[Rehabilitation after myocardial infarct--a multidisciplinary responsibility].
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Combined Modality Therapy↗
Biomedical subjects
P Schmid
Publications and source records attributed to P Schmid.
Determination of displacement, stress- and strain-distribution in the human heart: a FE-model on the basis of MR imaging.
The determination of characteristic cardiac parameters, such as displacement, stress and strain distribution are essential for an understanding of the mechanics of the heart. The calculation of these parameters has been limited until recently by the use of idealised mathematical representations of biventricular geometries and by applying simple material laws. On the basis of 20 short axis heart slices and in consideration of linear and nonlinear material behaviour we have developed a FE model with about 100,000 degrees of freedom. Marching Cubes and Phong's incremental shading technique were used to visualise the three dimensional geometry. In a quasistatic FE analysis continuous distribution of regional stress and strain corresponding to the endsystolic state were calculated. Substantial regional variation of the Von Mises stress and the total strain energy were observed at all levels of the heart model. The results of both the linear elastic model and the model with a nonlinear material description (Mooney-Rivlin) were compared. While the stress distribution and peak stress values were found to be comparable, the displacement vectors obtained with the nonlinear model were generally higher in comparison with the linear elastic case indicating the need to include nonlinear effects.
Algorithms↗
Heterogeneity of vacuolar H(+)-ATPase: differential expression of two human subunit B isoforms.
The catalytic domain of the vacuolar proton ATPase is composed of a hexamer of three A subunits and three B subunits. Here we describe the cloning and characterization of a cDNA isoform of subunit B, HO57, from an osteoclastoma cDNA library. HO57 is represented by three species of mRNA of 1.6, 2.6 and 2.8 kb and is expressed at low levels in a range of human tissues, but at significantly higher levels in brain, kidney and osteoclastoma, and is probably an ubiquitously expressed isoform. In contrast, the kidney-specific isoform has an mRNA of 2 kb and is specifically expressed at high levels only in kidney and, at a lower level, in placenta. Thus the HO57 isoform is integral to the vacuolar ATPase found in the general secretory system of all cells as well as in vacuolar-ATPase-rich sources such as neurones and osteoclasts, whereas both the kidney-specific isoform and HO57 are highly expressed in the kidney. Furthermore, we show by in situ hybridization that HO57 is the only isoform that is exclusively and highly expressed by osteoclasts.
Animals↗
Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis: stored maternal TGF-beta 2 message in oocytes.
The present in situ hybridisation study describes expression of TGF-beta 1, TGF-beta 2, TGF-beta 3, and TGF-beta type II receptor mRNA during follicular development, and the temporal pattern and abundance of TGF-beta 2 transcripts in early pre-implantation embryos. TGF-beta 1 hybridisation signals were most prominent in the outer granulosa cell layers of the post-antral follicles and in the corpus luteum, whereas strong expression of TGF-beta type II receptor mRNA was confined to thecal cells. Weak TGF-beta 3 mRNA expression was observed in all major cell types of pre- and post-antral follicles. Most notably, the very strong TGF-beta 2 hybridisation signals which were detected in developing oocytes declined rapidly following fertilization. Although still abundant in two-cell embryos, TGF-beta 2 hybridisation signals were barely detectable in four- and eight-cell embryos. These findings, and the presence of specific sequence motifs in the 3' untranslated region of TGF-beta 2 mRNAs, suggest that TGF-beta 2 transcripts are stored as maternal messages.
Animals↗
Transient production of TGF-beta 2 by postnatal cerebellar neurons and its effect on neuroblast proliferation.
