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Biomedical subjects

N Chung

Publications and source records attributed to N Chung.

At least 19 recordsLinked to original sources
PubMed2006

Delivering results to clients: a question of satisfying needs or desires?

Demand for genitourinary (GU) medicine services is outstripping supply. Improving efficiency can modulate the supply side of the equation, e.g. decreasing the number of clients having to return for their results. This survey explored how clients at two central London GU medicine clinics would like to receive their results and their views were reflected against what was offered by London GU medicine clinics. There was a significant difference between the result delivery services that the clients wanted and what the clinics provided (P <0.0001, chi(2)). Of the clients, 92% wanted to know their results regardless of outcome whereas 22% of London clinics would only inform clients of positive results. This study questions the importance and feasibility of patient choice, an important aspect of the National Strategy for Sexual Health and HIV. Clinics may not individually be able to provide choice but between them, they do provide a wide range of alternatives for the client.

HIV Infections↗
PubMed2004

Sildenafil improves cutaneous microcirculation in patients with coronary artery disease: a monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study.

UNLABELLED: Endothelial dysfunction of precapillary arterioles impairs nutritional microcirculation at rest as well as during post-ischemic reactive hyperemia. In this monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study we investigated the acute effect of 50 mg sildenafil, a selective PDE-5 inhibitor, on resting and post-ischemic capillary circulation in twenty patients with angiographically confirmed coronary artery disease not taking nitrates or NO-donors. Mean erythrocyte velocity in digital nail-fold capillaries was determined before and after sildenafil and placebo, both baseline and after a three-minutes supra-systolic occlusion of the upper arm. Primary efficacy parameter was the drug effect on peak velocity during reactive hyperemia (peak velocity: V(max)). Post ischemic maximal capillary erythrocyte velocity V(max) significantly increased by 47% one hour after 50 mg sildenafil (mean value+/-standard deviation: 0.85+/-0.42 mm/s vs. 0.58+/-0.18 mm/s at baseline, p=0.0023), whereas placebo had no effect (p=0.5248). The difference between sildenafil and placebo was significant (p=0.0129) and sildenafil's effect can be regarded as biometrically highly relevant with standardized difference according to Cohen of 0.81. In spite a small decrease of both systolic and diastolic blood pressure after sildenafil, sildenafil significantly increased capillary erythrocyte velocity at rest. CONCLUSION: A single oral dose of sildenafil significantly increased resting and post-ischemic cutaneous capillary circulation in patients with coronary artery disease. Future studies should assess whether sildenafil also improves nutritional capillary blood flow in other organs and in other diseases with impaired endothelial function and microcirculation, for example in diabetic microangiopathy.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Phytosphingosine as a specific inhibitor of growth and nutrient import in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, we have demonstrated a necessary role for sphingolipids in the heat stress response through inhibition of nutrient import (Chung, N., Jenkins, G. M., Hannun, Y. A., Heitman, J., and Obeid, L. M. (2000) J. Biol. Chem. 275, 17229-17232). In this study, we used a combination of pharmacological and genetic approaches to determine which endogenous sphingolipid is the likely mediator of growth inhibition. When cells were treated with exogenous phytosphingosine (PHS, 20 microm) or structurally similar or metabolically related molecules, including 3-ketodihydrosphingosine, dihydrosphingosine, C(2)-phytoceramide (PHC), and stearylamine, only PHS inhibited growth. Also, PHS was shown to inhibit uptake of uracil, tryptophan, leucine, and histidine. Again this effect was specific to PHS. Because of the dynamic nature of sphingolipid metabolism, however, it was difficult to conclude that growth inhibition was caused by PHS itself. By using mutant yeast strains defective in various steps in sphingolipid metabolism, we further determined the specificity of PHS. The elo2Delta strain, which is defective in the conversion of PHS to PHC, was shown to have slower biosynthesis of ceramides and to be hypersensitive to PHS (5 microm), suggesting that PHS does not need to be converted to PHC. The lcb4Delta lcb5Delta strain is defective in the conversion of PHS to PHS 1-phosphate, and it was as sensitive to PHS as the wild-type strain. The syr2Delta mutant strain was defective in the conversion of DHS to PHS. Interestingly, this strain was resistant to high concentrations of DHS (40 microm) that inhibited the growth of an isogenic wild-type strain, demonstrating that DHS needs to be converted to PHS to inhibit growth. Together, these data demonstrate that the active sphingolipid species that inhibits yeast growth is PHS or a closely related and yet unidentified metabolite.

Biological Transport↗
PubMed2001

Enhanced detection of right-to-left shunt through patent foramen ovale by transthoracic contrast echocardiography using harmonic imaging.

When the results of transesophageal echocardiography was regarded as the gold standard for detecting a patent foramen ovale (PFO) in 136 consecutive patients referred for evaluation of cardiac source of embolism, transthoracic harmonic imaging using saline contrast was superior to fundamental imaging in accuracy for detecting a PFO (sensitivity, 22.5%; specificity [p < 0.05] and sensitivity, 100%; specificity 100%, respectively.)

