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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 307 records · Page 17Linked to original sources
PubMed1996

Microinjection technique for pharmacological evaluation of microvascular permeability in human skin.

A new technique which combines skin microinjection of minute amounts of drugs (0.5 microliter) and measurement of capillary permeability by intravital fluorescence videomicroscopy and densitometry is introduced. Glass micropipettes with a tip diameter of 7-9 microns are inserted by a micromanipulator into the stratum papillare containing the capillary loops and used for microinjection by microsyringe and special dispenser. Transcapillary diffusion of sodium fluorescein applied by intravenous bolus injection is visualised by fluorescence videomicroscopy and stored on videotape. Perivascular fluorescent light intensity (FLI) is measured in arbitrary units (AU) by videodensitometry around the site of microinjection during playback of the videotapes. The method was tested by microinjection of 0.5 microliter histamine (1% solution) at the distal tibial plateau. Mean FLI values representing microvascular permeability were 2186 AU 10 min after microinjection of histamine, 420 AU after physiologic saline and 1228 AU after histamine combined with oral intake of 20 mg cetirizine. Cetirizine significantly reduced (P < 0.01) the increased permeability induced by histamine. However, the mean values after injection of the H1-blocker were still significantly enhanced (P < 0.01) when compared to the mean values observed after injection of physiologic saline solution, which provoked only minor microtrauma. The technique offers new scope for pharmacological testing in man.

Adult↗
PubMed1996

A sequential analysis of the mother-adolescent interactions of ADHD, ADHD/ODD, and normal teenagers during neutral and conflict discussions.

The sequential interactions of three groups of teenagers conversing with their mothers during both neutral and conflict discussion situations were evaluated. Groups consisted of (1) attention deficit hyperactivity disorder (ADHD) alone (n = 21), (2) ADHD with comorbid oppositional defiant disorder (ADHD/ODD; n = 40), and (3) a community control group of adolescents (n = 49). All groups had been followed concurrently for the past 8 to 10 years before being reevaluated in this study. Results indicated that (1) teens and parents in all groups interacted in a tightly linked manner, with the behavior of each member being significantly related only to the immediate antecedent behavior of the other; (2) mothers in all groups were more likely than teens to initiate positive behaviors; (3) teen interactions could be characterized as tit-for-tat while mothers could be typified as be-nice-and-forgive; (4) mother-teen dyads in the ADHD/ODD group displayed significantly higher rates of conflict behaviors than dyads in the other two groups, who did not differ significantly from each other on most measures; and (5) mothers in the ADHD/ODD group responded in a manner similar to their teens (greater negativity) and less like that of mothers in the other groups. The majority of conflict between ADHD children and their parents seemed due to comorbid ODD and such ODD is a family, not just a teen, characteristic.

Adolescent↗
PubMed1996

Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat.

OBJECTIVE: Successful resuscitation of the brain requires complete microcirculatory reperfusion, which, however, may be impaired by activation of blood coagulation after cardiac arrest. The study addresses the question of whether postischemic thrombolysis is effective in reducing cerebral no-reflow phenomenon. DESIGN: 14 adult normothermic cats were submitted to 15-min cardiac arrest, followed by cardiopulmonary resuscitation (CPR) and 30 min of spontaneous recirculation. The CPR protocol included closed-chest cardiac massage, administration of epinephrine 0.2 mg/kg, bicarbonate 2 mEq/kg per 30 min, and electrical defibrillation shocks. INTERVENTIONS: During CPR, animals in the treatment group (n = 6) received intravenous bolus injections of 100 U/kg heparin and 1 mg/kg recombinant tissue type plasminogen activator (rt-PA), followed by an infusion of rt-PA 1 mg/kg per 30 min. MEASUREMENTS AND RESULTS: Microcirculatory reperfusion of the brain was visualized by labeling the circulating blood with 300 mg/kg of 15% fluorescein isothiocyanate albumin at the end of the recirculation period. Areas of cerebral no-reflow--defined as the absence of microvascular filling--were identified by fluorescence microscopy at eight standard coronal levels of forebrain, and expressed as the percentage of total sectional area. One animal in the treatment group was excluded from further analysis because of intracerebral hemorrhage due to brain injury during trepanation. Autopsy revealed the absence of intracranial, intrathoracic, or intra-abdominal bleeding in all the other animals. In untreated animals (n = 8), no-reflow affected 28 +/- 13% of total forebrain sectional areas, and only 1 out of 8 animals showed homogenous reperfusion (i.e., no-reflow < 15% of total forebrain sectional areas). Thrombolytic therapy (n = 5) significantly reduced no-reflow to 7 +/- 5% of total forebrain sectional areas and all treated animals showed homogenous reperfusion at the microcirculatory level. CONCLUSIONS: The present data demonstrate that thrombolytic therapy improves microcirculatory reperfusion of the cat brain when administered during reperfusion after cardiac arrest.

