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Biomedical subjects

O Uzun

Publications and source records attributed to O Uzun.

At least 37 records · Page 2Linked to original sources

Progressive disease of the atrioventricular conduction axis in an infant of an anti-Ro positive mother.

A child of a mother with maternal anti-Ro and anti-La antibodies presented antenatally with abnormal myocardial function, and was found to have a first degree heart block at birth. The extent of the abnormality in the conduction system progressed, with appearance of left bundle branch block in addition to further prolongation of PR interval. A pacemaker was implanted prophylactically, but patient has remained well, with no further deterioration in her atrioventricular conduction.

Antibodies, Antinuclear↗

The role of nitric oxide in digoxin-induced arrhythmias in guinea-pigs.

We have investigated the effects of nitric oxide synthase inhibitor (L-NAME), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitroprusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mumol kg-1 min.-1 for 70 min.) caused a marked inhibition in mortality and arrhythmia score but L-NAME (10 mg kg-1) and L-arginine (30 mg kg-1 intravenous bolus followed by 10 mg kg-1 min.-1 for 60 min.) treatments were ineffective in anaesthetised guinea-pigs. None of the drugs markedly affected the time of onset of first arrhythmias or ventricular fibrillation incidence. In isolated heart experiments, nitric oxide generated by either L-arginine (1 mM) or sodium nitroprusside (1 mM) significantly reduced the arrhythmia score whereas L-NAME (1 mM) had no effect. Ventricular fibrillation incidence was totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decreased ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhythmias with these drugs in in vitro experiments. These results suggest that nitric oxide may play a modulatory role in the digoxin-induced arrhythmias in guinea-pigs.

Animals↗

Haemolysis following implantation of duct occlusion coils.

OBJECTIVES: To describe the incidence and management of haemolysis after transcatheter coil occlusion of the arterial duct. DESIGN: Prospective clinical and echocardiographic follow up of patients who have undergone implantation of the Cook detachable duct occlusion coil. SETTING: Tertiary paediatric cardiac centre. PATIENTS: Five cases of haemolysis (two girls aged 6 and 11 months; three boys aged 6, 17, and 14 months) from a series of 137 duct coil implantations. MAIN OUTCOME MEASURES: The occurrence of clinically significant haemolysis after implantation of duct occlusion coils and resolution of haematuria after completion of duct occlusion. RESULTS: Haemolysis was detected in five of 137 procedures following implantation of Cook detachable duct coils. Four patients became symptomatic 12 hours after the procedure but in one haemolysis was detected three months later. Resolution of ongoing haemolysis was achieved within 48 hours of detection with further coil implantations, but haematuria persisted for up to 10 days. In one patient the extensive destruction of erythrocytes resulted in acute renal failure requiring peritoneal dialysis. CONCLUSIONS: Haemolysis is an important complication after duct coil implantation. It occurred in 3.6% of 137 procedures in this series and is most likely to occur in young patients with relatively large ducts. Further coil implantation to occlude the duct completely is not only successful but technically relatively straightforward and should be undertaken early if major complications such as severe anaemia and renal failure are to be avoided.

Acute Kidney Injury↗

The role of tyrosine kinase in hypoxic constriction of sheep pulmonary artery rings.

Complex and incompletely understood mechanisms underline the vascular responses to hypoxia. Recent studies showed that the tyrosine kinase pathway is involved in vasoconstriction of vascular smooth muscle. Therefore, the aim of this study was to determine the tyrosine kinase pathway for the hypoxic contraction in large-diameter sheep pulmonary artery rings in vitro by studying the effects of selective inhibitors of tyrosine kinase and of a protein tyrosine kinase inhibitor. Lowering the pO2 from 96 to 5 mm Hg caused a contraction in arteries precontracted with 5-hydroxytryptamine (5-HT) but not under resting force. Preincubation of arteries with the tyrosine kinase inhibitors, genistein and tyrphostin, abolished the hypoxic contraction without affecting 5-HT contractions. Inhibition of tyrosine phosphatase activity by sodium orthovanadate increased the hypoxic vasoconstriction in 5-HT-precontracted arteries. These results suggest that the tyrosine kinase pathway is involved in hypoxic pulmonary vasoconstriction in sheep isolated pulmonary artery rings.

Animals↗

Predictors of adverse outcome in cancer patients with candidemia.

