An isolated single coronary artery supplying the entire myocardium in a patient with congenitally corrected transposition of the great vessels.
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Adult↗
Biomedical subjects
H Guven
Publications and source records attributed to H Guven.
Preperitoneal mesh repair of spigelian hernias under local anesthesia: description and clinical evaluation of a new technique.
We report on a new method for the repair of spigelian hernia, in which we combined the step-by-step local anesthesia and open preperitoneal mesh repair techniques. After initial infiltration of local anesthetics, we incised the attenuated fascia and slightly enlarged the fascial defect to facilitate easy return of hernial content into the abdominal cavity. We injected preperitoneally, in a radial fashion around the peritoneal sac, more saline solution, consisting of 1:200,000 epinephrine (g:g) and 1/3 bupivacain (v:v). We dissected the peritoneum away from the anterior abdominal wall to create a preperitoneal pocket of sufficient size. We spread open a 9 x 9-cm polypropylene mesh in the area, as if we were doing a GPRVS of Stoppa. We followed up our four patients for an average of 32 months. All four cases had an uneventful recovery and were discharged in an average of 3.5 days. They returned to normal daily activity on the 9th day after surgery. We suggest that the preperitoneal mesh repair of a spigelian hernia under local anesthesia is a simple and feasible technique with favorable early and late postoperative results and deserves further investigation in larger series.
Adult↗
Postcontusional Kluver-Bucy syndrome.
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Adult↗
Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy.
B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the Western world. It is currently an incurable disease, making new treatment options such as immunotherapy desirable. Monoclonal antibodies (Mabs) to surface antigens of the tumor cell is one option. Administration of cytotoxic cells such as natural killer (NK) and natural killer-like T (NKT) cells expanded in vitro might be a useful treatment modality alone or in combination with MAbs. A limiting step in the development of successful cellular immunotherapy has been the availability of appropriate cytotoxic cells. Here, we report the feasibility of expanding populations of the human killer cells, CD3-CD56+ NK and CD3+CD56+ NKT cells, from peripheral blood mononuclear cells (PBMCs) of B-CLL patients. The influence of tumor B cells on the in vitro expansion of killer cells was assessed by depleting B cells from PBMCs by microbead separation before culture. The 21-day cultures from both B-cell- and non-B-cell-depleted PBMC showed a marked expansion of NK cells, and also of T cells, among which almost half had the NKT phenotype. Depletion of B cells before culture did not change the expansion rates of NK and NKT cells significantly. In patients with progressive B-CLL, NK cell expansion capacity was improved after fludarabine treatment when compared to samples obtained before treatment. Repeated samples of PBMCs from individual untreated patients with both indolent and progressive disease cultured under identical conditions gave similar NK cell expansion rates. Expanded killer cell populations had cytotoxic function against the NK-sensitive target K562 cell line and expressed high levels of Granzyme B. From our studies, we conclude that NK cells as well as NKT cells from the peripheral blood of B-CLL patients can be expanded, and that these cells have cytotoxic capacity.
Aged↗
Electrocardiographic changes during migraine attacks.
OBJECTIVES: To clarify whether electrocardiographic (ECG) changes can be identified during a migraine attack and to determine whether there are ECG differences between periods with and without headache. BACKGROUND: The clinical signs and symptoms of migraine point to involvement of the autonomic nervous system, and especially to disrupted regulation of the circulatory system and autonomic balance. This disruption may be more marked during a migraine attack. During a migraine attack, autonomic imbalance within the heart and its vessels conceivably may result in ECG abnormalities. METHODS: In 30 patients with migraine, the ECG variables of heart rate, abnormalities of rhythm, PR interval, QRS duration, corrected QT interval, T inversion, and ST-segment changes were recorded during migraine attacks and pain-free periods. RESULTS: Of the 30 patients studied during a migraine attack, 9 (30%) had one or more abnormalities of rhythm (including sinus arrhythmia, atrial premature contraction, and ventricular premature contraction), 20% had PR intervals greater than 0.20 seconds, 40% had corrected QT intervals greater than 0.44 seconds, 66% had T inversion, and 40% had ST-segment abnormalities. No patient had arrhythmia, PR intervals greater than 0.20 seconds, or corrected QT intervals greater than 0.44 seconds during a pain-free period. No differences were noted for ST-segment changes, T inversion, and total ECG changes between periods with and without headache, but both PR and corrected QT intervals were significantly longer during migraine attacks than during pain-free periods. CONCLUSIONS: We conclude that ECG abnormalities often are present during a migraine attack, and for most of these, particularly PR and corrected QT interval lengthening, these abnormalities will be absent or less prominent during pain-free intervals.
