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K Sliwa

Publications and source records attributed to K Sliwa.

At least 19 recordsLinked to original sources
PubMed2006

Impact of beta2-adrenoreceptor gene variants on cardiac cavity size and systolic function in idiopathic dilated cardiomyopathy.

In heart failure, the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenoreceptor (beta2-AR) gene are associated with exercise-capacity, clinical outcomes and response to beta-AR blocker therapy. Whether beta2-AR gene variants mediate these effects in-part through an impact on cardiac structural remodeling and pump function independent of the effects of beta-blockers is uncertain. We evaluated whether the Arg16Gly and Gln27Glu variants of the beta2-AR gene predict left ventricular ejection fraction (LVEF) and LV end diastolic diameter (LVEDD) in patients with idiopathic dilated cardiomyopathy (IDC) before and 6 months after receiving standard medical therapy other than beta-AR blockers. In all, 394 patients with IDC and 393 age and gender-matched controls were genotyped for the beta2-AR gene variants using restriction-fragment length polymorphism-based techniques. LVEF and dimensions were determined in 132 patients (of whom 71 were newly diagnosed) both at baseline and after 6 months. Genotype of neither variant was associated with the presence of IDC. Moreover, beta2-AR genotype did not determine LVEF or LV dimensions prior to initiating therapy. After 6 months of therapy, LVEF increased by 7.1+/-1.0 absolute units (P<0.0001) and LVEDD decreased by 0.27+/-0.06 cm (P<0.02). Adjusting for baseline values as well as gender, age, and type of angiotensin-converting enzyme inhibitor therapy received, genotype was associated with neither final LVEF and LVEDD, nor change in LVEF and LVEDD. In conclusion, these data suggest that in heart failure, the functional Arg16Gly and Gln27Glu variants of the beta2-AR gene have no independent effect on adverse structural remodeling and pump function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study.

BACKGROUND: We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-alpha, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of beta-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and beta-blockers, the addition of pentoxifylline would have an additive beneficial effect. METHODS AND RESULTS: In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (P:=0.01), with an increment in exercise time from 9.5+/-5 to 12.3+/-6 minutes (P:=0.1). Left ventricular ejection fraction improved from 24+/-9% to 31+/-13%, P:=0.03, in the treatment group. CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Functions of WW domains in the nucleus.

The WW domain is a protein module found in a wide range of signaling proteins. It is one of the smallest protein modules that folds as a monomer without disulfide bridges or cofactors. WW domains bind proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. Although the WW domain was initially considered a 'cytoplasmic module', the proteins containing WW domains have also been localized in the cell nucleus. Moreover, these proteins have been documented to participate in co-activation of transcription and modulation of RNA polymerase II activity. The carboxy-terminal domain (CTD) of RNA polymerase II acts as an assembly platform for distinct WW domain-containing proteins that affect the function of the RNA polymerase II. The formation of complexes between CTD and WW domain-containing proteins is regulated by phosphorylation of the CTD. Since the CTD sequence is highly repetitive and a target of several post-translational modifications and conformational changes, it presents a unique structure capable of enormous molecular diversity. The WW domain has been implicated in several human diseases including Alzheimer's disease. The WW domain-containing iso-prolyl isomerase named Pin1, a protein known to be essential for cell cycle progression, was shown to be active in restoration of the microtubule-binding activity of Tau, a protein of neurofibrillar tangles found in the brains of Alzheimer's patients. It is the WW domain of Pin1 that interacts directly with Tau protein. In addition, the WW domain-containing adapter protein FE65 was shown to regulate processing of Alzheimer's amyloid precursor protein. It is expected that by understanding the details of the WW domain-mediated protein-protein interactions, we will be able to illuminate numerous signaling pathways which control certain aspects of transcription and cell cycle.

Alzheimer Disease↗
PubMed2000

Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1.