Animals↗
PubMed1996

Radial cortical and trabecular bone densities of men and women standardized with the European Forearm Phantom.

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P > 0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P < 0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe.

Absorptiometry, Photon↗
PubMed1996

A randomized controlled trial of postoperative nasogastric tube decompression in gynecologic oncology patients undergoing intra-abdominal surgery.

OBJECTIVE: To evaluate the effect of nasogastric decompression after extensive intra-abdominal surgery in gynecologic oncology patients. METHODS: Over a 1-year period, 110 gynecologic oncology patients undergoing extensive intra-abdominal surgery were enrolled in a randomized controlled trial of postoperative nasogastric tube versus intra-operative orogastric tube decompression. RESULTS: The nasogastric and orogastric groups were similar in age, case distribution, surgery length, and blood loss. The nasogastric group had significantly longer times to first passage of flatus and tolerance of a clear liquid diet than did the orogastric group. However, both groups were similar in time to tolerance of a regular diet and hospital stay. On average, the nasogastric tube was maintained for 3.2 +/- 2.1 days (range 1-8) after surgery. The average daily nasogastric output was 440 +/- 283 mL (range 68-1565). No patient in the orogastric group required a nasogastric tube postoperatively, but one patient in the nasogastric group had a nasogastric tube reinserted for recurrent nausea and vomiting. Use of a nasogastric tube led to significantly more subjective complaints, eg, ear pain, painful swallowing, and nasal soreness, but did not significantly reduce the incidence of abdominal distention or nausea and vomiting. Major complications, eg, pneumonia, atelectasis, gastrointestinal bleeding, and wound breakdown or infection, occurred equally in both groups. However, the incidence of febrile morbidity was significantly greater in the nasogastric group. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematological indices and electrolytes were comparable in both groups. CONCLUSION: Postoperative nasogastric tube decompression in gynecologic oncology patients undergoing extensive intra-abdominal surgery does not appear to provide any substantial benefit but significantly increases patient discomfort. As a result of this study, we have eliminated postoperative nasogastric decompression except in highly selected circumstances, such as extensive bowel surgery in patients with prior irradiation or substantial edema from bowel obstruction.

Female↗
PubMed1996

Volume expansion during cardiopulmonary resuscitation reduces cerebral no-reflow.

Resuscitation of the brain after cardiac arrest requires homogeneous blood recirculation which, however, may be impaired by low reperfusion pressure, intravascular coagulation, increased blood viscosity and endothelial cell swelling. Intravascular volume expansion induced by intravenous infusion of a small volume of hypertonic solution has previously been shown to improve nutritional flow to the brain after severe hemorrhage shock. We therefore investigated whether this therapy also improves cerebral reperfusion after cardiopulmonary resuscitation. Fourteen adult normothermic cats were resuscitated after 15 min of ventricular fibrillation by closed-chest cardiac massage in combination with epinephrine, bicarbonate and DC-defibrillations. Eight animals were submitted to the standard resuscitation protocol. Six cats received additionally 2 ml/kg/10 min 7.5% NaCl/6% hydroxyethyl starch solution for post-ischemic volume expansion. EEG, ECG, CBF, and the aortic, left ventricular, central venous and intracranial pressures were monitored. Reperfusion of the brain was visualized 30 min after cardiac resuscitation by labelling the circulating blood with fluorescein isothiocyanate albumin. Areas of impaired brain reperfusion (no-reflow)-defined by the absence of microvascular filling-were identified by fluorescence microscopy at eight standard coronal levels of the forebrain, and expressed as percent of total sectional area. All animals were successfully resuscitated although volume expansion decreased myocardial and cerebral reperfusion pressure during cardiopulmonary resuscitation. Treatment with hypertonic solution increased serum osmolality transiently and prevented hemoconcentration throughout the experiment. Cerebral no-reflow was significantly reduced from 28 +/- 13% to 15 +/- 6% of total forebrain sectional area. Volume expansion by small volume hypertonic solutions may, therefore, improve recovery of brain function following cardiac arrest.

