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2.
J Biol Regul Homeost Agents ; 32(6 Suppl. 1): 145-150, 2018.
Article in English | MEDLINE | ID: mdl-30644295

ABSTRACT

This retrospective study reports clinical and functional orthopedic outcomes and complications after 14 primary total knee replacement (TKR) performed between 2000 and 2014. The mean age at surgery was 42 years (range 26-59), with a removal-free survival of 100% at the end of follow-up (months 109.85). The KSS score was 49.64 pre-operatively (range 31-63) and 78.14 at final follow-up (range 45-90), the KSS function score was 64.64 pre-operatively (range 35-80) and 84.57 at final follow-up (range 45-100). According to this study, there are three main factors that can influence long-term and early surgical outcomes: post-operative fibrosis, a previous synovectomy and presence of inhibitors. Even if our results are slightly suboptimal compared to those obtained in non-hemophilic patients, this study shows that TKR is an effective surgical procedure in hemophiliacs.


Subject(s)
Arthroplasty, Replacement, Knee , Hemophilia A/complications , Knee Joint/surgery , Adult , Follow-Up Studies , Humans , Middle Aged , Postoperative Period , Retrospective Studies , Treatment Outcome
3.
Am J Hosp Palliat Care ; 32(6): 588-93, 2015 Sep.
Article in English | MEDLINE | ID: mdl-24782575

ABSTRACT

The increasing coexistence of cancer and diabetes within the elderly population requires specific palliative care skills on diabetes treatment. We report our experience of diabetes management in a palliative care setting. In our retrospective 3-year activity sample (n = 563), 27.2% of patients have a diagnosis of diabetes mellitus: 80% have cancer whereas 20% have a main diagnosis of other severe chronic diseases. As to the presence/absence of diabetes, no differences emerge in the examined clinical indicators and global survival, with the exception of body mass index and days of hospitalization. At lifetime analysis, Barthel index and palliative prognostic index are the only parameters significantly related to death. Even if diabetes seems not to modify the prognosis, it significantly influences the health care burden and the team engagement.


Subject(s)
Diabetes Mellitus/therapy , Neoplasms/complications , Neoplasms/therapy , Terminal Care/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies
4.
Diabet Med ; 29(1): 24-31, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21781149

ABSTRACT

AIMS: To compare the effects of losartan and amlodipine on myocardial structure and function in hypertensive patients with Type 2 diabetes and left ventricular hypertrophy. METHODS: After a 4-week placebo period, patients were randomized to losartan 50 mg (n = 90) or amlodipine 5 mg (n = 91) for 12 months, with a doubling of the dose in patients who did not respond after 4 weeks. Blood pressure was measured in the clinic every month, while conventional echocardiography and acoustic densitometry (integrated backscatter analysis) were performed at the end of the placebo period and after 12 months of treatment. RESULTS: Both drugs reduced systolic/diastolic blood pressure to a comparable extent. Losartan significantly reduced left ventricular mass index (-19%, P < 0.001), interventricular septal thickness (-16.6%, P < 0.01) and left ventricular posterior wall thickness in diastole (-13.7%, P < 0.01). Amlodipine also decreased such measurements (-10%, P < 0.01 for left ventricular mass index, -9.3%, P < 0.05 for interventricular septal thickness in diastole and -10.1%, P < 0.05 for posterior wall thickness in diastole), but to a lesser extent than losartan. Both drugs significantly increased the ratio of peak filling velocity at early diastole to that at atrial contraction (E/A ratio) and decreased isovolumetric relaxation time: +13.7% and -8.5% with losartan,(both P < 0.01), and +7.9% and -4.9%, with amlopidine (both P < 0.05). Losartan, but not amlodipine, significantly reduced the relative integrated backscatter compared to baseline of the intraventricular septum (-10%, P < 0.01), and of the left ventricular posterior wall (-12%, P < 0.01), while increasing the cyclic variation of integrated backscatter of both the intraventricular septum (+35%, P < 0.001) and the left ventricular posterior wall (+32%, P < 0.001). CONCLUSIONS: Losartan provided a greater attenuation of left ventricular hypertrophy than amlodipine, seemingly as a result of a greater reduction of myocardial fibrosis.


