Biomedical subjects
Publications and source records attributed to H Frank.
We report the results of using a tarsal plate flap from the upper lid hinged at the lateral canthus to repair a lower lid inner lamella defect in 54 patients. Good functional and cosmetic results were achieved.
Measurements of right ventricular (RV) ejection fraction (EF) and volumes using a new thermodilution technique were compared to serially performed magnetic resonance imaging (MRI) in 21 patients with dilated cardiomyopathy. For RVEF (%) and RV volume indices (ml/m2) the following correlation coefficients were found: RVEF r = 0.82; end-diastolic volume index (EDVI) r = 0.45; end-systolic volume index (ESVI) r = 0.65; stroke volume index (SVI) r = 0.61; all p < 0.05. However, RVEF by thermodilution was significantly lower (RVEF thermo = 31 +/- 14 vs. RVEF MRI = 50 +/- 14, p < 0.01) and RV EDV and ESVI were significantly higher compared to MRI, while SVI showed no significant difference. Exclusion of patients with atrial fibrillation (n = 8) improved the correlations (RVEF r = 0.94, EDVI r = 0.77, ESVI r = 0.87, SVI r = 0.65, all p < 0.05), but did not reduce the mean difference between both methods.
In nearly 60% of men over 50 years of age, dermato-/polymyositis is induced by malignancies. Till now, 9 patients with melanoma-induced dermatomyositis have been reported in the literature. Here we report on a patient suffering from classic pelvic and pectoral girdle proximal weakness, typical heliotrope rash, increased serum CPK values, and biopsy-proven myositis, who died from metastasizing melanoma one year later.
A magnetically labeled antimyosin (MION-AM) has previously been developed for immunospecific MR imaging in vivo. The current study was designed to extend previous feasibility studies and to correlate MR infarct size to that determined by histopathology. The left anterior coronary artery (LAD) was temporarily occluded in rabbits (n = 10) and subsequently reperfused for 1 h prior to the administration of 100 mumol Fe/kg of MION-AM (corresponding to 0.5 mg AM). One hour after i.v. administration, the infarcted myocardium appeared hypointense by MRI as a result of target-specific attachment of the magnetic T2 label to damaged but not normal myocardium. There was a close correlation between infarct size determined by MR and pathology (SE 2500/30: r = 0.92, p < or = 0.0001; SE 2500/60: r = 0.85, p < or = 0.0001). Our results are evidence that a) immunospecific magnetic probes can be utilized for cardiac MR imaging, and b) that these or similar agents may aid in the quantitation of myocardial infarct size.
Out of 1057 amputated canine toes with tumours, tumour-like or other lesions, 17 cases were histopathologically diagnosed as epidermoid cysts of the terminal phalanx (EP). They were accompanied by osteolysis, reactive bone formation and chronic inflammation of phalanx 3. Extension of reactive changes to the phalangeal joint and phalanx 2 was less frequent. Various breeds were involved. There was no breed predisposition. The average age was 10.8 years; the male-female ratio 2.4:1. Nine EP were located on the forelimbs, 4 on the hindlimbs. In 4 cases location was unknown. Toes 4 and 5 were most frequently affected. A traumatic origin is suspected.
Alginate is used as a matrix for immunoisolation of cells and tissues in vivo. We have demonstrated previously that commercial alginates contain various fractions of mitogenic impurities and that they can be removed by free flow electrophoresis. The use of purified material is a necessity in order to reveal the parameters that control biocompatibility of the implanted material (such as stability, size, surface charge and curvature, etc.). In this study, we present a protocol for the chemical purification of alginates on a large-scale. Beads made from alginates purified by this multi-step chemical extraction procedure did not induce a significant foreign body reaction when implanted for 3 weeks either intraperitoneally or beneath the kidney capsule of Lewis or non-diabetic BB/Gi rats.
Information processing (and cognitive ERPs as their concomitants) has been observed to be disturbed in chronic alcoholics and to recover with sustained abstinence. However, some specific components of ERPs appear to remain significantly decreased in long-term abstinent alcoholics. Using a longitudinal design we investigated the effect of abstinence and relapse on P300 and Late Slow Wave. P300 was evoked by a three-tone paradigm, which results in a two-stage process for evaluating and classifying stimuli. The amplitude of P300 in short-term abstinent alcoholics was reduced significantly and recovered with time of abstinence at least partly. In alcoholics abstinent for eight months the mean amplitude was lower than of the control group, but this difference failed to be significant. The long latency of the positive peak at about 600 ms seems to reflect delayed information processing in alcoholics, revealed by two-stage processing. This component arises later in alcoholics whether they stay abstinent or not.
