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Biomedical subjects

R Hoffmann

Publications and source records attributed to R Hoffmann.

At least 235 records · Page 13Linked to original sources
PubMed1996

Kinetics of subcutaneous versus intravenous epoetin-beta in dogs, rats and mice.

The total body clearance of recombinant human erythropoietin (rhEPO) calculated per kilogram of body weight increased in the order man = dog < rat << mouse. The differences disappeared or were reversed when clearance was expressed per square meter of body surface. There was no similar species difference in terminal half life. Total body clearance increased with the dose in dogs and mice, but not in rats. The bioavailability from a subcutaneous depot was 80% in dogs, 76% in rats, and 70% in mice. The absorption from the subcutaneous depot is rapid in rats and mice, but slow in dogs. The pharmacodynamic activity of rhEPO injected by both routes was compared in polycythemic mice. The equipotent doses were 2.44 times higher with intravenous than with subcutaneous injection. Taking into account the bioavailability of 70% from a subcutaneous depot, one obtains a potency ratio of 3.5 for absorbed subcutaneous versus intravenous rhEPO.

Animals↗
PubMed1996

Comparison of the substrate specificities of cAMP-dependent protein kinase from bovine heart and Ascaris suum muscle.

The catalytic subunits of cAMP-dependent protein kinases (protein kinase A) from bovine heart and Ascaris suum muscle exhibit only 48% sequence identity and show quantitative differences in substrate specificity. These differences were not obvious at the level of short synthetic substrate peptides but were distinct for some protein substrates. Phosphofructokinase from Ascaris, a physiological substrate, was a better substrate for the protein kinase from the nematode in comparison to the mammalian protein kinase due to a 10-fold lower Michaelis constant. Selective phosphorylation by the two kinases was also observed with some in vitro substrates. In addition, quantitative differences in the interactions between R- and C-subunits from Ascaris and bovine heart were observed. However, several synthetic peptides whose sequence reflected the phosphorylation site of Ascaris suum phosphofructokinase (AKGRSDS*IV), or variations of it, were phosphorylated with the same efficiency by both protein kinases. Based on the data the following are concluded: (1) In agreement with the conservation of structure in the catalytic cleft, the recognition of substrates by protein kinases from phylogenetically distant organisms exhibits similarity. (2) Non-conserved parts of the surface of the protein kinase molecule may contribute to binding of protein substrates and thus to selective recognition.

Amino Acid Sequence↗
PubMed1996

Growth factor mRNA levels in alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.

The early immune response in alopecia areata is characterized by a Th1 T helper cell cytokine pattern and an aberrant expression of ICAM-1 and HLA-DR molecules on lesional hair bulbs. A counteracting cytokine pattern induced by a therapeutic contact dermatitis is supposed to mediate the hair regrowth. In addition to cytokines, growth factors have been shown to influence immune responses, and we therefore investigated the expression levels for a panel of growth factors in untreated versus alopecia areata after treatment with the contact sensitizer diphenylcyclopropenone. Using semiquantitative reverse transcriptase polymerase chain reaction we detected a striking overexpression of transforming growth factor beta 1 mRNA in successfully treated patients. This cytokine has been shown to be a potent immune response modifier, which can suppress Th1 immune responses. The way in which topical immunotherapy induces hair regrowth in alopecia areata is unknown, but a lesional increased expression of transforming growth factor beta 1 may be a possible mechanism.

Administration, Topical↗
PubMed1996

Carotid Stent-Assisted Angioplasty: Preliminary Technique, Angiography, and Intravascular Ultrasound Observations.

Currently, surgical carotid endarterectomy has been the standard therapy for symptomatic and asymptomatic patients with significant carotid artery stenoses. However, there are high surgical risk and other patient subsets, wherein a Òlesser invasiveÓ catheter-based procedure may be worthwhile. Carotid stent-assisted angioplasty (CSSA) is a percutaneous interventional treatment approach for appropriately selected patients with common and internal carotid artery lesions. The present report discusses preliminary technique-related, angiographic, and intravascular ultrasound observations of CSSA. Five symptomatic patients (with six carotid stenoses) with other co-morbid states were treated by a multidisciplinary team under the aegis of an approved protocol using conventional equipment and available Palmaz tubular slotted stents. On-line quantitative angiography and intravascular ultrasound imaging was performed to guide stent insertion and monitor results. There were no procedure-related complications and angiographic results were excellent (final mean diameter stenosis 5%). Intravascular ultrasound imaging was feasible and safe. In two cases, the findings obtained from ultrasound images assisted in subsequent operator decisions. Thus far, there have been no additional clinical sequelae in these patients (@ 30 days). This preliminary experience with CSSA indicates that interventional neurovascular therapies may provide a useful alternative for selected patients requiring endoluminal reconstruction of carotid stenoses. Extensive additional studies are required to establish the appropriate clinical application of this technique.

