Pathology underrates colon cancer extranodal and nodal metastases; ex vivo radioimmunodetection helps staging.

PURPOSE: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases. EXPERIMENTAL DESIGN: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use. RESULTS: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected by AES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P<0.01). In addition 12 extranodal metastases were found in this study of which eight were detected by AES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone. CONCLUSIONS: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase.

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.

Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.

To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

Dose effect relationship of reviparin in chronic hemodialysis: a crossover study versus nadroparin.

Low molecular weight heparins (LMWHs) are used for prevention of clotting in the dialysis circuit. The aim of this trial was to define the optimal dose of a new LMWH and to test the efficiency of a single dose at the start of the session. Fifteen patients were treated according to a double blind and crossover design during 4 blocks of 5 consecutive reviparin doses assigned randomly as 50, 60, 70, 85, and 100 IU anti-Xa/kg. Assessment was carried out on screening of fibrin rings or clots in the arterial and venous air traps and on visual detection of fiber in the dialyzer after rinsing. These clinical results were compared to plasmatic anti-Xa activity and thrombin-antithrombin (TAT) complex generation. A standard dose of 70 IU anti-Xa/kg of nadroparin was used as the control. After a bolus of 50 to 100 IU anti-Xa/kg, the occurrence of fibrin rings and clots in the air traps was dependent on three factors: dose of LMWH, time of the session, and patient status. A bolus of 85 IU anti-Xa/kg of reviparin was effective and safe for sessions of 4 h. For this dose, plasmatic anti-Xa activity was 0.96 +/- 0.28 IU/ml at Hour 2 and 0.82 +/- 0.22 IU/ml at Hour 4. TAT complexes are good markers of the activation of the coagulation. They did not increase during a 4 h session after a reviparin bolus of 100 IU/kg. For the same LMWH dose, the trial shows a great variability of the clinical effect and anti-Xa activities from one patient to another. A single dose of 85 IU anti-Xa/kg of reviparin can be used at the start of the dialysis session as a loading dose. We advise adapting the dose during the subsequent sessions according to the appearance of the blood circuit. The benefit of monitoring anti-Xa activity and TAT complexes could be tested in a further trial.

A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double-blind controlled study.

OBJECTIVE: To analyse the efficacy of indapamide sustained-release (SR) 1.5 mg in reducing blood pressure versus amlodipine 5 mg and hydrochlorothiazide 25 mg, in elderly hypertensive patients. DESIGN: Double-blind, randomized, 12 week study using three parallel groups. SETTING: European teaching hospitals and general practices. PATIENTS: Randomized patients, (n = 524) including 128 patients with isolated systolic hypertension (ISH); mean age: 72.4 years; mean systolic/diastolic blood pressures (SBP/DBP): 174.5/97.9 mmHg. MAIN OUTCOME MEASURES: Clinic systolic and diastolic blood pressure variations. RESULTS: Indapamide SR 1.5 mg demonstrates a similar efficacy to that of amlodipine 5 mg, as well as to that of hydrochlorothiazide 25 mg (equivalence P < 0.001); the mean decreases in SBP/DBP were -22.7/-11.8 mmHg, -22.2/-10.7 mmHg and -19.4/-10.8 mmHg, respectively. In the ISH subgroup, indapamide SR 1.5 mg tends to have greater efficacy than hydrochlorothiazide 25 mg in reducing the SBP (-24.7 versus -18.5 mmHg, respectively; equivalence P = 0.117), while similar results are obtained with amlodipine 5 mg (-23 mmHg, equivalence P < 0.001). The normalization rate was relatively high for indapamide SR 1.5 mg (75.3%), when compared with amlodipine (66.9%) and hydrochlorothiazide (67.3%), especially in the subgroup of isolated systolic hypertensive patients: 84.2 versus 80.0% for amlodipine, and versus 71.4% for hydrochlorothiazide. CONCLUSIONS: Indapamide SR 1.5 mg shows similar antihypertensive efficacy to amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients, while in patients with isolated systolic hypertension, indapamide SR 1.5 mg shows a similar efficacy to amlodipine 5 mg but a greater efficacy than hydrochlorothiazide 25 mg.

Amelioration of arterial properties with a perindopril-indapamide very-low-dose combination.

BACKGROUND: Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections. AIMS: To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both. MATERIAL AND METHODS: This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry). RESULTS: For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections. CONCLUSION: Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.

