Biomedical subjects

S Grond

Publications and source records attributed to S Grond.

At least 19 recordsLinked to original sources

PubMed2006

[Expression und function of the ORL-1 receptor on human leukocytes].

BACKGROUND: The ORL-1 receptor is expressed by human leukocytes. Limited knowledge exists about the function and interaction between the nervous and immune systems. The aim of our study was to investigate the expression of the nociceptin-ORL-1 receptor system on different leukocyte subsets and the influence of the ORL-1 receptor on the intracellular production of cytokines. METHODS: Blood from healthy volunteers of different age and sex was analysed for the expression of the ORL-1 receptor by PCR and flow cytometry and the influence of nociceptin on the LPS-induced production of intracellular cytokines by flow cytometry. RESULTS: The ORL-1 receptor mRNA is expressed by granulocytes, lymphocytes and monocytes. We could also show the expression of the ORL-1 receptor protein on the cell surface of all types of white blood cells. Nociceptin has no influence on LPS-induced cytokine production in human monocytes. There was neither a difference between young and old nor between male or female volunteers. CONCLUSION: The ORL-1 receptor is expressed by all subtypes of leukocytes. The function of this receptor is not the modulation of cytokine production and requires further studies.

DNA Primers↗

PubMed2005

[Cardiac arrest caused by an ecstasy intoxication].

We report about a 19 years old man, suffering from an cardiac arrest (ventricular fibrillation) caused by an ecstasy intoxication. A supraventricular tachycardia was recorded on day three after resuscitation. No pathological findings were demonstrated by coronary angiography. An slow- fast- av -nodal- reentry- tachycardia (AVNRT) was detected and successfully treated by electrical ablation of the slow pathway during electrophysiological mapping. No severe neurological deficits were found in discharge from hospital.

Adult↗

PubMed2004

[Regulation of spinal nociceptin expression by neuropathic pain].

Nociceptin is the endogenous ligand of a new opioid receptor, the opioid receptor-like-1 (ORL1) receptor. Chronic inflammatory pain causes an increase in the expression of nociceptin and the ORL1 receptor in the dorsal horn of rat spinal cord, thus indicating an involvement of the endogenous nociceptin/ORL1 system in mechanisms of pathological pain. This study investigates the influence of neuropathic pain on the expression of nociceptin using immunohistochemistry. To induce neuropathic pain, a ligation of the sciatic nerve was performed in 12 rats under general anesthesia. A sham operation was performed in 12 rats of the control group. Nerve ligation caused a significant ipsilateral thermal hyperalgesia, a typical sign of neuropathic pain. The paw withdrawal latency was decreased by 45.7+/-4.9% ( p<0.05) at day 5 and by 37.3+/-1.8% ( p<0.05) at day 10. Although hyperalgesia was fully present after 5 days, no changes in nociceptin immunoreactivity in the lumbar spinal cord were detected at this time point. Ten days after nerve ligation, there was a 2.46+/-0.38 fold ( p<0.05) bilateral increase in nociceptin immunoreactivity in the lamina superficiales (I and II), with a notable increase in the inner lamina II at the level of L4. Further investigations are necessary to elucidate the relationship between neuropathic pain, the nociceptin-ORL1 receptor system and potential therapeutic options.

Animals↗

PubMed2004

[Not all vocal cord failure following thyroid surgery is recurrent paresis due to damage during operation. Statement of the German Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery concerning recurring paresis due to intubation].

Since the phoniatrician H. Bauer described the first case of recurrent laryngeal nerve palsy most likely caused by intubation some 45 years ago, several case reports have been published. However, systematic analyses regarding the frequency of recurrent laryngeal nerve palsies due to intubation are scarce, and none of them has used the proper methods to demonstrate clearly that such a mechanism exists. Currently available data justify the assumption that not every recurrent laryngeal nerve palsy following thyroid surgery is due to the operation itself and that the damage caused by intubation, however, may only account for a minority of these cases. The differential diagnosis of postoperative recurrent laryngeal nerve palsy requires the use of specific tools which go beyond simple laryngoscopy and include stroboscopy as well as intra- and extralaryngeal electromyography. A partial palsy of recurrent laryngeal nerve due to intubation would be associated with severe dysphonia or aphonia, not with dyspnea because of the typical intermediate position of the paralyzed vocal folds with a normal electromyographic function of the cricothyroid muscle. The use of these methods to identify the nature of postoperative recurrent laryngeal nerve palsy is recommended in cases of regular intraoperative neuromonitoring but postoperatively impaired function of the vocal cords.

