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P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 91 records · Page 5Linked to original sources
PubMed1998

[W enterocystoplasty with resorbable staples: technic and functional results. Preliminary study].

INTRODUCTION: The use of absorbable staples for enterocystoplasty allows a marked reduction of the operating time. The long-term results on continence need to be evaluated at result term before adopting this technique. METHODS: Eight patients underwent "W" enterocystoplasty performed with absorbable staples according to the so-called "Detroit" technique, with direct uretero-ileal anastomosis. The continence of these patients was evaluated by clinical follow-up and urodynamic assessment (3 patients). Quality of life was studied by a questionnaire sent to the patient. RESULTS: The mean operating time was 5 hours 20 minutes, the plasty was performed in 25 to 35 minutes. The mean follow-up was 18.7 months, during which two uretero-ileal strictures were diagnosed. 7 of the 8 patients have a good diurnal continence (no leaks) and 1 patient has moderate continence (1 protection). Nocturnal continence was considered to be good in 3 cases, moderate in 2 cases and poor in 3 cases (> 1 protection). Four of the patients evaluated by questionnaire reported urinary disorders. CONCLUSION: The use of absorbable staples allows a definite reduction of the operating time, for a modes excess cost and satisfactory functional results.

Absorption↗
PubMed1998

Prevention of thrombosis and enhancement of thrombolysis in rabbits by SR 121787, a glycoprotein II/III antagonist.

SR 121566, a novel nonpeptide antiplatelet agent with high affinity and specificity for the GP IIb/IIIa complex, exhibits potent in vitro antiaggregating activity in rabbit platelets. This paper reports results from a study in rabbits about the efficacy and tolerability of SR 121787, the prodrug of SR 121566. After p.o. pretreatment with SR 121787, ADP-, arachidonic acid- and collagen-induced rabbit platelet aggregation was inhibited ex vivo in a dose-dependent manner (ED50 between 2.3 and 6.1 mg/kg). Collagen-induced thrombocytopenia was totally abolished by SR 121787 at 20 mg/kg p.o. In a carotid artery lesion model of arterial thrombosis, p.o. administration of SR 121787 resulted in a dose-dependent inhibition of thrombosis with a maximum effect of 68% (ED50 = 16.0 +/- 0.3 mg/kg). Recombinant tissue plasminogen activator-induced thrombolysis of a preformed thrombus in the jugular vein was potentiated by SR 121787 at doses between 1 and 6 mg/kg i.v. In an ear incision bleeding model, SR 121787 at doses up to 15 mg/kg p.o. did not cause an increase in blood loss. These results demonstrate that SR 121787 exerts oral antiplatelet, antithrombotic and thrombolysis-enhancing efficacy in rabbits. SR 121787 appears to be a promising compound for evaluation under clinical conditions in the therapy of acute coronary syndromes.

Animals↗
PubMed1998

SR 121787, a new orally active fibrinogen receptor antagonist.

The aim of this study was to describe the pharmacological properties of SR 121787, a new antiaggregating drug which is metabolized in vivo into SR 121566, a potent non-peptide antagonist of Gp IIb/IIIa. In vitro, SR 121566 antagonized the binding of [125I]-fibrinogen (IC50 = 19.8+/-6.3 nM) and of [125I]-L-692,884, an RGD-containing peptide (IC50 = 291+/-96 nM) to activated human platelets. SR 121566 inhibited the aggregation of human platelets induced by ADP, collagen, thrombin, arachidonic acid and PAF at concentrations lower than 0.1 microM. Adhesion of human platelets to adhesive proteins was inhibited by SR 121566 (IC50 = 40.3+/-2.5 nM) only when Gp IIb/IIIa and fibrinogen were involved. No effect was found with regard to other adhesive proteins and/or other integrins. SR 121787 demonstrated a potent and sustained antiaggregating effect when administered intravenously to baboons at a dose 50 microg/kg, and eight hours after the administration of 100 microg/kg, ADP-induced aggregation was still strongly inhibited (more than 80%). A single oral administration of 2 mg/kg of SR 121787 produced a nearly complete inhibition of platelet aggregation for up to 8 h (ED50 at 8 h = 193+/-20 microg/kg), a significant residual antiaggregating activity being still observed 24h after the administration. When administered orally to rabbits, SR 121787 exhibited a potent antiaggregating (ED50 = 2.3+/-0.3 mg/kg) and antithrombotic activity in an arterio-venous shunt thrombosis model (ED50 = 10.4+/-0.8 mg/kg). After oral and IV administration, SR 121787 was well tolerated suggesting that SR 121787, the most potent and long lasting orally active Gp IIb/IIIa antagonist described to date, is a promising antithrombotic compound.

