 physicians registered at the time of the investigation (4/96), 89 (31 female doctors, 58 male doctors) sent back a questionnaire that proved useful (returns: approx. 28%). Significant sex-related or specialisation-related differences with regard to participation in the study were not observed. The ratio of female to male doctors and of general practitioners to specialists in the study collective corresponded more or less to the distribution in the total group. The participants had a median age of 41 years (minimum 31, maximum 71) and had been in practice for a median of 11 years (maximum 43 years, minimum 1 year). 36% were general practitioners, 64% specialists. 97% regarded sound knowledge in socio-medicine as essential for doctors wishing to set up practice. 70% regarded their own knowledge of socio-medicine as being in need of improvement. 85% regarded their knowledge as having been insufficient at the start of their medical careers. With regard to doctors gaining socio-medical competence, routine practice and their own autodidactic capabilities played an important role. 84% would like to see increased teaching of socio-medical themes during specialist training courses. For over 70% socio-medicine is a part of medical studies as a subject in its own right. The content and aims of New Public Health were known to 45%. Among the areas of socio-medical work the care of chronically ill persons was given highest priority. Preventive measures were also accorded high relevance by the participants, and they were particularly interested in preventive medicine. Taking into consideration conceptional problems (e.g. the size of the random sample/selection effects) it was found that: despite many years of practice in some cases, doctors feel there is a deficit in their socio-medical knowledge--prcctical knowledge is mainly gained autodidactically during routine practice ("learning by doing"). There is a clear wish for increased consideration of socio-medical themes in specialist training courses. The great importance of socio-medical tasks as part of medical practice is undeniable to the study collective. The results underline the necessity for improved communication and co-operation between doctors involved in primary medical activity and in socio-medicine.

Adult↗

[Quality circles in expert assessment as an instrument in quality management].

An intercomparison programme was carried out as part of the quality management of medical assessments in the public health service in Baden-Württemberg. All physicians who performed medical assessments in January 1997 were invited to participate. They received a case description adopted from medical records of a precedent case (56-year-old head of a department in an administrative authority, severely disabled after left-sided stroke with residual right-sided partial hemiparesis, reduced work performance), and were asked to assess whether the patient was permanently unable to work. Access to medical expert opinions was requested. Participation was voluntary. Assessments were reviewed twice as to whether five prospectively defined evaluation criteria were fully met, or only partially or not at all. Participants and reviewers remained unknown to each other. Among 246 eligible physicians, 103 returned an assessment (43%). Forty-five respondents had requested additional expert opinions. Anticipations for five criteria were met to their full extent with regard to: formal construction, all submissions; case description, 84%; sociomedical diagnosis, 65%; description of ability to work, 53%; and response to the question posed, 75% of submissions. The programme required considerable work time in its preparatory, field, and evaluation phases. The procedure was however found to be practicable, and a suitable element within a quality management programme can contribute towards motivation, quality assurance and the identification of possible deficits, and thus indicate possible topics and issues for continuing education and quality control programmes.

Cerebrovascular Disorders↗

Retrieval of specimens in laparoscopy using reclosable zipper-type plastic bags: a simple, cheap, and useful method.

Surgical specimens must often be extracted during laparoscopic surgery. Although the technologic advances in this field are amazing, simple measures may sometimes work even better than very sophisticated instruments. This is true of the reclosable plastic bags with zipper-type closure that we use for retrieving surgical specimens from the abdominal cavity in order to protect it as well as the abdominal wall. The bags are cheap, offer no problems for sterilization, are easy to obtain, and are available in many sizes. They are very simple to handle, making it easy to slip in the specimen and then extract it from the abdominal cavity. We describe our experience with these bags and a technique for manipulating them.

Humans↗

Interleukin-1 modulates protein tyrosine phosphatase activity and permeability of brain endothelial cells.

Interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6), both known to be able to open the blood-brain barrier (BBB), downregulated plasma membrane-associated tyrosine phosphatase activity in primary porcine brain endothelial cells (PBEC). In contrast, transforming growth factor beta (TGF-beta) upregulated PTP activity and tumor necrosis factor alpha (TNF-alpha) had no effect. Plasma membrane-associated PTP activity of PBEC was upregulated at contact inhibited growth arrest. Tightly confluent cells reduced 3H-inulin permeability by 34% compared with just confluent cells indicating the formation of barrier properties. The decrease in permeability temporally correlated with the elevated PTP activity of the cells at growth arrest and was reversed to control by IL-1 alpha. Vanadate, a broad-specificity PTP inhibitor, also enhanced 3H-inulin permeability. These data suggest that IL-1 alpha-induced endothelial permeability could be controlled through lowering PTP activity.

Animals↗

Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection.

An invading pathogen must be held in check by the innate immune system until a specific immune response can be mounted. In the case of Gram-negative bacteria, the principal stimulator of the innate immune system is lipopolysaccharide (LPS), a component of the bacterial outer membrane. In vitro, LPS is bound by lipopolysaccharide-binding protein (LBP) and transferred to CD14--the LPS receptor on the macrophage surface--or to high-density lipoprotein (HDL) particles. Transfer to CD14 triggers an inflammatory response which is crucial for keeping an infection under control. Here we investigate how LBP functions in vivo by using LBP-deficient mice. Surprisingly, we find that LBP is not required in vivo for the clearance of LPS from the circulation, but is essential for the rapid induction of an inflammatory response by small amounts of LPS or Gram-negative bacteria and for survival of an intraperitoneal Salmonella infection.

Acute-Phase Proteins↗

[Cardiovascular diseases caused by unemployment? An analysis from the viewpoint of social medicine].

Unemployment has become a sociopolitical problem of great importance in the Western industrialised countries. Although negative effects on social life and psyche resulting from unemployment are regarded as scientifically accepted today, a possible causal relationship between job loss and somatic illnesses is still a matter of controversy. A possible target organ is the cardiovascular system. The aim of this study was, therefore, to check by means of extensive literature analysis to what extent unemployment can be seen to influence cardiovascular morbidity. Particular attention was paid to the method used and the clinical relevance of the results. Person-related epidemiological studies published since 1980 which investigated changes in cardiovascular risk factors associated with unemployment or prevalence rates of manifest disease influenced by unemployment, were included in the final evaluation. In some cases statistically significant associations were found between unemployment and the increase in cholesterol levels or systolic/diastolic blood pressure, but the clinical relevance of such slight changes is questionable. To consider unemployment as an independent, social, cardiovascular risk factor is at present unwarranted. An increase in the prevalence rates of coronary heart disease or arterial hypertonia causally linked in some studies with unemployment is scientifically questionable due to severe methodological shortcomings. On the basis of the currently available methodologically acceptable studies, the question of a qualitative contribution of unemployment to cardiovascular disease cannot be answered conclusively.

Adult↗

Preclinical studies for cell transplantation: isolation of primate fetal hepatocytes, their cryopreservation, and efficient retroviral transduction.

Fetal hepatocytes are an attractive target for in utero cellular transplantation. Their use could provide a very efficient way for implanting normal or transduced cells into the livers of affected fetuses. Marking cells with recombinant retroviruses is a powerful tool for evaluating the chimerism of grafted animals. The technique relies on the ex vivo transduction efficiency of the engrafted cells. We have isolated fetal primary hepatocytes from nonhuman primates. The cells were cultured and transduced with a retroviral vector carrying the Escherichia coli beta-galactosidase gene. Optimal gene transfer efficiency was obtained 48-60 hr after plating and was as high as 90%. Cryopreservation had little effect on cell viability and infectivity: The viability of thawed hepatocytes remained high (75-85%) and the infection efficiency was identical to that of freshly isolated cells. Efficient ex vivo retroviral gene transfer into fetal hepatocytes provides an appropriate system for testing allogenic grafting and for modifying immunogenicity of engrafted cells. These results open up new perspectives for cell transplantation through cell banking.