Subject(s)
Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Diabetic Angiopathies/drug therapy , Hypertension/drug therapy , Hypertrophy, Left Ventricular/prevention & control , Losartan/therapeutic use , Ventricular Dysfunction, Left/prevention & control , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/etiology , Diabetic Angiopathies/physiopathology , Diastole/drug effects , Echocardiography , Female , Fibrosis/drug therapy , Humans , Hypertension/complications , Hypertension/physiopathology , Hypertrophy, Left Ventricular/etiology , Male , Middle Aged , Myocardium/pathology , Prospective Studies , Treatment Outcome , Ventricular Dysfunction, Left/etiology
5.
Horm Metab Res ; 41(12): 893-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19708000

ABSTRACT

The aim of this study was to compare the effect of telmisartan and eprosartan on insulin sensitivity in overweight hypertensive patients. Fifty overweight (BMI > or = 25 and <30 kg/m (2)) outpatients, aged 41-65 years, with mild to moderate hypertension [systolic blood pressure (SBP) >140 and diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg], after a 4-week placebo period, were randomized to receive telmisartan 80 mg or eprosartan 600 mg for 8 weeks. Following another 4-week placebo period, patients were crossed to the alternative regimen for further 8 weeks. At the end of each placebo and active treatment period, blood pressure (BP), insulin sensitivity (by euglycemic hyperinsulinemic clamp), fasting plasma glucose (FPG), insulin (FPI), total cholesterol (TC), LDL-C, HDL-C, and triglycerides (Tg) were evaluated. Insulin sensitivity was expressed as the amount of glucose infused during the last 30 min (glucose infusion rate, GIR) in micromol/min/kg. Both telmisartan and eprosartan significantly reduced SBP/DBP values (by a mean of 19.4/13.3 mmHg and 17.9/12.1 mmHg respectively, all p<0.001 vs. placebo), with no significant difference between the two treatments. GIR was significantly increased by telmisartan (2.25+/-0.61 micromol/min/kg, p<0.05 vs. placebo) but not by eprosartan (0.25+/-0.14 micromol/min/kg, p=ns), the difference between the two drugs being statistically significant (p<0.02). No change in FPG, FPI, HDL-C, and Tg was observed with either treatment. Telmisartan significantly reduced TC (-9.9 mg/dl, -5%, p<0.04 vs. placebo) and LDL-C (-8.8 mg/dl, -7%, p<0.03 vs. placebo), whereas eprosartan did not influence them. These findings indicate a superiority regarding an improvement of insulin sensitivity and plasma lipid profile in overweight hypertensives by telmisartan as compared to eprosartan, possibly related to the selective stimulating PPAR-gamma property of telmisartan.


Subject(s)
Acrylates/therapeutic use , Benzimidazoles/therapeutic use , Benzoates/therapeutic use , Hypertension/complications , Hypertension/drug therapy , Imidazoles/therapeutic use , Insulin/metabolism , Overweight/complications , Overweight/drug therapy , Thiophenes/therapeutic use , Adult , Aged , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Blood Glucose , Female , Humans , Hypertension/blood , Hypertension/physiopathology , Male , Middle Aged , Overweight/blood , Overweight/physiopathology , Telmisartan
6.
J Hum Hypertens ; 21(3): 220-4, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17215848

ABSTRACT

The aim of this study was to assess the effect of valsartan addition to amlodipine on ankle foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. After a 4-week placebo period, 80 grade 1-2 hypertensive patients (diastolic blood pressure (DBP)>90 mm Hg and <110 systolic blood pressure (SBP)>140 mm Hg) were randomized to amlodipine 10 mg or valsartan 160 mg or amlodipine 10 mg plus valsartan 160 mg for 6 weeks according to an open-label, blinded end point, crossover design. At the end of the placebo period and of each treatment period, blood pressure, AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed connecting the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and valsartan monotherapy significantly reduced SBP (-16.9 and -14.5 mm Hg, respectively, P<0.01 vs baseline), and DBP (-12.9 and -10.2 mm Hg, respectively, P<0.01 vs baseline) but the reduction was greater with the combination (-22.9 mm Hg for SBP, P<0.01 vs monotherapy; -16.8 mm Hg for DBP, P<0.01 vs monotherapy). Amlodipine monotherapy significantly increased both AFV (+23%, P<0.01 vs baseline) and PSTP (+75.5%, P<0.001 vs baseline) whereas valsartan monotherapy did not influence them. As compared to amlodipine alone, the combination produced a less marked increase in AFV (+6.8%, P<0.01 vs amlodipine) and PSTP (+23.2%, P<0.001 vs amlodipine). Ankle oedema was clinically evident in 24 patients with amlodipine and in six patients with the combination. These results suggest that angiotensin receptor blockers partially counteract the microcirculatory changes responsible for calcium channel blockers induced oedema formation.


