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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 775 records · Page 43Linked to original sources

The influence of pattern size on amplitude, latency and wave form of retinal and cortical potentials elicited by checkerboard pattern reversal and stimulus onset-offset.

Transient pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded with checkerboard pattern reversal and equiluminance stimulus onset-offset, elicited by a high quality moving mirror stimulator. Different sized checkerboard patterns (0.35-4.2 c/deg) were used as stimulus patterns. The wave forms of the equiluminance stimulus onset responses were similar to ERGs evoked with luminance decrease and the stimulus offset PERGs were like ERGs elicited by luminance increase. The PERG c wave and the VEP showed spatial frequency tuning with pattern reversal and stimulus offset. Spatial frequency tuning was not detectable with PERG a and b waves. Pattern reversal and stimulus onset evoked PERGs had no major spectral components above 40 Hz; stimulus offset evoked PERGs contained components up to 55.3 Hz. Retino-cortical time--measured as a latency difference of the PERG b wave to VEP P100--was identical with pattern reversal and stimulus onset and about 12 msec longer with stimulus offset. Our results suggest that the 3 stimulation modes, reversal, onset and offset induce different types of processing at the retinal and cortical levels. PERG a and b waves to our high luminance/contrast stimuli contain no pattern specific information and the c waves are the sum of luminance and pattern specific responses.

Cerebral Cortex↗

Synthesis and anti-HIV activity of alpha-thiophenoxy-hydroxyethylamide derivatives.

A series of new anti-HIV derivatives containing a novel alpha-thiophenoxyhydroxyethylamide core have been synthesized, using S-phenylbenzenethiosulfonate as the thiosulfenylating reagent. Some of the new synthesized compounds (1a, 1c, 1g, 1i, 1j and 1l) inhibited HIV replication in cell culture assays (syncytia formation) with effective concentrations (EC(50)) ranging from 0.1-1 microM. Incorporation of thiophenoxy substitution within various pseudomimetic peptide backbones provided a series of highly potent HIV inhibitors.

Alkanes↗

Similar cellular effects induced by diesel exhaust particles from a representative diesel vehicle recovered from filters and Standard Reference Material 1650.

Standard reference diesel exhaust particles (DEP) SRM 1650 are often used to evaluate the toxicity of DEP. However, these particles did not necessarily reflect the effects of DEP representative of present diesel automobiles. This study was designed to compare the effects of SRM 1650 to DEP from representative cars (RC-DEP) on airway epithelial cells. Therefore we established a method to recover RC-DEP impacted on filters after emission from diesel automobiles on test beds. Electron microscopy and flow cytometry showed that these two types of particles were phagocytosed to the same extent by epithelial cells. This phagocytosis is not dependent on the adsorbed organic compounds in contrast to the cytotoxic effect evaluated by measurements of LDH release. This is emphasized by the fact that RC-DEP equipped with an oxidation catalyst are less cytotoxic than particles from a non-equipped vehicle or SRM 1650. This type of catalyst also reduces significantly the release of GM-CSF by bronchial epithelial cells. We have shown in the present paper that SRM 1650 may be used as a surrogate of DEP. However, exhaust gas post-treatment devices of current diesel automobiles reduce the cytotoxicity as well as the inflammatory response of these particles.

Air Pollutants↗

Thioredoxin alkylation by a dihaloethane-glutathione conjugate.

Glutathione is a thiol-containing tripeptide which functions to protect cellular constituents from endogenous and xenobiotic electrophiles via conjugation and eventual excretion. In the case of compounds such as 1,2-dihaloethanes, however, conjugate formation results in bioactivation of the species rather than detoxification. The conjugate can then act as an alkylating agent toward cellular constituents including DNA, proteins, or lipids. Alkylation of protein thiols in cells exposed to dihaloethane may contribute substantially to the toxicity produced by these compounds. We examined the reactivity of the conjugate S-(2-chloroethyl)-glutathione (CEG) toward the model protein Escherichia coli thioredoxin. At physiological pH, treatment of thioredoxin by CEG resulted in the production of several bands visible on isoelectric focusing, which were determined by matrix-assisted laser desorption ionization (MALDI) mass spectrometry to be mono-, di-, tri-, and tetra-alkylated forms of thioredoxin. A concomitant loss of in vitro enzymatic activity was observed. These products were also observed when reaction was allowed to take place at pH 11.4. Treatment at pH 4.4 resulted in lesser alkylation of thioredoxin, with only the mono- and di-alkylated forms detected. Iodoacetic acid treatment of CEG-alkylated thioredoxin revealed that the iodoacetic acid-susceptible Cys32 was not carboxymethylated, suggesting that this is one of the sites alkylated by CEG.

