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Biomedical subjects

H Kasch

Publications and source records attributed to H Kasch.

10 recordsLinked to original sources

A double-blind, controlled study of botulinum toxin A in chronic myofascial pain.

BACKGROUND: Recent studies have reported a potential analgesic effect of botulinum toxin A (BTXA) in musculoskeletal pain. The present double-blind, randomized, placebo-controlled, parallel clinical trial studied the effect of BTXA on pain from muscle trigger points and on EMG activity at rest and during voluntary contraction. METHODS: Thirty patients with trigger points in the infraspinatus muscles received either 50 units/0.25 mL of BTXA or 0.25 mL of isotonic saline. Baseline measures were determined during a run-in period of 1 week. Outcome measures including local and referred spontaneous pain, pain detection and tolerance thresholds to mechanical pressure, and shoulder movement were assessed at 3 and 28 days after injection. The interference pattern of the EMG during maximal voluntary effort of infraspinatus muscle was recorded and a standardized search for spontaneous electrical motor endplate activity at the trigger points was performed before and 28 days after BTXA or saline injection. RESULTS: BTXA reduced motor endplate activity and the interference pattern of EMG significantly but had no effect on either pain (spontaneous or referred) or pain thresholds compared with isotonic saline. CONCLUSIONS: The results do not support a specific antinociceptive and analgesic effect of botulinum toxin A.

Analgesics↗

Distribution of estrone sulfatase in rat brain determined by in vitro autoradiography with 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate.

16Alpha-fluoroestradiol-3,17beta-disulfamate (FESDS) strongly inhibits estrone sulfatase (ES), an enzyme which is also present in the brain. The enzyme is probably involved in important regulatory functions of neurosteroids which may be disturbed in certain brain diseases. In the present study, [18F]FESDS was used to measure the amount of ES in various rat brain regions using quantitative in vitro autoradiography. The obtained values vary between 0.29 pmol (mg protein)(-1) (pons) and 11.5 pmol (mg protein)(-1) (striatum). They are positively correlated with the enzyme activity measured in homogenates of the corresponding regions. Because this radiotracer binds also to carbonic anhydrase in the brain it is only of limited use for in vivo imaging studies.

Adenocarcinoma↗

Distribution of 16alpha-[18F]fluoro-estradiol-3,17beta-disulfamate in rats, tumour-bearing mice and piglets.

Based on a high affinity to the enzyme estrone sulfatase (ES), 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate ([18F]FESDS) has been suggested as a potential PET radiotracer for imaging steroid-dependent breast tumours. The distribution of [18F]FESDS was studied in rats, tumour-bearing nude mice and piglets. In all species evidence for binding to a second target, the enzyme carbonic anhydrase (CA), was obtained. ES and CA inhibitors significantly reduced the radiotracer uptake in various organs but not in tumours. It is concluded that [18F]FESDS binds to ES and CA in vivo but this binding is not strong enough to allow tumour imaging with positron emission tomography (PET).

Animals↗

Handicap after acute whiplash injury: a 1-year prospective study of risk factors.

BACKGROUND: Exposure to a whiplash injury implies a risk for development of chronic disability and handicap, with reported frequencies ranging from 0% to 50% in follow-up studies. The exact risk for development of chronic whiplash syndrome is not known. OBJECTIVE: To prospectively determine the sensitivity and specificity of five possible predictors for handicap following a whiplash injury. METHODS: In a 1-year prospective study of persons with acute whiplash injury (n = 141) and control subjects who had acute ankle distortion (n = 40), pain intensity, number of nonpainful neurologic complaints, cervical mobility, workload during extension and flexion of the neck, and results of psychometric assessment were recorded. The consecutively sampled injured persons were assessed with structured and semistructured questionnaires, and underwent neurologic examination after 1 week and 1, 3, 6, and 12 months. After 3 to 4 years, participants with whiplash injury were questioned about legal issues. RESULTS: After 1 year, 11 (7.8%) persons with whiplash injury had not returned to usual level of activity or work. The best single estimator of handicap was the cervical range-of-motion test, which had a sensitivity of 73% and a specificity of 91% (p < 0.01, Cox regression analysis). Accuracy and specificity increased to 94% and 99% when combined with pain intensity and other complaints. This increase was gained at the expense of a reduced sensitivity. Initiation of lawsuit within first month after injury did not influence recovery. CONCLUSION: The cervical range-of-motion test has a high sensitivity in prediction of handicap after acute whiplash injury. The value of cervical range-of-motion test is further improved by additional recording of symptoms and pain intensity.

Adult↗

Headache, neck pain, and neck mobility after acute whiplash injury: a prospective study.

STUDY DESIGN: A 6-month prospective study of neck mobility in patients with acute whiplash injury and a control group with acute ankle distortion was conducted. OBJECTIVES: To assess active neck mobility after acute whiplash and ankle distortion injuries, and to relate neck mobility to headache, neck pain, and speed of car at the time of collision. SUMMARY OF BACKGROUND DATA: A major problem after whiplash injury is restriction of neck mobility immediately subsequent to trauma. It is, however, unclear whether neck mobility changes after the acute injury are related to the associated headache and neck pain. METHODS: Cervical range of neck motion, neck pain, and headache were assessed after 1 week, then 1, 3, and 6 months after injury in 141 patients with acute whiplash injury, and in 40 patients with acute nonsport ankle distortion. RESULTS: Patients with whiplash injury had significantly reduced flexion, extension, lateral flexion, and rotation of the neck immediately after injury, as compared with patients with ankle distortion injury. Neck mobility, however, was similar in the two groups after 3 months. In patients with whiplash injury, neck pain and neck mobility were found to be related inversely to reported headache and neck mobility. Neck mobility was not significantly related to a difference in car speed at the time of collision. CONCLUSIONS: Neck mobility is reduced immediately after, but not 3 months after, a whiplash trauma. Headache and neck mobility are related inversely and neck pain and neck mobility are related inversely during the first 6 months after acute whiplash injury.