Subject(s)
Amlodipine/therapeutic use , Blood Pressure , Edema/drug therapy , Hypertension/drug therapy , Tetrazoles/therapeutic use , Valine/analogs & derivatives , Adult , Age Factors , Aged , Ankle , Cross-Over Studies , Drug Therapy, Combination , Edema/complications , Edema/physiopathology , Female , Humans , Hypertension/complications , Hypertension/physiopathology , Male , Middle Aged , Placebos , Prospective Studies , Single-Blind Method , Treatment Outcome , Valine/therapeutic use , Valsartan
7.
Adv Ther ; 23(5): 680-95, 2006.
Article in English | MEDLINE | ID: mdl-17142202

ABSTRACT

This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) >or=99 and 110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP >or=90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5)-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients )-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and 17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.


Subject(s)
Antihypertensive Agents/therapeutic use , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Imidazoles/therapeutic use , Sodium Chloride Symporter Inhibitors/therapeutic use , Tetrazoles/therapeutic use , Valine/analogs & derivatives , Adult , Aged , Antihypertensive Agents/administration & dosage , Drug Therapy, Combination , Female , Humans , Hydrochlorothiazide/administration & dosage , Imidazoles/administration & dosage , Male , Middle Aged , Prospective Studies , Sodium Chloride Symporter Inhibitors/administration & dosage , Tetrazoles/administration & dosage , Valine/administration & dosage , Valine/therapeutic use , Valsartan
8.
J Hum Hypertens ; 20(3): 177-85, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16306998

ABSTRACT

The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61-75 years, with sitting diastolic blood pressure (DBP)>90 mmHg and <110 mmHg and systolic blood pressure (SBP)>140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (-33 and -30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Benzimidazoles/therapeutic use , Benzoates/therapeutic use , Blood Pressure/drug effects , Cognition/drug effects , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Lisinopril/therapeutic use , Sodium Chloride Symporter Inhibitors/therapeutic use , Aged , Analysis of Variance , Blood Pressure Determination , Drug Combinations , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Prospective Studies , Statistics, Nonparametric , Telmisartan , Treatment Outcome
9.
Eur J Cancer ; 41(1): 81-92, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15617993

ABSTRACT

This study compares two cytotoxic regimens comprising the same dose and schedule of cisplatin (CP) plus vinorelbine (VNR) or gemcitabine (GEM) administered under the same schedule to patients with advanced non-small cell lung cancers (NSCLC). From April 1998 to February 2003, 285 patients were randomised to receive either VNR 25 mg/m(2) on days 1 and 8 as an intravenous (i.v.) bolus plus CP 75 mg/m(2) on day 1 (regimen A) or GEM 1200 mg/m(2) on days 1 and 8 as an i.v. 30-min infusion plus CP 75 mg/m(2) on day 1 (regimen B). Both treatments were recycled every 21 days. If no progression had occurred after six cycles, the patients continued to receive VNR or GEM monochemotherapy weekly. Cross-over of the two single agents was considered if disease progression occurred. Objective response (OR), time to progression (TTP) and overall survival (OS) were analysed according to the intention-to-treat principle. 272 patients were ultimately eligible (137 on A and 135 on B). Their main characteristics were: male/female ratio 214/58; median age 63 (range 32-77) years; median Karnofsky Performance Status (PS) 80 (range 70-100); stage IIIB 34%, stage IV 61%, recurrent disease 5%; histology - epidermoid 29%, adenocarcinoma 53%, other NSCLC 18%. The characteristics of the patients in the two arms were well matched. The following response rates were observed in regimens A and B, respectively: complete response (CR) 0.7% and 3.7%, partial response (PR) 31.9% and 22.2% (P = 0.321). Median CR+PR duration was 8 months in both arms. Clinical benefit represented by an improvement in symptoms was evident in 25.7% and 28.1%, respectively. Median TTP was 5 months in both arms and median OS 11 months in both arms. Grade III-IV neutropenia occurred in 30.7% and 17.7% of the patients in arms A and B, respectively (P = 0.017); thrombocytopenia occurred in 0% and 9.3% (P = 0.004), respectively. No difference in the incidence of anaemia was observed. Non-haematological toxicity was generally mild: a higher incidence of grade 1-2 peripheral neurotoxicity and grade 1-2 local toxicity with regimen A and grade 1-2 liver toxicity with regimen B was reported. A pharmaco-economic comparison showed a difference between the two doublets, principally due to the different costs of VNR and GEM. Under the study conditions the combination of VNR or GEM with the same dose and schedule of CP produced similar OR, clinical benefits, TTP and OS in advanced NSCLC, and only mild toxicological differences were observed. Pharmaco-economic evaluation favoured the CP + VNR doublet.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/economics , Carcinoma, Non-Small-Cell Lung/economics , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/economics , Cost-Benefit Analysis , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/economics , Disease Progression , Female , Humans , Lung Neoplasms/economics , Male , Middle Aged , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/economics , Vinorelbine , Gemcitabine
10.
J Hum Hypertens ; 18(10): 687-91, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15071488