Adult↗
PubMed2001

Effects of left atrial compliance on left atrial pressure in pure mitral stenosis.

In mitral stenosis (MS), left atrial (LA) pressure is commonly elevated because of increased LA afterload. There is a wide spectrum of LA pressure in patients with MS, however, despite a similar mitral valve orifice area. LA compliance is an important determinant of both cardiovascular performance and pathological physiology. Few data are available, however, regarding the effects of LA compliance on LA pressure. We hypothesized that LA pressure may be higher in patients with decreased LA compliance. We analyzed the right heart and transseptal catheterization data in 47 patients (41 female, mean age 40 +/- 10 years) with pure MS and sinus rhythm. The magnitude of LA a and v waves was measured from transseptal catheterization. Fick's method was used to determine cardiac output. LA compliance was calculated by dividing the systolic rise in LA pressure (DeltaP(LA) = P(LA(v)) - P(LA(x))) into the stroke volume. LA size, mitral valve area (MVA), mean diastolic pressure gradient (MG), left ventricular (LV) end-diastolic and end-systolic dimensions were obtained by using two-dimensional and Doppler echocardiography. Multiple regression analysis was performed to identify independent factors determining LA pressure. The mean MVA was 0.95 +/- 0.22 cm(2). MG and LA dimension were 11.2 +/- 5.2 mm Hg and 50.6 +/- 5.2 mm, respectively. The mean LA pressure and cardiac output obtained by cardiac catheterization were 23.4 +/- 8.4 mm Hg and 4.3 +/- 1.5 L/min, respectively. The calculated LA compliance was 4.9 +/- 2.8 cm(3)/mm Hg. Univariate analysis showed that factors associated with increased LA pressure were smaller MVA (r = -0.33, P < 0.05), higher MG (r = 0.69, P < 0.01) and lower LA compliance (r = -0.55, P < 0.01); among them, MG (beta coefficient 0.59, SE 0.19, P < 0.01) and LA compliance (beta coefficient -0.26, standard error 0.34, P < 0.05) were the strongest predictors of LA pressure. In conclusion, LA compliance, along with MG that reflects the severity of MS, is an important contributing factor determining LA pressure in patients with pure MS and sinus rhythm.

Adult↗
PubMed2001

STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target.

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.

Aged↗
PubMed2001

Left atrial appendage stenosis.

We describe an unusual case with an anatomic narrowing at the opening of the left atrial appendage demonstrated by two-dimensional color Doppler and continuous-wave Doppler transesophageal echocardiography.

Atrial Appendage↗
PubMed2001

Flail aortic valve and acute aortic regurgitation due to spontaneous localized intimal tear of ascending aorta.

This report describes the transesophageal echocardiographic findings of acute severe aortic regurgitation resulting from localized transverse intimal tear of ascending thoracic aorta which could not be suspected as a cause of flail aortic valve preoperatively. In patients with chest pain and acute aortic regurgitation associated with flail aortic valve, localized intimal tear of aorta should be considered as a possible cause of flail aortic valve.

Aortic Rupture↗
PubMed2001

Assessment of left atrial appendage filling pattern by using intravenous administration of microbubbles: comparison between mitral stenosis and mitral regurgitation.

Mitral stenosis (MS) and mitral regurgitation (MR) are the most frequent conditions that cause a dilation and dysfunction of the left atrial appendage (LAA). Despite similarly dilated LAA in patients with MS and MR, the incidence of LAA thrombi and the risk of thromboembolism is different between these patients. The purpose of this study was to characterize the filling pattern of LAA by using intravenous administration of perfluorocarbon-exposed dextrose albumin (PESDA) during transesophageal echocardiographic examination in patients with MS and MR. Twenty-four patients with moderate to severe MS, 12 patients with severe MR, and a control group including 30 patients with conditions other than mitral valve disease underwent transesophageal echocardiographic examination with an intravenous bolus injection of PESDA. LAA emptying and filling velocities and maximal and minimal areas of LAA and LAA ejection fraction were measured. Digital gray-scale intensity (GSI) of the left atrial (LA) and LAA cavity after PESDA injection was measured by off-line analysis. Compared with control patients, patients with MS or MR had larger maximal and minimal areas of LAA and reduced LAA ejection fraction. LAA peak emptying flow velocity was significantly lower in patients with MS compared with those of MR or control patients. LAA peak filling velocity was significantly lower in patients with MS compared with that of control patients. However, there was no significant difference of LAA peak filling velocity between the patients with MS and MR. There was no significant difference of GSI ratio of LAA and LA between patients with MR and control patients; however, GSI ratio of LAA and LA was significantly lower in patients with MS compared with that of MR. The incidence of LAA spontaneous echo contrast and LAA thrombi in patients with MS was significantly higher than that of the patients with MR and control subjects (P <.005). Despite similarly dilated LAA area and depressed contractile function of LAA in patients with MS and MR compared with control patients, profoundly impaired LAA filling with resultant flow stasis was demonstrated by contrast echocardiography in patients with MS. These findings may explain the higher incidence of LAA spontaneous echo contrast and thrombus in patients with MS.

