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Biomedical subjects

M Schramm

Publications and source records attributed to M Schramm.

At least 37 records · Page 2Linked to original sources
PubMed1999

Relevance of the drainage along the linea aspera for the reduction of fat embolism during cemented total hip arthroplasty. A prospective, randomized clinical trial.

The aim of this study was to assess the relevance of drainage placed along the linea aspera for the prevention of fat embolism and cardiopulmonary impairment during the insertion of a cemented stem. We studied 40 patients with coxarthrosis randomly allocated to total hip arthroplasty with proximal drainage or without it. The venting hole for the drainage of the medullary cavity was placed posteriorly, between the greater and the smaller trochanter, in the prolongation of the linea aspera. The heart was monitored intraoperatively by a echocardiography probe positioned in the patient's oesophagus. During the operation we monitored the hemodynamics and blood gas values. Severe embolic events were observed in 85% of the control group and in 20% of the drainage group (P = 0.01). Embolism occurred during the insertion of the femoral component and continued after reduction of the hip joint. After major embolism, the pulmonary shunt values increased significantly in the control group (+22.7%), but there were no marked changes in the drainage group (+7.1%). The logical therapeutic measure to avoid intravasation of bone marrow, fat, and bone debris during the insertion of the femoral component is to prevent the rise of intraosseous pressure. The drainage of the venous system located along the linea aspera significantly reduces the risk of intraoperative embolism and cardiopulmonary impairment.

Aged↗
PubMed1999

Stability of RNA transcripts in post-mortem psychiatric brains.

RNA isolated from frozen human post-mortem brain tissue was used for analysis of five gene products with a recently developed sensitive and competitive RT-PCR technique. Samples varying in post-mortem intervals up to four days from controls, schizophrenics and alcoholics were analyzed. Evaluation of three housekeeping genes, as well as Trk B and Trk C demonstrated that the levels of mRNA transcripts were stable in brain samples at all time periods (one to four days) examined. This observation demonstrates that this RT-PCR protocol is a sensitive and reliable method to study relative amounts of mRNAs. The overall stability of housekeeping transcripts implicates the value of post-mortem brain samples for differential gene expression studies.

Actins↗
PubMed1999

Isoforms of alpha1E voltage-gated calcium channels in rat cerebellar granule cells--detection of major calcium channel alpha1-transcripts by reverse transcription-polymerase chain reaction.

In primary cultures of rat cerebellar granule cells, transcripts of voltage-gated Ca2+ channels have been amplified by reverse transcription-polymerase chain reaction and identified by sequencing of subcloned polymerase chain reaction products. In these neurons cultured for six to eight days in vitro, fragments of the three major transcripts alpha1C, alpha1A, and alpha1E are detected using degenerated oligonucleotide primer pairs under highly stringent conditions. Whole-cell Ca2+ current recordings from six to eight days in vitro granule cells show that most of the current is due to L-type (25%), P-type (33%) and R-type (30%) Ca2+ channels. These data support the correlation between alpha1A and P-type Ca2+ channels (G1) and between alpha1E and R-type channels (G2 and G3). By including specific primer pairs for alpha1E the complimentary DNA fragments of indicative regions of alpha1E isoforms are amplified corresponding to the three most variable regions of alpha1E, the 5'-end, the II/III-loop, and the central part of the 3'-end. Although the complementary DNA fragments of the 5'-end of rat alpha1E yield a uniform reverse transcription-polymerase chain reaction product, its structure is unusual in the sense that it is longer than in the cloned rat alpha1E complementary DNA. It corresponds to the alpha1E isoform reported for mouse and human brain and is also expressed in cerebellum and cerebrum of rat brain as the major or maybe even the only variant of alpha1E. While fragments of a new rat alpha1E isoform are amplified from the 5'-end, three known fragments of the II/III-loop and two known isoforms homologue to the 3'-coding region are detected, which in the last case are discriminated by a 129 base pair insertion. The shift of the alpha1E expression from a pattern seen in cerebellum (alpha1Ee) to a pattern identified in other regions of the brain (alpha1E-3) is discussed. These data show that: (i) alpha1E is expressed in rat brain as a structural homologue to the mouse and human alpha1E; and (ii) rat cerebellar granule cells in primary culture express a set of alpha1E isoforms, containing two different sized carboxy termini. Since no new transcripts of high-voltage-activated Ca2+ channels genes are identified using degenerate oligonucleotide primer pairs, the two isoforms differentiated by the 129 base pair insertion might correspond to the two R-type channels, G2 and G3, characterized in these neurons. Functional studies including recombinant cells with the different proposed isoforms should provide more evidence for this conclusion.

