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Biomedical subjects

G Meier

Publications and source records attributed to G Meier.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ligand-induced conformational changes in tissue transglutaminase: Monte Carlo analysis of small-angle scattering data.

Small-angle neutron and x-ray scattering experiments have been performed on type 2 tissular transglutaminase to characterize the conformational changes that bring about Ca(2+) activation and guanosine triphosphate (GTP) inhibition. The native and a proteolyzed form of the enzyme, in the presence and in the absence of the two effectors, were considered. To describe the shape of transglutaminase in the different conformations, a Monte Carlo method for calculating small-angle neutron scattering profiles was developed by taking into account the computer-designed structure of the native transglutaminase, the results of the Guinier analysis, and the essential role played by the solvent-exposed peptide loop for the conformational changes of the protein after activation. Although the range of the neutron scattering data is rather limited, by using the Monte Carlo analysis, and because the structure of the native protein is available, the distribution of the protein conformations after ligand interaction was obtained. Calcium activation promotes a rotation of the C-terminal with respect to the N-terminal domain around the solvent-exposed peptide loop that connects the two regions. The psi angle between the longest axes of the two pairs of domains is found to be above 50 degrees, larger than the psi value of 35 degrees calculated for the native transglutaminase. On the other hand, the addition of GTP makes possible conformations characterized by psi angles lower than 34 degrees. These results are in good agreement with the proposed enzyme activity regulation: in the presence of GTP, the catalytic site is shielded by the more compact protein structure, while the conformational changes induced by Ca(2+) make the active site accessible to the substrate.

Calcium↗
PubMed1999

Cost-effectiveness of azithromycin for preventing Mycobacterium avium complex infection in HIV-positive patients in the era of highly active antiretroviral therapy. The Swiss HIV Cohort Study.

We conducted a cost-effectiveness analysis to determine the clinical and economic consequences of Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in a health care system with access unrestricted by financial barriers. The analysis was performed from a health care perspective and compared azithromycin (1200 mg/week) with no prophylaxis over a period of 10 years based on data from the Swiss HIV Cohort Study (SHCS) and randomized controlled trials. The main outcome measures were: expected survival; average health care costs; and cost-effectiveness in 1997 Swiss francs ( pound1 corresponds to about 2.3 CHF) per life-year saved. In patients with an initial CD4 count <50 cells/mm(3) and no AIDS, azithromycin increased expected survival by 4 months. In patients with AIDS, HAART durability had a major impact on expected survival and costs. Incremental survival increased from 2 to 4 months if we assumed a 10 year, instead of a 3 year, HAART effect. The cost-effectiveness of azithromycin relative to no prophylaxis in patients without AIDS was between 47,000 CHF (3-year HAART effect) and 60,000 CHF (10-year HAART effect) per life-year saved. The cost-effectiveness ratio increased to 118,000 CHF per life-year saved in patients with symptomatic AIDS. In conclusion, in the era of HAART, MAC prophylaxis with azithromycin increases expected survival and reduces health care costs substantially. Starting MAC prophylaxis in patients without AIDS is more effective and cost-effective than in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1999

Uptake and glutathione conjugation of ethacrynic acid and efflux of the glutathione adduct by periportal and perivenous rat hepatocytes.

We assessed the impact of zonal factors on the hepatic reduced glutathione (GSH) conjugation of ethacrynic acid (EA). Uptake of EA by enriched periportal (PP) and perivenous (PV) rat hepatocytes was characterized by both saturable (V(max)(uptake) = 3.4 +/- 1.7 and 3. 2 +/- 0.8 nmol/min/mg protein and K(m)(uptake) = 51 +/- 13 and 44 +/- 15 microM) and nonsaturable (12 +/- 5 and 12 +/- 3 microl/min/mg protein) components. Values for the overall GSH conjugation rates of EA (200 microM) were similar among the zonal hepatocytes and resembled those for the influx transport rates. In the absence of the hepatocyte membrane, GSH conjugation in PV and PP hepatocyte cytosol was similar, but a higher perivenous GSH conjugation activity toward EA (PV/PP of 2.4) that mirrored the higher PV/PP ratios of immunodetectable GSTs Ya (1.7) and Yb2 (2.5) was found in cell lysates obtained by the dual-digitonin-pulse perfusion technique. The GSH conjugation rates in the subcellular fragments were, however, much greater than those observed for intact hepatocytes. Efflux rates of the glutathione conjugate EA-SG from zonal hepatocytes were similar, as were levels of the immunodetectable multidrug-resistance protein 2/canalicular multispecific organic anion transporter (Mrp2/cMoat) in the 100,000g pellets. The composite results suggest that the GSTs responsible for EA metabolism are more abundant in the PV region, albeit that the gradient of enzymatic activities is shallow. Despite the existence of zonal metabolic activity, the overall GSH conjugation rate of EA is homogeneous among cells because the reaction is rate limited by uptake, which occurs evenly. Results on EA-SG efflux suggest the acinar homogeneity in Mrp2/cMoat function for canalicular transport.