The beta transforming growth factors (TGF-beta) are suggested to regulate developmental processes since they are distinctly expressed during embryogenesis and exert pleiotropic effects on cell growth and differentiation, In the present study the expression of TGF-beta isoforms was investigated in the postnatal and adult mouse brain. As shown by in situ hybridization, TGF-beta 2 was expressed in the choroid plexus, hippocampus, dentate gyrus and cerebellar Purkinje neurons, both postnatally and in adults. Furthermore, TGF-beta 2 expression was observed postnatally in immature cerebellar neurons of both the external and internal granule cell layers. In the external granule cell layer, the frequency of TGF-beta2 transcripts increased until postnatal day 10 and declined thereafter. In contrast to TGF-beta 2, no TGF-beta 1 mRNA was detected in cerebellar granule cells. TGF-beta 3 expression was widely distributed in postnatal brains although at very low levels. The significance of TGF-beta 2 production by cerebellar granule cells was further investigated using cultures of small cerebellar neurons. In these cultures reverse polymerase chain reaction analysis revealed expression of TGF-beta 2 but low or almost undetectable levels of TGF-beta 1 or -beta 3 mRNAs. Likewise, only TGF-beta 2 protein in its latent form was identified in the culture supernatant; the release of TGF-beta 2 was maximal during the second day in vitro. Furthermore, TGF-beta was found to inhibit the proliferation of cultured small cerebellar neurons. Taken together, these data suggest that TGF-beta 2 is involved in the regulation of postnatal development of the cerebellum.
Animals↗
Sleep disturbance and appetite loss after lovastatin.
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Adolescent↗
Wound healing after laser injury to skin--the effect of occlusion and vitamin E.
The skin of Yorkshire pigs was irradiated with various doses of argon and copper-vapor laser and evaluated for effects on healing time of pretreatment with topical or intramuscular vitamin E or the Op-Site wound dressing. Incident irradiance for both lasers was between 3.5 and 4.5 W/cm2 for a 10-14-mm beam diameter with a nearly uniform intensity profile. Minimal erythemic dose for the copper-vapor laser was 35 +/- 2 J/cm2 (10 s exposure) and 22.4 +/- 0.1 J/cm2 (6-s exposure) for the argon laser. Three dose levels were administered: a low dose causing light erythema, an intermediate dose, and a high dose causing dermal stasis. The radiant exposures for low, intermediate, and high doses were 35, 70, and 138 J/cm2 for the copper-vapor laser and 22.4, 55, and 129 J/cm2 for the argon laser. Exposure to argon and copper-vapor lasers generally caused wounds with similar healing times. Healing time was significantly decreased for wounds caused by intermediate exposure of the copper-vapor laser and either pretreated with vitamin E or treated with the wound dressing. Healing times for corresponding argon-laser exposure were significantly decreased with pretreatment of intramuscular vitamin E only or after treatment with the wound dressing. These findings may be valuable in selecting treatment for accidental laser skin injuries in man.
Adipose Tissue↗
The influence of geometry on the stress distribution in joints--a finite element analysis.
The incongruity of human joints is a phenomenon which has long been recognized, and recent CT-osteoabsorptiometric findings suggest that this incongruity influences the distribution of stress in joints during their normal physiological use. The finite element method (FEM) was therefore applied to five different geometric configurations consistent with the anatomy of articular surfaces, and a program with variable contact areas (Marc) was used to calculate the stress distribution for loads of 100 to 6,900 N. The assumption of congruity between head and socket results in a "bell-shaped" distribution of stress with a maximum value of 61.5 N/mm2 in the depths of the socket, decreasing towards zero at its edges. In the model with a flatter socket the von Mises stresses are higher (max. 101.3 N/mm2); with a deeper socket, lower (max. 53.0 N/mm2). If the diameter of the head is greater, the stresses build up from the periphery of the socket and move towards its depths as the load increases. The combination of an oversized head and a deeper socket results in the most satisfactory stress distribution (max. 43.2 N/mm2). These results extend previous photoelastic findings with incongruous joint surfaces. The calculated mechanical conditions show a relationship to the location of osteoarthritic changes, and are reflected by the distribution pattern of subchondral bone density. A more satisfactory stress distribution is found with functionally advantageous, incongruous joint surfaces (oversized head and deepened socket) than in the congruous joint, and a better nutritive situation for the articular cartilage seems likely.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
A new experimental approach for monitoring postoperative bypass patency after coronary artery bypass grafting.
Little information is known concerning hemodynamic parameters of bypass grafts after open heart surgery during the postoperative period. As there is no easy to use bedside-method for monitoring, we developed a new implantable Doppler probe to measure blood flow velocity with a 20 MHz pulsed Doppler system. The accuracy of this method was proved in a circulatory model and in animal studies. Our conclusion is that the implantable pulsed Doppler system is a sensitive method for monitoring small vessel hemodynamics.
