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Biomedical subjects

M Janssen

Publications and source records attributed to M Janssen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Lubeluzole protects sensorimotor function and reduces infarct size in a photochemical stroke model in rats.

Posttreatment with lubeluzole, the S-isomer of a novel 3,4-difluoro benzothiazole, potently rescued tactile/proprioceptive hindlimb placing reactions contralateral to unilateral thrombotic infarcts in the hindlimb area of the parietal sensorimotor neocortex of rats. Administered at 5 min postinfarct, a single i.v. bolus of lubeluzole was three times as potent as the racemate, whereas the R-isomer was inactive. Neurological protection was near-maximal for treatment delays through 1 hr postinfarct, but declined with longer delays. However, when administered at 6 hr, 1.25 mg/kg i.v. still protected 60% of infarcted rats. An i.v. bolus followed by a 1-hr i.v. infusion produced equieffective neurologic protection at both 6- and 3-hr delays. This optimal lubeluzole regimen, started at 5 min postinfarct, reduced infarct volume by 22 to 24% at 4 hr postinfarct and by 28% at 7 days postinfarct. Again, the R-isomer was inactive. Down-regulation of the glutamate-activated nitric oxide synthase pathway leading to neurotoxicity and neuronal death may constitute a neuroprotective mechanism of action for lubeluzole.

Animals↗
PubMed1995

NMR evaluation of changes in myocardial high energy metabolism produced by repeated short periods of ischemia.

Following our previous results which demonstrated that repeated short periods (2 min) of ischemia are capable of protecting the isolated rat heart from a subsequent global ischemia (30 min), in the present study we have concentrated on the metabolic changes occurring in rat hearts during six 2 min ischemia/3 min reperfusion cycles. Cardiac high-energy phosphates were monitored using 31P-NMR. Phosphocreatine levels fell (50-60%) during each ischemic period, and recovered to 70-80% of their initial values during reperfusion. P(i) rose by 59% during the first ischemic period, but increased less during subsequent ischemias (30% during the 6th occlusion, P < 0.05 vs. the first ischemic period) returning to baseline levels after each reperfusion. [ATP], pH, and [Mg2+] remained almost unaffected, but there was a decrease in HPLC-determined effluent ATP catabolites. The first occlusion led to a 95% drop in contractile function (P < 0.001 vs. baseline), but this recovered to 73% upon reperfusion (P < 0.02 vs. baseline), and was 65% at the end of the protocol. Phosphorylation potential (PP = [ATP]/([ADP].[P(i)]) correlated exponentially with total purine (r = 0.90) and with adenosine + inosine release (r = 0.81), and by the 6th ischemia/reperfusion cycle, exceeded that observed in controls by 21% (P < 0.05). We conclude that repeated short periods of ischemia do not lead to any significant alteration in the absolute myocardial ATP, but are associated with an enhanced cytosolic energy state in the heart, that enables the myocardium to reach a steady albeit lower functional state. Adenosine (+inosine) release may be involved in the regulation of the energy supply-demand balance.

Adaptation, Physiological↗
PubMed1995

Interaction of glucagon-like peptide-I (GLP-I) and galanin in insulin (beta TC-1)- and somatostatin (RIN T3)-secreting cells and evidence that both peptides have no receptors on glucagon (INR1G9)-secreting cells.

The interaction of glucagon-like peptide-I (GLP-I) and galanin in clonal endocrine pancreatic cells was characterized. By Northern blot analysis the presence of GLP-I receptor mRNA was shown in B (beta TC-1 cells) and D (RIN 1048-38) cells but not in A (INR1 G9) cells, thus confirming functional data demonstrating the absence of active GLP-I receptors on glucagon-producing cells. Galanin receptors were detected on B and D cells but not on A cells. In B and D cells galanin inhibited the GLP-I stimulated adenylate cyclase activity. Treatment of insulin- and somatostatin-producing cells with GLP-I increased intracellular cAMP levels, and this was dampened by galanin, GLP-I stimulated the activity of protein kinase A in B and D cells, which was also inhibited by galanin. Galanin alone did not influence B- and D-cell function. These data show that in the endocrine pancreas B and D cells but not A cells express GLP-I and galanin receptors. The interaction of GLP-I and galanin might act in the endocrine pancreas as a physiological inhibitor of the potent incretin hormone GLP-I. Therefore, we suggest galanin is a 'decretin'.

