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Biomedical subjects

M Kunkel

Publications and source records attributed to M Kunkel.

At least 55 records · Page 3Linked to original sources

Central fatigue in sports and daily exercises. A magnetic stimulation study.

Previous transcranial magnetic stimulation (TMS) studies showed exercise-induced depression of motor evoked potentials (MEP). The purpose of the present study was to evaluate changes in MEP size and central motor conduction time (CMCT) after various kinds of exercise of daily life and sports. Changes of both central and peripheral motor conduction were recorded immediately after predominantly aerobic (climbing stairs and jogging) and anaerobic (press-ups, dumb-bell holding, and 400 m-run) exercise. Strength exercise resulted in a significant decrease of MEP amplitudes. Exhausting press-ups reduced the mean MEP amplitude by 33% as compared to pre-exercise value, exhausting dumb-bell holding reduced the mean MEP amplitude by 66%. Aerobic exercises (climbing 600 steps and jogging 50 minutes) did not significantly change MEP amplitudes. The compound motor action potentials (registered after supramaximal peripheral electrical stimulation) remained unchanged after each paradigm. CMCT was not significantly altered by any of the exercises under investigation. Peripheral motor conduction time (PMCT) was slightly lengthened by 4% after isometric dumb-bell holding. PMCT and total motor conduction time were decreased after aerobic exercises, probably due to an increase of temperature of the lower extremities. In conclusion, TMS is a suitable technique for objective evaluation of central fatigue. The present study is the first to show its possible use in sports medicine, indicating that only exhaustive or strength exercises result in reduced MEPs.

Adult↗

Ultrasonographic assessment of the prevalence of fasciculations in lesions of the peripheral nervous system.

In previous studies, ultrasonography was a very sensitive method in detecting fasciculations. The present study was intended to examine the prevalence of ultrasonographically visible fasciculations in patients with neuromuscular diseases affecting the lower extremities. Ultrasonography of 9 muscles (rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, semitendinosus, tibialis anterior, gastrocnemius, and soleus muscles) was performed bilaterally in 70 adult healthy subjects and 172 patients with various neuromuscular diseases. Fasciculations were detected in 109 (63%) of 172 patients. The median value of affected muscles was 10 (range 1-18). Patients with spinal muscular atrophy (37/38, p < 0.001), hereditary motor and sensory neuropathy (24/25, p < 0.001), and lumbosacral radiculopathy with motor deficits (24/29, p < 0.001) exhibited fasciculations more frequently than did healthy volunteers. Radiculopathy with sensory deficits, lesions of either plexus or peripheral nerves, compartment syndrome, and myopathy were not associated with a significantly enhanced prevalence of fasciculations in the patient group compared to the control group. In summary, fasciculations are a frequent ultrasonographic sign in neuromuscular diseases. They are almost regularly found in patients with spinal muscular atrophy and those with hereditary motor and sensory neuropathy. Thus, the absence of fasciculations in ultrasonographic assessment should give cause for reconsidering these diagnoses.

Adolescent↗

Redox active disulfides: the thioredoxin system as a drug target.

Thioredoxin, and particularly extracellular thioredoxin, presents an attractive target for developing novel agents to treat cancer. Our studies have involved the examination of a series of alkyl 2-imidazolyl disulfides as inhibitors of the growth-stimulatory activity of the thioredoxin system. We originally determined the disulfides to be weak reversible inhibitors of thioredoxin reductase. Subsequently, we have shown that alkyl 2-imidazolyl disulfides interact directly with thioredoxin, thioalkylating critical cysteine residues or causing dimerization of the protein leading to its loss of biological activity. One of the analogues that binds to thioredoxin, 1-methylpropyl 2-imidazolyl disulfide (IV-2), selectively inhibits the thioredoxin-dependent growth of tumor cells in culture and has antitumor activity against MCF-7 and HL-60 tumors in vivo. Our work involves the development of a parallel combinatorial synthetic method to produce a large number of disulfide analogues at one time. These analogues, which differ sterically, electronically, and physically, were produced in a 96-well plate. The biological activity of these analogues was evaluated, also in the 96-well plate format. This rapid method of evaluating biological activity is a means to identify agents with specificity for inhibition of the thioredoxin system, and may provide novel antitumor agents with activity against solid tumor cancers.

Animals↗

Fasciculations: clinical, electromyographic, and ultrasonographic assessment.