Animals↗
PubMed1996

Bilateral skeletonized mammary artery grafting: experience with 560 consecutive patients.

OBJECTIVE: To test the hypothesis that the skeletonized technique of harvesting the internal thoracic artery improves the surgical results of bilateral internal thoracic artery grafting, we reviewed our 7-year experience with this technique. METHODS: Between July 1987 and December 1994, 560 patients received bilateral internal thoracic artery grafts and 236 additional grafts (average 2.6 +/- 0.6 anastomoses per patient). There were 515 men (92%) and the average age was 56.9 +/- 8.8 years. There were 63 diabetic patients (11.3%). During harvesting, the internal thoracic arteries were always totally skeletonized from the surrounding tissues without the use of electrocautery. RESULTS: Postoperative complications included reoperation for bleeding, 17 patients (3%), phrenic nerve paresis, 17 patients (3%), acute respiratory distress syndrome, 9 patients (1.6%), digestive complications, 8 patients (1.4%), neurologic complications, 6 patients (1.1%), and sternal complications, 6 patients (1.1%). No wound complications were observed in diabetic patients. The hospital mortality rate was 1.6% (9 patients, 2 cardiac causes). The early patency of internal thoracic artery grafts was 97.9%. Follow-up averages 29 +/- 20 months. There were 14 late deaths (4 cardiac causes). Angina recurred in 51 patients and the maximal stress test was abnormal in 47 patients. CONCLUSION: Bilateral internal thoracic artery grafting with skeletonized harvesting carried low post-operative mortality and morbidity and therefore it could be applied routinely without the fear of increased complication rate.

Adult↗
PubMed1996

A vector for expressing foreign genes in the brains and hearts of transgenic mice.

An expression plasmid (MoPrP.Xho), for use in transgenic mice, was developed from the promoter, 5' intronic, and 3' untranslated sequences of the murine prion protein gene. Analyses of mice harboring the MoPrP.Xho construct with cDNA genes encoding the amyloid precursor protein (APP) and human presenilin 1 demonstrated that this vector provides relatively high levels of transgene-encoded polypeptides in brains and hearts of transgenic mice. The MoPrP.Xho vector should be very useful in strategies designed to overexpress a variety of wild-type and disease related mutant transgenes in the heart and brain.

Amyloid beta-Protein Precursor↗
PubMed1996

Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study.

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.

Adolescent↗
PubMed1996

Cyclandelate in the prophylaxis of migraine: a randomized, parallel, double-blind study in comparison with placebo and propranolol. The Study group.

Cyclandelate inhibits calcium-induced contraction of vascular smooth muscle cells, platelet aggregation induced by thrombin, platelet-activating-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelate may have a potential prophylactic effect in migraine. To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol. After a 4-week baseline period, eligible patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate (n = 81), placebo (n = 55) or 120 mg propranolol (n = 78). The number of migraine attacks (> or = 50% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylactic treatment. The percentage of patients with a reduction in migraine attacks of > or = 50% treated with cyclandelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; p > 0.025). The mean duration of migraine in hours (h) per month decreased in both active treatment groups (cyclandelate: 36.8 h, p = 0.046; propranolol: 34.4 h, p = 0.039) compared to placebo (13.7 h) without reaching statistical significance (alpha/2 = 0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences were reported by 13 patients (16.0%) treated with cyclandelate, by 5 patients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% (n = 6) of patients treated with cyclandelate and in 9% (n = 7) of patients treated with propranolol. In summary, cyclandelate has a comparable efficacy to that of propranolol, an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated.

Adult↗
PubMed1996

Identification of single amino acid residues of human IL-6 involved in receptor binding and signal initiation.