Alkylating Agents↗

Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve.

The Schwann cells and fibroblast-like cells of the intact sciatic nerve of adult rats synthesize very little nerve growth factor (NGF). After lesion, however, there is a dramatic increase in the amounts of both NGF-mRNA and NGF protein synthesized by the sciatic non-neuronal cells. This local increase in NGF synthesis partially replaces the interrupted NGF supply from the periphery to the NGF-responsive sensory and sympathetic neurons, whose axons run within the sciatic nerve. Macrophages, known to invade the site of nerve lesion during wallerian degeneration, are important in the regulation of NGF synthesis. Here we demonstrate that the effect of macrophages on NGF-mRNA levels in cultured explants of sciatic nerve can be mimicked by conditioned media of activated macrophages, and that interleukin-1 is the responsible agent.

Animals↗

[Is unicondylar knee prosthesis a current possibility in primary management of varus gonarthrosis?--A prospective matched-pair study].

AIM: In the present study, we performed a follow-up investigation comparing middle-term results after unicompartmental and bicompartmental knee arthroplasties. MATERIAL AND METHODS: We used matched pairs with 18 patients in each group. The first group was treated with the unicompartmental slegde prosthesis (Type Wessinghage), the second with the cementless nonconstrained bicondylar prosthesis (Type Natural knee). The mean time of follow-up was 4.5 years. (SD +/- 0.6). The average age of the patients in both groups was 59 years (SD +/- 3). Both groups included 12 female and 8 male patients. All patients suffered from primary medial osteoarthritis of the knee. In all cases, the contralateral knee also had signs of manifest osteoarthritis. The determination and evaluation of the results of the investigation were made according to the score of the American Knee Society. We also reviewed the radiological findings concerning placement of the prosthesis, radiolucent lines, and patella position in the femoral shield. RESULTS: At follow-up examination, there were no significant differences in the knee score between the patients undergoing unicompartmental or total knee replacement. However, patients with the Wessinghage sledge tended to show better results. The mean knee score was 94.3 +/- 4.9 in the Wessinghage group and 91.9 +/- 8.3 in the Natural knee group. Evaluation of the radiographs revealed radiolucent lines in the group with total replacement. In contrast, in 7 of 18 patients with the unicompartmental prostheses we found radiolucent lines at the tibial component of 1 mm or more, which, however, did not cause clinical symptoms. CONCLUSION: Our results show, that the unicompartmental arthroplasty is still an effective method for the treatment of the osteoarthritis, especially concerning the conditions for possibly needed revisions.

Aged↗

[Long-term changes in proton spin tomography following chemonucleolysis].

6.5 years after lumbar chemonucleolysis (CNL) we examined 40 patients by MRI. All MRI studies were performed by a 1.0 tesla MRI. We documented the height of the discs, the chondrosis, the intradiscal MRI signal, as well as the intraosseous signal within the vertebral bodies (end plate reaction). Preoperative MRI studies (Tvor) and/or postoperative MRI studies within the first postoperative year (T1) of 18 patients were available. We found an overall reduction of the sagittal disc height of 26%. This reduction was 19% in the male patients and 45% in the female patients (p < 0.02). Comparing the T1-studies with the T6.5-studies, we could still reveal a proceeded reduction of 13%. In those patients who underwent three MRI studies, there was a reduction of 20% between Tvor and T1. Among one half of the patients we found a further decrease in disc height of 15% between T1 and T6.5, whereas the other half showed an increasing disc volume of 15%. At time of follow up (T6.5) all treated discs showed a reduced MRI signal (STIR) within the disc. The signal further decreased comparing the MRI signal (STIR) preoperatively with the follow up evaluation in 64.3% of the cases. However, we found an increase of the signal in 70% of the cases between T1 and T6.5. 6.5 years after CNL we documented an end plate reaction in almost 70% of all patients. There was no correlation between end plate reaction and age of the patients, level of CNL, amount of injected chymopapain or the clinical outcome.

Adolescent↗

[Results of mobilization under anesthesia in adhesive capsulitis in relation to stage of the disease].

PROBLEM: Mobilisation under anaesthesia is a well approved method for the treatment of idiopathic adhesive capsulitis, the best time to perform the mobilisation, however, is difficult to define. MATERIAL AND METHODS: Thirty-nine patients who had been treated with mobilisation under anaesthesia for idiopathic adhesive capsulitis stage II or III were examined at an average follow-up time of 3.4 years. RESULTS: This therapy failed in 10.3% of the patients. There were no differences in the follow-up results between both groups of patients, limitations in the range of motion remained in 20% of all patients. At follow up the average CONSTANT Score of the stage II patients was 86.8, that of the stage III patients was 89.9 points. However, manipulation under anaesthesia showed a significantly better influence on the course of the disease in patients with stage III than in patients with stage II adhesive capsulitis. CONCLUSION: Mobilisation under anaesthesia is a successful therapy in adhesive capsulitis stage III, but should be performed in adhesive capsulitis stage II only in cases of decreasing pain in which the limitation in the range of motion is the main symptom.