Widespread fasciculations are an important clinical sign in, for example, degenerative lower motor neuron diseases (LMND). Usually they are detected by clinical inspection and electromyography. Recently myosonography has been proposed for the detection of fasciculations. This prospective study compares the value of these three modes of examination in patients with degenerative LMND. Seventy healthy control persons and 34 patients (11 women, 23 men; aged 43-78 years; median age 60.5) with LMND were included in the study. All participants were subjected to thorough visual screening for the presence of fasciculations. Fourteen muscles were examined bilaterally by myosonography and a median of 8 muscles were screened electromyographically (only in the patients); the investigators were blinded to the other findings. Clinical inspection and ultrasonography exhibited fasciculations in up to 5 and 8 muscles, respectively, in 8 healthy persons. Ultrasonography demonstrated fasciculations in all patients, clinical inspection in all but 2, and electromyography in 26 of 33 patients (1 patient was not examined electromyographically). Comparing the three methods, clinical observation revealed fasciculations in 42%, electromyography in 39%, and ultrasonography in 67% of all muscles. Thus, ultrasonography was significantly more sensitive than the other techniques (P < 0.001). The interrater agreement (correlation coefficient) r in respect of the presence or absence of fasciculation was 0.71 for the clinical, 0.85 for the electromyographic and 0.84 for the myosonographic examinations. Ultrasonography and electromyography were more reliable than the clinical examination (P < 0.001 and P < 0.01, respectively). Our study indicates that ultrasonography is more sensitive than clinical and electromyographic examination in visualizing fasciculations in patients with LMND. Additionally, it is more reliable than clinical examination.

Adult↗

Posttreatment with EPC-K1, an inhibitor of lipid peroxidation and of phospholipase A2 activity, reduces functional deficits after global ischemia in rats.

In this study the effect of an inhibitor of lipid peroxidation and of phospholipase A2 activity, EPC-K1, on spatial learning deficit and neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. EPC-K1 (10 mg/kg IP) was administered either a) 15 min before induction of ischemia, b) immediately after, or c) 30 min after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. EPC-K1 reduced the deficit in spatial learning when given immediately or 30 min after the onset of reperfusion but not when applied 15 min before ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was slightly, but not significantly attenuated by posttreatment. The present data demonstrate that posttreatment with EPC-K1 exerts a protective effect on deficits in spatial learning induced by 4VO. These results support the hypothesis that lipid peroxidation and activation of phospholipase A2 contribute to functional alterations of the brain during reperfusion following forebrain ischemia.

Animals↗

[Does velopharyngoplasty as a speech-improving measure in cleft palates lead to obstructive sleep apnea?].

Velopharyngoplasty performed to correct velopharyngeal insufficiency in cleft palate patients may cause obstructive sleep apnea in individual cases. The aim of this study was to answer the question, following velopharyngoplasty to what extent and with what frequency can signs of breathing disturbances during sleep be observed. Following the recommendations of the German Sleep Society, a step-by-step procedure was adopted. In 25 patients, in some cases before the operation and in all cases following surgery, nightly oxygen saturation, heart rate, and snoring were recorded. When observable pathological signs surfaced, a cardiorespiratory polygraph was taken. Up to this point only quickly passing signs of sleep related breathing disturbances have been observed. In not a single case could lasting sleep related breathing disturbances as a result of velopharyngoplasty be proven. Nevertheless, the call for pulse oximetric monitoring in the immediate postoperative phase together with corresponding pre-operative observation is legitimate. Even if at this point the danger of sleep related breathing disturbances following velopharyngoplasty appears to be minimal, these preliminary results should be polysomnographically studied within the framework of a much larger test study in order to reach still more reliable conclusions and in order to intercede if necessary with counter measures in the rare individual case of breathing disturbance during sleep following velopharyngoplasty.

Adolescent↗

Acoustic rhinometry: a new diagnostic procedure--experimental and clinical experience.

The diagnostic value of transnasal acoustic reflection measurements (Rhinoklack) was investigated in an experimental and clinical study. Within the range of nasal and epipharyngeal dimensions, in vitro and in vivo measurements showed satisfactory reproducibility. A simple maneuver helps to identify the transition from the rigid nasal cavity to the movable epipharynx. The location and the amount of nasal obstruction can be verified and traced back to their morphologic correlative. The effect of decongestion on nasal volume was measured for normal mucosa (41% enlargement) and mucosa altered by scar formation after septoplasty and turbinoplasty (21% enlargement). After maxillomandibulary advancement of 10 mm for obstructive sleep apnea, the EV index representing epipharyngeal volume (EV) showed an average increase of 6 cm3.

Acoustics↗

Acoustic rhinometry: rationale and perspectives.

Acoustic rhinopharyngometry provides a new, non-invasive access to upper airways geometry. In this experimental and clinical study the diagnostic value of acoustic rhinopharyngometry was investigated. In vitro measurements showed adequate accuracy, reliability and spatial resolution within the range of nasal and epipharyngeal dimensions. Clinical measurements confirmed reasonable reproducibility for the evaluation of nasal (NV) and epipharyngeal (EV) volume. Decongestion with xylometazoline resulted in a 36% enlargement of nasal volume on average. The alteration of pharyngeal soft tissues due to maxillomandibulary advancement of 10 mm correlated to an increase of the EV-index of 6 cm3. Acoustic rhinometry identifies location and amount of nasal obstruction and in addition allows differentiation between obstruction due to mucosal hypertrophy and that due to skeletochondral deformity. Changes in the epipharyngeal volume following maxillary and mandibular osteotomies can be estimated in comparison with the preoperative situation.

