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Biomedical subjects

P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 145 records · Page 8Linked to original sources
PubMed1994

The effects of selective opioid antagonists on somatosensory evoked potentials during relative cerebral ischemia in rats.

Hemorrhagic hypotension in spontaneously hypertensive rats induces attenuation of somatosensory evoked potentials. In this model of relatively mild cerebral ischemia, our previous studies have shown that naloxone stereospecifically enhances the evoked potentials, without changes in cortical blood flow. The high dose of naloxone needed to enhance the evoked potentials suggests that the attenuation is mediated by low affinity opioid receptors (delta or kappa). In the present study, we used this model to study the effects of naloxone-methobromide (5 mg kg-1, a quaternary derivative of naloxone with selective peripheral action when injected intravenously), MR 2266 (1 mg kg-1, a kappa receptor antagonist), and naloxone (5 mg kg-1) as well as saline injection (as control) in four different groups of rats. Following injection, we examined the changes in somatosensory evoked potentials, cortical blood flow and heart rate for 15 min while mean arterial pressure was held constant by a pressure-regulating reservoir. Only naloxone changed the somatosensory evoked potential amplitude significantly compared with the saline group in which no effect was seen. However, there was a tendency for a delayed effect of naloxone-methobromide on the evoked potentials, possibly indicating that the substance slowly passes the blood-brain barrier. Naloxone and MR 2266 caused a transient decrease in heart rate, while following naloxone-methobromide injection there was a slight increase in heart rate. Our results thus indicate that the beneficial effects of naloxone on somatosensory evoked potentials during relative cerebral ischemia may be centrally mediated by a non-kappa mechanism.

Animals↗
PubMed1994

H2O2-induced oxidative injury in rat cardiac myocytes is not potentiated by 1,1,1-trichloroethane, carbon tetrachloride, or halothane.

Free radical-induced oxidative stress has been linked to ischemia-reperfusion injury of the myocardium. The .OH radical is considered the most damaging radical and can be increased in cells by treatment in vitro with H2O2. The purpose of the present study was to determine if aliphatic halocarbons enhance H2O2-induced oxidative injury in isolated cardiac myocytes from neonatal rats. Oxidative damage was assessed by measuring release of thiobarbituric acid-reactive substances (TBARS) from lipid peroxidation, loss of lactate dehydrogenase (LDH) through damaged sarcolemmal membranes, and alterations in intracellular calcium ([Ca2+]i) transients in electrically stimulated (1 Hz, 10 ms, 60 V) myocytes. H2O2 increased TBARS release and LDH leakage in a concentration-dependent (20-200 microM) manner. Continuous suffusion with H2O2 first altered the configuration of [Ca2+]i transients, then eliminated them, and finally caused [Ca2+]i overload (basal [Ca2+]i exceeded peak systolic [Ca2+]i of control). The time to [Ca2+]i overload was inversely associated with concentration, and the shortest time to overload was obtained with 100 microM H2O2. A 1-h preincubation of myocytes with the iron chelator deferoxamine inhibited all effects of H2O2. 1,1,1-Trichloroethane, carbon tetrachloride, or halothane at 1 mM significantly and reversibly reduced [Ca2+]i transients but did not influence TBARS release or LDH leakage. Simultaneous exposure of myocytes to H2O2 and halocarbons did not affect the myocyte response to H2O2 exposure. Results indicate that the three halocarbons tested do not enhance H2O2-induced oxidative injury in isolated cardiac myocytes.

Animals↗
PubMed1994

[Change in the management of per-subtrochanteric femoral fractures--a retrospective 10 year analysis].

Surgical therapy of per- and subtrochanteric femur fractures is vital and unquestionable. Several competing osteosynthesis procedures are available. 298 of our patients were operated on during the past decade, the mean age of the total number of patients being 74 years. With an average mortality rate of 8.7% the mean length of hospitalisation was 30 days. 151 Ender nailings versus 120 DHS osteosyntheses were performed. The retrospective analysis shows the superiority of the dynamic hip screw, which exhibits significantly fewer complications and has replaced the other methods. This has resulted in a change in therapy in the treatment of this type of fracture.