Six primary and 10 secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons were tested for mutagenicity in Salmonella typhimurium TA98 in the presence of varying amounts of hepatic cytosol from adult male and female rats and 3'-phosphoadenosine-5'-phosphosulfate, the cofactor for sulfotransferases. With the exception of 1-(9-anthryl)ethanol, 4H-cyclopenta[def]-phenanthren-4-ol and 10-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, all the benzylic alcohols were activated to mutagens. For 1-(1-pyrenyl)ethanol (1-HEP), 1-(2-pyrenyl)ethanol (2-HEP), 6-hydroxymethylanthanthrene (6-HMAA), 2-hydroxymethylpyrene (2-HMP), 10H-indeno[1,2,7,7a-bcd]pyren-10-ol (OH-IP), 3-hydroxy-3,4-dihydrocyclopenta[cd]pyrene (3-OH-H2-CPcdP) and 1-(6-benzo[a]pyrenyl)ethanol (6-HEBP), this is the first observation of a mutagenic activity. The primary alcohols 1-hydroxymethylpyrene, 2-HMP, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 6-hydroxymethylbenzo[a]pyrene, as well as the secondary alcohols 1-HEP and 3-OH-H2-CPcdP, were more efficiently activated by hepatic cytosol from females than by preparations from males (2.6- to 8-fold). A further compound, 6-HEBP showed significant, but relatively weak, effects in the presence of cytosol from females, whereas it was inactive in the presence of hepatic cytosol from males. The reverse sex difference was observed in the activation of 4H-cyclo-penta[def]chrysen-4-ol, the activity of cytosol from males amounting to about four times that from females. Four other compounds, 2-HEP, 7-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, 6-HMAA and OH-IP, were activated with similar efficiency by hepatic cytosol from both sexes (< two-fold differences). The study indicates that different sulfotransferases are involved in the bioactivation of benzylic alcohols, including forms preferentially expressed in females as well as forms preferentially expressed in males, and that these enzymes qualitatively differ in their substrate tolerance for benzylic alcohols.
OBJECTIVES: Magnetic resonance imaging was used to assess the effects of ventilation with positive end-expiratory pressure (PEEP) on cardiac volumes, especially on atrial volumes as well as to determine semiquantitative measurements of spatial interactions between heart, lungs and chest. DESIGN: Prospective study with healthy volunteers undergoing mechanical ventilation with different levels of PEEP during magnetic resonance imaging. SETTING: Magnetic resonance unit, Institute of Diagnostic Imaging, Rudolfinerhaus Hospital. SUBJECTS: Twelve healthy volunteers. INTERVENTIONS: Volunteers were imaged, using a multislice-multiphase technique during spontaneous breathing and with PEEP values of 0, 7, and 15 cm H2O. MEASUREMENTS AND MAIN RESULTS: Atrial as well as ventricular volumes, chest diameters, and midventricular contact between the heart and anterior chest wall were determined on transverse-oblique sections. Atrial volumes showed a progressive decline beginning at a PEEP of 7 cm H2O. Diastolic filling of both ventricles was reduced. A PEEP level of 15 cm H2O induced a significant increase in the sagittal-oblique but not in the transverse-oblique chest diameter. PEEP values of 7 and 15 cm H2O shortened the length of the midventricular contact between the heart and anterior chest wall. CONCLUSIONS: Left and right ventricular end-diastolic volumes and stroke volumes decreased significantly during ventilation with PEEP at 15 cm H2O, as did end-systolic atrial volumes. Volume changes in association with changes of chest and heart configuration suggest external cardiac compression by the expanding lungs. Furthermore, this study illustrates the feasibility of magnetic resonance imaging in mechanically ventilated patients.