Adult↗

Using the Health Belief Model to examine and predict college women's cervical cancer screening beliefs and behavior.

The high prevalence of human papillomavirus (HPV) among adolescent and young adult women and the causal association between certain types of HPV and cervical cancer make regular gynecological screening and Pap smear testing essential health practices for young women. In this study, we used the constructs of the Health Belief Model (HBM) to examine the gynecological screening beliefs and behaviors of a sample of 400 college women. Although the constructs of the model were able to explain only 15% of the variance in screening behavior and 11% of screening intentions, the use of the HBM framework resulted in important information regarding the participants' beliefs.

Adolescent↗

Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis.

In 55 patients on continuous ambulatory peritoneal dialysis, the authors determined daily renal and dialysate clearances of urea nitrogen (CUN) and creatinine (CCr). Results are expressed as weekly CUN in liters (Kt) divided by liters of total body water determined from a nomogram (V). The authors calculated weekly CCr as the weekly dialysis clearance plus the average of renal CUN and CCr (to correct for creatinine secretion); they normalized total weekly CCr to 1.73 m2 body surface area. Mean weekly Kt/V and CCr were 2.1 and 65.2, respectively. Mean dietary protein intake by dietary survey was 0.85 g/kg body weight. Protein catabolic rate (PCR) calculated from urea kinetics was 0.94 g/kg standardized weight (V/0.58); PCR was significantly (p < 0.01) correlated with Kt/V (r = 0.53). The authors used linear regression to determine PCR, as follows: PCR = 0.80 [weekly Kt/V]/3 + 0.39. This slope is nearly 1.5 times that reported for the relationship of PCR to [weekly Kt/V]/3 in hemodialysis patients. Eighty-two percent of patients on continuous ambulatory peritoneal dialysis had more than the targeted minimum weekly Kt/V of 1.7, 71% had a weekly CCr more than the targeted minimum of 50, and 75% had a PCR > 0.8 g/kg/day. In support of the hypothesis that Kt/V requirements are related to peak concentration control rather than to time averaged blood urea nitrogen, patients on continuous ambulatory peritoneal dialysis have a higher PCR at given Kt/V values compared to hemodialysis patients. These patients are more likely to have a PCR > 0.8 if weekly Kt/V > 1.7.

Blood Urea Nitrogen↗

Outcomes for infants weighing less than 1000 grams cared for with a nasal continuous positive airway pressure-based strategy.

OBJECTIVE: To compare outcomes for infants weighing less than 1000 g treated with a predominantly nasal continuous positive airways pressure (CPAP) approach (modelled on that of Columbia University, New York) with outcomes audited by the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Data on all infants weighing less than 1000 g admitted for intensive care were collected prospectively for the 29 neonatal units contributing to the ANZNN database. Outcomes for infants treated at Middlemore Hospital over a 3-year period (1998-2001) were compared with the ANZNN data for 1999. RESULTS: Sixty-four infants were admitted to Middlemore Hospital and 954 to the other 28 neonatal units. The two groups were similar with respect to birthweight, Apgar scores, sex and delivery method. Gestational age was lower in the Middlemore infants and outcome variables were adjusted for this difference. Fewer babies at Middlemore were born to mothers who had completed antenatal corticosteroids. The Middlemore Hospital group spent longer on CPAP (P < 0.001) but had less time in oxygen (median 4 days compared to 54 days; P < 0.001). Fewer of the Middlemore cohort were in oxygen at both 28 days (odds ratio 0.17 with 95% CI 0.09-0.30) and 36 weeks corrected gestation (odds ratio 0.15 95% CI 0.07-0.32) and fewer infants were discharged home on oxygen (odds ratio risk 0.38 95% CI 0.16-0.90). Other outcomes were a reduction in the number of infants with culture proven sepsis at Middlemore Hospital but a higher rate of necrotizing enterocolitis. Length of hospital stay and survival rates were not significantly different. CONCLUSIONS: Improved respiratory outcomes for infants weighing less than 1000 g were evident at Middlemore Hospital. This was attributed to the use of a nasal CPAP-based respiratory support system.

Continuous Positive Airway Pressure↗

Lack of calbindin-D28k does not affect hearing level or survival of hair cells in acoustic trauma.