Adult↗
PubMed1993

Prognostic significance of benign proliferative breast disease.

BACKGROUND: Recent studies concerning an association between benign breast diseases and risk of subsequent breast cancer have focused on benign proliferative lesions recognized in biopsy specimens. Some have implicated atypical hyperplasia as being associated with the greatest risk. METHODS: The histologic sections of specified benign breast lesions from 1799 women were reviewed and reclassified, using published criteria for proliferative disease. Prognostic significance was assessed by relating the pathologic findings to the development of breast cancer observed during an average 21 years of follow-up, in which time 157 women developed the disease. RESULTS: Benign proliferative changes were recognized in 85% of the patients, with a corresponding relative risk of subsequent carcinoma equal to 2.2 times population rates (95% confidence limits, 1.9 and 2.6). Increasing levels of hyperplasia and atypia in lobules or ducts were associated with modest increases in risk, ranging from 2.1 to 2.3 to 3.0 for proliferative changes with no atypia, mild atypia, and moderate to severe atypia, respectively. This trend was not statistically significant. The most significant risk indicators in this study were the presence of adenosis (relative risk, 3.7), and moderate or severe atypia in ducts (relative risk, 3.9). CONCLUSIONS: Benign proliferative breast disease recognized in biopsy specimens is associated with an increased risk of future breast cancer, but fine distinctions among levels of hyperplasia and atypia did not significantly distinguish risk among patients in this study.

Adolescent↗
PubMed1993

Reproducibility and validity of pathologic classifications of benign breast disease and implications for clinical applications.

BACKGROUND: Research studies on the relationship between benign breast diseases and cancer risk typically identify certain conditions as risk factors, and others as carrying no prognostic significance. This study addresses several issues concerning the relevance of such research results for advising individual patients in a clinical setting. METHODS: Data were obtained as part of a "blinded" retrospective pathology review of benign breast biopsies. A random sample of cases was reviewed twice, providing information about reliability. Comparisons with diagnoses that used information from the operative reports and gross pathology descriptions as well as microscopic histology were used to assess validity. RESULTS: Among cases that were reviewed twice, excellent agreement was achieved for diagnosing carcinoma and lobular neoplasia, good agreement for adenosis and intraductal papilloma, and relatively poor agreement about levels of hyperplasia and atypia, and whether ducts or lobules were involved. Distinctions among levels of hyperplasia also apparently were influenced by the number of slides available for review. The "blinded" review diagnoses frequently differed from the diagnoses that used all information available at the time of surgery in detecting the presence or absence of gross cystic disease, and in distinguishing solitary from multiple papillomas. CONCLUSIONS: Problems with reliability of precise distinctions among levels and sites of hyperplasia and atypia seem to limit the usefulness of such classifications as guidelines for individual patient care. For conditions with some clinical manifestations, diagnoses based exclusively on histologic review of biopsy specimens often are not accurate.

Breast↗
PubMed1993

Comparison of clearance and metabolism of infused cholecystokinins 8 and 58 in dogs.

BACKGROUND: Cholecystokinin (CCK) 58 is the predominant molecular form of CCK in canine and human intestine and circulating blood. There is no report on the metabolism and clearance rate of CCK-58. The aim of this study was to compare the in vivo half-life and metabolism of CCK-58 with that of synthetic CCK-8. METHODS: CCK-58 was purified from canine intestine by consecutive high-performance liquid chromatographic (HPLC) and fast protein liquid chromatographic steps. The peptides were given to 12 dogs as an intravenous (IV) bolus injection to determine the half-life of circulating CCK. Six dogs were given CCK-58 or CCK-8 as a constant IV infusion to determine plasma clearance rates and stability in circulating blood. Circulating molecular forms of CCK were determined by radioimmunoassay after extraction of CCK from plasma and characterization by HPLC. RESULTS: The half-life of CCK-58 was 4.4 +/- 0.6 minutes compared with 1.3 +/- 0.1 minutes for CCK-8. Less than 5% of CCK-58 could be detected as smaller forms during constant IV infusion. CONCLUSIONS: The longer half-life of CCK-58 compared with CCK-8 and the minimal conversion into smaller forms during constant IV infusion are consistent with the finding that CCK-58 is not only the major stored form but also the circulating form of CCK after endogenous stimulation in dogs.