Journal Article↗
PubMed1996

[Current status of therapy of subtrochanteric femoral fractures].

Operative treatment of subtrochanteric femur fractures is demanding. The implants available follow different biomechanical and surgical principles. Extramedullary implants like the condylar blade plate and the dynamic condylar screw require subtle surgical and indirect reduction techniques. Intramedullary implants like intramedullary hip screws and interlocking nails are biomechanically advantageous. In contrast to the extramedullary implants these fixations can stand postoperative weight-bearing. The different operative techniques for the fixation of subtrochanteric fractures are presented and evaluated. Current trends in treatment rationales are outlined.

Adult↗
PubMed1996

Clinical experience with two types of pelvic C-clamps for unstable pelvic ring injuries.

The emergency stabilization of unstable pelvic injuries, in particular, injuries to the posterior pelvic ring, can be achieved following reduction by application of the pelvic C-clamp. This and other procedures contribute to controlling what is almost always a life-threatening blood loss. The pelvic C-clamp is a temporary measure preceding definitive treatment of the injury. If this procedure is to have an optimal and lasting effect, the clamp must be applied correctly, provide adequate compression and stability, and be easy to handle. In one year, we applied the AO and ACE pelvic clamps in 9 clinical cases. Satisfactory primary compression and stability were achieved for unstable injuries with both clamps. It was more difficult to achieve good rotational stability as required for subsequent treatment with the ACE clamp due to its construction design.

External Fixators↗
PubMed1996

[Intermittent impulse compression. An alternative in therapy of post-traumatic and postoperative edema].

In patients with foot and ankle trauma, surgery and postoperative mobilization are often delayed because of swelling. The aim of this study was to assess if intermittent impulse compression of the foot is better than the standard therapy of applying cool packs at intervals. For intermittent impulse compression the AV impulse device was used (Novamedix Inc.). From May to November 1993, 40 patients (20 ankle fractures, 8 ruptured ligaments, 6 calcaneal fractures, 4 distal tibial fractures, 1 talus fracture, 1 subtalar dislocation) were prospectively assigned at random to the two groups and treated. After 24 h of treatment, the patients with intermittent impulse compression of the foot showed an average reduction of swelling of 47% around the ankle, midfoot and forefoot. With cryotherapy it was 17%. After 4 days of treatment in the postoperative course the swelling subsided at a rate of 74% with impulse compression and 45% with cryotherapy. Intermittent impulse compression of the foot proved to be a highly effective method of treating post-traumatic and postoperative edema. It seems preferable to the standard therapy using cold packs.

Adult↗
PubMed1996

[A new procedure for determining leg length and leg length inequality using ultrasound. II: Comparison of ultrasound, teleradiography and 2 clinical procedures in 50 patients].

The clinical methods still in common use for measuring leg length and leg length discrepancy (LLD) cannot always meet the demands of precision and accuracy. A method using ultrasound is presented and shown to be a standardized, non-invasive method allowing accurate determination of leg length and LLD. Once the validity had been proved experimentally, practical handling, precision and accuracy of this method were tested on 50 patients in whom teleradiography of the lower extremity was performed for different reasons. The sonographically determined measures of LLD were compared with the radiographic measurements and in addition clinical measurements were taken by direct (tape measure) and indirect methods ("lengthening" of the shorter leg by wooden blocks of known thickness). Adjustments to the ventral hip joint and to the medial knee joint served as standardized, easily reproducible sonographic reference points. The mean variance of repeated sonographic measurements as a reflection of precision amounted to 3.5 mm2 for leg length measurement, with a maximum of 13.5 mm2. In the case of LLD the mean divergence between sonographically and radiographically determined LLD was 0.9 +/- 2.7 mm, with a maximum of 6.4 mm. The clinical methods with mean divergence of -1.2 +/- 9.6 mm (direct method) and -1.0 +/- 6.1 mm (indirect method) proved to be less accurate. The method examined for measuring leg lengths and LLD by means of ultrasound is easy to manage and non-invasive. Its precision and accuracy make it superior to clinical measuring methods and could even make some radiographical examinations superfluous.