Animals↗
The trace analysis of musk xylene in biological samples: problems associated with its ubiquitous occurrence.
Musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene) (MX), a synthetic musk often used in fragrances has previously been described to occur in human tissue. In this article a specific and sensitive method for the determination of MX in blood is described. It includes a simple clean-up by silica gel adsorption chromatography followed by GC/MS detection with negative chemical ionisation (NCI) and multiple ion detection of the molecular ion and M-30. The absolute detection limit in the MID-mode was 50 fg of MX. 11 human blood samples of 3 individuals were analysed to elucidate the suitability of this method. The MX concentrations ranged from 66 to 270 pg/g plasma or 12 to 49 ng/g blood lipids, respectively. In the course of the method evaluation the hazard of sample contamination during the clean-up procedure was investigated and MX was found to be present in several materials in the laboratory. Some of these contamination sources could be eliminated.
Adult↗
The neuropathological diagnosis of neuronal intestinal dysplasia (NID B).
Between 1986 and 1991 773 infants were investigated by biopsy. 209 children suffered from a neuronal dysplasia of the submucous plexus (NID B). 64 of these 209 cases had concomitant Hirschsprung's disease with NID. The combination of Hirschsprung's disease with NID was established at biopsy not earlier than at 12 +/- 6 months of age. The classical form of an isolated aganglionosis had a median age at diagnosis of 4 +/- 2 months. The preconditions for a reliable diagnosis of NID are mucosal biopsies with submucosa taken 1, 3 and 9 cm above the pectinate line, the preparation of 15 microns thick serial sections, a acetylcholinesterase- and lactate-reaction and a systematic examination of all serial sections. Giant ganglia, which are 2-3 times as large as normal ganglia and having more than 7 LDH-positive nerve cells (10 +/- 3 nerve cells in the mean), are the most relevant parameters in the diagnosis of NID. They can be observed in infants as well as in adults. The NID proximal to aganglionosis is in principle not different from an isolated form of NID. Increase of acetylcholinesterase-activity in muscularis mucosae and lamina propria mucosae and a "hyperplasia" of the submucous plexus in early infancy disappears with advancing age and are very seldom observed at 2 years of age or in adulthood. NID B is the mildest form of a developmental abnormality of the autonomic nervous system, which shows in most cases a spontaneous normalization of gut motility.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholinesterase↗
The type I interferon system is locally activated in psoriatic lesions.
The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin. The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have been found exclusively in cells of psoriatic lesions, and most likely represent a subpopulation of infiltrating leukocytes. Weak signals of IFN-alpha mRNA have been detected throughout the hyperkeratotic epidermis, although specific signals for IFN-beta mRNA expression were not detectable. The expression of two IFN-alpha-inducible gene products, namely the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha system. Expression of MxA mRNA and protein was observed in psoriatic keratinocytes, but not in normal appearing keratinocytes adjacent to the lesions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate that the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of this finding are discussed within the boundaries of current understanding of the cytokine network.
2',5'-Oligoadenylate Synthetase↗
Cerebrospinal fluid p24 antigen levels and intrathecal immunoglobulin G synthesis are associated with cognitive disease severity in HIV-1.
OBJECTIVE: To test the hypothesis that selected cerebrospinal fluid (CSF) markers [intrathecal immunoglobulin G (IgG) synthesis rate, oligoclonal IgG bands, and p24 antigen levels] are associated with the presence and severity of clinical HIV-1 neurologic disease. DESIGN AND METHODS: CSF and blood parameters from 142 HIV-seropositive subjects from the baseline examination of a longitudinal study were measured and analyzed in relationship with clinically derived cognitive impairment groups (none, mild, moderate) and with other neurologic and clinical classification groups. Subjects with opportunistic infections, lymphomas or neurosyphilis were excluded. RESULTS: The mean intrathecal IgG synthesis rate and mean CSF p24 antigen levels both differed significantly among cognitive impairment groups; more impairment was associated with a higher rate or level. Mean CSF p24 antigen levels were significantly higher in HIV-1-seropositive subjects with any HIV-1 neurologic disease than in subjects without neurologic disease. In contrast, there were no significant differences among seropositive groups in any CSF parameter when stratified by systemic disease classification (asymptomatic HIV-seropositives, AIDS-related complex, or AIDS), independent of neurologic status. CONCLUSION: We conclude that there may be a relationship between the severity of HIV cognitive disease and increasing levels of intrathecal IgG synthesis and CSF p24 antigen levels.
