Biomedical subjects

J H Schultz

Publications and source records attributed to J H Schultz.

At least 19 recordsLinked to original sources

PubMed2001

Heterogeneity of Kv2.1 mRNA expression and delayed rectifier current in single isolated myocytes from rat left ventricle.

Expression of the voltage-gated K(+) channel Kv2.1, a possible molecular correlate for the cardiac delayed rectifier current (I(K)), has recently been shown to vary between individual ventricular myocytes. The functional consequences of this cell-to-cell heterogeneity in Kv2.1 expression are not known. Using multiplex single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), we detected Kv2.1 mRNA in 47% of isolated midmyocardial myocytes from the rat left ventricular free wall that were positive for alpha-myosin heavy chain mRNA (n=74). Whole-cell patch-clamp recordings demonstrated marked differences in the magnitude of I(K) (200 to 1450 pA at V(Pip)=40 mV) between individual myocytes of the same origin. Furthermore, the tetraethylammonium (TEA)-sensitive outward current (I(TEA)), known to be partly encoded by Kv2.1 in mice, revealed a wide range of current magnitudes between single cells (150 to 1130 pA at V(Pip)=40 mV). Combined patch-clamp recordings and multiplex single-cell RT-PCR analysis of the same myocytes, however, showed no differences in I(K) or I(TEA) magnitude or inactivation kinetics between myocytes expressing Kv2.1 mRNA and those that did not express Kv2.1 mRNA. In contrast, in all midmyocardial myocytes expressing the transient outward potassium current (I(to1)), Kv4 mRNA, which has been shown to underlie I(to1), was detected (n=10). These results indicate that I(K) heterogeneity among individual left ventricular myocytes cannot be explained by the distribution pattern of Kv2.1 mRNA. Other mechanisms besides Kv2.1 mRNA expression appear to determine magnitude and kinetics of I(K) in rat ventricular myocytes.

Animals↗

PubMed2001

Regional alterations of repolarizing K+ currents among the left ventricular free wall of rats with ascending aortic stenosis.

The effect of cardiac hypertrophy on electrocardiogram (ECG), action potential duration (APD) and repolarizing K+ currents was investigated in epicardial, midmyocardial and endocardial myocytes isolated from the rat left ventricular free wall. Cardiac hypertrophy was induced by stenosis of the ascending aorta (AS), which led to an increased pressure load (+85 +/- 10 u1v1vZ mm11Z Hg) of the left ventricle; sham-operated animals served as controls. In ECG recordings from AS rats, the QTc interval was prolonged and the main vectors of the QRS complex and the T-wave pointed in opposite directions, indicating an abnormal sequence of repolarization. APD and K+ currents were recorded using the whole-cell patch-clamp technique. In the AS group, APD90 (90 % repolarization) was significantly prolonged in epicardial and midmyocardial, but not endocardial myocytes. Corresponding to the increase in APD, the magnitude of the transient outward K+ current (Ito1) was significantly smaller (-30 %) in epicardial and midmyocardial, but not endocardial myocytes. Inactivation and steady-state inactivation of Ito1 were not affected by hypertrophy. Recovery from inactivation was slightly prolonged in endocardial myocytes from AS rats. No differences in delayed rectifier currents (IK) or inwardly rectifying K+ currents (IK1) were detected between myocytes of the three regions of sham-operated or AS animals. However, both currents were reduced by AS. The present data show that cardiac hypertrophy caused by pressure overload leads to an increase in APD and a decrease in Ito1 primarily in epicardial and midmyocardial myocytes, which implies a major role of alterations in Ito1 for the reduced gradient in APD. The effects of AS on IK1 and IK may slightly counteract the decrease in APD gradient. The observed changes in APD and underlying ionic currents could well explain the alterations in repolarization observed in the ECG induced by cardiac hypertrophy.

Action Potentials↗

PubMed2001

[Anesthesiology education and training in Germany. Results from a representative questionnaire].

