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A Kheir

Publications and source records attributed to A Kheir.

16 recordsLinked to original sources
PubMed2006

[Porto-pulmonary hypertension].

INTRODUCTION: Porto-pulmonary hypertension (PoPH) is the association of pulmonary artery hypertension and portal hypertension. The diagnosis of PoPH is based on pulmonary haemodynamic criteria, obtained via right heart catheterisation, including an increase in mean pulmonary arterial pressure (> 25 mmHg) and in pulmonary vascular resistance (> 240 dyn.s.cm-5). STATE OF THE ART: The exact pathophysiological mechanisms of PoPH are unknown. However, since PoPH has been reported in patients with non-hepatic portal hypertension, the factor that determines the development must be portal hypertension rather than liver disease per se. Moreover, no simple relationship has been identified between the degree of hepatic impairment and the severity of PoPH. The clinical presentation is non-specific with haemodynamic failure occurring at the end stage. As a consequence, screening by annual transthoracic echocardiography is highly recommended in potential liver transplant candidates. Therapy with prostacyclin analogues may partially relieve pulmonary arterial hypertension (PAH). Liver transplantation has an uncertain effect in PoPH and because PoPH is associated with a high perioperative mortality, moderate to severe PoPH remains a contraindication for liver transplantation. PERSPECTIVES AND CONCLUSIONS: Recent advances in the management of PoPH have improved the prognosis. The safety and efficacy of oral endothelin receptor antagonists and oral phosphodiesterase inhibitors is currently under evaluation. A therapeutic approach utilising combinations of drugs should provide better long-term results.

Antihypertensive Agents↗
PubMed1998

Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase.

Drug resistance that occurs during cancer chemotherapy has been a major problem in controlling neoplastic progression. To study the cellular mechanisms of acquired drug resistance we developed 1,25-dihydroxyvitamin D3 (1,25D3)-resistant sublines of promyelocytic leukemia HL60 cells which have increased proliferation rates (Exp. Cell Res., 224, 312, 1996; Cancer Res., 50, 5513, 1996). We report here that the resistant sublines display varying degrees of shortening of the G1 phase as compared to the parental HL60-G cells. Protein levels of cyclins E, D1, D2 and D3 are elevated in these resistant cell lines, and cyclin D1 is especially high in 40AF cells, which has the shortest G1 length. The protein levels of cyclin-dependent kinase (Cdk)2, Cdk4 and Cdk6 are not altered in the resistant sublines. Both Cdk2 and Cdk6-associated kinase activites are increased in the resistant sublines, but not Cdk4 kinase activity. Protein levels of p27Kip1 are not consistently altered in the resistant sublines as compared to the parental HL60-G cells, but are reduced relative to HL60-G cells arrested by 96 h treatment with 1,25D3. Interestingly, the resistant cell lines constitutively express high levels of retinoblastoma protein (pRb), and pRb is highly phosphorylated, indicating that the G1 cyclin/Cdk complexes in the resistant cells are physiologically active. The results suggest that the increased activity of cyclin D/Cdk6, and perhaps cyclin E/Cdk2, lead to rapid hyperphosphorylation of pRb and consequently a shorter early G1 phase, and that in the resistant cells the increased ratio of cyclin E to p27Kip1 results in activation of Cdk2 and contributes to the abrogation of the 1,25D3-induced block to the S phase entry. Additionally, it is apparent that constitutively increased levels of pRb are compatible with increased rates of cell proliferation.

CDC2-CDC28 Kinases↗
PubMed1997

Synergistic induction of HL60 cell differentiation by ketoconazole and 1-desoxy analogues of vitamin D3.

BACKGROUND: The goal of differentiation therapy is to induce cancer cells to stop proliferating and to express characteristics of normal cells. Vitamin D analogues, such as the deltanoids, are being evaluated as differentiation agents in the treatment of several human cancers (e.g., myeloid leukemias); however, these compounds have a tendency to produce hypercalcemia in patients receiving therapy. A combination of a differentiation-inducing deltanoid with a compound that blocks entry of calcium into cells (e.g., ketoconazole) may offer a new approach to differentiation therapy and address the problem of hypercalcemia. We investigated whether various ketoconazole-deltanoid combinations would alter cellular differentiation or intracellular calcium homeostasis in comparison with deltanoids used alone. METHODS: Cultured human leukemia HL60 cells were treated with ketoconazole-deltanoid combinations. Markers of differentiation (expression of CD11b and CD14 antigens and of non-specific esterase) were measured by flow cytometry and cytochemistry; cell cycle distribution was measured by flow cytometry of propidium iodide-stained cells. Expression of differentiation-related genes was assessed by northern blotting and immunoblotting, and changes in intracellular calcium homeostasis were monitored by fluorescence analysis of fura-2-containing cells. RESULTS: Ketoconazole strongly potentiated the differentiating activity of the deltanoids, which exhibited low potency when used alone. Ketoconazole-deltanoid combinations had little effect on HL60 cell-cycle distribution, although the cells did stop proliferating and they differentiated. Ketoconazole-deltanoid combinations produced only minor changes in intracellular calcium homeostasis compared with changes produced by 1,25-dihydroxyvitamin D3, either alone or in combination with ketoconazole. CONCLUSION: These results suggest that ketoconazole may be useful in combination with vitamin D analogues in the differentiation therapy for myeloid leukemias.