Acute Disease↗

Automated synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate.

After 16alpha-[15F]fluoroestradiol ([18F]FES) has been successfully prepared in an automated module, the synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate ([18F]FESDS) is described as a module-assisted one-pot procedure which can provide 10GBq [18F]FESDS with a radiochemical purity better than 99%. The procedure is reliable and reproducible and requires a time of about 90 min. Because of its high sulphatase-inhibitory effect [15F]FESDS is thought to be a new PET tracer to image sites of high sulphatase activity.

Arylsulfatases↗

Has basic research contributed to chronic pain treatment?

Our understanding of nociceptive processing and of plastic changes after persistent noxious input has increased immensely within the last two decades. It is now clear that long-lasting noxious stimulation or damage to the nervous system give rise to a neuronal hyperexcitability and that this sensitisation of the nervous system plays an important role for development and maintenance of chronic pain. The manifestations of such hyperexcitability are numerous and include among others: increased neuronal response to a suprathreshold stimulus, expansion of the peripheral areas from where a central neurone can be activated and the recruitment of previous non-responding nociceptive neurones. Furthermore, it has been possible to modulate this neuronal hyperexcitability by the discovery of molecular targets for pain, by sequencing DNA of ion channels and receptors and by development of new molecules that exert their effects on these molecular targets. The changes in responsiveness appear to be partly time and intensity dependent and partly dependent on the cause of injury. Whereas relatively short-lasting and moderate noxious input leads to reversible plastic changes, more intense and long-lasting noxious stimulation implies a risk for persistent and more profound alterations in transmitters, receptors, ion channels and in neuronal connectivity. Despite the explosion of new knowledge in pain processing and in molecular background for neuroplasticity, this progress has unfortunately not resulted in a corresponding improvement of our ability to treat chronic pain. The number of patients with chronic unrelieved pain is still high and newer types of treatment have so far not resulted in a substantially better treatment. Nevertheless, there is now an ongoing systematic research in which chronic pain conditions are assessed in a fashion so that mechanisms underlying pain can be dissected. Moreover, controlled clinical trials together with systematic reviews are carried out which in the future should permit formulation of treatment algorithms for chronic pain. Finally, it is likely that the development of new specific types of treatment will show efficacy if they are evaluated and analysed not on the global pain experience, but more specifically on those targets and elements of the pain experience they are aimed to deal with.

Animals↗

Pain thresholds and tenderness in neck and head following acute whiplash injury: a prospective study.

UNLABELLED: OBJECTIVE OF THE INVESTIGATION: In a 6-month prospective study of 141 consecutive acute whiplash-injured participants, and 40 acute, ankle-injured controls, pain and tenderness in the neck/head, and at a distant control site, were measured. BASIC PROCEDURES: Muscle palpation and pressure algometry in five head/neck muscle-pairs were performed after 1 week and 1, 3 and 6 months after injury. Algometry was performed at a distant control site. MAIN FINDINGS: Whiplash-injured patients had lowered pressure-pain-detection thresholds and higher palpation-score initially in the neck/head, but the groups were similar after 6 months, and the control site was not sensitized. PRINCIPAL CONCLUSION: Focal, but not generalized, sensitization to musculoskeletal structure is present until 3 months, but not 6 months, after whiplash injury, and probably does not play a major role in the development of late whiplash syndrome. Pressure algometry and palpation are useful clinical tools in the evaluation of neck and jaw pain in acute whiplash injury.

Acute Disease↗

[Multiple system atrophy--a neurodegenerative disease entity].

Multiple system atrophy (MSA) is a nosological entity. Main clinical manifestations are parkinsonism, pyramidal signs, cerebellar signs and autonomic dysfunction. Postmortem studies of patients who while alive were diagnosed as having idiopathic Parkinson's disease show approximately 8% as having MSA at autopsy. Specific pathological findings are glial cytoplasmatic inclusions. It seems likely that patients with MSA are misdiagnosed or underrecognized. This review is an attempt to elucidate upon clinical and paraclinical approaches to MSA and to depict relevant research in this field. The aetiology is unknown.

Diagnosis, Differential↗

Preparation of 3-ketodesogestrel metabolites by microbial transformation and chemical synthesis.

Specific microbial reactions were used for the preparation of metabolites of 3-ketodesogestrel (13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one, the active from of the progestagen desogestrel. Clostridium paraputrificum transformed 3-ketodesogestrel (KDG) to the 5 beta-dihydro and tetrahydro metabolites 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yn-3-one and 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol, respectively. The epimeric compound 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol was obtained by chemical reduction of the 3-oxo compound. Mycobacterium smegmatis converted KDG to metabolites of the 5 alpha H-series: 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yn-3-one, 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol and 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol. The ring A-aromatized analog of KDG 13-ethyl-11-methylene-18,19-dinor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17 beta-diol was obtained by microbial 1-dehydrogenation with Rhodococcus rhodochrous. Additionally, chemical syntheses of the microbially obtained KDG metabolites listed above were carried out. These included Birch reduction, reduction of KDG with sodium borohydride in aqueous pyridine and in methanol, reduction of KDG with potassium selectride in tetrahydrofuran, and dehydrogenation of KDG with cupric-II bromide in acetonitrile. The problems encountered in chemical syntheses favor the microbial procedures. The compounds were characterized by mass spectra (MS), IR, and circular dichroism (CD). Complete assignments of 1H and 13C chemical shifts were made using homo- and heteronuclear 2-DN-NMR spectroscopy. Chromatographic [gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC)] data of all the prepared KDG metabolites are presented.

Clostridium↗