Administration, Oral↗
PubMed1997

Organ culture of human lymphoid tissue. II. Marked differences in cytokine production and proliferation between slice and suspension cultures of human spleen.

Recently, we have established a method for the culture of human spleen slices in vitro. The procedure allows thin slices (200-350 microns) of human spleen to be cultured for up to 7 days. Using this method, we have previously established that unstimulated spleen slices spontaneously synthesize and secrete considerably higher levels of immunoglobulin than suspension cultures of the same tissue run in parallel. In this study, we report that there are also marked differences in the cytokine secretion profile between slices and suspensions and in their proliferative response. In brief, control and PHA-stimulated spleen slices secrete high levels of IL-1 beta, IL-6, IL-8 and IL-11 while the levels found in suspension supernatants are appreciably lower. By way of contrast, high levels of IL-2, IL-4, IL-10 and TNF alpha are found in suspension culture supernatants following PHA stimulation while the response in slice cultures is extremely low. These differences are also reflected in the results obtained at the cellular (intracellular cytokine) level. Additional studies reveal that spontaneous immunoglobulin production observed in spleen slices can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha and that the bulk of the IL-6 and IL-1 beta detected in culture supernatants represents de novo synthesis. Finally, the background and mitogen-stimulated proliferative response of tissue slices is meagre compared with that observed in spleen suspensions suggesting that proliferation in the former is held under strict control. Collectively, we believe that the tissue slice procedure described provides us with a system for studying integrated events in lymphoid tissues in vitro and evaluating immunomodulatory substances of potential clinical importance.

Adolescent↗
PubMed1997

The synthetic pentasaccharide SR 90107A/Org 31540 does not release lipase activity into the plasma.

The present study was designed to find out whether the synthetic pentasaccharide SR 90107A/Org 31540, which is presently being evaluated in clinical trials as an antithrombotic agent, influences lipoprotein metabolism in rats as determined by plasma triglyceride (TG) lipase activity. A comparison with three clinically used sulphated polysaccharides-unfractionated heparin (UFH), low molecular weight heparin (LMWH) and pentosan polysulphate (PPS)- was performed. UFH evoked a dose-dependent increase in plasma TG lipase activity which plateaued at doses > or = 1 mg/kg i.v.. PPS and LMWH demonstrated a lower efficacy than heparin at 0.3 and 1 mg/kg i.v., but the maximum lipase releasing effect at 3 mg/kg i.v. was identical for UFH, PPS and LMWH. SR 90107A/Org 31540 did not release TG lipase activity at single i.v. doses up to 3 mg/kg. Repeated-dose experiments with SR 90107A/Org 31540 (1 mg/kg s.c. for 9 days) revealed no influence on the lipase releasing effect of UFH (1 mg/kg i.v. on day 10). These results demonstrate that SR 90107A/Org 31540 does not influence lipid metabolism in rats through lipase release, suggesting that SR 90107A/Org 31540 may offer an advantage over UFH and LMWH in clinical situations where an anticoagulant/antithrombotic effect is desired, but both an increase in plasma free fatty acids and atherogenic alterations of lipoprotein metabolism are considered harmful.

Animals↗
PubMed1997

Transforming growth factor alpha-immunoreactivity in neural tissues of the rat stomach.

We report TGF alpha immunoreactivity in neurons of the myenteric plexus and in nerve fibers in the muscle and submucosal layers of the rat stomach. Association of TGF alpha staining nerve fibers to vessels and smooth muscle cells gives morphological evidence that EGF/TGF alpha's actions to increase mucosal blood flow and gastric motility may be mediated by TGF alpha derived from neural structures. These data suggest that TGF alpha plays a role in the neural control of the gastric function.

Animals↗
PubMed1997

[Active music therapy for chronic pain: a prospective study].

There are only few publications about the effect of music therapy on pain relief. The intention of this prospective study is to demonstrate the influence of the Nordoff/Robbins method of active music therapy in a group of 12 patients with fibromyalgia, myofascial pain syndromes and polyarthritis on pain reduction, life quality and coping. The clinical parameters of each patient were related to the observations in the audio- and video-documented music therapy settings and to the self-reported changes in pain intensity and pain behaviour. There was a significant reduction of pain intensity and pain-related disability in the music group compared to a control group, but no change in the depression and anxiety score. The influence of music therapy could be even better demonstrated in the systematic analysis of the single cases by individual profiles. Active music therapy affects especially the communicative and emotional dimension of chronic pain. Psychophysiological and psychodynamic models are presented to explain the effectiveness of music therapy on pain reduction. Clinical studies on music therapy as well as on other "art therapies" should relate the analysis of clinical parameters to the descriptive-phenomenological documentation of the therapeutic process to demonstrate systematically the influence of music and art in the individual case.

