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Biomedical subjects

J Lewin

Publications and source records attributed to J Lewin.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacological characterization of adenosine A1 and A2 receptors in the bladder: evidence for a modulatory adenosine tone regulating non-adrenergic non-cholinergic neurotransmission.

1. The nerve-evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1 microM atropine plus 3.4 microM guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: R-phenylisopropyladenosine (R-PIA) greater than cyclohexyladenosine (CHA) greater than 5'N-ethylcarboxamido adenosine (NECA) greater than ADO greater than S-phenylisopropyladenosine (S-PIA). Tissue preincubation with 8-phenyltheophylline (8-PT) displaced to the right, in a parallel fashion, the NECA concentration-response curve. 2. The contractions elicited by application of exogenous adenosine 5'-triphosphate (ATP) were also inhibited by ADO and related structural analogues. The rank order of potency to reduce the motor response to ATP was: NECA greater than 2-chloroadenosine (CADO) greater than R-PIA greater than ADO greater than CHA greater than S-PIA. 3. The ADO-induced ATP antagonism was of a non-competitive nature and was not specific. Tissue incubation with 10 microM NECA not only reduced the motor responses elicited by ATP, but also 5-hydroxytryptamine, acetylcholine and prostaglandin F2 alpha. The action of NECA was antagonized following tissue preincubation with 8-PT. The inhibitory action of NECA was not mimicked by 10 microM CHA. 4. The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5-30 microM 8-PT. 5. The 0.15 Hz evoked muscular twitch was significantly increased by 8-PT while dipyridamole consistently reduced the magnitude of the twitch response. These results are consonant with the hypothesis that an endogenous ADO tone modulates the bladder neurotransmission. 6. A working model is proposed suggesting the presence of ADO-Al and A2 receptors in the mouse urinary bladder. The A1 receptor subpopulation is probably of presynaptic origin whereas the smooth muscle membranes contain a population of the A2 receptor subtype.

Adenosine↗
PubMed1992

Successful treatment of episodic dyscontrol with carbamazepine.

Following a road-traffic accident, an 18-year-old man developed episodic dyscontrol which brought him into conflict with the law. Two years after the accident, treatment with carbamazepine was initiated and further aggressive outbursts subsided. The efficacy and mode of action of carbamazepine is discussed and the literature reviewed.

Adolescent↗
PubMed1991

Ethical and legal responsibilities of the neurosurgeon: selected topics.

There are many ethical and legal implications in a variety of activities in the neurosurgeon's day-to-day practice. Awareness of and proper attention to these issues are a professional responsibility that should be attended to, to ensure that the practice of medicine is carried out efficiently and effectively, to maintain public confidence, and to try to avoid micromanagement by third parties. The authors discuss four such subjects of particular interest to them, namely: 1) reporting of certain diseases and conditions to authorities and third parties; 2) acting without the consent of the patient to prevent harm to him or her and/or others; 3) reporting problems with drugs and devices; and 4) the detection and treatment of colleagues impaired by alcohol, drugs, or mental or physical illness.

Confidentiality↗
PubMed1990

Bradykinin facilitates the purinergic motor component of the rat bladder neurotransmission.

The motor activity of the rat bladder elicited by transmural electrical stimulation was abolished in the presence of 200 nM tetrodotoxin but not of 1 microM atropine plus 3.4 microM guanethidine. Tissue preincubation with 20 microM, alpha, beta-methylene ATP reduced but did not obliterate the electrically-induced motor effect. Bradykinin (BK) caused a short-lasting motor response while it potentiated, in a concentration-dependent fashion, the 0.15-5 Hz-induced muscle twitching. The facilitatory action of the peptide lasted for at least 5 min and was blocked by the BK-B2 receptor antagonist D-Arg0 [Hyp3, Thi5,8, D-Phe7]-BK. The motor response caused by the exogenous application of adenosine 5'-triphosphate (ATP) was almost immediate and lasted less than 30 s; it was also potentiated by BK-B2 receptor activation, an effect that was reduced in a concentration-dependent manner by pretreatment with the BK-receptor antagonist.

Action Potentials↗
PubMed1990

Parenchymal and vascular magnetic resonance imaging of the brain after extracorporeal membrane oxygenation.

