The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing-induced preconditioning in conscious rabbits.

1. Tolerance to the hypotensive effect of nitroglycerin (NG) blocks preconditioning induced by rapid ventricular pacing (RVP) in rabbits. In the present work the effect of continuous versus intermittent treatment with transdermal nitroglycerin on the pacing-induced preconditioning phenomenon was studied in conscious rabbits. 2. RVP (500 beats min-1 over 5 min) increased left ventricular end-diastolic pressure (LVEDP) from baseline 4.1 +/- 0.9 to postpacing 13.8 +/- 2.9 mmHg (P < 0.001) with a right intraventricular ST-segment elevation of 1.25 +/- 0.13 mV, two indicators of myocardial ischaemia. These changes were significantly attenuated when the RVP period was preceded by a preconditioning pacing of the same rate and duration with an interpacing interval of 5 min. 3. Protection by preconditioning was abolished when the animals had been made tolerant to the vasodilator effect of 30 micrograms kg-1 NG by the application of transdermal NG (approx. 0.07 mg kg-1 h-1) over 7 days. Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment elevation and LVEDP-increase over the 7 day period. 4. With intermittent transdermal NG treatment (12 h 'patch on' vs 'patch off'), neither development of vascular tolerance nor attenuation of the NG- or preconditioning-induced anti-ischaemic effects were observed. However, the severity of pacing-induced myocardial ischaemia was significantly increased during the 'patch off' periods. 5. In a second set of experiments, postpacing changes in cardiac cyclic GMP and cyclic AMP levels were determined by means of radioimmunoassay in chronically instrumented anaesthetized open-chest rabbits with the same NG-treatment protocols. Preconditioning reduced postpacing increase in cyclic AMP with an increase in cyclic GMP concentrations in hearts of the untreated animals and in those given patches intermittently during both 'patch on' and 'patch off' periods. However, the preconditioning effect on either cyclic nucleotide was blocked in the tolerant animals. 6. Transdermal NG increased resting levels of both cardiac cyclic nucleotides in the non-tolerant but not in the tolerant state. The postpacing increase in cyclic AMP content was inhibited by transdermal NG, independent of vascular tolerance development, whereas an cyclic GMP content was exclusively seen in the non-tolerant animals. 7. We conclude that the anti-ischaemic effect of NG is independent of the cyclic GMP mechanism in the tolerant state. While intermittent NG therapy prevents development of vascular tolerance and preserves preconditioning, the nitrate-free periods yield an increased susceptibility of the heart to ischaemic challenges.

Loss of preconditioning in rabbits with vascular tolerance to nitroglycerin.

A preceding right ventricular overdrive pacing (VOP) of 500 b.p.m. for 5 min, markedly reduced the severity of global myocardial ischaemia produced by a subsequent 5-min VOP in conscious rabbits. This VOP-induced preconditioning developed in parallel with an increase in cardiac cyclic guanosine 3':5'-monophosphate (cyclic GMP) content. VOP-induced preconditioning was abolished when the animals had been made tolerant to the vasodilator effect of nitroglycerin (NG). In the heart of the NG-tolerant rabbits, neither VOP nor preconditioning increased cyclic GMP content. This suggests that changes by NG tolerance of cyclic GMP metabolism may account for the loss of VOP-induced preconditioning.

Regional differences in nitric oxide-mediated relaxation of the rabbit sphincter of Oddi.

We studied the role of the L-arginine-nitric oxide (NO) pathway in non-adrenergic, non-cholinergic (NANC) relaxation of the rabbit sphincter of Oddi by recording changes in isometric tension in response to electrical field stimulation in two series of experiments. In a first set of experiments, biliary sphincters of Oddi removed from New Zealand white rabbits were placed horizontally in an organ bath containing oxygenized, buffered (pH 7.4) Krebs solution. Contractile responses of the whole sphincter to field stimulation were determined. In the second set of experiments, sphincter of Oddi was divided into two parts and the effects of field stimulation were studied separately on areas close to the duodenal papilla (area I) and areas close to the common bile duct (area II). In the whole sphincter of Oddi, field stimulation induced an initial twitch-like contraction followed by relaxation proportional to the number of stimuli (3 and 10 stimuli at 20 Hz, 50 V, 0.1 ms). The magnitude of the contractile responses was considerably reduced by 1 microM atropine, phentolamine and oxprenolol (NANC solution). Field stimulation produced dose-dependent contractions of both segments of sphincter of Oddi in response to the same protocol as used with whole sphincter of Oddi. However, preincubation with NANC solution produced monophasic relaxations in response to field stimulation in area I, whereas area II preparations such as the whole sphincter of Oddi responded with contractions followed by minimal relaxations. Field stimulation failed to induce either contractions or relaxations in the presence of 1 microM tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired nitrergic relaxation of the sphincter of Oddi of hyperlipidaemic rabbits.