Acoustics↗

Quinolinic acid lesion of the striatum induces impairment in spatial learning and motor performance in rats.

Injection of quinolinic acid (QA) into the striatum of rats is known to produce neuropathological and neurochemical alterations similar to those observed in Huntington's disease (HD). One clinical feature of HD patients is cognitive impairment. Two weeks after stereotaxic injection of either QA (240 nmol) or solvent in rats spatial learning was tested in the Morris water maze. QA lesioned animals required more time to find the hidden platform. The swim speed was reduced in all trials compared to the controls. The swim distance itself was longer and the amount of swim distance along the side wall was significantly higher in QA lesioned rats. The present results suggest that QA lesion of the striatum leads to deficit in motor performance and in spatial learning.

Animals↗

[Functional anatomy of the upper airway: cephalometric and reflective acoustic studies].

Cephalometric analysis is an effective tool for the evaluation of craniofacial and pharyngeal changes in obstructive sleep apnoea. Meanwhile even for pharyngeal changes a lot of average values exist, which show significant differences for many cephalometric parameters. Approximately 40% of patients with obstructive sleep apnoea proved to have a retrognathic, dolichofacial appearance, which seems to contribute to obstructive apnoeas by retropositioning of the skeletal fixation for the muscles of the floor of the mouth and the tongue. Acoustic rhinometry for transnasal cross-sectional measurements of the upper airways is still under clinical trial. Whether it is a valuable supplement to cephalometric evaluation in the future will be mainly a question of software development.

Airway Resistance↗

Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection.

OBJECTIVE: To determine central nervous system (CNS) involvement in acutely disseminated Borrelia burgdorferi infection by measurement of borrelia-specific DNA using the polymerase chain-reaction (PCR) assay and to compare the results of this with standard serological tests. DESIGN: Prospective study with laboratory investigators blinded to clinical data. SETTING: Multicenter office practice with a central reference laboratory. PATIENTS: Cerebrospinal fluid (CSF) was collected from 12 patients with acute disseminated Lyme borreliosis with less than 2 weeks of active disease. The normal control specimens came from 16 patients whose CSF samples had been sent to the clinical laboratory for tests unrelated to the present study. MAIN OUTCOME MEASURES: Clinical evidence of disease and laboratory abnormalities. RESULTS: Eight of the 12 patients (four of six with multiple areas of erythema migrans and four of six with cranial neuritis without erythema migrans) had B burgdorferi-specific DNA in their CSF. Among the 12 patients studied, nine had acute cranial neuritis and six had multiple erythema migrans lesions. Just four of the eight who were found to have spirochetal DNA in their CSF had complaints suggestive of CNS infection. In three of the PCR-positive CSF samples, no other abnormalities were noted. None of 16 samples from controls were positive in the PCR assay. CONCLUSION: B burgdorferi can invade the CNS early in the course of infection. Careful consideration should be given to choosing antibiotics that achieve adequate CSF levels in patients with disseminated infection.

Antibodies, Bacterial↗

[EBV-specific antibodies in patients with nasopharyngeal cancer and tonsillar cancer. Follow-up of over 4 years].

26 NPC patients and 47 TC patients were investigated clinically, and in the sera of these patients EBV-specific antibodies were determined. No relapse occurred in 11 patients with NPC and in 17 patients with TC during the period of 4 years. In addition to the determination of antibodies we looked for EBNA in 3 undifferentiated NPC and 4 undifferentiated TC, and for EBV-DNA in 2 of these NPC and one of these TC. The 3 NPC and 4 TC tested for EBNA showed this antigen in the cells. 2 NPC and 1 TC showed EBV-DNA with in situ hybridization technique. In the blot hybridization according to Southern the Eco R 1 fragment of both NPC was identical with the Eco R 1 fragment of the positive control of P 3 HR 1 cells. The 15 NPC-patients with tumour (4 with primary NPC, 11 with relapse) in the observation period showed higher IgA-VCA titres than the NPC patients free of relapse during this time. Subsequent to therapy, IgG-VCA titres decreased. Most of the NPC-patients with tumour during the time of testing mentioned before had IgA-VCA once or several times. Most of half of these patients had IgA-EA, but there was no patient without relapse. IgA-VCA increase and the presence of IgA-EA may be the first sign of a relapse. Thus, intensive research into this phenomenon will be required. No remarkable difference could be found in EBV-specific antibody patterns between TC patients without relapse and TC patients with tumour progression or relapse.

Adolescent↗

[Herpes simplex virus infection in the first weeks of life].

Most neonatal Herpes-simplex-virus infections are the result of virus acquisition during passage through the birth canal. Transplacental transmission of HSV is seldom. The infection is mostly localized at the skin, eyes and central nervous system. The disseminated HSV-infection represents as the most severe clinical picture. It is reported about meningoencephalitis caused by HSV in 3 infants in the first weeks of life. The therapeutic success of antiviral chemotherapeutics depends very much on their application at an early stage of the disease, which can be recognized by cerebral sonography and detection of IgM-antibodies against HSV.

Acyclovir↗