Animals↗

Effect of nebulizer type and antibiotic concentration on device performance.

We compared the performance of selected ultrasonic and jet nebulizers when aerosolizing several antibiotic formulations to determine optimum combinations for delivery of a respirable antibiotic aerosol. Three ultrasonic devices were tested: the UltraNeb 99/100, the UltraAIR and the Aerosonic. The reusable jet nebulizers were the Dura ProNeb, Pari-LL and the Sidestream. The six disposable jet nebulizers were Marquest Acorn II, Hudson T Updraft II, Baxter MistyNeb, Pari-LC, Pari IS-2, and a disposable Sidestream. Each jet was tested with four compressors: a DeVilbiss AP-50, a Pulmo-Aide, a DuraNeb and a PariMaster. All nebulizing systems were initially tested with normal saline. From the initial data, six jet nebulizers and one ultrasonic device were tested with varying concentrations of tobramycin, gentamicin, ceftazidime, ciprofloxacin and colistin. Output was assessed by measuring volume (milliliters per minute), and amount of drug (milligrams per minute) nebulized. We then measured mean particle size of the antibiotic aerosol with seven jet nebulizers and two different compressors, Pulmo-Aide and PariMaster, and two ultrasonic devices. The rate of nebulization of saline and antibiotic solutions (milliliters per minute) was greater with the ultrasonic device(s) than all jet nebulizer systems tested. Increasing the reservoir antibiotic concentration increased the drug output (milligrams per minute) with the jet nebulizers to a maximum, followed by decreasing output. When antibiotic concentrations were increased the output decreased more precipitously with the ultrasonic devices than with the jet nebulizers. At the highest antibiotic concentrations tested, the ultrasonic devices had the lowest output. Particle size distribution was most dependent on the specific jet device, with particle size distribution less affected by a specific antibiotic or its concentration. Higher reservoir concentrations can be utilized for increasing output of respirable antibiotic aerosols by jet nebulizers. We conclude that antibiotic output is dependent upon both the nebulizing system and the reservoir concentration of antibiotic.

Aminoglycosides↗

The High-Resolution Infrared Spectrum of the nu1/2nu2 Fermi Dyad Bands of COF2

High-resolution FTIR data of carbonyl fluoride in the region of the C-O stretch nu1 fundamental have been analyzed. Satisfactory interpretation of the spectral data required a rigorous analysis that involved the inclusion of Fermi resonance with the 2nu2 state and Coriolis interaction with the 2nu3 + nu6 dark state. Deperturbed molecular constants for the three interacting states as well as perturbation parameters that fit the data within the limits of the experimental accuracy of approximately 0.00035 cm-1 have been obtained. Interesting evidence of "axis interchange" in the 2nu2 state has been observed. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

Bone replacement by ionomer cement in osteoplastic frontal sinus operations.

Ionomer-based cement is a new bone replacement material. After promising results in middle ear and skull base surgery, we started to use Ionocap as an alternative to metal osteosynthesis material. Between 1992 and 1995, 20 men and 9 women were treated with an osteoplastic approach for complicated frontal sinus diseases at Johann Wolfgang Goethe University. Ionocap as bonding material for bone was used in 22 of the patients. The indications for osteoplastic surgery were recurrent frontal rhinosinusitis, mucoceles, skull base fractures, osteomas and meningocele. The surgical procedure using bone cement was found to be much easier and shorter, the functional stability achieved was at least equal and the cosmetic outcome was clearly superior when compared to cases done with metal osteosynthesis. No rejection of the material or osteonecrosis was observed. In no case was the cement placed in direct contact to dura mater. Our findings show that ionomer-based cement can be recommened in osteoplastic frontal sinus surgery, but Ionocap should only be used strictly according to the guidelines of the supplier.