Field stimulation relaxed the sphincter of Oddi muscle rings of the rabbit after incubation with phentolamine, oxprenolol and atropine (all 1 microM). The relaxation was blocked by NG-nitro-L-arginine methyl ester (30 microM) and was reversed by 3 mM L-arginine but not D-arginine. Sphincter of Oddi preparations from hypercholesterolaemic rabbits exhibited contractions under the same conditions. We conclude that nitrergic relaxation is impaired in the sphincter of Oddi from hypercholesterolaemic rabbits.

Zaprinast, cicletanine, and verapamil attenuate overdrive pacing-induced myocardial ischemia in conscious rabbits.

In conscious rabbits equipped with right ventricular electrode and left ventricular polyethylene catheters, zaprinast and cicletanine, inhibitors of phosphodiesterase (PDE) V and PDEs I and V, respectively, as well as verapamil, a Ca2+ channel blocker, decreased intracavital ST-segment elevation induced by ventricular overdrive pacing (VOP). Zaprinast and cicletanine attenuated VOP-induced QT reduction and increase in left ventricular end-diastolic pressure (LVEDP), whereas verapamil increased LVEDP. These results suggest that inhibition of cGMP-PDEs can protect heart against ischemia.

Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits.

Myocardial ischemia assessed by intracavital ST-segment elevation, shortening of ventricular effective refractory period (VERP), and increase in left ventricular end-diastolic pressure (LVEDP) was provoked by ventricular overdrive pacing (VOP) in conscious rabbits. Cromakalim (10 micrograms/kg), an ATP-sensitive K+ channel opener, and cicletanine (30 mg/kg), a cGMP-phosphodiesterase inhibitor, reduced VOP-induced ST-segment elevation and LVEDP-increase. Under resting conditions, cromakalim lowered blood pressure, increased heart rate (HR), and shortened VERP, whereas cicletanine decreased HR, prolonged VERP without changing blood pressure. Co-administration of cromakalim and cicletanine additively reduced VOP-induced ST-segment elevation, shortening of VERP, and LVEDP-increase. Cicletanine did not change cromakalim-induced hypotension but abolished reflexogenic tachycardia. This suggests that VERP shortening is not a prerequisite for the anti-ischemic effect of cromakalim, and the combination of these drugs may afford a potent and safe anti-ischemic effect without affecting hypotension induced cromakalim.

Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in rabbits: possible role of cardiac cyclic nucleotides.

BACKGROUND: This study examined whether cicletanine, an antihypertensive drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits. METHODS: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation and ventricular effective refractory period (VERP). PQ and QT intervals were measured in the chest-lead ECG, and dP/dtmax as well as left ventricular end-diastolic pressure (LVEDP) were recorded through a left intraventricular catheter. In separate groups, mean arterial blood pressure (MABP) was monitored from the right carotid artery. Experiments were performed on conscious rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after drug treatment and/or overdrive pacing for determination of cGMP and cAMP contents by radioimmunoassay. RESULTS: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dtmax, and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VERP. Overdrive pacing produced intracavital ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. Cicletanine administered 15 minutes before pacing significantly attenuated ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. In anesthetized animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacing. CONCLUSIONS: These results suggest that in correlation with alterations of cardiac cycle nucleotide contents, cicletanine protects the heart against pacing-induced myocardial ischemia.

[Primary lymphoma of the bladder]. / Primer húgyhólyag lymphoma.

The authors present the case of a 74-year-old man in whom bladder tumor was detected the reason for haematuria. The histological investigation of transurethral resected pattern showed lymphocytic lymphoma. In possession of the histological finding detailed haematological examination has been carried out, the patient was without evidence of lymphoma dissemination. He received multichemotherapy (6 courses) and locoregional cytostatic therapy and complete clinical remission was detected. The authors report our experience with extranodal bladder lymphoma included diagnostic and therapeutical notes as well as a review of the relevant literature.

[Detection of human papillomavirus infection by the nucleic acid hybridization method (a multicenter study)]. / Human papillomavírus-fertözés kimutatás nukleinsav hibridizációs módszerrel (multicentrikus tanulmány).