Animals↗
PubMed1995

Intermittent v continuous ischemia decelerates adenylate breakdown and prevents norepinephrine release in reperfused rabbit heart.

Myocardium tolerates intermittent ischemia followed by short reperfusions better than continuous ischemia of the same duration. We attempted to delineate the differential mechanism(s) involved in intermittent v continuous ischemia. Isolated, paced rabbit hearts were perfused at 22 ml/min. Coronary flow was stopped intermittently 12 x for 2 or 4 min, with 3-min reperfusions (total reperfusion period: 36 min). In two other groups, flow was stopped continuously for 24 or 36 min followed by a flat 36-min reperfusion. Following the first intermittent 2-min ischemia, adenosine efflux increased ninefold; in all subsequent ischemia/reperfusion cycles, adenosine and total purine releases were substantially less despite identical heart rates, coronary flows and ischemic periods. The rate-pressure product prior to the intermittent ischemias exhibited exponential correlations with total purine efflux during the 3 min of reperfusion. When intermittent ischemia was extended to 4 min, the initial attenuation of ATP breakdown during the prior 2-min occlusions was overcome, but during subsequent 4-min ischemia/reperfusion cycles, ATP breakdown was again attenuated relative to the first 4-min ischemia. After the prolonged continuous ischemias, purine efflux was up to 6 x higher than with intermittent ischemias of the same total time of zero flow. Lactate release and hence cellular H+ export after intermittent ischemias remained consistently elevated, but following the continuous ischemia of 36 min, release of lactate, and thus H+, was subsequentially decreased. Glycogen mobilization occurred regardless of the ischemia's nature, but it was markedly enhanced during continuous ischemias, where no fall in proglycogen levels occurred. Similarly, myocardial norepinephrine release increased substantially only during the prolonged continuous ischemias. Thus short intermittent ischemia attenuates cardiac adenylate degradation and glycogen mobilization; such ischemic insult also provides for better lactate and H+ washouts immediately upon reperfusion. Another beneficial effect of intermittent ischemia was the near-complete absence of free interstitial norepinephrine, which exacerbates myocardial ischemic insults. In addition, the exponential correlations between preischemic rate-pressure product and postischemic purine release suggest that preischemic energy demand may determine ATP breakdown in ischemic rabbit myocardium.

Adenine Nucleotides↗
PubMed1995

Temporal location of unsignaled food deliveries: effects on conditioned withdrawal (inhibition) in pigeon signtracking.

Standard models of Pavlovian conditioning neglect local effects of unsignaled unconditioned stimuli (USs) on learning and performance. Using the approach-withdrawal behavior of pigeons toward keylights as conditioned stimuli (CSs), the authors varied the specific times (5-110 s) that USs occurred before or after a CS. Withdrawal from a CS generally increased as the time between a US before and/or after the CS was lengthened. Combinations of 2 distant USs produced more withdrawal from the CS than either US alone, whereas combinations of a distant and a nearby US yielded behavior intermediate between that for either US alone. Postacquisition retardation tests supported similar conclusions. Based on the temporal isolation of CSs and USs, a tentative model was offered to summarize these data. The results and the model suggest that a more molecular, possibly perceptual approach to Pavlovian excitation and inhibition is needed.

Animals↗
PubMed1995

Selective enhancement of alpha 2-adrenoceptor-mediated vasoconstriction in insulin-dependent diabetic patients with microalbuminuria.