ABSTRACT

The aim of this double-blind, double-dummy, parallel group study was to compare the effects of delapril-manidipine combination vs a irbesartan-hydrochlorothiazide combination on plasma tissue plasminogen activator (t-PA) and plasmogen activator inhibitor type I (PAI-l) activities in hypertensive patients with type II diabetes mellitus. After a 4-week run-in placebo period, 80 patients (37 male and 43 female), aged 41-65 years, were randomly allocated to an 8-week treatment with delapril 30 mg once daily or irbesartan 150 mg once daily. Thereafter, manidipine l0 mg once daily was added to delapril treatment and hydrochlorothiazide 12.5 mg to irbesartan treatment for a further 8 weeks. Blood pressure (BP), plasma t-PA and PAI-l activities were evaluated at the end of the run-in period, after 4-week monotherapy treatments, and at the end of the combination treatment periods. Both combination treatments, delapril-manidipine and irbesartan-hydrochlorothiazide, produced a greater reduction in systolic BP/diastolic BP (SBP/DBP) values (-27.6/21.8 mmHg and -26.4/20.2 mmHg, respectively) than the respective monotherapies (-15.2/11.7 mmHg with delapril and -16.3/11.3 mmHg with irbesartan). Delapril monotherapy significantly decreased plasma PAI-l activity (-10.4 IU/mI; P<0.05). The addition of manidipine produced a significant increase in t-PA activity (+0.27 IU/mI); P<0.05). Irbesartan monotherapy did not significantly affect the fibrinolytic balance, whereas the addition of hydrochlorothiazide worsened it, producing a significant increase in PAI-l activity (+9.5 IU/ml; P<0.05). In hypertensive patients with type II diabetes mellitus, the combination delapril-manidipine may determine a greater improvement of the fibrinolytic function than the respective monotherapy, while the association irbesartan-hydrochlorothiazide may worsen it.


Subject(s)
Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Fibrinolysis/drug effects , Hypertension/drug therapy , Adult , Aged , Biphenyl Compounds/therapeutic use , Dihydropyridines/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Hydrochlorothiazide/therapeutic use , Hypertension/complications , Indans/therapeutic use , Irbesartan , Male , Middle Aged , Nitrobenzenes , Piperazines , Plasminogen Activator Inhibitor 1/blood , Tetrazoles/therapeutic use , Tissue Plasminogen Activator/blood , Treatment Outcome
11.
J Hum Hypertens ; 17(11): 781-5, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14578918

ABSTRACT

The aim of this study was to compare the effect of the beta-adrenergic blocker atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on cognitive function in very elderly hypertensive patients. A total of 120 mild to moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75-89 years, were studied. After a 4-week wash-out period on placebo, they were randomized to receive atenolol 50 mg or losartan 50 mg for 24 weeks according to a parallel arm design. At the end of the placebo period and of each active treatment period, BP was measured (by mercury sphygmomanometer, Korotkoff I and V) and cognitive function was evaluated through three different tests (word list memory, word list recall and word list fluency). Both atenolol and losartan were equally effective in reducing SBP (-22.1 and -23.1 mmHg, respectively, P< 0.01 vs baseline) and DBP (-10.3 and -11.2 mmHg, respectively, P< 0.01 vs baseline). Atenolol treatment did not induce significant changes in any test score, whereas losartan significantly increased the score of both the word list memory (+2.2, P<0.05 vs baseline) and the word list recall test (+2.1, P<0.05 vs baseline). The comparison between losartan and atenolol was significant (P<0.05) for both memory tests. These data suggest that in very elderly hypertensive patients, chronic AT1 receptor blockade by losartan could improve cognitive function, in particular immediate and delayed memory.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Antihypertensive Agents/pharmacology , Atenolol/pharmacology , Hypertension/drug therapy , Losartan/pharmacology , Memory/drug effects , Adrenergic beta-Antagonists/therapeutic use , Aged , Aged, 80 and over , Angiotensin II Type 1 Receptor Blockers , Antihypertensive Agents/therapeutic use , Atenolol/therapeutic use , Cognition/drug effects , Cognition/physiology , Double-Blind Method , Female , Humans , Hypertension/psychology , Losartan/therapeutic use , Male , Memory/physiology , Psychological Tests
12.
J Hum Hypertens ; 17(3): 207-12, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12624612