Antineoplastic Agents↗
PubMed1996

Transition to tetraploidy in 1,25-dihydroxyvitamin D3-resistant HL60 cells is preceded by reduced growth factor dependence and constitutive up-regulation of Sp1 and AP-1 transcription factors.

Increased ploidy is an ominous event in the progression of human malignancies. It is usually associated with an increased growth rate of the neoplastic cells and a generally more autonomous and aggressive biological behavior. However, it has not been established whether the more rapid growth rate and growth factor independence are consequences of the polyploid, karyotypically increasingly aberrant nature of these cells or whether the accelerated, more autonomous growth contributes to polyploidization. In this study, we have examined a recently described (H. J. Wajchman et al., Exp. Cell Res., 224: 312-322, 1996) series of sublines of HL60 cells with increasing resistance to the monocytic differentiation-inducing steroid hormone 1,25-dihydroxyvitamin D3 (1,25D3) and found that growth factor independence, shown by reduced requirement for serum supplementation of the medium and the ability to grow at low seeding densities, precedes polyploidization of these cultures. The growth factor independence was found to be accompanied by constitutive changes in the DNA binding pattern of the ubiquitous transcription factor Sp1, characteristic of an exposure to 1,25D3. Similar changes in the pattern of AP-1 binding were also observed in the 1,25D3-resistant HL60 sublines, but the intensity of the DNA binding by AP-1 was increased only in sublines with resistance to 1,25D3 but still near-diploid. The data suggest that the culture of HL60 cells in the presence of 1,25D3 results in constitutive up-regulation of growth-related machinery that reduces the need for growth factors and cytokines and demonstrate that this increased growth potential precedes polyploidization of the culture populations.

Animals↗
PubMed1996

[Facilitating effect of propafenone pretreatment in the interruption of atrial flutter by transesophageal pacing].

Transesophageal atrial pacing is effective in the interruption of atrial flutter, and being simple and minimally invasive, is easily performed even on outpatients. The influence of antiarrhythmic drugs on this procedure is controversial. We investigated whether the administration of oral propafenone may facilitate the procedure. Thirty patients with type I atrial flutter were randomized into two groups in which transesophageal pacing was attempted, respectively, without treatment (Group A) and after oral administration of propafenone 600 mg (Group B). Transesophageal pacing was effective in interrupting atrial flutter in 53% (8/15) of patients in Group A and in 85% (13/15) of patients in Group B. A significant lengthening of the flutter cycle was observed in patients treated with propafenone (261 +/- 23 vs 217 +/- 25 ms, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in patients of Group A (166 +/- 13 vs 187 +/- 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in Group A (20.5 +/- 0.2 vs 23.3 +/- 1.2 mA, p < 0.01). In no patient the threshold for atrial capture was higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We can conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The depressing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and account for the beneficial effect of the drug on arrhythmia termination.

Adult↗
PubMed1996

[Fibrosing pneumopathy caused by labetalol].

A diffuse interstitial pulmonary fibrosis occurred in a 74-year-old woman treated for ten years with labetalol for systemic hypertension. Bronchoalveolar lavage (BAL) revealed lymphocytic and neutrophilic alveolitis. The lack of another etiologic factor and the spontaneously favorable course after withdrawal of the drug support the hypothesis of a labetalol induced pulmonary fibrosis.

Adrenergic beta-Antagonists↗
PubMed1995

Atrial flutter termination by overdrive transesophageal pacing and the facilitating effect of oral propafenone.

Transesophageal overdrive atrial pacing is effective and safe for atrial flutter termination. The influence of antiarrhythmic drug therapy on this procedure is controversial. In this study, we investigated whether oral propafenone may facilitate this procedure. Thirty patients with type I atrial flutter were randomized into 2 groups in which transesophageal pacing was attempted: group A, without treatment; and group B, after oral administration of propafenone 600 mg. Transesophageal pacing was effective in interrupting atrial flutter in 53% of patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A significant lengthening of the flutter cycle was observed with respect to the baseline in patients given propafenone (261 +/- 23 vs 217 +/- 25, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in group A patients (166 +/- 13 vs 187 +/- 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in group A (20.5 +/- 0.2 vs 23.3 +/- 1.2, p < 0.01). In no patient was the threshold for atrial capture higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The slowing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and accounting for the beneficial effect of the drug on arrhythmia termination.