Adult↗
PubMed1996

[Dens fracture and multiple fracture of the thoracic spine after fall from great height. Diagnostic standard].

Multiple level spine fractures after a fall from a great height frequently cause a neurological deficit with paraplegia. In general, survival after a free fall from 20 m height without any neurological deficit is very unlikely. Since a considerable part of the trauma may not be detected by conventional radiograms, it is recommended that CT scans of all affected spine regions always be carried out with 2 D reconstructions. In addition, 3 D reconstructions should be performed if rotatory instability is suspected. This case report illustrates the management and diagnostic problems of a serial spine trauma.

Accidental Falls↗
PubMed1996

[Blood parameters as an aid in the diagnosis of reptile diseases].

As ill reptiles only show nonspecific clinical signs, blood chemistry parameters are a valuable help in diagnosis. Practicable sites for obtaining blood of snakes, sauria and chelonians are vena coccygealis ventralis and cardiac puncture, of chelonians also vena jugularis, axillaris and coccygealis dorsalis. The following blood parameters were investigated: number of erythrocytes and leucocytes, urea, uric acid, creatinine, AST (GOT), ALT (GPT) GLDH, AP, total bilirubin, CK, LDH, lipase, alpha-amylase, calcium, phosphorus, sodium, potassium, chloride and total protein. Especially for diagnosing nephropathies evaluation of urea and uric acid proved to be valuable.

Animal Diseases↗
PubMed1996

[Advantages of the laser in laparoscopic cholecystectomy].

Use of the holmium and Nd:YAG laser is clearly advantageous in laparoscopic cholecystectomy, i.e., less perforation of the gallbladder when compared to the use of the hook electrode, shorter intervention time and less postoperative pain. Laser-operated patients can therefore be discharged 1.5 days earlier than those patients in whom cholecystectomy had been performed using electrocautery.

Cholecystectomy, Laparoscopic↗
PubMed1995

Separation and characterisation of bovine histone H1 subtypes by combined ion-exchange and reversed-phase chromatography and mass spectrometry.

In order to separate and identify histone H1 subtypes from calf thymus we used both electrospray mass spectrometry (ES-MS) and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) after a three-step chromatographic procedure consisting of reversed-phase high-performance liquid chromatography (RP-HPLC), size-exclusion chromatography (SEC) and ion-exchange chromatography (IEC). Under the RP-HPLC conditions described, we obtained two baseline-separated H1-fractions which were characterised by MALDI-TOF-MS. The determined masses ranged from 22,850 to 22,590 for the first fraction and from 22,070 to 21,250 for the second fraction. Further, it was shown that the first fraction contained at least four and the second one at least five subtypes of the histone class H1. Four homogeneous pure H1 subtypes were obtained by a combination of IEC followed by SEC and RP-HPLC. The molecular masses of these four subtypes determined by ES-MS were 22,606, 22,761, 21,347 and 21,263. We obtained six additional molecular masses of histone H1 subtypes from three heterogeneous fractions, namely 22,066, 21,802, 20,586 and 19,817 by ES-MS and 22,800 and 22,675 by MALDI-TOF-MS. The retention times of these fractions and the molecular masses were in agreement with the data obtained from RP-HPLC fractions by MALDI-TOF-MS.

Animals↗
PubMed1995

Comparative studies of cytotoxicity and the release of TNF-alpha, nitric oxide, and eicosanoids of liver macrophages treated with lipopolysaccharide and liposome-encapsulated MTP-PE.