Adolescent↗

[Chloride conduction of nasal fibroblasts in polyposis patients with cystic fibrosis and in patients without cystic fibrosis. Relevance for the ENT physician].

Cystic fibrosis (CF) is a complex systemic disease that has pathological alterations in the upper airways, including the recurrent formation of nasal polyps. Although the fibroblast is the predominant cell type in nasal stroma and nasal polyps, little is known about the electrophysiological properties of nasal fibroblasts. We investigated whether fibroblasts possess a cAMP-regulated chloride conductance which is impaired in patients with CF. Thus far the few studies concerning conductance in fibroblasts have been performed on skin fibroblasts using indirect methods and have yielded conflicting results. Therefore we studied chloride conductance in fused nasal fibroblasts by employing conventional microelectrodes. We have demonstrated that a cAMP-regulated chloride conductance is present in fibroblasts. However, this chloride conductance cannot be activated in fibroblasts from CF-patients. Thus, we present direct evidence that the impairment of the cAMP-regulated chloride conductance in CF is not confined to epithelial cells but also affects the fibroblast. We discuss how this conductance might modulate fibroblast proliferation to produce polyp formation.

Child↗

Familial glucocorticoid deficiency: one syndrome, but more than one gene.

Familial glucocorticoid deficiency is a rare autosomal recessive disease characterised by resistance to the action of ACTH. A number of mutations in the ACTH receptor have been demonstrated in patients with this disorder which are likely to lead to loss of receptor function and thus would account for the syndrome. Several patients, however, do not have mutations in the ACTH receptor gene coding region, and it can be demonstrated by segregation analysis that another distant gene must account for the disease in some of these cases. The nature of several candidate genes for this normal receptor form of the disease is discussed.

Animals↗

[Ossovenography as a diagnostic criterion of post-traumatic femoral head necrosis in internal fixation devices].

Despite advances in the field of orthopedic surgery, necrosis of the femoral head still remains a serious problem. Under normal conditions magnetic resonance tomography (MRT) is the gold standard for early diagnosis. Because of magnetic interference, this technique is not applicable in the diagnosis of posttraumatic necrosis with internal fixation, however. This seems to be an ideal indication for ossovenography: contrast medium is injected into the femoral head under X-ray control and the venous flow is documented. Furthermore, it is possible to get histological samples from suspicious areas. Ossovenography was performed in 12 patients and the results were compared with histological samples. In every patient in whom necrosis of the femoral head was diagnosed by ossovenography (91.6%), we also found necrosis on histological examination. In one patient in whom physiological flow was found, there was a corresponding absence of necrosis in the histological sample. There were no complications during ossovenography. The results suggest that ossovenography is a promising and reliable method for early diagnosis of necrosis of the femoral head in the presence of internal fixation devices.

Adult↗

A study of the factors affecting the metabolic clearance of quinine in malaria.