1. Microalbuminuria, the earliest clinical marker of microvascular disease, is an important predictor of early death in insulin-dependent diabetes, and abnormal vascular reactivity may contribute to microvascular disease. We have previously found that vasoconstrictive responses to noradrenaline are exaggerated in insulin-dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin-dependent diabetic patients and non-diabetic control subjects. 2. To determine whether this is due to increased sensitivity at alpha 1- or alpha 2-adrenergic receptors, we compared vascular responses to the alpha 1-adrenergic agonist phenylephrine and the alpha 2-adrenergic agonist clonidine. 3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with normal urinary albumin excretion and 14 non-diabetic subjects. Vascular constrictive responses were measured in dorsal hand veins. 4. No difference in vasoreactivity to phenylephrine was demonstrated between any of the three groups. However, enhanced vascular responsitivity to clonidine at infusion rates of 16-2048 ng/min (analysis of variance, P < 0.001) was found in insulin-dependent diabetic patients with microalbuminuria as compared with both non-diabetic control subjects and normoalbuminuric insulin-dependent diabetic patients. There were no significant differences between the dose-response curves of the diabetic group with normal urinary albumin excretion and the non-diabetic group. 5. Vasoconstriction mediated by alpha 2-adrenergic receptors is therefore enhanced in normotensive insulin-dependent diabetic patients with microalbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to systemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy.

Adult↗
PubMed1995

NSAID-associated upper gastrointestinal damage in patients with rheumatoid arthritis.

AIM OF THE STUDY: The main aim of the present study was to identify the patient with rheumatoid arthritis (RA) taking non-steroidal anti-inflammatory drugs (NSAIDs) at risk for peptic ulcer disease (PUD) and its life-threatening complications. PATIENTS AND METHODS: During a retrospective study in which more than 1000 patients were interviewed, current gastrointestinal (GI) complaints were of no use in detecting current PUD. RESULTS: A history of PUD was an important predictor of current PUD, while the predictive value of serologic parameters, such as serum values of pepsinogen and antibodies to Helicobacter pylori, was disappointingly low. A prospective study in which 81 consecutive RA patients underwent a gastroscopy revealed 16% PUD; again a history of PUD was the most important predictive parameter. Since no study had been undertaken into the effects of a NSAID on intragastric pH we performed such a study, the main conclusion being that indomethacin does not influence the intragastric pH of RA patients. A placebo-controlled study of ranitidine 300 mg b.i.d. for the prevention of recurrent PUD in RA patients on NSAIDs is underway.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Serum values of pepsinogens and antibodies to Helicobacter pylori in relation to a history of peptic ulcer disease and NSAID use.

The present study was undertaken to investigate whether patients with a history of peptic ulcer disease (PUD) have serological features indicative of the presence of more severe gastritis, compared to patients without a history of PUD. In addition we investigated whether current chronic use of non steroidal anti-inflammatory drugs (NSAIDs) was associated with serological features indicative of a chemical (type C) gastritis. In total 850 consecutive outclinic patients were interviewed by a standard questionnaire with emphasis on demographic data, diagnosis, chronic use of NSAID, and history of PUD. Serum pepsinogen A (PgA) and pepsinogen C (PgC), the PgA:PgC ratio, and IgA and IgG antibodies to H. pylori were measured in all patients. After controlling for age, sex, H. pylori seropositivity, and presence of RA, a correlation was found between a decreased pepsinogen A:C ratio and the use of NSAID. Patients with a history of PUD have serological features indicative of a persistently more severe gastritis. Secondly we found serological evidence for the existence of a chemical (type C) gastritis in NSAID users.

Adolescent↗
PubMed1994

A prospective, randomized study of pefloxacin versus teicoplanin in the treatment of gram-positive coccal infections in cancer patients: early termination due to emergence of resistance to fluoroquinolones.