Algorithms↗
PubMed1998

Flow cytometry as a sensitive tool to assess testicular damage in rat.

The aim of this study was to compare results obtained by flow cytometry (FCM) with those obtained from testicular histopathology with regard to testicular damage following acute exposure of adult rats to the known testicular toxicant, methoxyacetic acid (MAA). Special emphasis was given to defining the sensitivity of three-parameter FCM compared with testicular histopathology. Furthermore, the effect on the male reproductive system of a single oral dose of MAA was evaluated with traditional methods, e.g. testicular sperm head counts, and organ weights. Adult, male Han/Wistar rats were randomly assigned to four groups of ten animals to be treated with a single dose of 0, 65, 325 and 650 mg MAA/kg body wt. (p.o., gavage). The animals were killed 2 days after treatment, and testicular and epididymal weights were recorded. One testis and the corresponding epididymis were used for histopathology. The other testis was used partly to determine sonication-resistant, testicular sperm-head counts (SHC), and partly for enzymatic digestion followed by FCM. The results obtained in this study are in agreement with the literature, and show that, in the adult male rat, 2 days after administering a single oral dose of MAA, specific depletion of spermatocytes is evident. Detectable testicular effects were produced by the high (650 mg/kg body wt.) and mid (325 mg/kg body wt.) doses, whilst the low dose (65 mg/kg body wt.) did not produce any noticeable effect. There was a strong correlation between results obtained by FCM and those obtained by testicular histopathology, and no difference in sensitivity between the two methods was observed. In summary, three-parameter FCM represents a sensitive and reliable method for the detection of testicular injury in the rat. It requires only small amounts of tissue, and the sensitivity was shown to be similar to that of histopathology. Moreover, FCM has the advantages of being quick and objective, which permits large numbers of cells to be analysed. The potential use of this method as a fast screening tool for testicular toxicity in routine toxicology studies should be considered.

Acetates↗
PubMed1998

Adverse effects of tribromoethanol as used in the production of transgenic mice.

Tribromoethanol is widely used as an anaesthetic agent for embryo-transfer surgery for the generation of transgenic mice. Potential side effects such as local irritation, fibrous adhesions in the abdominal cavity, and mortalities of unknown cause have been reported. Mice of three different strains (CD-1, OF-1, NMRI) received intraperitoneal injections of pentobarbiturate (60 mg/kg, 0.4%), tribromoethanol (240 mg/kg, 1.2%), tribromoethanol (450 mg/kg, 2.5%), ketamine/xylazine (120 mg/kg, 1.2%/16 mg/kg, 0.16%) or saline (NaCl, 0.9%). After 24 h the animals were sacrificed and blinded histopathological examination of abdominal organs was performed by light microscopy. Tribromoethanol caused focal to diffuse necrosis primarily of subperitoneal muscle fibres of the abdominal wall, and, occasionally, necrotic changes on the surface of abdominal organs. These changes were associated with acute peritoneal inflammation and fibrinous serositis of the abdominal organs. The severity of the findings increased with the concentration of tribromoethanol. The use of ketamine/xylazine yielded a comparable success rate in embryo transfer without undesirable side effects. Further use of tribromoethanol is not recommended.

Anesthetics↗
PubMed1998

[Leg pain from the orthopedic viewpoint].

The purpose of this paper is to analyze the etiology of pain in the lower limb provoked by the locomotor apparatus. Vertebral, pseudoradicular, radicular syndromes, the hip pain including the acetabular rim syndrome, the generally localized knee and foot pain are discussed. Major symptoms and clinical findings necessary for an effective differential diagnosis of the lower limb pain are pointed out.

Diagnosis, Differential↗
PubMed1997

Decrease in kidney calbindin-D 28kDa as a possible mechanism mediating cyclosporine A- and FK-506-induced calciuria and tubular mineralization.