OBJECTIVES: 1) To evaluate the outcome of patients with peripartum cardiomyopathy (PPC) on current treatment for heart failure, 2) to assess the circulating plasma levels of cytokines and Fas receptors and 3) to identify predictors of prognosis. BACKGROUND: Previous studies in patients with PPC were done when angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents were not routinely used in heart failure. Inflammatory cytokines play an important role in the pathogenesis and progression of heart failure of other etiologies. However, there is a paucity of data regarding cytokine expression in patients with PPC. Plasma concentrations of Fas receptors (an apoptosis-signalling receptor) have not been reported in this population. METHODS: We followed prospectively 29 consecutive black women with PPC. All patients were treated with diuretics, digoxin, enalapril and carvedilol. Echocardiograms were performed at baseline and after six months of treatment. Cytokine and soluble Fas/APO-1 plasma levels were measured at baseline. RESULTS: Tumor necrosis factor-alpha, interleukin-6 and Fas/APO-1 levels were significantly elevated in the study patients compared with 20 healthy volunteers. Eight patients died. sFas/APO-1 levels were significantly higher in patients who died compared with survivors (8.98 +/- 4.5 vs. 5.33 +/- 3 U/ml, respectively, p = 0.02). At six months, ejection fraction improved from 26.7 +/- 10 to 42.7 +/- 16%, p = 0.00003, with an increment of more than 10 U in 10 patients (28.1 +/- 4 to 51.9 +/- 8%, p = 0.000008). CONCLUSIONS: Cytokine and sFas levels are elevated in patients with PPC. Despite treatment with ACE inhibitors and beta-blockers, mortality remains high. However, in 34% of the patients, left ventricular function almost completely normalized.

Adult↗
PubMed1999

Association of left ventricular systolic performance and cavity size with angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy.

The insertion-deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is a marker linked to differences in plasma and cardiac ACE activity as well as to an increased mortality in patients with idiopathic heart failure. We examined the possibility that ACE gene ID variants are associated with differences in left ventricular (LV) systolic performance or internal LV dimensions in a high-risk cohort of patients with idiopathic dilated cardiomyopathy (IDC). The ACE genotype was determined in 171 patients selected with IDC in New York Heart Association functional class II to III heart failure and with a LV ejection fraction of < or = 40%. Left ventricular performance and dimensions were assessed using echocardiography (n = 161) and radionuclide ventriculography (n = 169). The frequency of ACE gene ID alleles was not different in the study versus non-age-matched (n = 171; odds ratio 0.94) and age-matched (n = 106, odds ratio 0.88) control groups. Ejection fraction was found to be worse in patients with the DD genotype (echocardiography, DD = 23.5 +/- 0.70, ID + II = 26.8 +/- 0.8, p = 0.009; ventriculography, DD = 21.7 +/- 0.9, ID + II = 25.3 +/- 0.8, p = 0.003). LV end-systolic and end-diastolic diameters were increased in patients with the DD genotype. Multifactor regression analysis showed the ACE genotype to be an independent predictor of both ejection fraction (echocardiography, p <0.02; ventriculography, p <0.03) and end-diastolic diameter (p <0.02). In conclusion, the results of this study indicate that the DD genotype of the ACE gene is independently associated with both a reduced LV systolic performance and an increased LV cavity size in patients with IDC.

Aged↗
PubMed1998

Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy.

BACKGROUND: There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure. Plasma concentrations of tumour necrosis factor alpha (TNF-alpha) are high in heart failure and have been correlated with the severity of symptoms. Pentoxifylline suppresses the production of TNF-alpha. This study aimed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy. METHODS: We undertook a single-centre, prospective, double-blind, randomised, placebo-controlled trial, in which 28 patients with idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times daily or matching placebo. Clinical, echocardiographic, and radionuclide assessments were done at baseline and after 6 months of treatment. Primary endpoints were New York Heart Association (NYHA) functional class and left-ventricular function. FINDINGS: Baseline characteristics were similar in the two groups. Four patients died during the study period, all in the placebo group. After 6 months of treatment, the proportion of patients in NYHA functional class I or II was higher in the pentoxifylline group than in the placebo group (14/14 vs 10/14; p=0.01), and ejection fraction was higher in the pentoxifylline group than in the placebo group (mean 38.7% [SD 15.0] vs 26.8% [11.0], p=0.04). At 6 months, TNF-alpha plasma concentrations were significantly lower in the pentoxifylline-treated group than in the placebo group (2.1 [1.0] vs 6.5 [5.0] pg/mL, p=0.001). INTERPRETATION: Our results suggest that pentoxifylline improves symptoms and left-ventricular systolic function in patients with idiopathic dilated cardiomyopathy. These results must be confirmed in larger-scale trials.

Cardiomyopathy, Dilated↗
PubMed1997

Repeated automated versus daytime ambulatory blood pressure measurement in mild, moderate and severe untreated black hypertensive patients.