ABSTRACT

The aim of this study was to evaluate the effect of benazepril addition to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. A total of 32 mild to moderate essential hypertensives (DBP>90 and <110 mmHg), aged 30-70 years were studied. After a 4-week placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril 10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks, according to a crossover design. At the end of the placebo period and of each active treatment period, blood pressure,AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed using a system, the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and benazepril monotherapy significantly reduced SBP (-18.2+/-4 and -17.8+/-4 mmHg, respectively, P<0.01 vs baseline) and DBP (-12.1+/-3 and -11.7+/-3 mmHg, respectively, P<0.01); the reduction was increased by the combination (-24.2+/-5 mmHg for SBP, P<0.001 and -16.8+/-4 mmHg for DBP, P<0.001). Amlodipine monotherapy significantly increased both AFV (+17.1%, P<0.001 vs baseline) and PSTP (+56.6%, P<0.001 vs baseline). As compared to amlodipine alone, the combination produced a less pronounced increase in AFV (+5.5%, P<0.05 vs baseline and P<0.01 vs amlodipine) and PSTP (+20.5%, P<0.05 vs baseline and P<0.01 vs amlodipine). Ankle oedema was clinically evident in 11 patients with amlodipine monotherapy and in three patients with the combination. These results suggest that ACE-inhibitors partially counteract the microcirculatory changes responsible for Ca-antagonists-induced oedema formation.


Subject(s)
Amlodipine/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Benzazepines/therapeutic use , Calcium Channel Blockers/therapeutic use , Edema/drug therapy , Hypertension/drug therapy , Adult , Aged , Ankle , Cross-Over Studies , Diagnostic Techniques, Cardiovascular/instrumentation , Double-Blind Method , Drug Therapy, Combination , Edema/complications , Edema/diagnosis , Edema/physiopathology , Female , Humans , Hydrostatic Pressure , Hypertension/complications , Male , Middle Aged
13.
Am J Hypertens ; 14(9 Pt 1): 921-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11587159

ABSTRACT

The aim of this study was to compare the effects of trandolapril and losartan on plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood pressure >90 and <110 mm Hg) postmenopausal women, aged 51 to 60 years not taking any hormone replacement therapy. Diabetic, obese, and smoking patients were excluded. After a 4-week placebo period, they were randomized to receive 2 mg of oral trandolapril (n=45) or 50 mg of oral losartan (n=44) for 12 weeks according to a double-blind, parallel group design. At the end of the placebo and active treatment periods, blood pressure (BP) was measured, plasma samples were drawn to evaluate PAI-1 antigen levels, and insulin sensitivity was assessed. Both trandolapril and losartan reduced systolic BP (by a mean of 16.9 mm Hg and 15.2 mm Hg, respectively, P < .01 v placebo) and diastolic BP (by a mean of 13.1 mm Hg and 11.9 mm Hg, respectively, P < .01 v placebo) with no difference between the two treatments. The PAI-1 antigen levels were significantly decreased by trandolapril (from 36.9+/-21 ng/dL to 27.2+/-17 ng/dL, P < .05), but not by losartan (from 35.3+/-22 ng/dL to 37.1+/-23 ng/dL, P=not significant). Glucose infusion rate was significantly increased by trandolapril (from 6.67+/-0.56 mg/min/kg to 7.9+/-0.65 mg/min/kg, P < .05), but was not significantly modified by losartan (from 6.7+/-0.47 mg/min/kg to 6.9+/-0.50 mg/min/kg, P= not significant). In the trandolapril group the PAI-1 decrease correlated with glucose infusion rate increase (r=0.36, P=.045) These results provide evidence of different effects of angiotensin converting enzyme inhibitors and AT1 antagonists on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin converting enzyme inhibitors is related to their action on insulin sensitivity and is not dependent on angiotensin II antagonism but rather on other mechanisms. It remains to be seen whether these findings apply to other patient populations than postmenopausal women.