The aim of the present investigation, initiated by the German Academy of Education in Anaesthesiology (DAAF), was to obtain valid information about education and training strategies of German anaesthetists, in order to highlight weaknesses and strengths for better planning and performance of future efforts in this area. For this reason, a questionnaire with 23 items was distributed to 2000 German anaesthetists during the years 1993-1995 and of these 1290 questionnaires could then be evaluated (response rate 64.5%). The most important means of education and training were classical media such as text books and journals. Modern techniques such as videos, tapes or computer-assisted anaesthesia simulators were poorly used. Refresher courses, repetitoria and hospitations in other departments were, despite infrequent use, considered to be effective means of education and training and should be made more available. Systematic theoretical education was provided particularly seldom in most hospitals. Respondents considered anaesthetic complications and mishaps, intensive care and pain medicine to be the main top topics for continuing medical education. German anaesthetists seem highly motivated for education and training and spend on average about 5.5 h per week for personal learning and refreshing, a figure that is quite comparable to international standards. Hospital and department heads are mostly believed to have positive attitudes to education and training. Most respondents were in favour of strict rules for education and training measures, which includes the obligation to prove their certified attendance (as yet not required in Germany). On the other hand, the majority voted against making the continued recognition as a specialist in anaesthesiology dependent on completion of a performance control.

Anesthesiology↗

PubMed1999

Relationship between transient outward K+ current and Ca2+ influx in rat cardiac myocytes of endo- and epicardial origin.

1. The transient outward K+ current (Ito) is a major repolarizing ionic current in ventricular myocytes of several mammals. Recently it has been found that its magnitude depends on the origin of the myocyte and is regulated by a number of physiological and pathophysiological signals. 2. The relationship between the magnitude of Ito, action potential duration (APD) and Ca2+ influx (QCa) was studied in rat left ventricular myocytes of endo- and epicardial origin using whole-cell recordings and the action potential voltage-clamp method. 3. Under control conditions, in response to a depolarizing voltage step to +40 mV, Ito averaged 12.1 +/- 2.6 pA pF-1 in endocardial (n = 11) and 24.0 +/- 2.6 pA pF-1 in epicardial myocytes (n = 12; P < 0.01). APD90 (90 % repolarization) was twice as long in endocardial myocytes, whereas QCa inversely depended on the magnitude of Ito. L-type Ca2+ current density was similar in myocytes from both regions. 4. To determine the effects of controlled reductions of Ito on QCa, recordings were repeated in the presence of increasing concentrations of the Ito inhibitor 4-aminopyridine. 5. Inhibition of Ito by as little as 20 % more than doubled QCa in epicardial myocytes, whereas it had only a minor effect on QCa in myocytes of endocardial origin. Further inhibition of Ito led to a progressive increase in QCa in epicardial myocytes; at 90 % inhibition of Ito, QCa was four times larger than the control value. 6. We conclude that moderate changes in the magnitude of Ito strongly affect QCa primarily in epicardial regions. An alteration of Ito might therefore allow for a regional regulation of contractility during physiological and pathophysiological adaptations.

Action Potentials↗

PubMed1998

Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus.

We have examined gating and pharmacological characteristics of somatic K+ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K+ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal inhibitory concentrations <0.1 mM) predominated, contributing an average of 58% to the total K+ current in these cells. By contrast, in pyramidal neurons of the CA1 region a rapidly inactivating A-type K+ current component that was TEA-resistant prevailed, contributing 61% to the total K+ current. Both types of neurons also showed small amounts of the K+ current component mainly found in the other type of neuron and, in addition, a slow delayed rectifier K+ current component with intermediate properties (slow inactivation, intermediate sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K+ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.

4-Aminopyridine↗

PubMed1997

The courageous follower.

With the recent changes in the delivery of medical care in the United States, physicians are being thrust into new and unsettling roles. Many are finding themselves for the first time in the role of the follower, subject to myriad types of leadership. Leaders frequently complain that leading physicians is like "herding cats." What are the characteristics of followers? Do physicians make good followers? This article examines the role of the "cats"--what is effective followership, why physicians may fall short in followership skills, and how physicians might become better "followers."

Decision Making, Organizational↗

PubMed1996

Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.