Adult↗
The effect of propofol (anesthetic and inhibitor of CYP3A4) on serum lidocaine concentrations in smokers and chronic alcohol consumers.
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Adult↗
Morgagni hernia: rare presentations in elderly patients.
Morgagni hernia, which is both infrequent and generally asymptomatic, is often diagnosed when complications occur. Herein we present two elderly patients with Morgagni hernia, which were complicated with bowel perforation and upper gastro-intestinal bleeding. The recognition and management of these cases are discussed.
Aged↗
Basic toxicological approach has been effective in two poisoned patients with amitraz ingestion: case reports.
Amitraz, a formamidine insecticide and acaricide used in veterinary practice, presents side effects in humans related to its pharmacological activity on alpha 2-adrenergic receptors. There is little information available in the literature about the toxicology of the product in man and the treatment of this poisoning. In this report, the clinical and laboratory features of amitraz poisoning in two patients by a veterinary formulation also containing xylene are presented. The major clinical findings were unconsciousness, drowsiness, respiratory failure requiring mechanical ventilation, miosis, hypothermia and bradycardia. The laboratory findings were hyperglycemia, hypertransaminasemia and increased urinary output. Supportive management of this poisoning in humans is suggested in only a few articles and there is no specific antidote for the subsequent possible pharmacological effects of amitraz. In our two cases, we performed supportive treatment such as mechanical ventilation, atropine, gastric lavage, active carbon, oxygen and fluid administration. We concluded that the basic approach to the patient with amitraz poisoning, including initial stabilization to correct immediate life-threatening problems, treatment to reduce absorption and measures to improve elimination of the toxin, is effective.
Adult↗
Effects of subchronic parathion exposure on cyclosporine pharmacokinetics in rats.
Parathion undergoes enzymatic oxidation by hepatic cytochrome P-450 (CYP450) enzymes to the active metabolite paraoxon. Consequently, alterations in CYP450-dependent oxidation may affect the pharmacokinetics and pharmacodynamics of drugs that are metabolized in the liver. The CYP3A family is known to be responsible for the majority of cyclosporine metabolism. The aim of the present study was to assess the disposition kinetics of cyclosporine during subchronic parathion exposure. Male Wistar rats were administered either water or two different doses of parathion (1/100 LD50, 1/25 LD50; LD50 = 14 mg/kg) by gavage for 6 wk. Subsequently, rats in each experimental group received a single oral dose of cyclosporine (10 mg/kg), and serial blood samples were drawn from the carotid artery over a period of 48 h. Pharmacokinetic analysis showed that parathion increased the blood cyclosporine concentration twofold as evidenced by AUC (area under the curve), half life (t 1/2) and peak plasma concentration (Cmax). This may be due to inhibition of cyclosporine metabolism, an interaction that may be of clinical relevance in immunosuppression therapy.
Animals↗
A new method for in vitro expansion of cytotoxic human CD3-CD56+ natural killer cells.
Adoptive transfer of immunocompetent cells may induce anti-tumor effects in vivo. However, a significant obstacle to the development of successful cellular immunotherapy has been the availability of appropriate cytotoxic cells. Among the immunologic effector cells that are considered mediators of anti-tumor effects, those with the highest per-cell cytotoxic capacity express a natural killer (NK) cell phenotype, i.e., CD56(+)CD3(-). However, such cells are normally present only in low numbers in peripheral blood mononuclear cells (PBMCs), lymphokine activated killer (LAK), and cytokine induced killer (CIK) cell preparations. To optimize the expansion of human NK cells, PBMCs were cultured in different serum free medium supplemented with monoclonal anti-CD3 antibodies and interleukin (IL)-2 at varying concentrations. By using Cellgro stem cell growth medium supplemented with 5% human serum and IL-2 (500 U/ml) cells expanded 193-fold (median, range 21-277) after 21 days, and contained 55% (median, range 7-92) CD3(-)CD56(+) cells. The remaining cells were CD3(+) T cells, 22% (median, range 2-68) of which co-expressed CD56. The expanded cell population lysed 26 to 45% of K562 targets in a 1:1 effector to target ratio, signifying substantial cytotoxic efficacy. The described method is a simple and efficient way of expanding and enriching human NK cells. We have termed these high-yield CD3(-)CD56(+) cells cytokine-induced natural killer (CINK) cells.
CD3 Complex↗
The effects of captopril on serum digoxin levels in patients with severe congestive heart failure.