Administration, Oral↗
PubMed1993

[Comparison of bronchodilator effects and site of action of fenoterol and ipratropium in chronic obstructive bronchitis].

There is no lack of data in the literature reporting on the efficacy of different bronchodilators. However, the discussion concerning the superiority of one bronchodilator over another in patients with chronic bronchitis and airflow obstruction is, and remains, a controversial subject. This has been particularly so since the perfection of synthetic anticholinergics delivered by inhalation without any side-effects. The aim of the present work is to compare the bronchodilator effects of a sympathomimetic, fenoterol (Berotec), and of an anticholinergic, ipratropium bromide (Atrovent), compared to a placebo in twelve unselected chronic bronchitics who had airflow obstruction and were in a stable clinical state. The bronchodilator effect of the two drugs was judged at the same time by variations on forced expired volume (FEV1) which was taken as a reference value, and of the maximum mid-expiratory flow (MEF) measured by spirography and also the variations of pulmonary resistance (delta Rrs) measured by the forced oscillatory method. The comparison of these indices enables the site of action of these agents to be specified. The dose response curve and the duration of action over six hours was assessed for each of the three agents. These were administered in succession and at random over three days by inhalation using an inhalation chamber. All the patients who were included were capable of producing a bronchodilator response but two of them responded only to one agent. The change in the FEV1 was comparable with the two active products. The change in MEF (an index of peripheral airways) was significantly greater following ipratropium.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

[Drug-induced pulmonary diseases: diagnostic, therapeutic and prognostic aspects. Apropos of 10 personal case reports].

The authors report ten cases of drug induced lung diseases, complicated by respiratory failure of whom five were attributed to cytotoxic drugs and five to non cytotoxic drugs. The drug induced lung disease presented as acute respiratory distress syndrome in two cases, alveolar interstitial lung disease in three cases, purely interstitial in five cases. There was acute respiratory failure (ARF) in eight cases and chronic respiratory failure (CRF) in two cases. Among the five patients admitted for cytotoxic drug induced lung disease and ARF, four recovered and one died of diffuse destructive pulmonary fibrosis. Among the five patients having non cytotoxic drug induced lung disease, three were in ARF and recovered. The other two had CRF and died of diffuse pulmonary fibrosis. The diagnostic of drug induced lung disease was established in each case with the chronology of the clinical events, the exclusion of other possible causes of the lung disease and the evolution after removal of the incriminated drug. Broncho-alveolar lavage (BAL) had a major diagnostic value. It was contraindicated by respiratory failure in five cases. The predominant alveolar cell type was lymphocyte (four cases), eosinophil (three cases) and neutrophil (one case), BAL was realized with a provocation test and demonstrated the pathogenic role of cyclothiazide in one case. No specific information was given by histology. The prognosis did not seem to be linked to the severity of the initial clinical picture, or to the nature of the underlying neoplastic disorder, but to the degree and evolution of the pulmonary fibrosis.

Adrenal Cortex Hormones↗
PubMed1992

[Fibrosing pneumopathy induced by cyclothiazide. Apropos of a case].

A diffuse interstitial pulmonary fibrosis associated with an idiopathic hepatic cirrhosis occurred in a 79 years old man treated during five years with cyclothiazide and triamterene for a mild systemic hypertension. The outcome was fatal. A provocation test was positive with BAL lymphocytic reaction. Cyclothiazide induced fibrosis is likely.

Aged↗
PubMed1989

[Acute and long-term effects of captopril in patients with left ventricular dysfunction and dilatation: evaluation of function and work capacity].

To assess acute hemodynamic effects and exercise capacity of an intravenously administered single dose of captopril and to compare the acute response with chronic variation in hemodynamic and functional parameters after long-term oral administration, (in order to determine the profile of responders and non-responders) we studied 12 patients with chronic congestive heart failure due to primary dilated cardiomyopathy (11 pts) and ischemic heart disease (1 pt). Hemodynamic response was assessed using transthoracic electric impedance with cardiac output measurement. The exercise capacity was determined using multistage bicycle ergometer symptoms limited stress test. The hemodynamic and functional evaluation--resting cardiac output, exercise capacity (Ex. Dur.) and cardiac output rise at maximum workload (% CO)--were investigated at first as a control; after i.v. captopril administered in 10 min (25 mg) (acute); after captopril per os (25-75 mg for 30 days) (chronic) and after 5 days of withdrawal (wash out). (Table: see text). Improvement of left ventricular performance mainly during exercise after acute and chronic administration of captopril occurred, as evidenced from cardiac output increase at maximum work load, and rise of exercise duration. Moreover, our data suggest that captopril may have a sustained beneficial effect, for a few days, even after drug withdrawal. Nevertheless, the lack of correlation in single cases between acute and chronic response, also indicates that captopril deserves further study to determine its role in acute and/or chronic management of congestive heart failure in order to choose the ideal strategy.

Aged↗