Potassium (K+) homeostasis is controlled by the secretion of K+ ions across the apical membrane of renal collecting duct cells through a low-conductance inwardly rectifying K+ channel. The sensitivity of this channel to intracellular pH is particularly high and assumed to play a key role in K+ homeostasis. Recently, the apical K+ channel has been cloned (ROMK1,2,3 = Kir1.1a, Kir1.1b and Kir1.1c) and the pH dependence of ROMK1 was shown to resemble closely that of the native apical K+ channel. It is reported here that the steep pH dependence of ROMK channels is determined by a single amino acid residue located in the N-terminus close to the first hydrophobic segment M1. Changing lysine (K) at position 80 to methionine (M) removed the sensitivity of ROMK1 channels to intracellular pH. In pH-insensitive IRK1 channels, the reverse mutation (M84K) introduced dependence on intracellular pH similar to that of ROMK1 wild-type. A detailed mutation analysis suggests that a shift in the apparent pKalpha of K80 underlies the pH regulation of ROMK1 channels in the physiological pH range.

Amino Acid Sequence↗

PubMed1996

Extracellular K+ and intracellular pH allosterically regulate renal Kir1.1 channels.

The channels that control K+ homeostasis by mediating K+ secretion across the apical membrane of renal tubular cells have recently been cloned and designated ROMK1, -2, and -3. Native apical K+ channels are indirectly regulated by the K+ concentration at the basolateral membrane through a cascade of intracellular second messengers. It is shown here that ROMK1 (Kir1.1) channels are also directly regulated by the extracellular (apical) K+ concentration, and that this K+ regulation is coupled to intracellular pH. The K+ regulation and its coupling to pH were assigned to different structural parts of the channel protein. K+ regulation is determined by the core region, which comprises the two hydrophobic segments M1 and M2 and the P region. Decoupling from pH was achieved by exchanging the N terminus of ROMK1 by that of the pH-insensitive channel IRK1 (Kir2.1). These results suggest an allosteric regulation of ROMK1 channels by extracellular K+ and intracellular pH, which may represent a novel link between K+ homeostasis and pH control.

Allosteric Regulation↗

PubMed1996

[Dangers and risks of thoracic drainage at the accident site].

For several years it has been argued that a chest tube should be placed at the scene of an accident if thoracic trauma is suspected. However, during emergency treatment in hospital it has been observed that a high number of such tubes have been placed incorrectly. To validate this impression, we conducted a retrospective analysis of the clinical course of 33 trauma victims who had chest tubes placed at the scene of accident. It was found that 39.4% of the chest tubes were placed completely incorrectly and 21.2% required some correction; 39.4% were placed correctly. In two cases (6.1%) life-threatening complications developed because of the chest tube, necessitating a thoracotomy in 1 patient and repeated pericardial punction in the other. Based on the results of our study we believe that a more critical attitude should be adopted to the placement of chest tubes at the scene of the accident.

Chest Tubes↗

PubMed1995

Subunit-specific inhibition of inward-rectifier K+ channels by quinidine.

Distinct inward-rectifier K+ channel subunits were expressed in Xenopus oocytes and tested for their sensitivity to the channel blocker quinidine. The 'strong' inward-rectifier K+ channel IRK1 was inhibited by quinidine with an EC50 of 0.7 mM, while the 'weak' rectifier channel ROMK1 was only moderately inhibited. ROMK1(N171D)-IRK1C-term chimeric channels, which carry both sites for strong rectification of IRK1 channels (the negatively charged D171 in the second transmembrane domain and the IRK1-C-terminus including E224), displayed strong rectification like IRK1, but showed weak sensitivity to quinidine-like ROMK1, suggesting independence of quinidine binding and rectification mechanisms. Moreover, BIR10 and BIR11, two strong rectifier subunits originally cloned from rat brain, exerted subunit-specific sensitivity to quinidine, being much higher for BIR11. Quinidine blockade of IRK1 was not voltage-dependent, but strongly dependent on the pH in the superfusate. These results strongly suggest a subunit-specific interaction of inward-rectifier K+ channels with neutral quinidine within membrane lipid bilayers.