Animals↗
PubMed1993

Cerebrospinal fluid dynorphin-converting enzyme activity is increased by voluntary exercise in the spontaneously hypertensive rat.

The activity in cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) has been studied after voluntary exercise in the spontaneously hypertensive (SH) rat. The exercise consisted of spontaneous running in wheels for 4-5 weeks and the average running distance during the last two weeks was 4.0 km/24h. CSF samples were obtained under anaesthesia from the cisterna magna after penetration of the atlanto-occipital membrane. DCE transforms the members of the dynorphin family of opioid peptides into Leu-enkephalin-Arg6. In the present investigation a radioimmunoassay was used for quantitation of Leu-enkephalin-Arg6 release from dynorphin A1-17 and dynorphin B1-13. The rats that were running had a DCE activity (vs. both substrates) in CSF that was approximately 6-12 times higher than in animals not given the running opportunity. A statistically significant correlation between the two prodynorphin-derived substrate peptides was found in terms of DCE activity. We therefore propose that a single enzyme activity may be responsible for the hydrolysis of dynorphin B1-13 and dynorphin A1-17. Furthermore, a significant correlation was also found between running activity and DCE activity 12-14 h before the CSF was withdrawn. Besides measurement of DCE activity by radioimmunoassay, the formation of Leu-enkephalin-Arg6 was identified by reversed-phase micro-column liquid chromatography and plasma desorption mass spectrometry. The experiment shows that voluntary exercise affects opioid peptidergic mechanisms.

Amino Acid Sequence↗
PubMed1993

The Hoffmann-Tinel sign. 1915.

The aim of this article is to show that the well-known Tinel sign is really a Hoffmann-Tinel sign. The translation of the two papers of Hoffmann, published in the same year that Tinel wrote his article (1915), is completed by a short biography of Paul Hoffmann.

Germany↗
PubMed1993

Protection from reperfusion-induced arrhythmias by polyethylene glycol 600.

The effects of polyethylene glycol (PEG) 600 on cardiovascular parameters and reperfusion-induced arrhythmias were investigated using a 5-min period of ligation of the left anterior descending coronary artery followed by reperfusion in an anaesthetized open-chest rat model. PEG 600 was effective in reducing reperfusion arrhythmias, such as ventricular fibrillation and ventricular tachycardia. Mortality was decreased from 29.4% (5/17) in the saline-control to 0% (0/14) in the PEG-treated group (P < 0.05). Biochemical investigations during the ischaemia/reperfusion period revealed that PEG infusion resulted in a reduction of cardiac lactate as well as a striking maintenance of the glutathione content of the heart.

Animals↗
PubMed1993

Pathology of benign and malignant kidney tumors.

This article includes brief discussions of several renal parenchymal neoplasms. Gross and histologic findings are described. New techniques that can provide diagnostic and prognostic information are summarized where applicable.

Adenoma↗
PubMed1993

Alterations by a thromboxane A2 analog (U46619) of calcium dynamics in isolated rat cardiomyocytes.