To evaluate the effect of lung transplantation on right ventricular (RV) and left ventricular (LV) volumes and function, magnetic resonance imaging (MRI) was performed in 11 patients before and 6 to 24 months after single (n = 7) or double (n = 4) lung transplantation as well as in 15 healthy control subjects. Prior to transplantation, RV end-diastolic (RVEDVI, ml/m2) and end-systolic (RVESVI, ml/m2) volume indices were significantly increased in patients compared with those in control subjects. RV ejection fraction (RVEF, %), although within the lower normal range, was significantly reduced. In contrast, LV volume indices (ml/m2) were significantly smaller in patients than in control subjects, whereas LV ejection fraction (LVEF, %) was not different from that in normal subjects. After lung transplantation, MRI revealed a significant reduction in RVEDVI from 73 +/- 29 to 54 +/- 14 (p = 0.03) and RVESVI from 38 +/- 23 to 20 +/- 6 (p = 0.01) with a concomitant significant increase in RVEF from 48 +/- 14 to 63 +/- 6 (p = 0.01). Consecutively, the LV expanded to normal (LVEDVI from 49 +/- 12 to 65 +/- 14, p = 0.01; LVESVI from 23 +/- 9 to 28 +/- 7, p = 0.05), whereas LVEF remained unchanged (55 +/- 9 versus 56 +/- 8).
We measured fibrinogen levels as well as the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in plasma samples obtained at basal conditions and after stimulating the fibrinolytic system by venous occlusion (VO). Samples were taken from patients with primary pulmonary hypertension (PPH), with secondary thromboembolic pulmonary hypertension (SPHTH), with secondary pulmonary hypertension due to congenital heart disease with Eisenmenger's reaction (SPHCD), and from healthy control individuals (CON). Fibrinogen levels were not significantly different between the groups with PPH and SPHTH or between SPHCD and CON. The latter groups, however, exhibited significantly lower fibrinogen plasma levels compared with PPH or SPHTH (p < 0.01). Basal plasma levels of t-PA antigen, t-PA activity, and PAI-1 activity, respectively, did not differ significantly between the study groups. After VO, mean t-PA activity levels increased to a higher extent in control subjects compared with patients with PPH, or SPHTH, or SPHCD, with significant differences only between CON and SPHTH or CON and PPH (p < 0.03). Patients with PPH and SPHTH exhibit both increased fibrinogen plasma levels and a diminished fibrinolytic response compared with healthy subjects. Moreover, the fibrinogen plasma levels in patients with SPHCD are in normal range, and the fibrinolytic response is similar to CON compared with PPH and SPHTH, thus indicating the existence of a comparable prothrombotic situation in patients with PPH and SPHTH.
OBJECTIVE: We hypothesized that the previously observed T1 effect of a small monocrystalline iron oxide preparation can be exploited to decrease T1 relaxation time of blood. Such a decrease, particularly if present for a long time, could be used to improve the quality of MR angiograms. To test the hypothesis, we performed phantom studies and in vivo animal experiments. MATERIALS AND METHODS: The effect of the monocrystalline iron oxide preparation on the MR signal intensity (spoiled gradient-recalled acquisition in the steady state pulse sequences, various timing parameters) of human whole blood was first tested in a phantom (dose range of monocrystalline iron oxide preparation, 0-3 mumol Fe/ml). Subsequent experiments were performed in rats (n = 7) and in rabbits (n = 6) to determine whether predicted changes in signal intensity could be observed in vivo. RESULTS: Dose optimization studies in rats indicate that injected doses of 15-50 mumol Fe/kg (0.8-2.8 mg Fe/kg) of monocrystalline iron oxide preparation resulted in threefold to fourfold increases of aortic signal-to-noise ratio. Because of its long plasma half-life (180 min in rats), the iron oxide preparation markedly improved the quality of images of the vasculature of the lungs, abdomen, and extremities. CONCLUSION: Our experimental results suggest that this and possibly other iron oxide preparations are alternatives to compounds containing macromolecular gadolinium and could be useful for clinical MR angiography.
OBJECTIVE: A macromolecular MR contrast agent (MPEG-PL-GdDTPA), which consists of Gd-DTPA covalently attached to a polyamino acid (PL) derivatized by monomethoxy ether of polyethylene glycol (MPEG), has recently been developed. This contrast agent exhibits long intravascular retention, which makes it suitable for MR angiography. The current study was performed to test whether this agent would improve visualization of the pulmonary vasculature during MR angiography and whether it aids in the detection of pulmonary emboli in an animal model. MATERIALS AND METHODS: All experiments were performed in rabbits (n = 21), six of which were healthy and 15 of which had induced pulmonary emboli. Contrast-enhanced MR angiograms (0.02 mmol Gd/kg) were obtained at 1.5 T by using time-of-flight and phase-contrast sequences. MR images were ultimately compared with polymer casts of pulmonary arteries and/or pathologic sectioning. RESULTS: MR angiograms obtained before the administration of a contrast agent were of low quality primarily because of low vessel/background signal-to-noise ratio, presumably due to slow and complex flow in the pulmonary vasculature. After IV administration of the contrast agent, pulmonary arteries could be visualized up to the third-order branches. Of the 18 pathologically or angiographically proved emboli, 16 could be detected with contrast-enhanced MR angiography. CONCLUSION: Our results indicate that macromolecular contrast agents with long blood half-lives, such as MPEG-PL-GdDTPA, increase signal intensity of pulmonary vessels, improve the quality of MR angiography, and increase the detectability of pulmonary emboli.