The pleiotropic cytokine interleukin-6 (IL-6) has been predicted to be a protein with four antiparallel alpha-helices. On target cells, IL-6 interacts with a specific ligand binding receptor subunit (IL-6R), and this complex associates with the signal-transducing subunit gp130. Human IL-6 acts on human and murine cells, whereas murine IL-6 is only active on murine cells. The construction of chimeric human/murine IL-6 proteins has allowed us to define a region (residues 77-95, region 2c) within the human IL-6 protein that is important for IL-6R binding and a region (residues 50-55, region 2a2) that is important for IL-6R dependent gp130 interaction. Guided by sequence alignment and molecular modeling, we have constructed several IL-6 variants with point mutations in these regions and have tested them for receptor binding and signal initiation. Within region 2c, phenylalanine 78 was involved in receptor binding, whereas lysine 54 within region 2a2 participated in gp130 activation. Furthermore, some IL-6 variants with lysine 54 replacements could be used to construct muteins that retained receptor binding but failed to activate gp130. Such IL-6 muteins were efficient IL-6 receptor antagonists.

Amino Acid Sequence↗
PubMed1996

Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by evoked potentials.

The aim of this study was to see if an analgesic effect of subanaesthetic concentrations of isoflurane could be detected with evoked potentials elicited by nociceptive stimuli. We studied 10 healthy volunteers breathing three steady-state subanaesthetic concentrations of isoflurane (0.08, 0.16 and 0.24 vol% end-tidal). Reaction time, subjective pain intensities and evoked vertex potentials to laser (LEP) and electrical (SEP) stimuli were recorded and compared with auditory evoked potentials (AEP). Compared with baseline, the subanaesthetic concentrations of isoflurane did not change the latencies of the evoked potentials, but caused a significant reduction in the amplitudes of the LEP and SEP at 0.16 and 0.24 vol% and of the AEP at all three concentrations. There were no changes in perceived pain intensity, and isoflurane produced similar reductions in evoked potentials elicited by both nociceptive and non-nociceptive stimuli. The reaction time was increased significantly at 0.24 vol% isoflurane. The results demonstrated that subanaesthetic isoflurane concentrations caused similar changes in evoked potentials with both painful and non-painful stimuli, with no effect on perceived pain intensity.

Acoustic Stimulation↗
PubMed1996

Fuzzy logic control of inspired isoflurane and oxygen concentrations using minimal flow anaesthesia.

In order to evaluate the performance of feedback fuzzy logic control of inspired oxygen and isoflurane concentrations, we studied 30 patients undergoing discectomy for lumbar (n = 26) or cervical (n = 4) disc herniation. Patients were allocated random to one of two groups: a standard group (n = 15) with low flow anaesthesia (1.2-1.3 litre min-1) and manual control of gas concentrations; and a fuzzy group (n = 15) with minimal flow (0.5 litre min-1) and fuzzy logic feedback control of gas concentrations. Fuzzy logic control achieved and maintained very accurately the desired isoflurane concentration. Oxygen concentration was controlled more precisely than in the standard group. Delivery and costs of oxygen and nitrous oxide were significantly lower in the fuzzy group (P < 0.01). Accumulation of foreign gases was observed in one patient during low flow and in 11 patients during minimal flow anaesthesia. In conclusion, fuzzy logic control of inspired oxygen and isoflurane concentration during minimal flow anaesthesia was reliable and reduced anaesthetic gas delivery and costs.

Adult↗
PubMed1996

Psychophysical and electrophysiological responses to experimental pain may be influenced by sedation: comparison of the effects of a hypnotic (propofol) and an analgesic (alfentanil).

Sedation may influence the responses of some experimental pain models used to test analgesic efficacy. In this study we compared the effects of a sedative (propofol) and analgesic (alfentanil) on: nociceptive reflex to single and repeated electrical stimulations; mechanical pressure pain; and evoked potentials elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation. We studied 12 healthy volunteers with two subanaesthetic concentrations of propofol and two analgesic concentrations of alfentanil. Both propofol and alfentanil increased the threshold for nociceptive reflex to single electrical stimulations, but only alfentanil increased the threshold for nociceptive reflex to repeated electrical stimulations. The pressure pain tolerance thresholds were increased significantly by alfentanil, whereas propofol significantly decreased the thresholds (hyperalgesia). Propofol and alfentanil induced similar reductions in the amplitudes of the evoked potentials elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation, whereas only alfentanil reduced the perceived pain to nociceptive stimulations. We have shown that sedation can influence both the psychophysical and electrophysiological responses of some experimental pain tests used to measure analgesic efficacy, and that propofol in subhypnotic doses, has no analgesic effect on painful electrical and heat stimulations, but has a hyperalgesic effect on mechanical pressure pain.

Adult↗
PubMed1996

Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States.

BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS: We performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection. RESULTS: There were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness. CONCLUSIONS: We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

Child↗