The effects of captopril on serum digoxin concentrations were studied in 8 patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin concentrations were determined before and after the administration of captopril for 1 week in patients on chronic digoxin therapy. Each patient who was taking 0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7 days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0 and 7) captopril administration was 1.7+/-0.2 ng/ml and 2.7+/-0.2 ng/ml, the time to peak (tmax) was 2.4+/-0.5 h and 1.3+/-0.2 h, and the area under the 24-hour digoxin concentration-time curve (AUC0-24h) was 30.0+/-1.5 ng x h/ml and 41.7+/-3.4 ng x h/ml, respectively. While captopril caused a significant increase in peak serum concentration and the area under the digoxin concentration-time curve, it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01, respectively). No patient developed evidence of digoxin toxicity. Concomitant administration of captopril with digoxin increases serum digoxin concentration in patients with severe congestive heart failure.
Administration, Oral↗
The effects of propofol on normal and hypercholesterolemic isolated rabbit heart.
The aim of the present study was to compare the effects of propofol on cardiac contractile force in normal and hypercholesterolemic isolated rabbit hearts. While one group was fed with standard chow pellets (150 g/day), the other group received cholesterol (1% w/w) in addition to the same amount of rabbit chow pellets during 1 month. Hearts from standard-fed rabbits were given intralipid solvent or 25, 50 and 100 microM propofol by infusion. Hypercholesterolemic rabbit hearts were administered 25, 50 and 100 microM propofol by infusion. All concentrations of propofol did not result in any significant change of the heart rates (HR) in two groups. Propofol (25, 50 and 100 microM) infusion induced a concentration- and time-dependent inhibition in left ventricular pressure (LVP) in standard chow diet group (P<.05,.05 and.05, respectively). In hypercholesterolemic rabbit hearts, 25 and 50 microM propofol infusion developed a significant inhibition in LVP when compared with the standard chow diet group (P<.05 and.05, respectively). Propofol (100 microM) infusion developed a significant increase in LVP after 20 min in hypercholesterolemic rabbit hearts when compared with normal rabbit hearts (P<.05). Supratherapeutic concentration of propofol might have cardioprotective effect on hypercholesterolemic rabbit hearts.
Anesthetics, Intravenous↗
Midazolams cardiac depressant effects and their lack of reversal by flumazenil in isolated rabbit hearts.
Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 microM midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.
Anesthetics, Intravenous↗
Severe uvular angioedema caused by intranasal administration of Ecbalium elaterium.
A 54-y-o woman presented to the Emergency Department with shortness of breath and sore throat after intranasal administration of Ecbalium elaterium as a folk remedy for her sinusitis. The patient's history included nasal aspiration of the juice of the squirting cucumber (Ecbalium elaterium) for acute maxillary sinusitis. An airway obstruction due to severe uvular angioedema was detected and confirmed by airway X-ray. The patient was treated with 100% oxygen with mask, 0.3 mg epinephrine s.c., and 80 mg prednisolone i.v. Renal and hepatic function tests were normal. After a 24-h observation, the patient was discharged in her previous state of health.
Administration, Intranasal↗
The probable role of nitric oxide on the relaxations obtained by caffeine and aminophylline in rat uterus.
The aim of the present study was to investigate the effect of nitric oxide (NO) on the relaxant activity of caffeine and aminophylline on rat myometrial strips. Uteri of pregnant Wistar rats were removed and suspended in 10-ml organ baths containing 37 degreesC Krebs bicarbonate solution gassed with 95% O2 and 5% CO2. The significance of the results was assessed by Student's t-test and P<0.05 was considered significant. A relaxant effect was observed with 10(-5)-10(-2) M caffeine (n=8) and aminophylline (n=6) on pregnant rat myometrial strips precontracted with 64 mM K+ (IC50=4.21+/-0.35 and 4.25+/-0.26, respectively). Incubation with 10(-5) M methylene blue, 10(-5) M haemoglobin, 10(-6) M Nomega-nitro-L-arginine methyl ester (L-NAME), 2x10(-7) M forskolin and 10(-6) M zaprinast exerted no effect on the relaxations (P>0.05). When the concentration of external Ca2+ was decreased to 0.5 mM or increased to 4.5 mM from the control level of 1.5 mM, the concentration-inhibition curves for caffeine and aminophylline shifted to the left or to the right, respectively. Our results suggest that: (1) the L-arginine-NO-cGMP system has no effect on the inhibition induced by caffeine and aminophylline on K+ induced contractions of pregnant rat myometrium; (2) this inhibitory effect is not mediated by cAMP; (3) cGMP does not play a role on the relaxant effect of these drugs; and (4) that Ca2+ plays the major role on the relaxations obtained with methylxanthine derivatives on pregnant rat uterus. (c) 1998 The Italian Pharmacological Society.
Aminophylline↗
Characterization of 5-HT receptors in rat proximal colon.