Diagnosis, Differential↗

PubMed2004

[Effectiveness and results of intraoperative neuromonitoring in thyroid surgery. Statement of the Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery].

Intraoperative neuromonitoring (IONM) has yielded an increasing effect on thyroid surgery. During IONM, the recurrent laryngeal nerve is stimulated electrically and an acoustically transformed electromyographic signal is derived via either a needle electrode placed in the vocalis muscle or an electrode adjusted to the intubation tube. The IONM is used for identifying and predicting the function of the recurrent laryngeal nerve. Especially under difficult anatomic conditions, IONM has proven a valuable tool for identification of recurrent laryngeal nerves. This can lead to decreased occurrence of nerve palsy rates, as shown in numerous studies. The reliability of the IONM signal (defined as the correlation between intraoperative signal interpretation and postoperative vocal cord function) is reflected by a specificity as high as 98.2%, as shown by German multicenter studies. Thus, normal vocal cord function could be demonstrated postoperatively in over 98.2% of patients with intraoperatively unchanged neuromonitoring signals. If the neuromonitoring signal changed during operation, 39% of the patients suffered from transient vocal cord immobility and 12% had permanent loss of vocal cord function.

Electrodes↗

PubMed2004

[Efficacy and safety of 0.1 mg of intrathecal morphine in arthroscopic knee joint surgery].

BACKGROUND AND OBJECTIVE: Intrathecal morphine provides effective postoperative analgesia but is associated with the risk of respiratory depression. A dose of only 0.1 mg has been shown to be optimal for effective and safe pain relief after abdominal surgery. This study was designed to determine whether the addition of 0.1 mg of morphine to the local anesthetic for spinal anesthesia produces adequate analgesia following arthroscopic knee joint surgery. METHODS: A prospective, randomized, placebo-controlled, double-blind clinical trial was performed. Forty ASA I/II patients undergoing knee arthroscopy under spinal anesthesia were randomized to receive either mepivacaine 4% with 0.1 mg of morphine or mepivacaine 4% with saline (placebo) intrathecally. Postoperative analgesia consisted of intravenous morphine delivered by patient-controlled analgesia (bolus: 2 mg, lockout time: 5 min). During the study period of 24 h, pain intensity at rest and on movement (visual analogue scale, 0: no pain, 100: maximum pain), vigilance, and vital parameters were recorded every hour. RESULTS: There were no statistically significant differences between the two groups in postoperative pain scores, morphine requirements, vigilance, blood pressure, heart rate, and breathing frequency. The patients of the morphine group required 12.3+/-10.2 mg (mean+/-SD) and those of the placebo group 11.6+/-8.4 mg of intravenous morphine from patient-controlled analgesia. The pain scores at rest and on movement were 10.0+/-8.1 and 16.0+/-12.6 in the morphine group and 8.2+/-7.9 and 11.7+/-11.3 in the placebo group. We did not observe severe side effects in any of the patients. CONCLUSION: Intrathecal administration of 0.1 mg of morphine does not contribute to postoperative analgesia after arthroscopic knee joint surgery.

Adult↗

PubMed2003

Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery.