OBJECTIVE: To assess the factors that contribute to impaired quinine clearance in acute falciparum malaria. PATIENTS: Sixteen adult Thai patients with severe or moderately severe falciparum malaria were studied, and 12 were re-studied during convalescence. METHODS: The clearance of quinine, dihydroquinine (an impurity comprising up to 10% of commercial quinine formulations), antipyrine (a measure of hepatic mixed-function oxidase activity), indocyanine green (ICG) (a measure of liver blood flow), and iothalamate (a measure of glomerular filtration rate) were measured simultaneously, and the relationship of these values to the biotransformation of quinine to the active metabolite 3-hydroxyquinine was assessed. RESULTS: During acute malaria infection, the systemic clearance of quinine, antipyrine and ICG and the biotransformation of quinine to 3-hydroxyquinine were all reduced significantly when compared with values during convalescence. Iothalamate clearance was not affected significantly and did not correlate with the clearance of any of the other compounds. The clearance of total and free quinine correlated significantly with antipyrine clearance (rs = 0.70, P = 0.005 and rs = 0.67, P = 0.013, respectively), but not with ICG clearance (rs = 0.39 and 0.43 respectively, P > 0.15). In a multiple regression model, antipyrine clearance and plasma protein binding accounted for 71% of the variance in total quinine clearance in acute malaria. The pharmacokinetic properties of dihydroquinine were generally similar to those of quinine, although dihydroquinine clearance was less affected by acute malaria. The mean ratio of quinine to 3-hydroxyquinine area under the plasma concentration-time curve (AUC) values in acute malaria was 12.03 compared with 6.92 during convalescence P = 0.01. The mean plasma protein binding of 3-hydroxyquinine was 46%, which was significantly lower than that of quinine (90.5%) or dihydroquinine (90.5%). CONCLUSION: The reduction in quinine clearance in acute malaria results predominantly from a disease-induced dysfunction in hepatic mixed-function oxidase activity (principally CYP 3A) which impairs the conversion of quinine to its major metabolite, 3-hydroxyquinine. The metabolite contributes approximately 5% of the antimalarial activity of the parent compound in malaria, but up to 10% during convalescence.

Adolescent↗

Internal exposure to hazardous substances of persons from various continents: investigations on exposure to different organochlorine compounds.

UNLABELLED: The aim of the study was to investigate the concentration of organochlorine compounds of environmental-medical relevance in biological materials from refugees with regard to their countries of origin and to compare these concentrations with the internal exposure of the German general population. METHODS: During medical examination after entry to Germany specimens could be taken from the refugees to determine the following parameters of biological monitoring: 1,1-dichloro-2,2-bis(-chlorophenyl)-ethylene (DDE-P), polychlorinated biphenyls (PCB-P), pentachlorophenol (PCP-P) and the beta- and gamma-hexachlorocyclohexanes (beta-HCH-P, gamma-HCH-P) in plasma and the excretion of chlorophenols (4-MCP-U, 2,4-DCP-U, 2,5-DCP-U, 2,4,5-TCP-U, 2,4,6-TCP-U, 2,3,4,5-TeCP-U, 2,3,5,6-TeCP-U) in urine. One hundred and three men (13 from former Yugoslavia, 29 from the former USSR, 33 Africans and 28 Asians) ranging from 16 to 53 years of age (median 27 years) were investigated. Thirty four male Germans without occupational exposure to these substances and a similar age structure (age 25-36 years; median 26 years) served as a control group. RESULTS: A much higher level of internal exposure was found for the DDT metabolite, DDE, for those persons from Asia, the former USSR and Africa compared with the German controls (medians: 16.9 micrograms/l, 11.9 micrograms/l and 10.9 micrograms/l) and 1.1 micrograms/l). The levels of PCB in plasma were below the detection limit in the majority of refugees. In the control group, however, the PCB levels were higher (sigma PCB; median: 2.1 micrograms/l, maximum: 13.3 micrograms/l). The highest beta-HCH concentrations, up to a maximum of 15.5 micrograms/l, were detected in the persons from the former USSR and Asia. The five groups do not differ with regard to internal exposure to PCP and gamma-HCH. Renal excretion of 4-MCP, 2,4-DCP and TeCP did not differ between the five groups. The concentrations of 2,5-DCP in urine, however, were significantly lower in the Germans than the refugees from the four regions investigated. The median for the Germans was 3.0 micrograms/l and for the refugees between 10.8 and 14.7 micrograms/l. Also the levels of 2,4,5-TCP and 2,4,6-TCP in urine were lower in the German controls than in the men from the former USSR, Africa and Asia. CONCLUSIONS: Organochlorine compounds exist worldwide due to their extensive use. There are, however, regional differences for the various substance groups, which during biological monitoring are seen in the different background exposures of the general population. Particularly characteristic are markedly higher levels of DDE in plasma from the refugees compared with the German population.

Adolescent↗