Calbindin is a cytosolic calcium-binding protein abundant in the hair cells of the inner ear and in distinct neurons of the auditory pathway. It is suggested to speed the return of potentially toxic calcium levels to normal. In this study, we show the basic hearing functions and the result of noise trauma from the calbindin null mutant mice generated by gene targeting. Auditory brainstem evoked response and distortion product otoacoustic emissions appear similar as in the control group. A moderate noise-induced trauma produced a similar loss of hair cells in calbindin null mutant mice than in wild-type controls. The result suggests that although calbindin is abundant in hair cells, it is not essential for the main hearing function and it does not provide physiological protection against a moderate noise-induced inner ear trauma in mice.

Animals↗

Fibrinogen kaiserslautern III: a new case of congenital dysfibrinogenemia with aalpha 16 arg-->cys substitution.

An abnormal fibrinogen was identified in a man with suspicious prolonged prothrombin time and a mild bleeding tendency. Coagulation studies showed marked prolonged thrombin and reptilase clotting times and a discrepancy between functional fibrinogen test and fibrinogen antigen. The rate of fibrinopeptide B release by thrombin was slightly delayed while the release of fibrinopeptide A was only half the normal amount. DNA sequencing revealed a heterozygous C to T point mutation in position 1202 of exon 2 of the Aalpha chain, resulting in the substitution of Arg-->Cys at position 16, the thrombin cleavage site. This mutation was found also in his 2 children. Both had a mild bleeding tendency too.

Blood Coagulation Disorders↗

Adequate dietary calcium mitigates osteopenia induced by chronic lead exposure in adult rats.

The purpose of the present study was to investigate bone changes in the adult rat exposed to low lead levels during intake of normal dietary calcium and to contrast these findings with data from our earlier studies performed with animals receiving low dietary calcium concurrent with lead exposure. The present study exposed adult rats to 100 ppm lead via drinking water for 12 weeks and assessed bone histology, 1,25-dihydroxyvitamin D, 25(OH)vitamin D and parathyroid hormone levels. No osteopenia was evident by quantitative bone histology, and circulating levels of 1,25-dihydroxyvitamin D, 25(OH) vitamin D and parathyroid hormone were normal. Bone ash findings documented incorporation of significant amounts of lead into bone mineral. These findings document absence of interference with vitamin D metabolism, absence of secondary hyperparathyroidism and absence of osteopenia following 12 weeks of low lead exposure in the adult rat maintained on normal calcium intake. Results stress the importance of adequate calcium intake in our elderly population who may be exposed to cumulative, low-level lead exposure.

Animals↗

Estrogen replacement increases beta-adrenoceptor-mediated relaxation of rat mesenteric arteries.

The purpose of the present study was to determine whether estrogen replacement in ovariectomized rats could modulate arterial diameter responses to beta-adrenoceptor activation. Under relaxed conditions (0.1 mM papaverine) there were no differences in the lumen diameter of isolated, pressurized (50 mm Hg) mesenteric arteries from nontreated (191.7 +/- 13.8 microns; n = 19) versus those from estrogen-treated (190.1 +/- 11 microns; n = 14) ovariectomized Sprague-Dawley rats. In arteries precontracted with noradrenaline (0.3-1 microM), isoprenaline (0.01-10 microM)-induced relaxation was significantly increased in arteries from ovariectomized estrogen-treated rats (52.4 +/- 2% of the maximal relaxation induced by 0.1 mM papaverine, vs. 33.3 +/- 6.5%; p < 0.01). The half-maximal concentration value was 0.04 +/- 0.05 microM in estrogen-treated rats and 0.4 +/- 0.1 microM in nontreated rats (p < 0.01). This response was inhibited by propranolol (1 microM) in both groups to a comparable extent (61.5%), and was unaffected by endothelial removal. Forskolin (0.01-10 microM) induced similar concentration-dependent vasodilation in arteries of both groups of rats with no differences in sensitivity or maximal response. These results suggest that isoprenaline acts through beta-adrenoceptors present on vascular smooth muscle and that estrogen replacement enhances the relaxant responses induced by beta-adrenoceptor activation by an endothelium-independent mechanism.

Animals↗

The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson's disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers.

A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, which had been manipulated to secrete glia cell line-derived neurotrophic factor (GDNF) (approximately 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impaired coordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging (MRI) scan, and a series of dynamic PET recordings. After the first series of PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PET scans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the brains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated that the rate constant for the decarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [11C]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups of pigs. No significant difference was found in the binding potential of [11C]raclopride to the dopamine D2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive that the activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum.

Animals↗