OBJECTIVE: Cardiopulmonary bypass is often associated with pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated plasma levels of pro- and anti-inflammatory cytokines in survivors and non-survivors from MODS in the early postoperative course following open heart surgery. DESIGN: Prospective clinical study. SETTING: A University Cardiothoracic Intensive Care Unit. METHODS: Levels of cytokines (IL-6, IL-8, IL-10, IL-18, and TGF- ) and procalcitonin (PCT) were measured at the first four postoperative days in 16 adult male patients with an Apache II-score >24 and two or more organ dysfunctions after myocardial revascularization. MAIN RESULTS: All pro-inflammatory cytokines, except for IL-6, were significantly elevated in non-survivors from MODS, with peak values at the first two postoperative days. The plasma levels of immunoinhibitory cytokines showed no differences between the groups. CONCLUSIONS: The results of our study show a different expression of pro-inflammatory cytokines in survivors and non-survivors from MODS following operations with extracorporeal circulation. In addition to Apache-II score, especially IL-8, IL-18, and PCT may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery.

APACHE↗

PubMed2003

Inhibition of intracellular tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 production in human monocytes by iloprost.

BACKGROUND: To investigate the effects of iloprost as a stable prostacyclin analogue on intracellular expression of IL-6 and TNF-alpha of lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system assessed by flow cytometry. MATERIAL AND METHODS: Whole blood of six healthy volunteers processed immediately after withdrawal and twice on different days (six measurements per experiment) was stimulated in two different settings with LPS (final concentrations 0.2 ng mL(-1) and 10 ng mL(-1)) and incubated with iloprost (final concentrations in each experiment were 0.01 nm, 0.1 nm, 0.3 nm, 1 nm, 3 nm, 10 nm, 30 nm and 100 nm) for 3 h at 37 degrees C and 5% CO2. Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry. RESULTS: Our investigations showed, for the first time, that iloprost (0.1 nm up to 100 nm) caused a dose-dependent inhibitory effect of IL-6 production in human monocytes stimulated with LPS (10 ng mL(-1)), which was even more obvious in monocytes stimulated with lower concentrated LPS (0.2 ng mL(-1)). Iloprost (0.1 nm up to 100 nm) was found to inhibit TNF-alpha production of LPS-stimulated monocytes in a dose-dependent fashion not influenced by LPS concentration. CONCLUSIONS: Apart from the vasodilatory and antithrombotic effects, iloprost may also down-regulate the intracellular expression of IL-6 and TNF-alpha in human monocytes.

Adult↗

PubMed2003

Brain tissue oxygen monitoring for assessment of autoregulation: preliminary results suggest a new hypothesis.

Brain tissue oxygen monitoring (P(ti)O2 (Neurotrend, Codman, Germany) was employed in addition to standard intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in seven patients with severe neuronal damage of heterogeneous etiology. The correlation between P(ti)O2 changes and CPP fluctuations during periods of 30 minutes were analyzed, when CPP was above 70 mmHg and lower than 100 mmHg. A new ratio, the CPP-oxygen-reactivity (COR) index was calculated as COR=delta p(ti)O2 %/delta CPP%. The patient COR values were compared to those found in the brain of six noninjured anesthetized piglets. The analysis was performed to determine the significance of synchronous fluctuations of CPP and P(ti)O2, when CPP is above the lower threshold of autoregulation. The correlation between CPP variations and p(ti)O2 variations was found to be strong (R(mean)) = 0.74 +/- 0.17) in the patients and was weak in the uninjured animals (R(mean)) =0.38 +/- 0.43). The COR (mean) was 2.05 +/- 0.57 in patients and 0.78 +/- 0.6 in the animals. In the injured brain of our patients, we observed an unexpectedly close correlation between P(ti)O2 and CPP variations when CPP levels were within a therapeutically targeted range (70 to 100 mmHg). In a porcine model, we could not find this relationship in the noninjured brain. We speculate that an increased COR might be indicative for an impaired local pressure autoregulation. The preliminary data suggest that COR values above "1" might be pathologic. However, the reported sample sizes are too small to provide sufficient statistical power to justify inferential statistical analyses. As such, results are presented with descriptive statistics only, and should be regarded as a hypothesis.

Algorithms↗

PubMed2002

[Nociceptin and the ORL1 receptor: pharmacology of a new opioid receptor].