Three-dimensional (volume) magnetic resonance angiography is a new and noninvasive method for imaging the intracranial vasculature. The combination of magnetic resonance angiography and conventional magnetic resonance imaging was used to evaluate brain parenchyma and vessels in 30 survivors of extracorporeal membrane oxygenation. Magnetic resonance imaging findings were abnormal in 33% of the patients, with no increased frequency of right hemispheric lesions. Magnetic resonance angiography demonstrated good intracranial flow in all infants and demonstrable right internal carotid arterial flow in 35% of those patients with permanent carotid ligation. An abnormal magnetic resonance imaging study was found more often in infants with abnormal predischarge neurologic examination results. These techniques have several advantages over other neuroimaging modalities, including better definition of deep structures, myelin formation, and intracranial vasculature, the absence of bone artifact, and the elimination of catheter or contrast use.

Brain↗
PubMed1989

The use of ryanodine and calcium channel blockers to characterize intra- and extracellular calcium pools mobilized by noradrenaline in the rat vas deferens.

Ryanodine (0.03-10 microM) abolished the phasic component of the contractile response to noradrenaline in the rat vas deferens but had less effect on the tonic component of this response. In contrast, nifedipine and methoxyverapamil (D600, 0.3-0.8 microM) blocked only the tonic component of the noradrenaline, adrenaline or phenylephrine-induced contractions. These results suggest that the phasic component of the noradrenaline-induced response is related to the release of intracellular calcium whereas the tonic phase of the contraction involves calcium influx via membrane channels sensitive to dihydropyridine and diphenylalkylamine calcium channels blockers.

Alkaloids↗
PubMed1989

Attenuation of ischemic renal injury with fructose 1,6-diphosphate.

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.

Animals↗
PubMed1989

Effect of acetyl salicylic acid on increased production of thromboxane after aortic graft surgery.

Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

Aged↗
PubMed1988

Gastric mucosal reactions in patients with food allergy.

The aim of our study was to determine whether patients suffering from food allergy show any pathologic reactions on the mucosa of the gastrointestinal (GI) tract after allergen contact. For this reason, we included in the study 30 patients whose food-allergic history had been proven through double-blind challenge tests; 20 healthy volunteers also were included as controls. The patients and volunteers underwent standard laboratory investigations and allergy tests with PRICK and RAST. To observe possible mucosal reactions, we applied the proposed allergens via endoscope to the gastric mucosa. Macroscopic reactions were observed blindly by two independent physicians. Biopsies were taken from the challenged areas for histological and histochemical analysis. The examinations included the estimations of tissue histamine concentrations and of mast cell and lymphocyte counts. In all 30 patients, macroscopic reactions (swelling, erosions, bleedings) were observed. Patients with food allergy had, in contrast to healthy volunteers, elevated lymphocyte counts, tissue histamine concentrations, and mast cell counts. After provocation, tissue histamine concentrations and mast cell counts fell significantly. Skin and RAST tests showed positive results in only 46.7% and 50.0%, respectively, of food-allergic patients. We conclude, first, that through intragastric provocation under endoscopic control (IPEC), food-allergic reactions on the mucosa of the GI tract can be verified and, second, that the liberation of tissue histamine seems to play an important role in the establishment of food-allergic reactions on the mucosa.

Adult↗
PubMed1988

Treatment of appendiceal abscess.

Appendiceal abscess occurring in 193 patients during a 14-year period is reviewed. Treatment was nonsurgical in 98 patients, with a complication rate of 3%. In the 95 surgically treated patients the complication rate was 32%. One patient died. 'Interval' elective appendectomy was performed in 80 cases and the complication rate was 23%. Among the 32 patients without surgery or in whom the appendix was not removed at laparotomy, the recurrence rate was 3%. No malignancy was found at colonic radiography in 84 conservatively treated patients. Based on these findings, the following strategy is recommended for management of appendiceal abscess. 1) Initially conservative treatment, with surgical intervention if this fails. 2) 'Interval' elective appendectomy not routinely undertaken. 3) For patients older than 40, follow-up with colonic radiography, possibly colonoscopy and, if necessary, also exploratory laparotomy to exclude intraabdominal malignancy.

Abscess↗
PubMed1987

Apparent absence of local response to bone screws in guinea pigs with contact sensitivity.

Guinea pigs sensitized to nickel, cobalt, or chromium were used to study if impaired fixation occurred as a result of allergy against metal implants in bone. Screws made from stainless-steel (ASTM F55, F138-139) or cobalt chromium (ASTM F75-76) were inserted in the right and left proximal tibiae, and the mechanical strength of the fixation to the bone was evaluated after 4 months. In addition, we studied the histology on decalcified sections of the implant bone interface from the distal femur where the same type of screws had been inserted. To see if changes in bone density occurred in the proximal tibia as a result of allergy, the amount of ash was determined. Although the animals maintained their contact sensitivity throughout the experimental period, there were no differences between allergic and control animals for any of the parameters studied. All screws were well fixed in the tibia at the end of the experiment, and histologically we did not find any significant differences between allergic and control animals by qualitative examination. The experiment supports our earlier results from a 6-week experiment and indicates that contact allergy may be unimportant for the fate of orthopedic implants.