Animals↗

PubMed1995

[Treatment of severe concomitant injuries in severely burned patients].

Over a period of almost 6 years, 18 out of 320 burn patients treated in the burn centre had sustained additional severe trauma; for the most part the trauma was due to a motor vehicle accident or a fall. The risk of overlooking such additional injuries can be minimized by systematic examination and a team approach, the same as in normal multiple-trauma patients. Apart from the burn, life-threatening complications such as intra-abdominal bleeding or haemopneumothoracic injuries are to be treated immediately. In order to facilitate appropriate burn wound care and optimize mobilization, early internal or external fixation of unstable orthopaedic injuries should be performed as soon as possible. In our experience, operations carried out within 48 h after the injury have neither led to complications in wound healing nor to osteomyelitis.

Adolescent↗

PubMed1995

[In vitro and in vivo studies of a temporary absorbable dressing].

The major advantage of biodegradable synthetic wound dressings compared to other synthetic materials and biological tissue derivatives is avoidance of the necessity to change the dressing. The copolymer films used in this study were made of lactic and caproic acid. They pose no problems concerning immunology or transmission of diseases. Moreover, the substances released by degradation may possibly influence the process of wound healing. The material proved to be non-toxic and was used successfully as a carrier for cell culture with keratinocytes. The permeability for bacteria is determined by degradation. Evaluation of the bacteriological studies indicates secure protection against secondary contamination of the films for at least 15 days, however. Concerning application, dressing properties, wound healing and wound retraction, no disadvantages were found in comparison with the results of the competition's film Opsite. Based on these findings, the films are now used in a clinical study as a wound dressing for split-skin donor sites.

Animals↗

PubMed1994

[Treatment concepts and results in non-infected post-traumatic pseudarthroses of the femur and tibia].

AIM OF INVESTIGATION: Different methods of internal and external fixation are used to treat aseptic posttraumatic nonunion of the femur and tibia. The advantages and disadvantages of the different methods will be demonstrated by analysing the clinical course and the outcome of our patients. Utilizing these data, a therapeutic concept tailored to the individual situation is recommended. METHODS: Depending on the form of reaction we distinguish between vital and non-vital nonunions. The classification is made according to the clinical course, x-ray-findings and in special cases the results of scintigraphy. Due to anatomic differences in vascularisation and soft tissue coverage nonunion of the femur and the tibia are discussed separately. Stabilisation is achieved by intramedullary nail, plate or external fixator. As new methods the internal plate fixator was used for the femur and the Ilizarov ring fixator for the tibia. If there has been a mistake in the choice of the method of the primary stabilisation a change of method is done. If the indication for the initial method of stabilisation was correct, the therapy of nonunions is limited to the correction of technical mistakes. Additionally, a biologic stimulation is required for the therapy of non-vital nonunion. RESULTS: The clinical data of 77 patients treated from 1985-1993 were analysed retrospectively. Vital nonunions of the femur (11) healed after 9.5 months on the average, those of the tibia (49) after 10 months. The duration of treatment of non-vital nonunions was much longer and required 20 and 16 months, respectively. The treatment of two non-vital nonunions of the tibia could not be completed. For the femur only intramedullary nail (4) and plate (8) were used, for the tibia mainly the fixator (43), of these in 18 cases the Ilizarov-apparatus. Differences in the duration of treatment due to the choice of implant could not be recognized. Complications were pin problems (14) and one lesion of the peroneal nerve in the fixator group and superficial wound infection (2), nerve irritation (1) and fracture (1) in the group treated with intramedullary nailing. CONCLUSIONS: Due to the good soft tissue coverage and vascularisation internal fixation is favored for the treatment of femoral nonunions. The fixator should only be used if distraction osteogenesis is necessary because of a bony defect. Due to the problematic soft tissue situation and poorer vascularisation on the external fixator is preferred in the treatment of tibial nonunions if a change of method is indicated. For this purpose, we currently use predominantly the Ilizarov-apparatus because of its biomechanical properties and the convincing results. Initial problems with its use could markedly be reduced with growing experience.