Amino Acid Sequence↗
PubMed1999

Block of quantal end-plate currents of mouse muscle by physostigmine and procaine.

of quantal end-plate currents of mouse muscle by physostigmine and procaine. Quantal endplate currents (qEPCs) were recorded from hemidiaphragms of mice by means of a macro-patch-clamp electrode. Excitation was blocked with tetrodotoxin, and quantal release was elicited by depolarizing pulses through the electrode. Physostigmine (Phys) or procaine (Proc) was applied to the recording site by perfusion of the electrode tip. Low concentrations of Phys increased the amplitude and prolonged the decay time constants of qEPCs from approximately 3 to approximately 10 ms, due to block of acetylcholine-esterase. With 20 microM to 2 mM Phys or Proc, the decay of qEPCs became biphasic, an initial short time constant taus decreasing to <1 ms with 1 mM Phys and to approximately 0.3 ms with 1 mM Proc. The long second time constant of the decay, taul, reached values of </=100 ms with these blocker concentrations. The blocking effects of Phys and Proc on the qEPC are due to binding to the open channel conformation. A method is described to extract the rate constants of binding (bp) from the sums 1/taus + 1/taul, and the rates of unbinding (b-p) from tau0. taus-1. taul-1 (tau0 is the decay time constant of the control EPC). For Phys and Proc bp of 1.3 and 5. 10(6) M-1 s-1 and b-p of 176 and 350 s-1, respectively, were found. Using these rate constants and a reaction scheme for the nicotinic receptor together with the respective rate constants determined before, we could model the experimental results satisfactorily.

Acetylcholine↗
PubMed1999

Immunohistochemical detection of alpha1E voltage-gated Ca(2+) channel isoforms in cerebellum, INS-1 cells, and neuroendocrine cells of the digestive system.

Polyclonal antibodies were raised against a common and a specific epitope present only in longer alpha1E isoforms of voltage-gated Ca(2+) channels, yielding an "anti-E-com" and an "anti-E-spec" serum, respectively. The specificity of both sera was established by immunocytochemistry and immunoblotting using stably transfected HEK-293 cells or membrane proteins derived from them. Cells from the insulinoma cell line INS-1, tissue sections from cerebellum, and representative regions of gastrointestinal tract were stained immunocytochemically. INS-1 cells expressed an alpha1E splice variant with a longer carboxy terminus, the so-called alpha1Ee isoform. Similarily, in rat cerebellum, which was used as a reference system, the anti-E-spec serum stained somata and dendrites of Purkinje cells. Only faint staining was seen throughout the cerebellar granule cell layer. After prolonged incubation times, neurons of the molecular layer were stained by anti-E-com, suggesting that a shorter alpha1E isoform is expressed at a lower protein density. In human gastrointestinal tract, endocrine cells of the antral mucosa (stomach), small and large intestine, and islets of Langerhans were stained by the anti-E-spec serum. In addition, staining by the anti-E-spec serum was observed in Paneth cells and in the smooth muscle cell layer of the lamina muscularis mucosae. We conclude that the longer alpha1Ee isoform is expressed in neuroendocrine cells of the digestive system and that, in pancreas, alpha1Ee expression is restricted to the neuroendocrine part, the islets of Langerhans. alpha1E therefore appears to be a common voltage-gated Ca(2+) channel linked to neuroendocrine and related systems of the body.

Animals↗
PubMed1999

Long-term results of spherical acetabular osteotomy.