1. In view of its multiple sites of action, we investigated the activity of 5-hydroxytryptamine (5-HT, serotonin) on various potential receptors in the isolated proximal colon of rats. 2. 5-HT induced concentration-dependent contractions of colonic strips (pEC50=7.54+/-0.12). 3. The 5-HT1 receptor agonist, 5-carboxamidotryptamine, induced concentration-dependent contractions (pEC50=5.93+/-0.27); however, neither the 5-HT3 receptor-agonist, phenylbiguanide, nor the 5-HT4 receptor-agonist, renzapride, caused contractions at concentrations as high as 10(-4) M. 4. The 5-HT 1/2 receptor antagonist, methiothepin, caused concentration-dependent nonsurmountable antagonism. The 5-HT3 receptor antagonist, tropisetron, inhibited the contractions to a concentration of 5-HT> or =10(-6) M. Ketanserin had no effect on responses to 5-HT. 5. Tetrodotoxin and atropine had no effect on responses to 5-HT. 6. We conclude that contractions to 5-HT are mediated by 5-HT1-like and probably 5-HT3 receptors that activate tetrodotoxin insensitive mechanisms.
Animals↗
Circadian rhythmicity in serotonin-induced acute gastric mucosal injury in rats.
Time-dependent patterns in the susceptibility of the rat gastric mucosa to ulcerogenic stimuli involving stress or chemical injury have been described. The purpose of this study was to evaluate whether serotonin (5-HT)-induced gastric mucosal injury is produced in a circadian fashion in the rat model. In fasted Wistar rats (adapted for 3 weeks to a standard 12-h light-dark cycle), 5-HT administered subcutaneously (20 mg/kg, 4 h before autopsy) produced gastric mucosal injury. The stomachs were removed and the ulcers were scored for intensity, using a scale of 0-4. In studies performed at 4-h intervals, beginning 1 h after lights-on, most of the mucosal injury occurred at 2000 h, i.e. early in the dark phase. Likewise, serum corticosterone levels were also found to be high at the same time period. The time of 2000 h is approximately determined to be the beginning of the rats' active period. These results suggest that the extent of acute 5-HT-induced gastric mucosal injury varies with the time of day and that elevations in corticosterone concentrations might be responsible for the 5-HT-induced gastric mucosal injury.
Acute Disease↗
The effects of 4-aminopyridine and Bay K 8644 on verapamil-induced cardiovascular toxicity in anesthetized rats.
OBJECTIVE: To determine the effects of 4-aminopyridine and Bay K 8644 on mean arterial pressure and heart rate in an anesthetized rat model of verapamil toxicity. METHODS: The study was a randomized, controlled animal study. Rats were anesthetized and the carotid artery was cannulated for mean arterial pressure and heart rate measurements while both jugular veins were cannulated for drug administration. All animals were infused with verapamil (15 mg/kg/h i.v.) until 45-60% reduction of mean arterial pressure and 30% reduction of heart rate were observed. After verapamil, control animals were given normal saline solution and the other groups received 4-aminopyridine (1 and 2 mg/kg/h) or Bay K 8644 (0.3 and 0.6 mg/kg/h) for 60 minutes. RESULTS: While 4-aminopyridine (1 mg/kg/h i.v.) did not significantly increase mean arterial pressure (75.9 +/- 5.5%) when compared with the control group (64.3 +/- 5.1%, p > 0.05), 2 mg/kg/h i.v. of 4-aminopyridine improved mean arterial pressure within 40 minutes (87.4 +/- 6.6%, p < 0.05, 95% CI 66.4-108.6%). Because the 2 mg/kg/h 4-aminopyridine produced side effects including seizures, secretions, and fasciculations at 35 +/- 5 minutes, the infusion was stopped at that time. Only the 2 mg/kg/h 4-aminopyridine infusion increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 283.2-364.4). Bay K 8644 (0.3 and 0.6 mg/kg/h i.v.) significantly enhanced mean arterial pressure within 5 minutes (68.0 +/- 4.1% and 73.0 +/- 2.9%, respectively, p < 0.05), (95% CI 56.8-78.0% and 95% CI 64.9-81.1%, respectively) but no significant changes in mean arterial pressure were observed after 5 minutes. The 4-aminopyridine (2 mg/kg/h) increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 311.3-358.7). Bay K 8644 did not produce a significant effect on heart rate (p > 0.05). CONCLUSIONS: 4-Aminopyridine improved mean arterial pressure and heart rate in a dose-dependent fashion; however, the higher infusion rate (2 mg/kg/h) necessary to improve mean arterial pressure and heart rate resulted in convulsions and excessive secretions. The reversal effects of Bay K 8644 on mean arterial pressure were transient and did not affect heart rate.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