The mechanism by which thromboxane A2 (TXA2) causes its detrimental actions on the myocardium during ischemia and reperfusion injury is unknown. The present study was designed to investigate the influence of U46619, a stable TXA2 analog, on intracellular Ca transients in electrically stimulated single neonatal rat ventricular myocytes by using spectrofluorometric analysis of fura-2-Ca binding. Administration of U46619 increased basal and peak Ca concentrations as well as width of electrically induced Ca transients in a concentration-dependent manner (0.1-1 microM) during a 1-hr exposure. Exposure to 10 microM U46619 caused irregular Ca transients and a marked increase in cytosolic-free Ca concentration. The effects of U46619 were antagonized by the TXA2 receptor antagonist SK&F95585 (2 microM), dibutyryl cyclic AMP (1 mM), verapamil (1 microM) and ryanodine (1 microM). U46619 did not affect the increase in cytosolic Ca induced by KCl (90 mM) depolarization. Caffeine (10 mM)-induced Ca release from the sarcoplasmic reticulum was enhanced markedly in U46619-treated cells. Significant lactate dehydrogenase leakage from the myocytes did not occur at 1 to 10 microM U46619. These results indicate that the increase in Ca transients by U46619 is a receptor-mediated process leading to a Ca accumulation in the sarcoplasmic reticulum which is likely to be responsible for an enhanced cytosolic Ca during excitation-contraction coupling. Thus, the identification of U46619-induced alterations of Ca dynamics appears to provide, at the cellular level, a direct role for TXA2 during myocardial ischemia and reperfusion.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Decrease of epinephrine-induced arrhythmia threshold in ethanol exposed rats.

An association between cardiac arrhythmias and ethanol use has been observed for some time. The sympathetic nervous system presumably plays an important role in the manifestation of cardiovascular ethanol responses. Therefore, we investigated the effects of ethanol treatment on epinephrine-induced arrhythmias. Female Wistar rats received 10 vol% ethanol or 2.5% glucose (control group) in their drinking water for 45 days. In ether anesthetized animals of both groups epinephrine (10 micrograms/kg.min) was infused via a lateral tail vein. The threshold dose for arrhythmias after epinephrine infusion (mainly 2nd and 3rd degree AV-blocks) was reduced beginning 2 days after the start of the ethanol treatment and the incidence of AV-blocks during epinephrine infusion was increased. During the ethanol treatment the prohypertensive epinephrine effect was slightly increased. The reflex bradycardia was not changed after repeated epinephrine infusion by ethanol treatment, whereas it was nearly abolished in the control group. No blood ethanol could be detected during the time of epinephrine infusion (9-12 a.m.), but determinations at 11 p.m. yielded a concentration of 0.13 +/- 0.02 mg/g. The results show that the epinephrine-induced bradyarrhythmia threshold is reduced and the frequency of arrhythmic events is augmented in rats exposed to ethanol in the drinking fluid.

Animals↗
PubMed1992

Calcium transients in isolated cardiac myocytes are altered by 1,1,1-trichloroethane.

1,1,1-Trichloroethane is a widely used solvent that is annually linked to several cases of sudden death following accidental exposure or abuse. Sudden death is believed to be due to ventricular fibrillation or myocardial depression. The purpose of this study was to investigate the mechanism of myocardial depression by assessing the influence of 1,1,1-trichloroethane on intracellular Ca transients in single neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2-Ca binding. Cells were exposed to 1,1,1-trichloroethane in Hanks' balanced salt solution aliquoted as a 0.2% DMSO solution by a single pass suffusion in an environmentally controlled chamber. 1,1,1-Trichloroethane (0.25 mM-8 mM) reduced the height of electrically (1 Hz, 60 V, 10 ms) induced Ca transients concentration dependently and reversibly to a maximum of about 50% with no effect on diastolic Ca concentration. Video motion analysis revealed an inhibition of contractility in the same concentration range. 1,1,1-Trichloroethane inhibited cytosolic Ca increase in response to KCl-induced (90 mM) depolarizations and further decreased the limited Ca transients in ryanodine (1 microM) pretreated myocytes. Increased external Ca (5 mM) antagonized the effect of 0.5 mM 1,1,1-trichloroethane on the Ca transients. 1,1,1-Trichloroethane reduced the caffeine (10 mM) releasable Ca pool in myocytes. These results show that 1,1,1-trichloroethane inhibits Ca mobilization during excitation-contraction coupling in ventricular myocytes. An inhibitory action on the influx of extracellular Ca as well as on sarcoplasmic reticulum Ca release and sequestration is likely to be responsible for this action.