We have examined the effect of the Wagner spherical acetabular osteotomy on preserving the joint in 38 hips with a mean follow-up of 17 years. At the time of the initial operation, 55% of patients had clinical symptoms and 30 joints showed minimal or absent radiological signs of osteoarthritis. At follow-up, 54% of patients had a good functional result. The osteotomy improved the mean centre-edge angle from -3 degrees to +15 degrees, the mean anterior centre-edge angle to 23 degrees and the acetabular head index to 75%. The obliquity of the acetabular roof decreased from 28 degrees to 16 degrees. One patient improved, but 14 deteriorated with joint degeneration. Of these, one progressed because of postoperative deep-tissue infection and five due to undercorrection. One patient needed total joint replacement after 14 years. At 17 years after operation, Wagner osteotomy had prevented progression of secondary arthritis in 63% of cases.

Acetabulum↗
PubMed1999

[Primary stability of press-fit acetabulum cups using a new acetabulum reamer].

The aim of the present study was to assess the initial stability of uncemented press-fit acetabular components using a newly developed reamer designed to optimize the surgical preparation of the acetabulum. Ten synthetic human pelves were used to investigate the stability of 20 uncemented press-fit acetabular components, each of which was tested in a servohydraulic testing machine for 6 cycles under an axial load of 2.4 kN. The results of the micrometric measurements revealed satisfactory stability for a reaming depth of 2 mm, and a press-fit of 2 mm. Micromotion was less than 200 microns in all the anatomical sections of the acetabulum (ischium 63 microns, pubis 150 microns, ilium 85 microns). A press-fit of 4 mm and the smaller reaming depth of 1 mm were associated with a substantial decrease in mechanical stability.

Acetabulum↗
PubMed1999

[3-dimensional registration of micro-movements of vertebral implants by a specially adapted measuring system using magnetic transducers].

The aim of this study was to develop a biomechanical experimental set-up to quantify motion of ventrally inserted spinal implants at the implant/bone interface. The model we used was the vertebral column of the calf. Lumbar vertebrae L2 to L4 were "instrumented" with a screw-rod system. The adjacent vertebrae L1 and L5 were connected to a servohydraulic testing machine and axial compression applied. Shortening of the specimen and three-dimensional movement of the most cranial implant relative to the bone was recorded using 3 electromagnetic transducers. 100,000 cycles of axial loading varying between -0.5 kN and -1 kN were applied. Static shortening of the specimen of 8.5 mm and an elastic movement of 180 to 280 microns were measured. The greatest amplitude of single-plane motion was recorded in the sagittal plane in both static and elastic modes. Implant motion within each cycle was recorded accurately as load-displacement curves within a range of 1.35 to 30 microns. With this test set-up, primary stability of different spinal implant systems can be compared. The use of electromagnetic transducers permits three-dimensional implant motion analysis even when only a mono-axial servohydraulic testing machine is available.

Animals↗
PubMed1999

Familial nevoid sebaceous gland hyperplasia affecting three generations of a family.

Familial sebaceous gland hyperplasia is a benign entity with onset at puberty and a tendency to worsen with age. It is characterized by a nevoid symmetric pattern in the sebaceous areas of the face sparing the orbital, perinasal, preauricular and perioral areas showing prominent follicular openings and interfollicular dermal yellowish or white prominent skin. Usually, the face is affected, with the neck, column and thorax affected in a milder pattern. We describe a family with familial nevoid sebaceous gland hyperplasia in three consecutive generations. All the patients were successfully treated with oral isotretinoin. The pedigree suggests autosomal dominant inheritance with incomplete penetrance.

Adult↗
PubMed1998

Reduced tyrosine kinase receptor C mRNA levels in the frontal cortex of patients with schizophrenia.