Aged↗
PubMed2001

Long-term results with St. Jude Medical and CarboMedics prosthetic heart valves.

BACKGROUND AND AIM OF THE STUDY: The clinical evaluation and comparison of St. Jude Medical (SJM) and CarboMedics (CM) prosthetic heart valves implanted between 1988 and 1997 is presented. METHODS: In total, 648 SJM valves were implanted in 641 patients, and 601 CM valves in 591 patients. There were 684 mitral valve replacements, 256 aortic valve replacements, 252 mitral and aortic (double) valve replacements, 16 triple valve replacements, and 41 other tricuspid-related valve replacements. Total follow up was 98%. The overall incidence of valve-related events was compared before and after establishment of a 'valve clinic' in 1993. RESULTS: The overall hospital mortality was 3.4%; late mortality was 8.2%. The five- and ten-year survival for all patients was 92.1% and 86.2%, respectively. There were 31 episodes of thromboembolism in 27 patients (including valve thrombosis in three), 21 episodes of bleeding events in 20 patients, and 18 re-replacements of implanted valves. No structural valve deterioration was observed. Freedom from thromboembolism was 97.8% at five years and 96.3% at ten years; freedom from bleeding episodes was 98.1% and 97.6%, respectively. In terms of hospital and late mortality, and incidence of thromboembolism, hemorrhagic episodes and structural valve failure, no statistically significant differences were found between the SJM and CarboMedics patient groups. Freedom from thromboembolism was 96.7% at five years before initiation of an intensive follow up program, and 99.0% thereafter (p = 0.031). In contrast, freedom from bleeding episodes fell from 99.3% to 96.1% during the same time period (p = 0.0004). CONCLUSION: Both the SJM and CM prosthetic heart valves performed well in our study, and no discernible differences in clinical performance of the two valves were detected. The intensive follow up program resulted in a reduced incidence of thromboembolism, but an increased number of bleeding complications. An optimum anticoagulation regimen to manage these two conflicting problems has yet to be elucidated.

Adolescent↗
PubMed2000

Sphingolipids signal heat stress-induced ubiquitin-dependent proteolysis.

Sphingolipids are essential eukaryotic membrane lipids that are structurally and metabolically conserved through evolution. Sphingolipids have also been proposed to regulate eukaryotic stress responses as novel second messengers. Here we show that, in Saccharomyces cerevisiae, phytosphingosine, a putative sphingolipid second messenger, mediates heat stress signaling and activates ubiquitin-dependent proteolysis via the endocytosis vacuolar degradation and 26 S proteasome pathways. Inactivation of serine palmitoyltransferase, a key enzyme in generating endogenous phytosphingosine, prevents proteolysis during heat stress. Addition of phytosphingosine bypasses the requirement for serine palmitoyltransferase and restores proteolysis. Phytosphingosine-induced proteolysis requires multiubiquitin chain formation through the stress-responsive lysine 63 residue of ubiquitin. We propose that heat stress increases phytosphingosine and activates ubiquitin-dependent proteolysis.

Acyltransferases↗
PubMed2000

Is the left atrial v. wave the determinant of peak pulmonary artery pressure in patients with pure mitral stenosis?

A large left atrial (LA) v. wave can be observed in patients with pure mitral stenosis (MS) because of decreased LA compliance. Few data are available regarding the relation between the magnitude of the LA v wave and pulmonary artery pressure in MS. We hypothesized that pulmonary artery pressure may be higher in patients with decreased LA compliance and thus a large v. wave. We analyzed the right-sided cardiac and transseptal catheterization data in 113 patients (16 men and 97 women, mean age 39 years) with pure rheumatic MS in sinus rhythm. Peak systolic, diastolic, and mean pulmonary artery pressures were measured with right-sided cardiac catheterization. The magnitude of LA a and v. waves were measured through transseptal catheterization. Two-dimensional and Doppler echocardiography were also performed to measure LA size, mitral valve area, mean mitral gradient, and valvular regurgitation. Multiple regression analysis was performed to identify the most important factor in the determination of pulmonary artery pressure. A large v wave, defined if peak v wave height exceeded the mean LA pressure by > or =10 mm Hg, was observed in 43 of 113 patients (38%). Increased pulmonary artery systolic pressure (> or =50 mm Hg) was observed in 38 patients (34%). Univariate analysis showed that the factors associated with increased pulmonary artery systolic pressure were smaller mitral valve area, higher mean mitral gradient, higher mean LA pressure, and higher LA v. wave; among them, LA v wave (p <0. 001) and mean mitral gradient (p<0.001) were significant independent factors for pulmonary artery systolic pressure in multivariate analysis. In conclusion, in patients with pure MS and sinus rhythm, the magnitude of the LA v. wave is strongly associated with pulmonary artery pressure. This finding may suggest that LA compliance is a major contributing factor determining pulmonary artery pressure in pure MS.

Adult↗