OBJECTIVE: To examine the extent to which one session of repeated automated (30-45 min) blood pressure measurements in non-treated, hypertensive patients can be used to predict daytime ambulatory blood pressure (ABP). METHODS: Two hundred untreated black hypertensive patients (mean age 50.2+/-11.2) were retrospectively stratified on the basis of the daytime ambulatory diastolic blood pressure (DBP) into mild, moderate and severe hypertensives (90 mmHg <DBP < 140 mmHg). Office blood pressure was determined at 3 min intervals for a total of 30-45 min using the Dinamap Critikon 1846 SX monitor. Twenty-four hour ambulatory blood pressure (ABP) was performed on the same day in all patients using a SpaceLabs 90207 device. RESULTS: The mean diastolic Dinamap measurements compared with the mean ambulatory daytime DBP were very similar in terms of 'traditional' statistics (mean: 114 +/- 14.6 versus 113 +/- 12 mmHg, correlation: 0.80). However, agreement analysis according to Bland and Altman showed a poor agtreement with an error as high as 19 mmHg. The mean systolic Dinamap measurements compared with the mean ambulatory daytime SBP were significantly overestimated (mean: 185 +/- 25.0 versus 170 +/- 19.3 mmHg, correlation 0.82) and the error was as high as 43 mmHg. On residual analysis, 75% of the diastolic Dinamap values and only 35% of the systolic Dinamap measurements were within an error of +/- 10 mmHg. The average of the first five Dinamap measurements had the greatest predictive ability for the daytime ABP. CONCLUSION: As a result of the poor agreement between the two methods, we suggest that, from the clinical point of view, the two techniques should be treated as two separate entities.

Journal Article↗
PubMed1996

Volvulus of the sigmoid colon at Baragwanath Hospital.

Fifty-six patients treated for sigmoid volvulus over a period of 5 years are reviewed. The purpose of this study is to evaluate our management policy and to compare it with other studies, particularly from other parts of Africa. The patients were evaluated by retrospective allocation into one of three treatment modalities. Patients with clinical evidence of ischaemia underwent a Hartmann's procedure. There was a 33% mortality rate in this group. In those patients who had sigmoidoscopic reduction, a second-stage sigmoidectomy and primary anastomosis were performed. The results in this group were excellent. In the group of patients with failed sigmoidoscopic resection the majority underwent a Hartmann's procedure with a mortality rate of 15%.

Adult↗
PubMed1995

Penetrating injuries of the brachial artery.

This is a retrospective study of 72 patients with non-iatrogenic penetrating injuries of the brachial artery treated between 1991 and 1993. The mechanism of injury was stabbing in 39 per cent, a bullet in 51 per cent, pellets in 4 per cent and a dog bite in 6 per cent. We believe that angiography is rarely indicated, as in all our patients the diagnosis was made on clinical grounds. The proximity of the injury to neurovascular bundles was a poor predictor of arterial injury. One month after discharge 95 per cent of the patients had palpable distal pulses. Long-term morbidity is mainly attributed to associated nerve injuries.

Adolescent↗
PubMed1992

Human cutaneous leishmaniasis: in-vitro parasite--mononuclear cell interactions in immune and naive individuals.

The aim of this study was to compare the ability of Leishmania parasites to survive in mononuclear cells from immune individuals with their ability to survive in cells from naive individuals. For this purpose we established an in vitro system based on the co-culture in suspension of human peripheral blood leukocytes derived from immune and naive subjects and L. major promastigotes. The proportion of monocytes containing intracellular parasites and the number of amastigotes per 100 infected monocytes (parasite burden) were determined 24 and 72 h after in-vitro infection. The proportion of infected cells from naive individuals did not change, and the number of amastigotes either did not change or increased by 1.2 to 1.7-fold between 24 and 72 h incubation. In contrast, in the immune subjects, the proportion of infected monocytes 24 h after infection was lower than in the naive individuals, and a 30-90% decrease in both the proportion of infected monocytes and the parasite burden was observed after 72 h incubation. Based on these results, three characteristics of leishmanicidal activity of mononuclear cells from immune individuals were determined: (a) the proportion of infected monocytes 24 h after infection was lower than 22%; (b) there was a decrease of more than 30% in the proportion of infected monocytes between 24 and 72 h after infection; and (c) there was a significant decrease in the number of amastigotes between 24 and 72 h after infection. The results of this study demonstrate an enhanced leishmanicidal activity of mononuclear cells from immune individuals.

Humans↗