The use of the immunosuppressant cyclosporine A (CsA) is limited by its adverse renal effects. Most recently, we reported that the drug markedly decreases the levels of the calcium-binding protein calbindin-D 28kDa in kidneys of male Wistar rats. In the present study, the potential relationship between drug-induced nephrotoxicity and the decrease in kidney calbindin-D 28kDa was investigated. Four groups of male Wistar rats were treated for 10 or 31 days with either the immunosuppressant CsA (50 mg/kg/day), FK-506 (5 mg/kg/day), rapamycin (5 mg/kg/day) or with the nonimmunosuppressive cyclosporine derivative 3'keto-[Bmt1]-[Val2]-CsA (SDZ PSC-833) (50 mg/kg/day), and the effects on calcium homeostasis, kidney histology and renal calbindin-D 28kDa were examined. Similar effects were found with CsA and FK-506; both drugs strongly reduced kidney calbindin-D 28kDa protein levels, increased urine calcium excretion, caused intratubular calcification, and induced basophilic tubules. In contrast, rapamycin and SDZ PSC-833 caused no decrease in renal calbindin-D 28kDa levels, no noticeable alterations in calcium metabolism, and no renal calcification. The results provide evidence for a link between decreased renal calbindin, increased calcium urine excretion, and intratubular kidney calcification. The present data show no correlation between the decrease in renal calbindin and the induction of basophilic tubules; however, it needs to be investigated if these apparently independent kidney effects may have a common origin upstream of calbindin expression.

Animals↗
PubMed1997

[Interscalene brachial plexus catheter for anesthesia and postoperative pain therapy. Experience with a modified technique].

OBJECTIVES: This study was conducted to evaluate a modified technique of interskalene brachial plexus anaesthesia (ISB) and postoperative catheter analgesia for shoulder surgery. The original method described by Winnie bears some rare but life-threatening complications (inadvertent subarachnoid or intra-arterial injection, pneumothorax). MATERIALS AND METHODS: Ninety-one patients with chronic rheumatoid arthritis who were scheduled for open or closed shoulder surgery received a modified ISB with catheter insertion. The injection site was more cephalad than that described by Winnie and the cannula was directed towards the junction between the medial and lateral third of the clavicle. Intra- and postoperative management, complications, and patients' satisfaction were recorded and evaluated. RESULTS: Implementation of ISB was possible in all cases, however, 3% of these presented technical problems. Anaesthesia with 300 mg mepivacaine 1% was successful in 94% of patients without and in 96% with augmentation after an average of 32 min; 10% of the patients suffered a drop in blood pressure after being placed in the beach-chair position for surgery. Postoperatively, all patients received 20 ml bupivacaine 0.25% for pain management via the catheter; 11% needed an additional analgesic drug. The catheter was removed after an average of 5 days. Signs of superficial local infection were noticed in 8 cases. Side effects occurred in 13% as Horner's syndrome, in 6.5% as recurrent laryngeal nerve block, and in 3.3% as phrenic nerve block. The acceptance of this anaesthetic technique among the patients was very high (96.7%). CONCLUSION: We consider the modified ISB with catheter a safe and effective procedure for anaesthesia and postoperative pain management of open and closed shoulder surgery.

Adult↗
PubMed1995

Outcome analysis of total knee-replacements in patients with rheumatoid arthritis versus osteoarthritis.

A total of 524 knees underwent a primary PCA knee arthroplasty between 1982 and 1989. Of these 415 suffered from osteoarthritis (OA) and 61 from rheumatoid arthritis (RA). They were analyzed for differences regarding the outcome. Neither survivorship analysis nor number or type of revisions revealed statistical differences among these two groups. The knee score rose in the OA group from a median of 28 to 89 points after 1 year and then dropped to 87 points between 54 and 118 months. In the RA group the median of the knee score rose from a preoperative value of 21 points to 90 points after 1 year but then dropped to 77 points at the most recent follow-up. This development was probably the result of general progression of the disease. Even in the RA group the rating was still "good" at the latest follow-up. Regarding the benefit of such a procedure in a polyarticular disease and its preservation over a long period of time, total knee arthroplasty can be recommended for patients with RA, and preferably the cemented version.

Adult↗
PubMed1994

Quantification of hepatocytic proliferation in the laboratory mouse. A comparative study using immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression.

The proliferation rate in livers of 120 mice (60 males and 60 females) was analyzed by immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression on ethanol-fixed/paraffin-embedded specimens. Mice were divided into three groups, with 20 males and 20 females in each group: mice in the first group served as controls, while mice in the second and third groups were treated with a low and a high dose, respectively, of a non-genotoxic drug candidate for 2 weeks. A dose-related increase of the proliferating hepatocyte fraction was disclosed by both immunohistochemical methods, reaching statistical significance already in the low-dose male group for BrdU incorporation and in both male and female low-dose groups for PCNA expression. A good correlation between the degree of BrdU and PCNA labeling was observed and, as expected, the percentage of PCNA expressing cells was generally higher than the percentage of BrdU-positive cells. We concluded that the detection of PCNA expression represents a reliable method for the quantification of the hepatocytic proliferating fraction in rodents and allows the use of archival material for cell kinetic investigations in toxicologic pathology.

Animals↗
PubMed1994

Proliferating cell nuclear antigen expression in Wistar rat livers. A retrospective immunohistochemical study of normal and neoplastic livers.