AIDS Dementia Complex↗
Frequency of sensitization to 13 common preservatives in Switzerland. Swiss Contact Dermatitis Research Group.
From February 1989 to January 1990, the Swiss Contact Dermatitis Research Group conducted a 1-year study to examine the frequency of sensitization to a series of 13 common preservatives. A group of 2295 consecutive outpatients with suspected allergic contact dermatitis (age range 7-90 years, with a mean age of 42; 911 males, 1384 females) was tested. The %s of positive reactions to the preservatives studied are as follows, in descending order: formaldehyde 5.7%, benzalkonium chloride 5.5%, Kathon CG 5.5%, thimerosal 4.2%, chlorhexidine digluconate 2.0%, DMDM hydantoin 1.7%, paraben mix 1.7%, chloroacetamide 1.5%, Bronopol 1.2%, imidazolidinyl urea 1.0%, quaternium 15 1.0%, triclosan 0.8%, 2,4-dichlorobenzyl alcohol 0.4%. These relatively high values suggest a heavy exposure of the Swiss population to topical preservatives. Compared to previous studies, the sensitization rate to Kathon CG has stabilized in Switzerland over the last 2 years. Sensitization to formaldehyde portrayed impressive geographical variation, with sensitization rates up to 9% in western and only 3% in eastern Switzerland. The low sensitization rate to parabens argues for their inclusion in a medicament or preservative series, rather than in the standard series.
Administration, Cutaneous↗
Role of Mac-1 and ICAM-1 in ischemia-reperfusion injury in a microcirculation model of BALB/C mice.
The leukocyte beta 2-integrin Mac-1 (CD11b/CD18) and its endothelial ligand intercellular adhesion molecule 1 (ICAM-1) are involved in leukocyte adhesion to and macromolecular leakage from postcapillary venules during inflammatory reactions. Both events are also encountered after ischemia-reperfusion of striated muscle, suggesting a central role of both adhesion proteins in reperfusion injury. Using intravital fluorescence microscopy and a microcirculation model in awake BALB/C mice, we investigated the effects of monoclonal antibodies (MAb) and Fab fragments to Mac-1 and MAb to ICAM-1 on leukocyte-endothelium interaction and macromolecular leakage of fluorescein isothiocyanate-dextran (1.5 x 10(5) mol wt) in striated skin muscle after 3 h of ischemia followed by reperfusion. We demonstrated that administration of MAb and Fab to Mac-1 before reperfusion was as effective as administration of MAb to ICAM-1, which was found to be significantly upregulated in the postischemic tissue by immunohistochemical analysis, in preventing postischemic leukocyte adhesion to and macromolecular leakage from postcapillary venules, whereas postischemic leukocyte rolling was not affected after MAb administration. Postischemic capillary perfusion was efficiently preserved in animals treated with anti-Mac-1 and anti-ICAM-1 MAb compared with animals receiving the isotype-matched control antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Leukocyte rolling in venules of striated muscle and skin is mediated by P-selectin, not by L-selectin.
Leukocyte rolling in post-capillary venules is mediated by adhesion molecules of the selectin family expressed on both leukocytes (L-selectin) and endothelial cells (E- and P-selectin). With the use of intravital fluorescence microscopy, the effects of antibodies against these selectins were analyzed in the skinfold chamber model of BALB/c mice and the ear model of homozygous hairless mice (hr/hr) that permit chronic observation of striated muscle and skin microcirculation in awake animals, respectively. Mice were injected intravenously with monoclonal antibodies (MAb) to murine L-selectin and E-selectin and affinity-purified polyclonal antibodies to P-selectin. The antibodies, which are known to block cell adhesion, were tested by immunoprecipitation to selectively bind to L-, E-, or P-selectin. Leukocyte rolling was a constant finding in both microcirculation models in the absence of inflammatory stimuli. In both models, injection of anti-P-selectin antibodies completely prevented baseline leukocyte rolling over an observation period of 2 h (P < 0.01 vs. baseline), while no effects were seen after administration of either anti-L-selectin or anti-E-selectin MAb. Treatment with the isotype-matched control antibodies did not affect leukocyte rolling in either model. We conclude that leukocyte rolling in postcapillary venules of murine striated muscle and skin is a physiological process mediated via P-selectin, whereas L- and E-selectin appear not to play a significant role under these circumstances.