A randomized prospective study comparing pefloxacin to teicoplanin in the treatment of gram-positive infections in cancer patients was prematurely terminated because of the emergence of pefloxacin resistance associated with oxacillin resistance in Staphylococcus aureus and coagulase-negative staphylococci. Among 56 patients evaluated for efficacy (26 pefloxacin and 30 teicoplanin) and infected with bacteria susceptible to both antibiotics, the clinical cure and eradication rates were similar for pefloxacin (80.5% and 77.3% respectively) and teicoplanin (66.6% and 52.2% respectively). The relapse rates (15% and 10% for pefloxacin and teicoplanin respectively) and the overall mortalities within 1 month (42% and 31%) were similar.

4-Quinolones↗
PubMed1994

Primary femoral shortening osteosynthesis in the management of comminuted supracondylar femoral fractures.

Supracondylar fractures are most often the result of high-energy vehicular trauma in the young population, and the result of low-energy injuries in the elderly. Therefore, these fractures are generally associated with comminution or osteoporosis. Anatomic reconstruction with stable medial buttressing is often not possible. Utilization of AO principles and techniques with anatomic reduction and internal fixation often fails to yield sufficient stability. We have developed a technique for the treatment of these distal femoral fractures which involves shortening by impaction. Rather than achieving anatomic reduction, the femur is shortened by telescoping the fragments to reestablish inherent stability of the bone prior to internal fixation. Over a 20-year period we treated 25 comminuted supracondylar femoral fractures with primary shortening osteosynthesis in 24 patients. Sixteen patients were available for review at an average follow-up of 10 years (range 4-24 years). Ninety-four percent of the patients demonstrated complete radiographic consolidation by 14 weeks after the operative intervention. One patient required secondary bone grafting and reached consolidation at 30 weeks. Primary cancellous grafting was utilized in only 25% of the patients. One-third of the patients in review were given a heel lift; the average shortening in these patients was 2.6 cm (range 2.1-5 cm). Two-thirds of the patients did not require a heel lift, the average shortening in this group of patients being 1.2 cm (range 0.8-2.0 cm). At follow-up the average range of motion of the knee was 114 degrees (range 90 degrees-130 degrees).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Treatment of subtrochanteric fractures of the femur: reduction on the traction table and fixation with dynamic condylar screw.

In the subtrochanteric region of the femur high tensile forces are active in the lateral cortex and even higher compressive forces in the medial cortex. Subtrochanteric fractures are often comminuted. The implant of choice for osteosynthesis of subtrochanteric femoral fractures is the condylar plate. Usually the various fragments are dissected intraoperatively and the medial cortex is reconstructed anatomically for improved abutment. This devitalizing of fragments leads to disturbed healing, so that failure are frequent despite cancellous bone grafting. The osteosynthesis technique introduced by Mast and Ganz of indirect reduction by distractor without dissection of the fragments and the medial cortex allowed the complication rate to be reduced to 0%. We have modified this technique in that we performed closed reduction on the traction table rather than using the distractor to achieve axial and rotational alignment, after which the fracture is stabilized with dynamic condylar screw (DCS) under image intensifier control. The proximal femur is dissected only laterally and only in so far as in necessary to place the DCS. We never use cancellous bone grafting. From 1988 to 1990 this technique was used in 12 patients. All fractures had healed uneventfully after 4 months.

Adult↗
PubMed1994

Achlorhydria does not protect against benign upper gastrointestinal ulcers during NSAID use.