BACKGROUND: Many factors, including severity of illness, neutropenia, intravenous catheter management, and drug therapy may affect the outcome of candidemia in cancer patients. METHODS: The records of all patients at M. D. Anderson Cancer Center who developed one or more positive blood cultures for Candida spp between January 1, 1988, and December 31, 1992, were retrospectively reviewed. Four hundred ninety-one episodes of candidemia were identified, for which 476 had complete medical records, which were reviewed in detail. RESULTS: By 3-month follow-up, 52% of the patients had died. Neutropenia, higher APACHE III score, and visceral dissemination were associated with poor prognosis. Cure rates, adjusted for severity of illness, were similar for fluconazole and amphotericin B treatment. Exchange of central venous catheters was associated with a modest improvement in prognosis. CONCLUSION: Several factors that influence the outcome of candidemia in cancer patients have been identified. These factors may be relevant for the clinical management of cancer patients with candidemia, and for the design of therapeutic trials.

Adult↗

In vivo Ty1 reverse transcription can generate replication intermediates with untidy ends.

Ty1 retrotransposition, like retroviral replication, is a complex series of events requiring reverse transcription of an RNA intermediate, RNA-primed minus- and plus-strand DNA synthesis, multiple strand transfers, and precise cleavages of the template and primers by RNase H. In this report, we examine the structure of in vivo Ty1 replication intermediates, specifically with regard to the behavior of reverse transcriptase upon reaching template ends and to the precision with which RNase H might generate these ends. While the expected 3' termini were always identified, terminal nontemplated bases were also observed at all of the RNA and DNA template ends examined. Nontemplated A residues were most common at all 3' ends, although C residues were preferentially added to minus-strand termini paused at the 5' end of capped Ty1 RNA. In addition, we observed that RNase H removal of the tRNA primer and of the polypurine tract was not always precise or efficient. Finally, we noted numerous instances of Ty1 reverse transcriptase transferring from normal Ty1 template ends to various tRNA templates, with continued synthesis to specific modified bases. A similar pattern was obtained for Ty2, indicating that template ends offer unique opportunities for these two related reverse transcriptases to generate errors.

Base Composition↗

Replication errors during in vivo Ty1 transposition are linked to heterogeneous RNase H cleavage sites.

We previously identified a mutational hotspot upstream of the Ty1 U5-primer binding site (PBS) border and proposed a novel mechanism to account for this phenomenon during Ty1 replication. In this report, we verify key points of our model and show that in vivo RNase H cleavage of Ty1 RNA during minus-strand strong-stop synthesis creates heterogeneous 5' RNA ends. The preferred cleavage sites closest to the PBS are 6 and 3 bases upstream of the U5-PBS border. Minus-strand cDNA synthesis terminates at multiple sites determined by RNase H cleavage, and DNA intermediates frequently contain 3'-terminal sequence changes at or near their template ends. These data indicate that nontemplated terminal base addition during reverse transcription is a real in vivo phenomenon and suggest that this mechanism is a major source of sequence variability among retrotransposed genetic elements.

DNA Replication↗

Residual and recurrent shunts after implantation of Cook detachable duct occlusion coils.

OBJECTIVE: To assess the presence and outcome of Doppler detectable shunts following implantation of the Cook detachable PDA coil. DESIGN: Prospective study. SETTING: Tertiary paediatric cardiac centre. PATIENTS: 76 consecutive patients undergoing coil implantation (80 procedures). MAIN OUTCOME MEASURES: Detection and colour Doppler echocardiographic appearance of residual or recurrent shunts, the timing of the appearance of recurrent shunts, and the time taken for spontaneous resolution of these shunts. RESULTS: Immediate occlusion was achieved in 52 patients. At one month 63 patients had complete occlusion and after three months the duct was completely occluded in 67 patients. In 27 cases small residual shunts were detected on echocardiography 10 minutes after the completion of the implantation procedure; 15 of these had resolved by 24 hours and 20 had resolved by three months. Recurrent shunts were detected after apparent initial complete occlusion in 11 cases 24 hours after coil implantation and in two cases one month after the procedure. Six recurrent shunts resolved on later follow up. Residual shunts appeared as single jets after implantation of a single coil, but up to three separate jets were detected after implantation of multiple coils. CONCLUSIONS: Spontaneous resolution of small residual shunts occurs in most patients. The recurrence of small shunts after apparent complete occlusion suggests that recanalisation of the duct may occur in a small percentage of patients up to one month after occlusion. Residual shunts may take the form of multiple residual jets that may require implantation of further coils to achieve complete duct occlusion.

Ductus Arteriosus, Patent↗

The epidemiology of hematogenous candidiasis caused by different Candida species.