English Abstract↗
PubMed1997

Pathogenesis of non-traumatic atlanto-axial subluxation (Grisel's syndrome).

Non-traumatic atlanto-axial subluxation (AAS) is an uncommon complication of upper neck inflammatory processes and head and neck surgery. It is also known under the eponym of Grisel's syndrome (GS). We present a case report of a 6-year-old boy with GS that resulted from a retropharyngeal abscess. A diagnosis was not made until 2 months after the occurrence of infection. Re-evaluation of repeated CT scans of the neck showed the sequential development of AAS. These findings implied that the pathogenesis of GS is a distention of the ligaments between the atlas and axis rather than loosening of the ligaments caused by the spread of an inflammatory edema from the soft tissues of the neck as has been proposed by others.

Atlanto-Axial Joint↗
PubMed1997

Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis.

BACKGROUND & AIMS: There is indirect evidence that transforming growth factor alpha (TGF-alpha) is an important mediator of mucosal defense and repair. TGF-alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-alpha in preserving the integrity of the colon. METHODS: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wa-1 mice, and BALB/c mice. TGF-alpha was also administered intraperitoneally to wa-1 mice to evaluate the effect of exogenous TGF-alpha in DSS colitis. RESULTS: In response to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa-1 mice, compared with 22% in GC mice and 16% in BALB/ c mice. Body weight loss was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and Balb/c mice (12%). TGF-alpha application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls. CONCLUSIONS: The marked susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-alpha application in wa-1 mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms in the colon.

Animals↗
PubMed1997

Drug specific antibodies: T-cell epitope-lipopeptide conjugates are potent adjuvants for small antigens in vivo and in vitro.

To generate conventional or monoclonal antibodies for the serological detection of drugs, antibiotics, toxins and other low molecular mass substances, a suitable and effective adjuvant is needed. Lipopeptides derived from a major component of the bacterial cell wall constitute potent nontoxic and nonpyrogenic immunoadjuvants when mixed with conventional antigens. Here we demonstrate that the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl- serine (P3CS) coupled to a Th-cell epitope (P3CS-Th) can efficiently enhance the specific immune response against low molecular weight compounds in different species. In the presence of the synthetic lipopeptide P3CS-Th, the peptides which are per se non-immunogenic stimulated a specific humoral immune response in mice after intraperitoneal application. Mixtures containing adjuvants without the Th sequence showed no significant antibody induction. A marked enhancement of the humoral immune response was obtained with the low molecular mass antigens Iturin AL, Herbicolin A and Microcystin (MLR) coupled to poly-l-lysin (MLR-PLL), in rabbits and in chickens. Lipopeptide-Th cell epitope conjugates also constituted adjuvants for the in vitro immunization of either human mononuclear cells or mouse B-cells with MLR-PLL; after fusion of the immunized cultures with the heteromyeloma cell lines CB-F7 or the mouse myeloma cell line SP 2/0, respectively, we observed a significantly increased yield of antibody secreting hybridomas.

Adjuvants, Immunologic↗
PubMed1997

Duration and mechanisms of the increased natural cytotoxicity seen after chronic voluntary exercise in rats.

We have recently shown that in vivo natural cytotoxicity is enhanced after chronic exercise in spontaneously hypertensive rats (SHRs). In the present report, we have studied the duration of this augmentation and some possible mechanisms involved. Exercise consisted of voluntary running for 4-5 weeks, with the running distance ranging from 2.7-15.6 km day(-1) during the last week of running. In vivo cytotoxicity was measured as clearance of injected 51Cr-labelled YAC-1 lymphoma cells from the lungs. The in vivo natural cytotoxicity was increased in running SHRs, and also in SHRs that had their running wheel locked for 24 and 48 h prior to the experiment, and was still present after 96 h. The enhancement of in vivo cytotoxicity after 5 weeks of exercise was abolished after an acute injection of the beta-adrenergic receptor antagonist timolol (0.5 mg kg(-1) i.v.), indicating that catecholamines are involved in this augmentation. Interestingly, 24 h after the last exercise bout, the increased natural cytotoxicity could be blocked by timolol. The opioid receptor antagonist naloxone given subcutaneously for 7 days by osmotic pumps (6 mg kg(-1) h(-1)) could not reverse the increased in vivo cytotoxicity seen in the running SHRs, suggesting that opioid receptor mechanisms are not involved, or at least not the naloxone-sensitive mu-receptor. Natural immunity was not influenced by the histamine H2 receptor antagonist ranitidine, either in controls or in runners, indicating that the natural killer cell-regulatory effect of histamine is not present in SHRs and does not seem to be involved in the exercise-induced changes in natural immune function. We conclude that the augmentation of in vivo natural cytotoxicity after voluntary chronic exercise in rats is long-lasting and that the augmentation is partly mediated by beta-adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1997

A comparative study of guidewire electrical resistance.