Molecular biological investigations led to the discovery of the ORL1 receptor ( opioid receptor like-1 receptor) and its endogenous ligand nociceptin. Although its sequence and structure are closely related to traditional opioid receptors, the ORL1 receptor shows low binding affinities for selective opioid agonists and antagonists. On the other hand, the ORL1 ligand nociceptin does not bind to the three traditional opioid receptors. The activation of the G protein-coupled ORL1 receptor inhibits adenlylate cyclase activity, reduces the intracellular concentration of the second messenger cAMP and regulates ion channels. The supraspinal administration of nociceptin produces hyperalgesia. unlike opioids. Spinal intrathecal and peripheral administration of nociceptin causes hyperalgesia in low doses and analgesia in high doses. The physiological role and detailed mechanisms of these dose-dependent nociceptin effects in opposite directions are not yet known. In addition, nociceptin modulates other biological phenomena such as feeding, locomotion, gastrointestinal function,memory, cardiovascular function,immunity, renal function, anxiety,dependence and tolerance.Future research on the physiological and pathophysiological importance of the nociceptin/ORL1 receptor systems may provide a target for novel therapeutics.

Analgesia↗

PubMed2001

Blockade effects of (Nphe1)Nociceptin(1-13)-NH(2) on anti-nociception induced by intrathecal administration of nociceptin in rats.

The present study investigated the roles of the opioid-receptor-like (ORL1) receptor and its endogenous ligand nociceptin on nociception in the spinal cord of rats. Intrathecal administration of 10 nmol of nociceptin produced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation. There were no significant changes of average maximum angles in inclined plane tests after intrathecal injection of 10 nmol of nociceptin in rats. The intrathecal nociceptin-induced increases in HWL were antagonized by intrathecal administration of (Nphe1)Nociceptin(1-13)-NH(2), a selective antagonist of ORL1 receptor, in a dose-dependent manner. The results demonstrated that ORL1 receptor is involved in the nociceptin-induced anti-nociceptive effect in the spinal cord of rats.

Animals↗

PubMed2001

[Latex allergy. Perioperative management in anesthesia and cardiac anesthesia].

The frequency of perioperative allergic responses to latex has markedly increased over the last 10 years. High risk groups to develop sensitivity to latex include healthcare workers, workers in the latex industry, children suffering from congenital malformations such as spina bifida or urogenital deformities and patients who have undergone multiple surgical procedures. During surgery, patients have contact to a variety of products containing latex. To prevent anaphylactic reactions, all hospitals have to develop strategies to identify and manage patients sensitised to latex or belonging to high risk groups. The aim of this paper is to describe safe perioperative management in a latex-free environment.

Anesthesia↗

PubMed2001

Bi-directional modulation of 5-hydroxytryptamine-induced plasma extravasation in the rat knee joint by nociceptin.

The role of nociceptin, the endogenous ligand for the opioid receptor-like (ORL1) receptor, in nociceptive processing is controversial. Most studies demonstrate hyperalgesia following supraspinal administration, analgesia following intrathecal and peripheral administration at higher doses, and hyperalgesia following intrathecal and peripheral application at lower doses. The present study investigates the effect of nociceptin on synovial plasma extravasation and its ability to modulate 5-hydroxytryptamine-induced synovial plasma extravasation using the rat knee joint model of inflammation. Nociceptin alone does not alter synovial plasma extravasation from baseline. Nociceptin at concentrations up to 1 nM enhances 5-hydroxytryptamine-induced synovial plasma extravasation (up to 50%) and nociceptin at concentrations above 100 nM inhibits 5-hydroxytryptamine-induced synovial plasma extravasation (down to 45%). The novel, selective ORL1 receptor antagonist J-113397 potently inhibits the pro-inflammatory effect of nociceptin, but only partly inhibits, at higher concentrations, the anti-inflammatory effects of nociceptin.These findings demonstrate a dose-dependent bi-directional effect of nociceptin on inflammatory processes and may indicate a target for novel therapeutics.

Animals↗

PubMed2001

Inhibition of synovial plasma extravasation by preemptive administration of an antiinflammatory irrigation solution in the rat knee.