The medical records of patients with hematogenous candidiasis at M. D. Anderson Cancer Center (Houston) between 1988 and 1992 were retrospectively reviewed. There were 491 episodes of infection (6 per 1,000 admissions), 79% of which occurred outside the intensive care unit setting. A significant decrease in incidence was observed among patients with leukemia over the study period, together with a relative decrease in Candida albicans and Candida tropicalis infections and an increase in Candida krusei and possibly Candida glabrata infections. In the multivariate analysis, fluconazole prophylaxis provided strong protection against the development of C. tropicalis infection (odds ratio [OR] = 0.08) and C. albicans infection (OR = 0.15), in comparison with protection against infections due to other species, but it was the single most important determinant for the relative increase in C. krusei (OR = 27.07) and C. glabrata (OR = 5.08) infections. In conclusion, there has been a substantial shift in the epidemiology of hematogenous candidiasis caused by different Candida species in recent years. Fluconazole appears to be playing a major role in this observed shift.

Adult↗

In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates.

The in vitro activity of LY303366, a new echinocandin derivative, was evaluated with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of the isolates were inhibited were 0.125 microg/ml for Candida albicans and C. tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0 microg/ml for C. parapsilosis.

Amphotericin B↗

Congenital total lipodystrophy and peripheral pulmonary artery stenosis.

Multiple peripheral pulmonary artery stenoses were detected in three patients with congenital generalised lipodystrophy. This association, which has not been described before, may be clinically important in patients with lipodystrophy who present with impaired exercise tolerance or heart murmurs.

Adolescent↗

Right ventricular outflow stent implantation: an alternative to palliative surgical relief of infundibular pulmonary stenosis.

OBJECTIVE: Preliminary assessment of the use of stents for palliative relief of right ventricular infundibular stenosis as an alternative to palliative surgical ventricular outflow enlargement. DESIGN: Descriptive clinical study. PATIENTS: Four patients with right ventricular outflow obstruction, aged between 2 and 15 years. One had had previous palliative surgery for pulmonary atresia, one had hypoplastic pulmonary arteries after palliative surgery for tetralogy of Fallot, one had multiple congenital abnormalities, and one had hypertrophic cardiomyopathy. SETTING: Tertiary paediatric cardiac centre. METHODS: After initial echocardiographic diagnosis the extent of right ventricular outflow obstruction was assessed by angiography. Balloon expandable stainless steel stents (Johnson & Johnson) were deployed in the right ventricular infundibulum. MAIN OUTCOME MEASURES: Improvement in right ventricular outflow assessed by ventriculography and change in right ventricular/ left ventricular pressure ratio, change in systemic oxygen saturation, freedom from arrhythmias, and sustained improvement in echocardiographic indices of obstruction. RESULTS: Mean right to left ventricular pressure ratio fell from 0.95 to 0.35 in the three patients with intact ventricular septum. Oxygen saturation increased from 76% to 91% in the patient with tetralogy. No arrhythmias were detected. Improvement was maintained at mean follow up of 9.7 months in three cases, but one patient required stent enlargement 17 months later because of neoendothelial proliferation within the stent. CONCLUSION: Stent implantation provides an effective alternative to palliative surgical enlargement of the right ventricular infundibulum. Neoendothelial proliferation causes reduction in lumen in some cases, but this may respond to redilatation.

Adolescent↗

Laser valvotomy with balloon valvoplasty for pulmonary atresia with intact ventricular septum: five years' experience.

OBJECTIVE: To assess immediate and medium term results of transcatheter laser valvotomy with balloon valvoplasty in selected infants with pulmonary atresia and intact ventricular septum. DESIGN: Prospective study. SETTING: Tertiary cardiac unit. PATIENTS: All infants with pulmonary atresia and intact septum with no more than minor tricuspid valve hypoplasia referred between November 1990 and June 1995. Laser valvotomy was attempted in nine infants of median age 4-5 days and median weight 3.6 kg. INTERVENTION: The pulmonary valve was perforated using a 0.018 inch fibreoptic guidewire attached to a NdYag laser and introduced through a catheter positioned beneath the valve. After perforation the valve was dilated with progressively larger balloons. MAIN OUTCOME MEASURES: Successful laser valvotomy and balloon dilatation, complications, pulse oximetry, right ventricular outflow velocities, and need for surgical treatment. RESULTS: Valvotomy was successful in all but one case, the failure being due to laser breakdown. After perforation the valve was dilated to 6-8 mm diameter. Prostaglandin E was withdrawn immediately in six of the eight duct dependent infants, and 28 and 49 days later in two. No patient required an aortopulmonary shunt. Two patients had repeat valvoplasty at 20 days and three months of age, respectively; one required infundibular resection and closure of the atrial septum at age four and one is awaiting similar treatment. CONCLUSIONS: Laser valvotomy with balloon valvoplasty is safe and effective treatment for selected patients with pulmonary atresia and intact ventricular septum and should be considered as first line treatment in place of surgical valvotomy.

Catheterization↗