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Trans-stilbene oxide, trans-beta-methylstyrene 7,8-oxide, trans-beta-ethylstyrene 7,8-oxide, trans-beta-propylstyrene 7,8-oxide and 4-fluorochalcone oxide were investigated for genotoxic activity in bacterial and mammalian cells, in the absence of external xenobiotic-metabolising systems. All compounds strongly enhanced the frequency of sister-chromatid exchanges (SCE) in cultured human lymphocytes. None of them was mutagenic in Salmonella typhimurium (reversion of the his- strains TA98, TA100 and TA104). The limit of detection was 1/20,000 to 1/10(6) of the activity of the positive control, benzo[a]pyrene 4,5-oxide, depending on the compound and the bacterial strain. Trans-beta-methylstyrene 7,8-oxide and 4-fluorochalcone oxide were additionally tested for induction of SCE and gene mutations in the same target cells, namely Chinese hamster V79 cells. Their influence on the level of SCE was similar to that observed in human lymphocytes, whilst gene mutations (at the hprt locus) were not induced. The four investigated styrene oxide derivatives are known to be excellent substrates for a mammalian enzyme, cytosolic epoxide hydrolase (cEH). 4-Fluorochalcone oxide is a potent selective inhibitor of this enzyme and is structurally similar to the investigated styrene oxide derivatives. These properties of the test compounds however cannot explain the observed discrepancies in the results, since the genetic end point (SCE versus gene mutations) was decisive, and SCE were induced in cEH-proficient human lymphocytes as well as in cEH-deficient V79 cells.
1-Hydroxymethylpyrene (HMP), a primary benzylic alcohol, and 4H-cyclopenta[def]chrysen-4-ol (OH-CPC), a secondary benzylic alcohol, were investigated for mutagenicity in Salmonella typhimurium (reversion of the his- strain TA98) in the presence of various xenobiotic-metabolizing systems. In the direct test, HMP was inactive and OH-CPC was very weakly active. In the presence of NADPH-fortified postmitochondrial fraction from rat liver (S9/NADPH), no activation of OH-CPC was observed, whereas strong mutagenic effects were elicited by HMP. In the presence of cytosol and 3'-phosphoadenosine-5'-phosphosulfate (PAPS), both alcohols were activated to potent mutagens. For equal mutagenic effects, approximately 650-fold lower concentrations of HMP were required in the cytosol/PAPS-mediated assay than in the S9/NADPH-mediated assay. The cytosol/PAPS-mediated mutagenicity of both alcohols was 3- to 4-fold enhanced, when KCl (125 mM) was present during the exposure. The authentic chloromethylarenes, 1-chloromethylpyrene and 4-chloro-4H-cyclopenta[def]chrysene, showed very strong direct mutagenicity. These results, taken together with previous findings, indicate that both primary and secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons may be activated by sulfotransferases to electrophilic sulfuric acid esters, and by subsequent substitution reaction to further active species such as benzylic chlorides.
RATIONALE AND OBJECTIVES: The authors synthesized and tested a novel hydrogel system proposed for use in extra- and intravascular radiologic interventions, such as chemoembolizations and embolizations, and as a vehicle for sustained drug release. MATERIALS: The material was specifically designed to meet the prerequisites of biodegradation, biocompatibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA). RESULTS: PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After administration, PDH is degraded by proteases release from macrophages; implantations of 1 mL samples into paraspinal muscles of rats were completely absorbed within 4 weeks and its constituents were metabolized. Antibody titers (total Ig response) against the PDH were not detectable 1 week after implantation, whereas protein control substances elicited a strong response. CONCLUSIONS: PDH and its derivatives are relatively nontoxic, biodegradable materials for use in radiologic interventions and as a vehicle for sustained drug release.