OBJECTIVE: To evaluate the electrical resistance to current conduction of different guidewires used routinely in endourology and thus determine the risk of short circuits between the active electrode and the guide. MATERIALS AND METHODS: Using a standard resistance meter, the electrical resistance of four different types of guidewires was measured. Pure stainless-steel, polytetrafluoroethylene (PTFE)-painted, PTFE-sheathed and hydrogel-sheathed guidewires were tested, both when new and after mechanical abrasion of the external layer to reproduce their condition after use. RESULTS: The pure stainless-steel guidewire had no resistance to electrical current. The electrical insulation of the PTFE-painted guidewires was poor and was eliminated by mechanical abrasion of the paint. New PTFE-sheathed and hydrogel-sheathed guidewires had a safe electrical resistance (> 10 K omega) but this insulation was easily eliminated by mechanical abrasion of the external layer. CONCLUSIONS: To minimize the risk of electrosurgical adverse effects during a guidewire-assisted endoscopic procedure, the operator should preferably use a new guidewire for each procedure, use sheathed guidewires and ensure that the guidewire is in good condition, or cover it with a ureteric catheter, before applying current.

Electric Conductivity↗
PubMed1997

Antiplatelet and antithrombotic efficacy of SR 121787, a nonpeptide orally active GP IIb/IIIa antagonist, in rabbits: comparison with clopidogrel and aspirin.

Previous reports indicate that rabbits are not an appropriate species for testing glycoprotein (GP) IIb/IIIa antagonists because tested compounds caused only a weak inhibitory action on aggregation of rabbit platelets. SR 121566 is a novel low-molecular-weight antiplatelet agent with high affinity and specificity for the GP IIb/IIIa complex. In this study, SR 121566 exhibited a potent dose-dependent inhibition of adenosine diphosphate (ADP)-induced aggregation of rabbit platelets in vitro [median inhibitory concentration (IC50), 0.8 +/- 0.04 microM], whereas the GP IIb/IIIa antagonists SC 52012A and GR 144053F were devoid of antiplatelet activity. After oral administration of SR 121787, the prodrug of SR 121566, rabbit platelet aggregation ex vivo was inhibited in a dose-dependent manner [median effective dose (ED50) for ADP- arachidonic acid (AA)- and collagen-induced aggregation 2 h after gavage, 2.3 +/- 0.3, 6.1 +/- 0.9, and 2.5 +/- 0.4 mg/kg], a 58% inhibition of ADP-induced platelet aggregation being still observed 6 h after single oral treatment with 20 mg/kg. In an arteriovenous-shunt model, oral administration of SR 121787 resulted in a dose-dependent inhibition of thrombus growth (ED50, 10.4 +/- 0.8 mg/kg). Clopidogrel revealed a maximal inhibitory efficacy of 40% at 20 mg/kg p.o., and aspirin, at 100 mg/kg p.o., was without effect in this model. SR 121787 at oral doses < or = 10 mg/kg, did not cause an increase in blood loss after incision of the rabbit ear. In conclusion, SR 121787 is the first GP IIb/IIIa antagonist with oral antiplatelet and antithrombotic activity in rabbits.

Animals↗
PubMed1997

Induction of an epitope-specific humoral immune response by lipopeptide-hapten conjugates: enhancement of the anti-melittin response by a synthetic T helper (Th)-cell epitope.

Lipopeptides of bacterial origin constitute potent immunoadjuvants when combined with antigens. After the immunization with lipopeptides covalently coupled to non-immunogenic low-molecular-mass antigens or haptens, a hapten-specific humoral immune response can often be obtained. The response against synthetically prepared melittin fragments was further enhanced by the additional introduction of a T helper (Th)-cell epitope into the lipopeptide-hapten conjugate. The Th-cell epitope applied, which is presented by the MHC class II molecule of the BALB/c (H-2d) haplotype, consisted of a synthetic 16-amino-acid oligopeptide derived from sperm whale myoglobin. The immune-enhancing effect was most pronounced for the melittin-derived peptide fragments [Mel(1-16)] and [Mel(17-26)-CONH2]. Antibodies obtained after 3 immunizations with the conjugates recognized the synthetic as well as the native melittin molecule. Our results show that it is possible to markedly enhance a weak hapten-specific immune response by coupling the haptens to a lipopeptide conjugated to a haplotype-specific T helper-cell epitope. The novel conjugates are well suited for the optimization of immunization procedures, and for the development of novel synthetic vaccines.