The human papillomaviruses (HPV) are regarded as one of the important agents of cervical carcinoma. A multicentre study was organized to determine the prevalence of HPV in the fertile female population in Hungary. Parallel with the clinical sample collection, a questionnaire interview was performed to acquire data on the life style, socioeconomic status, sexual practice, etc. 1200 women were examined colposcopically and cervix samples were collected for cytology and the detection of HPV DNA. 17.4% of the samples were HPV-infected. 3.9% of the patients had acquired low-risk, and 10.1% 10.2% high-risk HPV types; 3.4% of the women were at the same time infected with both low-risk and high-risk HPV types. Simultaneously performance of cytology and the HPV hybrid capture assay contribute to recognise and treat the precancerous status and risk factors.

Neuropsychological evaluation and rehabilitation in mental retardation.

A discussion is provided of issues related to neuropsychological assessment of mentally retarded individuals. The first matters considered are test selection in relation to mental age and diagnostic issues. Various methods of evaluation are then considered, including assessment of orientation to sound and visual stimuli, language comprehension, right-left discrimination, and abstract and symbolic processes. Methods are also reviewed for detailed evaluation of language functions including testing for aphasia and for academic skills such as reading, writing, and calculation, as well as for spatial and constructional abilities. A section is devoted to use of neuropsychological assessment for rehabilitation of various disorders such as congenital aphasia, alexia, and spatial-constructional disorders.

Short-term effect of thioridazine tablets versus suspension on emotionally disturbed/retarded children.

A 10-week study was conducted in four phases comparing the short-term efficacy of thioridazine tablets and thioridazine suspension for decreasing severe behavioral symptoms of psychotic retarded children. Behavioral observations were conducted in the classroom before and after medication, both during structured activity and during free play. Thioridazine was dispensed in phases I and III in tablet form and in phases II and IV in suspension, in the same amount of milligrams per subject throughout all four phases. Across all four phases the difference between the effects of thioridazine tablet and suspension was nonsignificant. On short-term observation both forms of thioridazine proved to be effective in reducing aggression, disruptive tantrumming, self-abuse, stereotype self-stimulation, and pica eating. The cumulative average symptom reduction was 27.4% within 35 minutes following medication intake.

Basal ganglia calcification and psychosis in mongolism.

An 18-year-old mongoloid girl (trisomy 21) of Asian descent presented two symptoms rarely associated with mongolism (Down's syndrome). (1) Brain stem calcification; the first case diagnosed in vivo in mongolism on computerized axial tomography. (2) Hallucinatory psychotic depression; the first case successfully treated, to full recovery from the psychosis, in a mongoloid child with known brain stem calcification. The psychotic depression was related to moderate environmental stress. While being treated in her parent's home, in their native land, for more than 1 year, the psychosis remained unresponsive to tranquilizers. Following hospital admission in the USA, rapid improvement was obtained within a few weeks through intensive milieu therapy.

Psychopathology of expression and psychoanalysis. The influence of the therapist's analytic orientation on the patient's art product.

The graphic symbols produced by patients in analysis are essentially determined by the therapist's interpretations in the early stages of graphic communication. The patient learns the 'symbol language' of the therapist. The more intense the transference, the more evident is the adaptation of the graphic symbolism in the patient's art product to the symbol language of the therapist's analytical school. Sample cases, with predominantly Freudian or Jungian symbols in the patient's sequential graphic expressions, document that conflict resolution can be achieved equally well through different methods of graphic symbol interpretation. In any of the analytic methods, the impact of therapy can be enhanced by the use of graphic language between the analyst and patient.

Effect of tetracycline on lymphocyte antigen expression.

Nowadays the existence of bearing both T and B marker lymphocytes has generally been accepted, but their role and nature is still unknown. The effect of tetracycline on lymphocytes was examined in 26 patients with different, mainly respiratory infections. Examinations were carried out on lymphocyte populations with T and B cell count using E rosette and surface immunoglobulin as a marker. It has been shown that on the lymphocytes of patients receiving tetracycline, regularly high number of D cells are found.

Glibenclamide sensitivity of neural relaxation of the rabbit sphincter of oddi.

In this article we studied whether the nitrergic relaxation of the rabbit sphincter was sensitive to glibenclamide. Field stimulation relaxed the sphincter of Oddi rings after incubation with atropine (1 microM) and guanethidine (4 microM) with threefold and fourfold increases in tissue guanosine 3':5'-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate contents, respectively. These changes were blocked by 30 microM NG-nitro-L-arginine methyl ester. Glibenclamide (0.1-10 microM) attenuated the field stimulation-induced relaxation and completely abolished the relaxation produced by 0.1 microM cromakalim. We conclude that nitrergic relaxation of the rabbit sphincter of Oddi comprises a mechanism sensitive to glibenclamide.