Animals↗
PubMed1987

Synthetic arterial grafts cause prolonged increase in the in vivo formation of thromboxane and prostacyclin in humans.

To evaluate the in vivo production of thromboxane A2 and prostacyclin their major urinary metabolites were measured in patients following graft replacement of the abdominal aorta. Specific methods based on gas chromatography-mass spectrometry were used to measure the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. The excretion of these metabolites increased tenfold and almost fortyfold during post-operative Day 1 and remained elevated 6-10 days p.o. In a group undergoing cholecystectomy smaller changes of shorter duration were seen. It is concluded from this study that synthetic grafts cause prolonged increase in the in vivo formation of thromboxane A2 and prostacyclin. The reason for the increased TxA2 formation is probably platelet interaction with the foreign surface, whereas the increase of PGI2 could be part of a vascular defense against induced thrombotic activity. Those increases may have pathophysiologic implications.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Misoprostol prevents damage to the gastric mucosa by stabilizing the mast cells.

Prostaglandins have been shown to prevent the damage to the gastric and intestinal mucosa which has been induced by diverse necrotizing substances. These damaging stimuli increase the liberation of histamine from mast cells. Because of its well known effects on cellular permeability, histamine may serve the initial stimulus for mediating cellular damage. The aim of our study was to investigate the effect of misoprostol, a synthetic PGE1 analog, on tissue histamine concentration and mast cell counts after damage to the gastric mucosa induced by stress, histamine, aspirin and concentrated ethanol in guinea pigs. Misoprostol or its matching placebo were administered intragastrically 3 minutes prior to the ulcerogenic stimulus. After the induction of the injury, the animals were sacrificed, stomachs were examined for ulceration. Gastric and duodenal histamine concentrations were determined. Mast cells from these organs were stained and counted. All four ulcerogenic stimuli resulted in significant gastric ulcer formation. This ulcerogenic action was accompanied by a significant decrease in mucosal histamine concentration and mast cell counts. Misoprostol induced a dose-dependent inhibition of gastric damage, histamine depletion and mast cell destruction. These results indicate that the stabilization of mast cells by misoprostol is an important mechanism for its mucosal protective effects against ulcerogens.

Alprostadil↗
PubMed1987

[Clarifying the pathophysiologic mechanism of food allergy].

Various lymphocyte populations, dendritic cells and macrophages contribute to the intake of antigen. The transportation of antigen in the intestinal wall is possible with the help of receptive endocytosis, including extracellular protein in fluid droplets, bacterial and vegetable toxins, as well as certain viruses, which seem to be able to penetrate the cell membrane and enter directly into the cell. Own investigations: After endoscope controlled allergy-irritation of the gastro-intestinal tract, 20 people used in the clinical test showed acute signs of mucosal reaction with inflammation and swelling of the mucous membrane as well as haemorrhagic lesions. A histamine release from the mastcell was proved.

Antigens↗
PubMed1986

Automated repetitive microsampling of blood: growth hormone profiles in conscious male rats.

A system is described for the automatic collection of small samples of blood from conscious rats. Rats bearing chronic indwelling i.v. catheters were connected via swivels to a multichannel peristaltic pump, solenoid valves and a fraction collector. A microcomputer controlled the operations involved in the removal of blood and its deposition into a fraction collector for subsequent direct radioimmunoassay for GH. Blood samples of 10-20 microliter could be collected, into a total volume of 100 microliter heparinized saline, from up to eight rats simultaneously every few minutes for many hours. This collection method avoided major blood loss and did not require transfusions of donor blood to maintain blood volume. Using a double-lumen cannula it was possible to inject or infuse into the animals while sampling blood. The system was used to investigate in detail the secretion of GH in conscious male rats. The 3-hourly endogenous secretory rhythm of GH was maintained for up to 44 h with episodes of GH secretion being multicomponent. Endogenous secretion was suppressed by constant i.v. infusions of somatostatin, with repetitive sampling showing in detail a rapid rebound secretion of GH after terminating the somatostatin infusions. Four injections of a fragment of GH-releasing factor, given at 3-hourly intervals, produced entrained GH responses, but the subsequent recovery of endogenous GH pulsing was delayed for up to 12 h. This method for the automatic microsampling of blood in small animals gives a very detailed description of the blood levels of hormones secreted in a highly episodic fashion, and could be widely applicable to other endocrine studies.

Animals↗