Animals↗
PubMed1992

Effect of chronic ethanol consumption upon cardiovascular reactivity, heart rate and blood pressure in spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Clarification of the effect of chronic ethanol consumption upon cardiovascular reactivity in rats. DESIGN: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats were randomly allocated in groups of 10 to ethanol in tap water [20% (v:v) after the first week or tap water for 7-12 weeks]. METHODS: Intra-arterial blood pressure and heart rate were measured at rest and in response to vibration and noise stress. Vascular reactivity was assessed in isolated paired perfused hindquarters and in mesenteric arterioles in a Mulvany-Halpern myograph. RESULTS: Resting intra-arterial blood pressure but not heart rate was lower in both ethanol-treated groups. The ethanol treatment increased the SHR heart rate response to sudden noise but the WKY response did not increase. Pressor responses to noise were initially greater in the ethanol-treated SHR. The ethanol had no effect upon isolated perfused hindquarter resistance at maximal dilation, dose-response curves in response to noradrenaline or vasopressin, or maximal contractile strength. Isolated mesenteric arterioles showed that ethanol had no effect upon responses to nerve stimulation or upon the 50% effective dose required for a response to noradrenaline or vasopressin. CONCLUSIONS: Ethanol treatment heightened the heart rate reactivity to stress without substantially affecting vascular neuro-effector characteristics in SHR. This is likely to be a central effect, caused by suppression of the central nervous inhibitory systems that influence the heart rate and baroreflex activity in a strain of rat already showing evidence of an impaired ability to modulate the heart rate and blood pressure in response to stress. The small reduction in resting blood pressure may be a consequence of the lower weight in the ethanol-treated rats, and/or may reflect a direct depressing action by the alcohol on vascular and cardiac muscle. These findings are discussed in the context of ethanol-induced hypertension in humans and possible genetic variations in central nervous, cardiac and vascular effects.

Alcoholism↗
PubMed1992

In vitro and in vivo evaluation of BMY 45243, a new 5-amino-naphthyridone derivative.

BMY 45243 is the first representative of 5-amino naphthyridone derivatives prepared following a new methodology developed by the authors. BMY 45243 is a highly lipophilic compound, very active in vitro and in vivo on S. aureus and was found to be as potent as ciprofloxacin on Gram-negative organisms with identical in vivo activity against Pseudomonas aeruginosa. Pharmacokinetics in mice showed better AUC and Cmax and longer t1/2 for BMY 45243 than for sparfloxacin and ciprofloxacin.

Animals↗
PubMed1992

[Oncocytic tumors of the kidney apropos of 2 cases. Actualities in the preoperative diagnosis and therapeutic attitude].

The authors report two cases of renal oncocytoma treated by radical nephrectomy. There is still a controversy because the term oncocytoma is used for all tumors containing oncocytes, either true oncocytoma or adenocarcinoma with oncocytoma cells. The main problem is to distinguish, prior to surgery, between renal oncocytoma, a tumor with benign evolution, and renal adenocarcinoma with oncocytes, to offer conservative surgery for renal oncocytoma.

Adenoma↗
PubMed1992

[Therapy of acute lung failure with nifedipine. A study with interventional analysis].

In 24 patients with severe ARDS after major gastro-intestinal surgery the effect of the calcium antagonist nifedipine on pulmonary function was investigated. Besides descriptive statistics and comparison between group means, intervention analysis was employed to assess the treatment effect for the individual patient. The treatment effect could always be assessed after 12 hours. 14 out of 15 patients with initially high PVR showed a significant decrease of PVR followed by an improvement of AaDO2. 8 out of 9 patients with initially normal PVR did not improve in pulmonary function as no significant changes in PVR occurred. No unwanted side-effects on cardio-vascular function (MAP, CI, LVSWI, RVSWI) could be observed. 9 out of 24 patients decreased. Lethality among patients who showed a significant decrease of PVR under nifedipine infusion was 3 out of 15, whereas 5 out of 9 patients died without changes in PVR. Thus nifedipine can improve pulmonary function in ARDS. Especially in the early stages of ARDS with elevated PVR the administration of nifedipine p.i. appears advantageous.

Aged↗