Using a quantitative RNA-PCR approach tyrosine kinase receptor (trk) C mRNA levels were determined in brain material from the frontal cortex (BA10), temporal cortex (BA20) and cerebellum of control specimen and patients with schizophrenia, bipolar disorder or non-psychotic depression (15 subjects each). In the frontal cortex of schizophrenics there was a 5.8-fold reduction of trk C mRNA levels, which reached statistical significance (P < 0.05). Trk C levels in the cerebellum were positively correlated with lifetime fluphenazine equivalents (r = 0.54), suggesting that neuroleptics influence TRK C gene activity in the cerebellum. Moreover, the distinct medication-independent reduction of trk C mRNA may point to a disturbed neurotrophic gene activity in the frontal cortex of schizophrenic patients.

Adult↗
PubMed1998

New isoform of the neuronal Ca2+ channel alpha1E subunit in islets of Langerhans and kidney--distribution of voltage-gated Ca2+ channel alpha1 subunits in cell lines and tissues.

The expression of Ca2+ channel alpha1E isoforms has been analyzed in different cell lines, embryoid bodies and tissues. The comparison of the different cloned alpha1E cDNA sequences led to the prediction of alpha1E splice variants. Transcripts of two cloned alpha1E isoforms, which are discriminated by a carboxy terminal 129-bp sequence, have been detected in different cell lines and tissues. Transcripts of the shorter alpha1E isoform have been assigned to the rat cerebrum and to neuron-like cells from in vitro, differentiated embryonic stem cells. The shorter isoform is the major transcript amplified from total RNA by reverse transcription (RT)-PCR and visualized on the protein level by Western blotting with common and isoform-specific antibodies. Transcripts of the longer alpha1E isoform have been identified in mouse, rat and human cerebellum, in in vitro, differentiated embryoid bodies, in the insulinoma cell lines INS-1 (rat) and betaTC-3 (mouse), in the pituitary cell line AtT-20 (mouse) when grown in 5 mM glucose, and in islets of Langerhans (rat) and kidney (rat and human). The detection of different isoforms of alpha1E in cell lines and tissues shows that the wide expression of alpha1E has to be specified by identifying the corresponding isoforms in each tissue. In islets of Langerhans and in kidney, a distinct isoform called alpha1Ee has been determined by RT-PCR, while in cerebellum a set of different alpha1E structures has been detected, which might reflect the functional heterogeneity of cerebellar neurons. The tissue-specific expression of different isoforms might be related to specific functions, which are not yet known, but the expression of the new isoform alpha1Ee in islets of Langerhans and kidney leads to the suggestion that alpha1E might be involved in the modulation of the Ca2+-mediated hormone secretion.

Amino Acid Sequence↗
PubMed1998

Topical drug treatment in acne.

The main part of acne treatment uses the topical route. More than 50% of acne patients belong to the group presenting with acne comedonica and papulopustulosa. Whenever small nodes or scarring occur, systemic comedication is indicated, however. Topical treatment affects at least three of the four main pathogenetic factors responsible for the development of acne, i.e. hyperseborrhea, hyperkeratosis, microbial colonization and inflammation. The agents currently available influence at least one of these factors but often have additional properties. Those which act in a comedolytic and anticomedogenic manner are the retinoids tretinoin, isotretinoin, adapalene and tazarotene and azelaic acid as well, some of the retinoids having additional anti-inflammatory potency. Azelaic acid has strong antibacterial potency without inducing bacterial resistance similar to benzoyl peroxide. Unfortunately, bacterial resistances are beginning to emerge as a significant problem. Propionibacterium acnes resistance to the commonly used erythromycin can also be transferred to clindamycin, whereas no resistance has been reported to nadifloxacin so far. Today, more and more evidence comes up that topical antiandrogenic agents will soon be available to treat the important factor seborrhea, because patients with marked hyperseborrhea frequently relapse. Finally, liposome encapsulation of agents including phospholipids can enhance penetration and efficacy but, particularly with regard to retinoids, can lead to higher absorption and adverse drug reactions.

Acne Vulgaris↗
PubMed1998

Topical therapy in acne.

The majority of acne patients will receive a topical treatment either as monotherapy or in combination with a systemic drug therapy depending on the severity of the disease. The currently available topical agents affect at least one of the four main pathogenetic factors responsible for the development of acne, i.e. hyperkeratosis, microbial colonization, immune response and inflammation. Retinoids, azelaic acid, benzoyl peroxide and topical antibiotics represent the spectrum of the established and proven topical agents. Presumably, antiandrogenic agents will soon be available for topical use to treat the important factor of seborrhea. In general, by combining topical agents, their potency can be enhanced and toxicity diminished. Unfortunately, bacterial resistances are beginning to emerge as a significant problem.