Adolescent↗

PubMed1994

[Change in the treatment method of infected pseudarthrosis with bone loss of the tibia].

AIM OF INVESTIGATION: The treatment of nonunions complicated by infection and bone loss is divided into two stages. Having calmed down the infection by stabilizing, removal of infected and necrotic tissue and local antibacterial measures, the bone loss has to be filled up. Bridging the gap by means of autogenous cancellous bone grafting is complicated by a high rate of refractures depending on the length of bone loss. Therefore after changing the method and using the Ilizarov procedure it is of interest, whether this method offers advantages. Our experience is to be reported and discussed. METHODS: According to the clinical course two groups of patients with nonunions of the tibia complicated by infection and bone loss were compared. 25 previously evaluated patients of the years 1980/81 whose tibial bone loss was bridged by cancellous bone grafting (1st group) were compared with 16 patients who were treated by the Ilizarov method from May 1990 to October 1993 (2nd group). The average age was nearly the same (32.6/32.9 years). In the first group the average of bone loss measured 4 cm, in the second 7.8 cm. The number of initial operations to eliminate infection and the duration of fixator application from the beginning of bridging bone loss were compared as well as early and late complications, especially the rate of refracture and reinfection. RESULTS: 1.2 operations were needed to eliminate infection in the first group, in the second only one was necessary. The handling of the Ilizarov device is more difficult and needs training. The higher rate of early complications at the beginning decreased with increasing experience. The average of fixation time could be reduced by about ten days per cm of bone loss using the Ilizarov technique. By segmental transport new cortical bone is generated which surpasses cancellous bone grafting in regard to stability. This seems to be an important reason that refracture did not occur in the second group. Furthermore, reinfection could be avoided up to now obviously due to sufficient segmental resection of infected and necrotic tissue. Limited stores of autogenous cancellous bone are not to be feared. The total number of operations can be reduced. At the docking side early single cancellous bone grafting is recommended.

Adolescent↗

PubMed1992

[Fracture treatment in the area of the tibia].

From May 1990 to March 1992 17 open and 6 closed fractures of tibia and fibula with second- to third-degree soft tissue injuries were treated by external fixation using the Ilisarov technique. In 14 patients this external fixation was used as the primary treatment. In nine cases it was used secondarily, mainly in patients transferred after stabilization with other internal or external devices. The mean duration of fixation for diaphyseal tibial fractures was 127 days and for metaphyseal fractures, 107 days. After removal of the fixation device, a brace was temporarily fitted for full weight-bearing. Disadvantages observed include less comfort for the patient and longer operation time compared to other external fixation systems. On the other hand, this method allows full weight-bearing soon after the operation and involves minimal damage of soft tissue. Furthermore, injured soft tissue was well protected during healing.

Adolescent↗

PubMed1992

[Treatment of aseptic post-traumatic pseudarthrosis].

We report our first experience of using the Ilisarov technique in the treatment of ten patients with aseptic nonunions of fractures. In nine cases there was a nonunion of the tibia. One 76-year-old woman suffered from a nonunion of a supracondylar fracture of the humerus with concomitant rheumatoid arthritis. In this case, treatment failed. In two other cases we had to change the procedure. The mean duration of fixation for the successful cases was 22 weeks. The Ilisarov technique is sophisticated and needs special experience but has advantages in difficult cases.

Adult↗

PubMed1992

[Treatment of chronic joint malposition].

We report three cases of chronically dislocated joints of the lower extremities that were treated by the Ilisarov method. As the results show, it is possible to reduce such dislocations step by step, causing less operative trauma.

Adult↗

PubMed1992

[Indications and technique of combined dorso-ventral stabilization of the spine].

In delayed treatment of fracture dislocations or luxation of the cervical spine, combined dorsoventral operative treatment is necessary. After anatomical reduction from dorsal, stabilization is performed from ventral using autologous bone grafting and a plate. The injured intervertebral disk is removed to avoid protrusion. At the thoracolumbar spine this technique includes ventral bone grafting with a corticocancellous sandwich block and dorsal transpedicular fixation using an internal fixator system. This simplifies removal of the implant.

Adult↗