Subject(s)
Angiotensin II/antagonists & inhibitors , Angiotensin II/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Fibrinolysis/drug effects , Hypertension/blood , Hypertension/drug therapy , Insulin/blood , Postmenopause/blood , Postmenopause/drug effects , Women's Health , Blood Glucose/drug effects , Blood Pressure/drug effects , Double-Blind Method , Female , Humans , Indoles/therapeutic use , Insulin Resistance , Lipids/blood , Losartan/antagonists & inhibitors , Losartan/therapeutic use , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Sensitivity and Specificity
14.
J Chemother ; 13(4): 434-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11589488

ABSTRACT

Fifty consecutive patients with stage IIIB-IV non-small cell lung cancer (NSCLC) received the ICE regimen at intermediate doses (ifosfamide 1 g/m2, carboplatin 120 mg/m2, etoposide 80 mg/m2, day 1 to 3, q.4 weeks, for a maximum of 6 cycles). Overall 2 complete response (CR) and 10 partial response (PR) (overall response, OR: 24%, 95% C.I. 14-37%) were observed. An additional 7 patients had stable disease (SD) lasting more than 6 months, therefore a clinical benefit (CR+PR+SD >6 mos) was achieved in 19 patients (38%). Median time-to-progression (TTP) was 7 months and median overall survival (OS) was 11 months; 1- and 2-year survival rates were 36% and 10%. The ICE regimen was well tolerated and devoid of any cardiac, hepatic or neurologic toxicity. Moderate nausea and vomiting were easily manageable, grade 2 alopecia was universal, while hematological toxicity was mild (grade 2 leuko- and thrombocytopenia). Due to its efficacy and safety profile, this 3-drug regimen can be considered for routine community use.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Etoposide/therapeutic use , Ifosfamide/therapeutic use , Lung Neoplasms/drug therapy , Adult , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Dose-Response Relationship, Drug , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Survival Rate , Treatment Outcome
15.
Am J Clin Oncol ; 24(6): 614-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11801766

ABSTRACT

The purpose of this study was to evaluate the efficacy and tolerability of single-agent gemcitabine in untreated elderly patients with stage IIIb/IV non-small-cell lung cancer (NSCLC). Since April 1997, 46 consecutive patients have been enrolled in this multicenter study. Gemcitabine 1,000 mg/m2 was administered as a 30-minute intravenous infusion on days 1, 8, and 15 every 28 days. Primary patient characteristics were: male/female 38/8; median age 73 years (range: 70-82 years); median Karnofsky performance status (PS) 90 (range: 70-100); stage IIIb 61% and stage IV 39%; histotype: epidermoid 48%, adenocarcinoma 43%, and large cell carcinoma 9%. No complete response was observed, but 10 (21.7%) patients achieved partial response (PR) (95% confidence limits: 11-36%), 27 (58.7%) had stable disease (SD), and 7 (15%) progressed early (at the first evaluation). The median duration of PR and SD was 8 months (range: 4-23+ months) and 4 months (range: 2-9 months), respectively. Subjective response evaluating PS and symptoms such as dyspnea, pain, and cough was evaluated in 40 patients; 11 (27.5%) improved, 15 (37.5%) remained stable, and 14 (35%) worsened. The median time to progression was 4 months, the median survival was 9 months, and 1-year survival was 44%. After a median follow-up of 10.5 months, 14 patients are still alive. There were no grade 4 toxicities. Grade 3 neutropenia and thrombocytopenia occurred in 19% and 2% of patients, respectively. Nonhematologic toxicities were mild. Grade I/II side effects of nausea/vomiting, transient fever, increase of hepatic transaminases, transient peripheral edema at lower extremity (not related to cardiac or renal disease or phlebothrombosis) were reported. This phase II study confirms the activity and favorable toxicity profile of single-agent gemcitabine in the treatment of elderly patients with advanced NSCLC.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Lung Neoplasms/drug therapy , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/secondary , Female , Humans , Lung Neoplasms/pathology , Male , Neoplasm Staging , Prospective Studies , Remission Induction , Survival Analysis , Gemcitabine
16.
G Ital Med Lav Ergon ; 23(4): 435-7, 2001.
Article in English | MEDLINE | ID: mdl-11758146

ABSTRACT

The aims of the study were the identification and optimization of the radiation protection measures for in-patients who underwent palliative radionuclide therapy for bone metastases with 153Sm-EDTMP activities lower than 3 GBq. The suitability of the preventive procedures from the contamination of places and objects, and for the protection of the hospital staff, other patients and relatives from the danger of external radiation and internal contamination has been evaluated by carrying out a series of measurements both of superficial contamination inside the confinement room and of the dose near the treated patients. The results show that the contamination of the places and the objects close to treated patients is really low. The greatest risk of contamination depended on the management of the physiological waste that, therefore, should be collected and disposed as radioactive one. The measurements of external radiation show that nearby the confinement room the dose limit for public is not exceeded. The same is true for the dose limit of 3 mSv established for relatives who, when taking care treated patients, receive a dose lower than 20 microSv a patient. The fulfillment of the proposed radiation protection measures assures the containment of the risk of exposure and contamination for nursing and medical staff involved in radionuclide-based therapy.