It is widely accepted that the absence of acid-peptic activity excludes the presence of a benign upper gastrointestinal ulcer. We assessed the frequency of a history of benign upper gastrointestinal ulcer disease in patients with and without serological evidence of achlorhydria with reference to the use of nonsteroidal antiinflammatory drugs (NSAIDs). In total 857 patients were interviewed, using a standard questionnaire with emphasis on demographic data, chronic use of NSAID, and history of upper gastrointestinal ulcers. The frequency of achlorhydria was determined by extremely low serum levels of pepsinogen A (PgA < 17 micrograms/liter). Of the total group of patients, 36 patients (4.2%; 95% CI 2.9-5.5) had a PgA lower than 17 micrograms/liter. A history of benign upper gastrointestinal ulcer was found in 57/827 (6.9%) of patients with serum PgA higher than 17 micrograms/liter and in 3/36 (8.3%) of patients with serum PgA lower than 17 micrograms/liter (NS). The three patients with upper gastrointestinal ulcer and PgA lower than 17 micrograms/liter were known to have pernicious anemia (PA) before (two patients) or simultaneously (one patient) with the diagnosis of the upper gastrointestinal ulcer and were using NSAIDs at that time. The presence of gastric acid is not obligatory for the development of ulcers during NSAID use.

Achlorhydria↗
PubMed1994

Teratozoospermia and in-vitro fertilization: a randomized prospective study.

A prospective randomized study was conducted to assess the prognostic value of sperm morphology in an in-vitro fertilization (IVF) programme, using strict criteria. The first group (T, teratozoospermic) included 32 couples with an isolated teratozoospermia in the male partner (morphology < 9% normal). The second group (C, control) contained 36 couples with normal semen parameters, including morphology (> 9% normal, strict criteria). In both groups, 50 IVF cycles were performed. Patients were matched for indication for IVF. There was no difference between the two groups regarding age, duration of infertility, stimulation protocol, catheter used for embryo transfer and different sperm parameters. A statistically significant difference between the T and C groups respectively was observed regarding the fertilization rate (69.2 and 79.4%, P < 0.05), pregnancy rate per cycle (12.0 and 42%, P < 0.001), the pregnancy rate per transfer (13.9 and 42.0%, P < 0.01) and per embryo transferred (6.1 and 14.8%, P < 0.05). No pregnancy occurred in the poor prognosis group (morphology < 5% normal). In cases of moderate teratozoospermia, the fertilization rate appeared normal (78.6%) but the conception rate remained low. We concluded that the use of strict criteria in the assessment of sperm morphology is useful in predicting fertilization and pregnancy rate in the human in-vitro model.

Embryo Transfer↗
PubMed1994

A gastroscopic study of the predictive value of risk factors for non-steroidal anti-inflammatory drug-associated ulcer disease in rheumatoid arthritis patients.

Peptic ulcer disease (PUD) in RA patients is associated with NSAID use. This study aimed to validate the predictive value of presumed risk factors for NSAID-associated PUD in a prospective gastroscopic study in RA patients. Eighty-one NSAID using RA patients were prospectively divided into four presumed risk groups according to Helicobacter pylori status and history of PUD. As additional risk factors the following were analysed: upper gastrointestinal GI complaints; disability; daily dose of NSAID and antral gastritis. The presence of PUD in the four risk groups did not differ. Additionally it was found that a history of PUD was predictive for current PUD [odds ratio (OR) 3.9; 95% CI 1.1-14]. H. pylori status was not predictive. Transformation from one ulcer type to another was rare. NSAID dose was not a risk factor, while disability was of borderline importance (OR 2.1; 95% CI 1-4.8). Current upper GI complaints were bad predictors. PUD only occurred with a concomitant antral gastritis. A history of PUD, disability and antral gastritis were the most important predictors for current PUD. When an ulcer relapsed it was of the same ulcer type as had been present earlier. This may have practical implications for prophylaxis enabling stratification by previous ulcer type.

Adult↗
PubMed1994

No effect of intramuscular gold therapy on serological parameters of Helicobacter pylori infection in patients with rheumatoid arthritis: a 12 month prospective study.

OBJECTIVES: To assess prospectively the influence of intramuscular gold therapy on Helicobacter pylori serology in patients with rheumatoid arthritis (RA). METHODS: Fifty patients with RA were started on intramuscular gold or chloroquine, as the control group and were followed serologically for H pylori infection for 12 months. RESULTS: Twelve patients treated with gold and eight control patients treated with chloroquine, all with serological evidence for H pylori infection, showed no significant decline of IgA and IgG anti-H pylori antibody levels or serum pepsinogen A and C levels. Total serum IgA and IgG levels declined significantly during gold therapy, while they remained unchanged during chloroquine therapy. CONCLUSIONS: Intramuscular gold therapy in patients with RA does not influence the serological parameters of H pylori infection.