UNLABELLED: Inflammation and hyperalgesia during surgical procedures are caused by the local release of multiple inflammatory mediators. We used a rat knee joint model of acute inflammation (synovial plasma extravasation) to determine whether preemptive intraarticular irrigation of the antiinflammatory drugs ketoprofen, amitriptyline, or oxymetazoline, alone or in combination, can reduce inflammatory soup-induced plasma extravasation. These three drugs were selected because of their abilities to collectively inhibit the inflammatory effects of biogenic amines, eicosanoid production, and the release of neuropeptides from C-fiber terminals. Synovial perfusion of each one of the three drugs 10 min before, and then in combination with, the inflammatory soup (bradykinin, 5-hydroxytryptamine, and mustard oil) did not reduce plasma extravasation. Similarly, two-drug combinations did not significantly reduce inflammatory soup-induced plasma extravasation. The combination of all three drugs (amitriptyline, ketoprofen, and oxymetazoline) produced a dramatic inhibition of plasma extravasation and was more effective than any of the two-drug combinations. A comparison between the preemptive (10 min before inflammatory soup perfusion) and postinflammatory administration (10 min after inflammatory soup perfusion) showed that the postinflammatory administration of the three-drug solution lost all ability to inhibit inflammatory soup-induced plasma extravasation. We conclude that acute synovial inflammation, which is induced and maintained by multiple mediators, can be substantially inhibited only by the preemptive administration of a drug combination that targets multiple inflammatory mediators. IMPLICATIONS: Preemptive, intraarticular irrigation of a combination of multiple antiinflammatory drugs is a novel and potentially effective method for reducing the synovial inflammatory response, such as that during arthroscopy. In this study, a three-drug combination infusion was statistically superior to one- or two-drug infusions in a rat model.

Amitriptyline↗

PubMed2001

Transdermal fentanyl for the management of cancer pain: a survey of 1005 patients.

Transdermal fentanyl was released in Germany in 1995. From October 1996 to February 1998 transdermal treatment was documented for 1005 patients (506 men and 499 women with a mean age of 60 years, range 20-92 years) with chronic pain in an open survey including 290 physicians from hospitals and general practitioners throughout Germany. Most patients suffered from cancer pain and only 11 patients had chronic pain from non-malignant disease. Physicians were asked to complete a questionnaire for patients treated with transdermal fentanyl on initiation of therapy (day 0), and days 3, 6, 18, 30 thereafter, followed by monthly follow-up intervals. Patients were asked to complete a pain diary. Transdermal therapy was documented from day 0 for 824 patients, while 181 patients had been treated with transdermal fentanyl before admission in the survey. Most of the other 824 patients had been treated with other step 3 opioids (55% of the patients) or step 2 opioids (23%) before conversion to transdermal fentanyl, whereas 8% had been treated only with non-opioids and 14% had received analgesics only as required or not at all before initiation of transdermal therapy. The most important reasons for switching to transdermal opioid therapy were insufficient pain relief with the previous medication followed by a variety of gastrointestinal symptoms impeding oral analgesic therapy. Initial fentanyl doses ranged from 0.6 to 9.6 mg/day (25 to 400 microg/h) with a median of 1.2 mg/day (50 microg/h). Median doses slowly increased throughout the observation period to 2.4 mg/day (100 microg/h) after 4 months of treatment. Most patients continued transdermal therapy until the time of death (47% of patients). Other reasons for discontinuation were inadequate pain relief (10%), pain relief with other analgesic regimens (10%), other symptoms than pain (5%), rejection of transdermal therapy by the patient (6%) or miscellaneous (16%). Adverse events were documented as the reason for discontinuation of transdermal therapy in 49 patients (5%). Dyspnoea was documented for seven patients as the reason for discontinuation. One of these patients, as well as another patient with an episode of apnoea, had to be treated with artificial respiration for several hours, but both patients recovered without sequelae. Transdermal therapy with fentanyl was safe and efficient in this national survey. Transdermal fentanyl can be recommended for treatment of moderate to severe cancer pain and probably may even be used as a first-line drug on step 3 of the World Health Organization recommendations in selected patient groups.