Subject(s)
Bone Neoplasms/radiotherapy , Organometallic Compounds/therapeutic use , Organophosphorus Compounds/therapeutic use , Radiation Monitoring/methods , Radiation Protection/methods , Radioisotopes/therapeutic use , Bone Neoplasms/secondary , Health Physics , Humans , Palliative Care , Patient Isolation
17.
Int J Prosthodont ; 14(1): 9-14, 2001.
Article in English | MEDLINE | ID: mdl-11842913

ABSTRACT

PURPOSE: The influence of different types of posts and cores on light transmission through all-ceramic crowns was assessed by spectrophotometric analysis and clinical evaluation. MATERIALS AND METHODS: Three extracted natural teeth were replicated in acrylic resin, with roots prepared to receive standardized posts and cores. Using a silicone impression material as a template, various prosthodontic reconstructions were obtained by combining four types of posts and cores (polished and matte-finished gold alloy, all-ceramic, and ceramized metal alloy) and three types of all-ceramic crowns (IPS-Empress 2 surface-colored, IPS-Empress 2 stratified, and In-Ceram). The spectrophotometric analysis was performed in the dark at 25 degrees C. The teeth were backlit with an incandescent lamp at the color temperature of A illuminant and shielded to avoid spurious light entering the spectrophotometer. The transmitted light was analyzed in terms of luminance at four points of the sample surface (cervical, middle, incisal, and proximal). Twelve measurements were performed for the natural teeth, and 144 were performed for the artificial teeth. RESULTS: Natural teeth had the highest luminance. Among all-ceramic crowns, surface-colored IPS-Empress 2 had the highest luminance, and stratified IPS-Empress 2 had the lowest. Regarding posts and cores, the luminance was highest with the all ceramic, lower with the ceramized and the polished gold alloy (which had very similar luminance), and lowest with the matte-finished gold alloy. No significant difference among prosthodontic combinations was detected under clinical observation. CONCLUSION: The surface-colored glass ceramic (IPS-Empress 2) was the most translucent crown. At the standard crown thickness used, there were small, significant spectrophotometric, but not clinical, differences among the combinations tested. These findings show no esthetic contraindications for the use of polished gold alloy posts and cores with all-ceramic crowns.


Subject(s)
Ceramics/chemistry , Crowns , Dental Porcelain/chemistry , Dental Prosthesis Design , Post and Core Technique , Acrylic Resins , Aluminum Oxide/chemistry , Aluminum Silicates/chemistry , Color , Colorimetry , Darkness , Esthetics, Dental , Gold Alloys/chemistry , Humans , Light , Metal Ceramic Alloys/chemistry , Models, Dental , Palladium/chemistry , Photometry , Post and Core Technique/instrumentation , Potassium Compounds/chemistry , Spectrophotometry , Statistics as Topic , Surface Properties , Temperature , Tooth Crown/anatomy & histology , Tooth Preparation, Prosthodontic , Transillumination
18.
J Hypertens ; 18(12): 1871-5, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11132613

ABSTRACT

OBJECTIVE: The aim of this study was to compare the chronic effects of four dihydropyridine calcium antagonists with different pharmacologic characteristics, amlodipine, felodipine, lacidipine and manidipine,on blood pressure (BP), heart rate (HR) and plasma norepinephrine (NE) levels in patients with mild to moderate essential hypertension. METHOD: After a 4-week placebo period, 60 patients of both sexes were randomly administered amlodipine 5-10 mg once daily (o.d.) (n = 15); felodipine 5-10 mg o.d. (n = 15); lacidipine 4-6 mg o.d. (n = 15); manidipine 10-20 mg o.d. (n = 15), for 24 weeks, according to a double blind, parallel group design. Initially, for the first 2 weeks, the lowest dose of each drug was used, then higher doses were administered if sitting diastolic blood pressure (DBP) was > 90 mmHg. BP, HR and plasma NE were evaluated at the end of the placebo and active treatment periods. NE was assessed at trough, at peak and after 12 h from drug ingestion. RESULTS: Administration of all four drugs reduced clinic BP to the same level after 24 weeks, whereas HR increased only with felodipine (+ 3.1 bpm; P< 0.05). Significant increases in plasma NE levels were observed after chronic therapy with amlodipine and felodipine (+ 34.9 and + 39.4% respectively; P< 0.01 versus placebo) but not with lacidipine (+ 7.1%, NS) and manidipine (+ 2.9%, NS). CONCLUSIONS: These findings suggest that sympathetic activation occurred during chronic treatment with amlodipine and felodipine, whereas manidipine and lacidipine did not increase plasma noradrenaline at the times measured. The reasons for this difference are unclear; they could be related to the different pharmacological characteristic of the two drugs, lacidipine and manidipine.