Antibodies, Bacterial↗
PubMed1994

Loss of elastic recoil in postischemic myocardium induces rightward shift of the systolic pressure-volume relationship.

Ischemia-induced systolic dysfunction has been ascribed to changes in cellular excitation-contraction coupling and diastolic dysfunction because of disruption of the extracellular collagen matrix. Therefore, systolic and diastolic pressure-volume relationships and O2 consumption were determined before and after 5 min of global ischemia in isolated blood-perfused porcine hearts. The slope of the systolic pressure-volume relationship was 7.2 +/- 0.6 (SE) mmHg.ml-1.100 g-1 (n = 18) at baseline and did not change during reperfusion, but the systolic volume intercept shifted from 1.0 +/- 0.4 ml/100 g at baseline to 3.7 +/- 1.4, 4.1 +/- 1.1, and 4.2 +/- 0.9 ml/100 g at 15, 30, and 60 min of reperfusion, respectively (all P < 0.05). The diastolic volume intercept was 8.2 +/- 0.7 ml/100 g at baseline and remained unchanged during reperfusion. Therefore, the difference of the systolic-diastolic volume intercepts, an index of elastic recoil forces, was decreased to 57 +/- 8, 49 +/- 7, and 47 +/- 9% of baseline values (P < 0.05). The shift of the systolic pressure-volume relationship was accompanied by a transient decrease of contractile efficiency (slope of O2 consumption-pressure-volume-area relationship) at 15 min of reperfusion (from 43 +/- 6 to 27 +/- 7%). We hypothesize that the rightward shift of the systolic pressure-volume relationship was compatible with a decrease of elastic-restoring forces, probably induced by alterations in the extracellular collagen matrix and/or the cytoskeleton, and thereby our data imply that left ventricular dysfunction of postischemic myocardium does not result solely from disturbances in excitation-contraction coupling.

Animals↗
PubMed1994

Adenosine, added to St Thomas' Hospital cardioplegic solution, improves functional recovery and reduces irreversible myocardial damage.

St Thomas' Hospital cardioplegic solution is commonly used to arrest hearts during surgery. Pursuing the hypothesis that the cardioprotective properties of adenosine could be a beneficial adjunct to a solution containing high K+ and Mg2+, we tested a low and a high adenosine concentration added to this cardioplegic solution, aiming at improved recovery of function and energy status. We arrested 18 working rat hearts by a 3-minute infusion with the solution without or with 50 microM or 5 mM adenosine. We induced 30 minute stop-flow ischemia at 37 degrees C, followed by 10 minute washout (Langendorff mode) and 20 minute reperfusion (working heart). Control cardioplegia induced electrical arrest in 19.8 +/- 5.5 s. This took 9.1 +/- 0.9* and 12.7 +/- 1.8 s in the presence of 50 microM and 5 mM adenosine, respectively (*p < 0.05 vs no adenosine). During reperfusion a regular electrocardiogram appeared after 1.9 +/- 0.3 minutes in controls, after 1.0 +/- 0.0* and 1.7 +/- 0.2 minutes in hearts treated with low and high-dose adenosine, respectively (*p < 0.05 vs no adenosine). After 20 minute reperfusion, the pressure-rate product had recovered to 65 +/- 17% in controls, and to 107 +/- 11** and 72 +/- 11% of preischemic values in hearts treated with 50 microM and 5 mM adenosine, respectively (**p < 0.05 vs other groups). There was a good correlation between reperfusion function recovery and the postischemic release of creatine kinase, an index for irreversible cellular damage. This association was absent with ATP content, which increased with the adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