Animals↗
Intrathecal IgG synthesis and albumin leakage are increased in subjects with HIV-1 neurologic disease.
We analyzed matched cerebrospinal fluid and blood samples from 139 subjects enrolled in a study of the effects of human immunodeficiency virus type 1 (HIV-1) on the nervous system. Mean total intrathecal IgG synthesis rate was significantly higher in subjects with HIV-1-related neurologic disease (NeuroPos) than in HIV-1-seropositive (HIV+) subjects without neurologic disease (NeuroNeg) or at-risk seronegative controls (SNC). Mean trans-blood-brain barrier (BBB) albumin leakage (AL) rate increased significantly across groups (SNC < NeuroNeg < NeuroPos). AL was significantly higher in subjects with absolute CD4 counts < 100/mm3 versus those with > or = 100 cells/mm3 and significantly higher in AIDS compared with asymptomatic HIV+. Elevated total intrathecal IgG synthesis rate could not be accounted for solely by the presence of a damaged BBB, because 79% of subjects with elevated IgG synthesis rates had a normal BBB as assessed by the AL formula. Furthermore, the Tourtellotte formula inherently corrects for BBB leakage. We confirmed, using state-of-the-art albumin and IgG determinations, that intrathecal IgG synthesis is prevalent in all stages of HIV-1 disease. In the absence of a CNS opportunistic infection or tumor, mean total intrathecal IgG synthesis rate and trans-BBB AL are significantly higher in subjects with clinical HIV-1 CNS disease than in neurologically normally HIV+ subjects.
Adult↗
Quantifying HIV-1 proviral DNA using the polymerase chain reaction on cerebrospinal fluid and blood of seropositive individuals with and without neurologic abnormalities.
To quantify the number of human immunodeficiency virus type 1 (HIV-1) proviral copies per 1,000 CD4+ cells in cerebrospinal fluid (CSF) and blood in relationship to stage of infection and HIV-1 neurologic disease (HND), 87 HIV-1 seropositive men without CNS opportunistic infections, tumors, or neurosyphilis, 9 high-risk, and 14 not-at-risk seronegative controls underwent a structured interview, and physical and neurologic examination followed by blood and CSF collection. A custom-designed, fully automated polymerase chain reaction (PCR) system performed amplification with use of two HIV-1 gag primer pairs, Southern blotting, and hybridization with product-specific probes. Image analysis was used to quantify band intensities relative to a dilution series. Eighty-one of 87 (93%) seropositive patients, 1 of 9 high-risk patients, (11%) and none of 14 seronegative controls had PCR-detectable HIV-1 in their blood. Fifty-seven of 63 (90%) seropositive patients, 2 of 5 (40%) high-risk seronegative patients, and none of 14 controls had HIV-1 in their CSF. The proviral load in seropositive patients, all stages, was significantly greater in CSF than blood [median 25 vs. 0.6 copies/1,000 CD4+ cells (p = 0.0001)]. The median proviral load in blood was 0.09 copies/1,000 CD4+ cells in seropositive, asymptomatic subjects, 10.7 in patients with AIDS, and 1.4 in patients with AIDS-related complex (p = 0.0281). CSF proviral load was greater in seropositive patients with HND than those without HND, median 43.5 vs. 17.6 copies/1,000 CD4+ cells (p = 0.0614). Proviral load was greater in the blood and CSF of subjects with more advanced systemic disease and HND. There was a substantial penetration of HIV-1 into the CNS/CSF in both systemically and neurologically asymptomatic HIV-1 disease.
AIDS Dementia Complex↗