Formalin-fixed, paraffin-embedded liver specimens from 27 2-year-old Wistar rats, including 10 normal livers, 11 hepatocellular adenomas, 2 hepatocellular carcinomas, and 4 cystic cholangiomas, were immunostained using the streptavidin/peroxidase method and the PC10 monoclonal antibody (Mab), which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above four groups of liver specimens: normal livers, 0.43 +/- 0.31%; hepatocellular adenomas, 1.51 +/- 0.59%; hepatocellular carcinomas, 24.80% +/- 10.28%; and cystic cholangiomas, 0.61 +/- 0.21%. Our findings indicate that PCNA LI clearly separates liver malignancies from other benign liver tumors, as well as from normal, non-neoplastic, liver tissues. Although the mean PCNA LI values seemed to reflect histological grading (i. e. normal, neoplastic benign, neoplastic malignant), overlapping between normal livers and hepatocellular adenomas was observed in five cases (i. e. in 2 normal livers and 3 hepatocellular adenomas, where the PCNA LI values varied between 0.74% and 0.96%). It thus appears that PCNA immunohistochemistry represents a promising tool for investigating liver cell proliferation in laboratory rats, and permits distinguishing between benign and malignant liver parenchymal tumors.

Animals↗
PubMed1992

[Forces and turning moments of hip and knee joints in locomotion].

In order to be helpful to orthopedic surgeons in planning operations, and providing quality control, gait analysis must provide information on forces and moments at major joints because kinematic data alone have proved to be unsatisfactory. A practical procedure for this purpose was developed and applied to 20 children and young adults, using the inverse dynamic approach. Segmental body volumes were obtained by stereophotogrammetry. Together with density values, this permits individual calculation of segmental mass center positions even in the presence of severe deformity. Segmental anatomical coordinate systems were defined and tagged by skin markers. Subsequent stereophotogrammetric gait recording by high-speed cameras and 3D force plates allowed the calculation of reactive forces and moments with their changing values over each gait cycle. For the two peaks of force transmission in the early and late stance phases, vector diagrams demonstrate 3D components of forces and moments as related to the anatomy of the thigh and shank of a normal young adult. The peak reaction force component in the longitudinal axis during initial loading about reaches body weight, the anteroposterior force 2/5th and the mediolateral component 1/25th of body weight.

Adolescent↗
PubMed1991

Quantity of protein deposited on hydrogel contact lenses and its relation to visible protein deposits.

The purposes of this study were to determine if the quantity of protein deposited (QPD) upon hydrogel lenses was affected by enzymatic cleaning and to test the potential relation between QPD and visible protein deposition (VPD) and change. Seventy-four contact lens patients classified as "heavy depositors" wore new lenses for an average of 80 (SD = 32) days. Cleaning and disinfection solutions varied. One lens was cleaned weekly by a papain enzymatic treatment. The distribution of QPD measurements was bimodal and was related to the FDA material for nonionic, low water content lenses (FDA Materials Group no. 1). The mean deposition was 45 micrograms/cm2 (N = 112) compared with that of ionic, high water content lenses (FDA Materials Group no. 4), which was 1010 micrograms/cm2 (N = 30). VPD distributions were the same for the FDA Group no. 1 and no. 4 lenses. Enzymatic treatment did not significantly reduce QPD; however, enzymatic treatment did reduce VPD. Thus QPD and VPD are independent phenomena and possible reasons for this are given.

Adult↗
PubMed1990

[Augmentation of the coraco-clavicular ligament suture. Comparison between wire cerclage, vicryl tape and PDS cord].

A total of 71 patients (average age 32 years) with acute grade III acromio-clavicular dislocation were all treated with the same surgical procedure: open reduction, transfixation of the acromio-clavicular joint with a Kirschner wire and suture of the coraco-clavicular ligaments with augmentation. The augmentation was done with a 1.2-mm wire cerclage in the first group (22 patients), a 3-mm wide Vicryl tape in the second group (30 patients) and a 1.5-mm PDS cord in the third group (19 patients). At follow-up (average time 4.4 years) the patients were questioned as well as being examined radiologically and clinically. Only two patients were not satisfied with the outcome of surgery. On clinical evaluation after wire cerclage augmentation of the suture, the distal end of the clavicle was found to be dislocated in 23% of cases. The incidence was 20% after Vicryl taping and 58% after PDS cord augmentation. At X-ray examination with 8 kg suspended from the wrist acromio-clavicular dislocation was found in 45% after wire cerclage, 23% after Vicryl taping and 58% after PDS cord augmentation of the suture. The results show that dislocation is more likely to persist after augmentation of the suture of the coraco-clavicular ligaments with wire cerclage or PDS cord than when the suture is augmented with a Vicryl tape. We conclude that a resorbable material is suitable for augmenting the suture of the coraco-clavicular ligaments, but that a filiform augmentation is less appropriate than a band.

Acromioclavicular Joint↗