Subject(s)
Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Dihydropyridines/therapeutic use , Hypertension/blood , Hypertension/drug therapy , Norepinephrine/blood , Adult , Aged , Amlodipine/therapeutic use , Blood Pressure/drug effects , Double-Blind Method , Felodipine/therapeutic use , Female , Heart Rate/drug effects , Humans , Hypertension/physiopathology , Male , Middle Aged , Nitrobenzenes , Piperazines , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiopathology
19.
Cardiovasc Drugs Ther ; 13(3): 243-8, 1999 May.
Article in English | MEDLINE | ID: mdl-10439887

ABSTRACT

To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure (BP) and heart rate (HR) in very elderly hypertensive patients, 54 patients aged 76-89 years (mean age 81.8 years) with systolic blood pressure (SBP) > 160 mmHg and diastolic blood pressure (DBP) > 90 mmHg were studied. After a 4-week placebo washout period, patients were randomized to receive manidipine 10 mg or placebo, both administered once daily for 8 weeks. Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter. At each visit casual BP and HR were measured. At the end of the placebo period and after 8 weeks of active treatment, noninvasive 24-hour ambulatory blood pressure measurement (ABPM) was performed. Manidipine significantly lowered casual sitting and standing SBP (P < 0.001) and DBP (P < 0.001) at the trough level. ABPM showed a significant decrease in 24-hour SBP and DBP values (P < 0.001), daytime SBP and DBP (P < 0.001), and night-time SBP (P < 0.001) and DBP (P < 0.005). In addition, ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval, without effect on the circadian BP profile. The trough/peak ratio was 0.67 for SBP and 0.59 DBP. No statistically significant change in HR was observed. The treatment was well tolerated, and there were no serious side effects. In conclusion, in very elderly hypertensive patients, once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP.


Subject(s)
Antihypertensive Agents/administration & dosage , Calcium Channel Blockers/administration & dosage , Dihydropyridines/administration & dosage , Hypertension/drug therapy , Hypertension/physiopathology , Aged , Aged, 80 and over , Blood Pressure/drug effects , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Double-Blind Method , Drug Administration Schedule , Female , Heart Rate/drug effects , Humans , Male , Nitrobenzenes , Piperazines , Placebos
20.
J Cardiovasc Pharmacol ; 33(4): 534-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10218722

ABSTRACT

The aim of this study was to compare the effects of long-term monotherapy with four different beta-blockers on plasma lipids in hypercholesterolemic hypertensive patients. We studied 152 subjects with essential hypertension [diastolic blood pressure (DBP) >90 mm Hg], total cholesterol (TC) >240 and <330 mg/dl, and triglycerides (TGs) <300 mg/dl. After a 4-week washout period with placebo, patients were randomized to receive propranolol, 160 mg/day (n = 37), atenolol, 100 mg/day (n = 38), bisoprolol, 10 mg/day (n = 39), or celiprolol, 400 mg/day (n = 38), for 18 months. No cholesterol-reducing drug was allowed. Blood samples for evaluation of TC, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol (HDL-C), and TGs were taken before and after the placebo period and subsequently every 6 months. No beta-blocker worsened TC or LDL-C. Nonselective propranolol caused the most pronounced changes in HDL-C and TGs. Beta1-Selective atenolol produced the same qualitative effects, but to a lesser extent. The more beta1-selective bisoprolol did not affect HDL-C and TGs. Celiprolol significantly improved the lipid profile by significantly decreasing TC, LDL-C, and TGs, and increasing HDL-C. These findings suggest that in hypercholesterolemic hypertensive patients, (a) beta1-selective beta-blockers are likely to adversely affect plasma lipids to a lesser extent than nonselective ones; and (b) celiprolol is able to improve the lipid pattern, which could be because of its peculiar ancillary properties.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Hypercholesterolemia/drug therapy , Hypertension/drug therapy , Lipids/blood , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Agonists/therapeutic use , Adrenergic beta-Antagonists/pharmacology , Adult , Analysis of Variance , Atenolol/pharmacology , Bisoprolol/pharmacology , Celiprolol/pharmacology , Double-Blind Method , Humans , Hypercholesterolemia/complications , Hypertension/complications , Male , Middle Aged , Propranolol/pharmacology
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