LPS and liposome-encapsulated MTP-PE induce liver macrophages cytotoxicity against tumor target cells and a release of TNF-alpha, nitric oxide, and eicosanoids but not a generation of superoxide anions. Neither agent elicits a formation of inositol phosphates, a change in intracellular free calcium, or a translation of protein kinase C-beta. Inhibition or down-regulation of protein kinase C does not inhibit the release of TNF-alpha and nitric oxide but inhibits the formation of prostanoids. In contrast to LPS, liposome -encapsulated MTP-PE induces an elevation of diacylglycerol mass and an enhanced expression of protein kinase C-delta. LPS, but not liposome-encapsulated MTP-PE, elicits an enhanced expression of cytosolic phospholipase A2 and a predominant formation of PGE2. Both agents elicit different responses when given to cells pretreated with one of the immunomodulators, with dexamethasone, or with PGE2. In contrast, to liposome-encapsulated MTP-PE, LPS induces only cytotoxicity when added to liver macrophages simultaneously or a maximum of 2 h before the addition of tumor target cells. The observed differences might reflect partly differences in the potencies of LPS and some liposome-encapsulated MTP-PE as immunomodulators.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

The catalytic subunit of cAMP-dependent protein kinase from Ascaris suum. The cloning and structure of a novel subtype of protein kinase A.

A complete cDNA clone encoding the catalytic subunit of cAMP-dependent protein kinase of Ascaris suum was constructed from two overlapping partial clones. The encoded sequence of 337 amino acids is 48% identical with the sequence of mouse C alpha subunit. Approximately the same low similarity was found with the sequence of the C subunit from another nematode, Caenorhabditis elegans. The N-terminal 14 amino acids and the myristoylation site of the mammalian protein are not contained in the enzyme from Ascaris. Two cysteines (Cys33 and Cys319) replace a basic residue in the N-terminal region and an acidic amino acid near the C-terminus which are conserved in all known C subunits from other sources. The substitutions provide the possibility of disulfide bridge formation between the N-terminal and C-terminal parts of the protein. There is strong evidence that a single gene encodes cAMP-dependent protein kinase in Ascaris. Modelling of the sequence into the coordinates of the X-ray structure of the mammalian enzyme suggest a high degree of conservation in the three-dimensional structure. However, structural variations occur at the surface of the protein near the catalytic cleft and are likely to account for the variations in substrate specificity previously observed between the purified protein kinase from Ascaris [Thalhofer, H. P., Daum, G., Harris, B. G. & Hofer, H. W. (1988) J. Biol. Chem. 263, 952-957] and the mammalian enzyme.

Amino Acid Sequence↗
PubMed1995

A comparison of period amplitude and power spectral analysis of sleep EEG in normal adults and depressed outpatients.

Three experiments were carried out to evaluate the relationship between two techniques for quantifying electroencephalographic (EEG) data during sleep: period amplitude analysis (PAA) and power spectral analysis (PSA). In Experiment 1, canonical correlations and regression analyses were computed on PSA and PAA data from 40 undergraduate volunteers. The results yielded an average canonical correlation of 0.98. Further, multiple regression analyses demonstrated that the PSA variables accounted for approximately 66% of the variance in the PAA data, whereas PAA variables captured 88% of the variance in the PSA data. Epoch-to-epoch correlations were higher for PAA measures than for PSA data, perhaps indicating greater stability of PSA measures across epochs of sleep. In Experiment 2, PSA and PAA data were compared in 17 unmedicated outpatients with unipolar depression. Canonical correlations and regression analyses indicated that the overlap in variance between PSA and PAA did not exceed 50%, regardless of whether PSA or PAA variables were used as predictors. Epoch-to-epoch correlations between PAA measures were significantly higher than correlations among PSA variables, again suggesting greater stability of PAA data across epochs of sleep. The range of correlations for either data set was, however, substantially lower in the depressed than in the normal group. Experiment 3 evaluated the possibility that filter settings and artifact-rejection procedures had contributed to reduced overlap in PSA-PAA variance and reduced stability in depressed patients. An additional group of eight healthy volunteers served as subjects. Findings in Experiment 3 indicated that methodological differences between Experiments 1 and 2 did not account for the reduced correlations in the depressed group. It was concluded that PSA and PAA data should be comparable in normal subjects but are relatively independent in depressed patients. Epoch-to-epoch correlations were higher for PAA data than those found between PSA measures in both normal subjects and depressed patients, suggesting that PAA may be more stable across sleep epochs. Reduced stability may be a reflection of nonstationarity in the EEG of depressed patients.

Adolescent↗