Administration, Cutaneous↗

PubMed2000

[Morphine dose and side effects: a comparison of older and younger patients with tumor pain].

UNLABELLED: BACKGROUND AND GOAL OF STUDY: Older patients are said to be more sensitive to analgesics and to have a higher risk of side effects due to pharmacokinetic changes developing with old age. On account of this many elderly patients with cancer pain are denied adequate analgesic treatment. We compared efficacy and side effects of cancer pain management in different age groups. METHODS: From 1994 to April 1996 577 cancer patients were treated in our pain clinic according to WHO-Guidelines. Efficacy and side effects were evaluated for 508 patients (< 65 years = G1: 323 patients, 65-74 years = G2: 127 patients, > 74 years = G3: 58 patients) with a computerised documentation system. RESULTS: 508 patients were treated on 42,123 days and revisited on 5572 controls. 30 patients were treated longer than 1 year (G1 21 patients, G2 6 patients, G3 3 patients). 143 patients were treated until death. 286 patients were treated on 19,448 days with oral morphine. (G1: 1712 days; G2: 3645 days; G3: 2364 days). Geriatric patients (G3) received significantly higher doses of morphine than younger patients. Adjuvant drugs were given on 81% of treatment days (G1 84%, G2 75%, G3 75%). Incidence and intensity of side effects were not increased in older patients with the exception of urinary disorders. CONCLUSIONS: Geriatric patients with cancer pain can be treated as effectively according to WHO-Guidelines as younger patients. In our study patients in the old age group received significantly higher doses of oral morphine. When analgesic drugs are titrated according to individual needs, side effects are not more frequent or severe than in younger patients.

Administration, Oral↗

PubMed2000

Treatment of severe low back pain with opioids during pregnancy in a patient with incomplete tetraplegia.

We report a case of severe low back pain during pregnancy in a woman with incomplete tetraplegia due to viral myelitis. The pain was interpreted as a radiculopathy in the presence of multiple herniated discs. Surgical intervention was not indicated and physiotherapy failed; therefore, a symptomatic drug treatment with oral analgesics was initiated. To minimise the total daily opioid dosage and the potential risk of a neonatal withdrawal syndrome due to opioids, the route of administration was changed from oral to epidural. Adequate pain relief was maintained with this regimen until caesarean section was necessary. The neonatal withdrawal symptoms after delivery were mild. Residual pain slowly diminished after delivery and the patient was able to discontinue opioid therapy. The aetiology of low back pain remains unclear and may be multifactorial.

Adult↗

PubMed2000

Constipation and the use of laxatives: a comparison between transdermal fentanyl and oral morphine.

Constipation and the use of laxatives were investigated in patients with chronic cancer pain treated with oral morphine and transdermal fentanyl in an open sequential trial. Forty-six patients were treated with slow-release morphine 30-1000 mg/day for 6 days and 39 of these patients were switched to transdermal fentanyl 0.6-9.6 mg/day with a conversion ratio of 100:1. Median fentanyl doses increased from 1.2 to 3.0 mg/day throughout the 30-day transdermal treatment period. Twenty-three patients completed the study. Two patients died from the basic disease while treated with transdermal fentanyl, 12 patients were excluded for various reasons, and not enough data for evaluation were available for two patients. Mean pain intensity decreased slightly after conversion although the number of patients with breakthrough pain or requiring immediate-release morphine as a rescue medication was higher with transdermal fentanyl. The number of patients with bowel movements did not change after the opioid switch but the number of patients taking laxatives was reduced significantly from 78-87% of the patients per treatment day (morphine) to 22-48% (fentanyl). Lactulose was used mainly and was reduced most drastically, but other laxatives were also used less frequently. In this study transdermal fentanyl was associated with a significantly lower use of laxatives compared to oral morphine. The difference in the degree of constipation between the two analgesic regimens should be confirmed in a randomized double-blind study that takes into account both constipation and use of laxatives.

Administration, Cutaneous↗