Adjuvants, Immunologic↗
PubMed1997

Increased expression of transforming growth factor alpha precursors in acute experimental colitis in rats.

BACKGROUND AND AIM: Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha), members of the EGF family of growth factors, protect rat gastric and colonic mucosa against injury. Having shown previously that exogenously applied EGF protects rat colonic mucosa against injury, the aim of the present study was to evaluate the endogenously expressed ligand mediating the protective effect of EGF/TGF-alpha in vivo. METHODS: In an experimental model of trinitrobenzene sulphonic acid (TNBS)/ethanol induced colitis in rats EGF and TGF-alpha expression was evaluated using a ribonuclease protection assay, northern blot analysis, western blot analysis, and immunohistochemistry. RESULTS: TGF-alpha mRNA increased 3-4 times at 4-8 hours after induction of colitis and returned to control levels within 24 hours. TGF-alpha immunoreactive protein with a molecular size of about 28 kDa representing TGF-alpha precursors increased markedly after induction of colitis with a peak at 8-12 hours. No fully processed 5.6 kDa TGF-alpha protein was detected in normal or inflamed colon tissue. Only a weak signal for EGF mRNA expression was detected in the rat colon and no EGF protein was observed by immunohistochemistry or western blot analysis. CONCLUSIONS: TGF-alpha precursors are the main ligands for the EGF receptor in acute colitis. It is hypothesised that TGF-alpha precursors convey the biological activity of endogenous TGF-alpha peptides during mucosal defence and repair.

Acute Disease↗
PubMed1997

Expression of insulin-like growth factor I receptors and binding proteins by colonic smooth muscle cells.

We recently demonstrated upregulation of insulin-like growth factor I (IGF-I) binding sites in the smooth muscle layer of inflamed rat colon. The increase in binding sites was due to increased expression of IGF binding proteins (IGFBPs), which modulate the effects of IGF. To further study the role of IGF in the colon, we investigated whether cultured colonic smooth muscle cells (SMC) express IGF-I receptors and IGFBPs. SMC were isolated by collagenase digestion from rat colonic smooth muscle and grown in primary culture. Equilibrium binding experiments using (125)I-labeled IGF-I showed the presence of an IGF-I receptor with a dissociation constant of 1.96 nM and a maximal binding constant of 53,000 receptors/cell. Competition binding studies with IGF-II and insulin, together with chemical cross-linking experiments, corroborated this conclusion. Western ligand blotting of conditioned medium and Northern analysis of total RNA demonstrated that the cells expressed and secreted IGFBP-4, -5, and -3 with molecular masses of 25, 31, and 45 kDa, respectively. These results, together with our in vivo studies in the rat, support a role for IGF in tissue fibrosis and stricture formation during chronic intestinal inflammation.

Animals↗
PubMed1997

[Effect of moldy grass on intraluminal fermentation and thiamine metabolism in cattle (in vitro)].

The influence of mouldy grass (kind of moulds: Fusarium sp., Epicoccum oryzae, Ulocladium spp., Mucor spp.) on the in-vitro-fermentation especially the thiamine-metabolism of bovine rumen fluid was investigated using the longterm rumen simulation technique (RUSITEC). Four investigation periods keeping 23 days each were carried out. After a control period of nine days (normal hay) an eight days lasting testphase followed. During this time two reaction vessels (KF) were charged with normal hay, two vessels (VF II) with mouldy grass and two (VF I) with a 50:50-mixture of normal hay and mouldy grass. During the last five days of the testperiod 0.3 mg thiamine/reaction vessel were added daily. In the last six days all reaction vessels were fed with normal hay. The following effects of mouldy grass during the investigation period on the rumen fluid and rumen gas, respectively, could be noted: changes of short volatile fatty acids concentrations (acetate -9.9% [p < 0.05] propionate up to -12.2% [ns], i-butyrate up to +39.9% [p < 0.001], n-butyrate up to +25% [p < 0.01]); increase of ammonia concentrations up to 68% (p < 0.01); small increase of pH for 0.08 units (p < 0.01); decrease of the methane production up to 16.6% (p < 0.001); increase of thiamine input due to the mouldy grass up to 310% (p < 0.05); increased breakdown of substituted thiamine for 44%.

Animal Feed↗