Acne Vulgaris↗
PubMed1997

Metabotropic glutamate autoreceptors on nerve terminals of crayfish muscle depress or facilitate release.

In lobster and crayfish neuromuscular junctions superfusion of the excitatory transmitter L-glutamate (L-Glu) has been shown to depress release from motor axon terminals. In crayfish the effect depended on the level of depolarization of the terminal, Glu facilitating release when large depolarizing stimuli were applied. The presynaptic inhibition by Glu could be blocked only with a combination of blockers of Glu channels of the AMPA and N-methyl-D-aspartate (NMDA) types. We report that the effects of Glu can be mimicked by superfusion of (1S,3R)-1-aminocyclo-pentane-1.3-dicarboxylic acid (t-ACPD), an agonist of vertebrate metabotropic Glu-receptors. However, in the recent run of experiments the majority of terminals reacted with facilitation of release on superfusion by Glu or t-ACPD, even when the depolarizing stimuli to the terminal or the control rate of release were low. Average facilitation by 5 microM Glu was by a factor of 4.5. Facilitory responses were not blocked by the combination of APV and CNQX, and thus two types of metabotropic receptors seem to be present, their proportion varying for unknown reasons.

Animals↗
PubMed1997

Opiate modulation of dynorphin conversion in primary cultures of rat cerebral cortex.

Rat brain cortical cells in primary culture were used to investigate long-term effects of opiates on endopeptidases acting on dynorphin peptides. Enzyme activity in the soluble fraction of the cells converted dynorphin B to Leu-enkephalin-Arg6 and to a lesser extent to Leu-enkephalin. Five day treatment with 10 microM morphine increased the conversion to Leu-enkephalin-Arg6 by 370%. This effect was prevented by the presence of naloxone in the culture medium. The opiate-inducible activity was directed to the Arg-Arg bond in dynorphins with preference for dynorphin B > alpha-neoendorphin > > dynorphin A. The Km for the generation of Leu-enkephalin-Arg6 from dynorphin B was 40 microM. Enzyme activity was inhibited by dynorphin fragments, in the following order of potency: dynorphin A(1-13) > A(2-13) > A(1-17) > A(2-17) and by SH-reagents, suggesting the presence of a cysteine-protease. The opiate-stimulated dynorphin-converting enzyme (DCE)-activity affects the balance between dynorphin peptides (selective for kappa-opioid receptors) and enkephalin peptides (selective for delta-opioid receptors). Since both types of opioid peptides can influence the development of opiate tolerance, the change in the extent of this transformation may be functionally important.

Animals↗
PubMed1997

A new type of Ca-channel modulation by a novel class of 1,4-dihydropyridines.

Both Ca-antagonistic as well as Ca-agonistic 1,4-dihydropyridines (DHPs) have become extremely important tools to investigate the role of Ca-channels under various physiological and pathophysiological conditions. While Ca-antagonists stabilize the inactivated state of the Ca-channel without influencing the voltage dependent open and closed times, Ca-agonists prolong the mean open time of the channel. We here report for the first time the effects of a novel DHP, BAY Y 5959, which modulates Ca-channel gating in a unique manner: It increases both the mean open time and the mean closed time of the Ca-channel by binding to the DHP receptor. This results in a reduced rate of Ca-current activation, an increased peak current, and a strongly prolonged tail current decay. All these effects are strongly voltage dependent. Therefore it depends on resting membrane potential and shape of the action potential whether and how the Ca-influx into the cell is influenced. This novel mode of action of BAY Y 5959 results in an interesting pharmacological profile: It has a strong positive inotropic effect in the heart without influencing vessel tone. Therefore the term Ca-promoter is suggested; it could become a new approach for the drug treatment of congestive heart failure.

Action Potentials↗