Induction of labour with a viable infant: a randomised clinical trial comparing intravaginal misoprostol and intravaginal dinoprostone.

OBJECTIVE: To compare the efficacy and safety of vaginal misoprostol (50 microg) with vaginal dinoprostone. DESIGN: Double-blind randomised trial. SETTING: Obstetrics Department, Poissy Hospital, France. PARTICIPANTS: 370 patients with medical indications for induction of labour. OUTCOME MEASURES: Vaginal deliveries within 24 hours, as well as time to vaginal deliveries, caesarean rates, costs, and fetal, neonatal and maternal condition. RESULTS: Compared with vaginal dinoprostone, vaginal misoprostol resulted in greater efficacy in several areas: vaginal delivery within 24 hours; time to vaginal delivery; and vaginal delivery within 12 hours. There was a non-significant increase in the caesarean section rate for fetal distress in the misoprostol group, but fewer caesarean sections for failed induction. Fetal tolerance was similar in the two groups, although significantly more neonates had a cord pH <7.20 and (non-significantly) none had meconium stained amniotic fluid in the misoprostol group. The incidence of poor neonatal outcome was similar in both groups. Subgroup analysis by indication for induction showed that the higher rates of arterial cord pH <7.20 and of meconium-stained amniotic fluid with misoprostol persisted only in possible fetal compromise. Poor neonatal outcome was less frequent in the misoprostol group in cases of induction for non-fetal indications. CONCLUSIONS: Vaginal misoprostol resulted in successful and earlier induction of labour more often than dinoprostone, but the safety of misoprostol raises some concern in potentially compromised infants. Misoprostol should be preferred to dinoprostone in cases of induction for non-fetal indications.

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study.

OBJECTIVE: To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). DESIGN: The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. SETTING: European hospitals, general practitioners and cardiologists. PATIENTS: Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. INTERVENTIONS: Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. MAIN OUTCOME MEASURES: LVMI variation in the perprotocol population. RESULTS: Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. CONCLUSIONS: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA.

OBJECTIVE: Intestinal microsporidiosis caused by Enterocytozoon bieneusi is a cause of chronic diarrhoea in patients with HIV infection for which there is no current therapy. This study was designed to assess the safety and efficacy of oral fumagillin in this infection. DESIGN: A dose-escalation trial. METHODS: Twenty-nine HIV-infected patients with E. bieneusi infection were consecutively enrolled in the trial. Oral doses of fumagillin were given to four groups of patients for 14 days: 10 mg/day (group 1), 20 mg/day (group 2), 40 mg/day (group 3), and 60 mg/day (group 4). Patients were seen at weeks 1, 2, 4 and 6 to assess safety and efficacy. Efficacy was assessed primarily by the clearance of microsporidia from stools and follow-up duodenal biopsies. RESULTS: Thirteen patients complained of abdominal cramps, vomiting or diarrhoea during the study, and three patients had fumagillin withdrawn because of adverse events. Thrombocytopenia, neutropenia and hyperlipasaemia were the most frequent biological adverse events. Twenty-one out of 29 patients transiently cleared microsporidia from their stools during the study. By week 6, however, all patients in groups 1, 2 and 3 had parasitic relapse. Interestingly, eight out of 11 (72%) patients treated with 60 mg/day (group 4) apparently cleared microsporidia from their gastrointestinal tract and gained weight. No parasitic relapse was documented in these eight patients during a mean follow-up of 11.5 months. CONCLUSION: Treatment with fumagillin at 60 mg/day for 14 days has promise as an effective oral treatment for E. bieneusi infections.

Percentage of cancer on biopsy cores accurately predicts extracapsular extension and biochemical relapse after radical prostatectomy for T1-T2 prostate cancer.

PURPOSE: To perform a multivariate analysis to investigate the usefulness of eight preoperative variables as predictors of final pathological stage (pT), positive surgical margins (PSM) and biological progression after radical prostatectomy (RP). MATERIALS AND METHODS: In 143 patients undergoing RP for T1-T2 prostate cancer, the respective values of age, clinical stage, preoperative prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), number of positive biopsies (NPB), Gleason score, length of tissue core invaded by cancer (LTI) and topography (uni/bilaterality) of positive biopsies for predicting extracapsular extension, PSM and biochemical failure (PSA> or =0.05 ng/ml) were evaluated retrospectively. Univariate and multivariate analyses were applied to define the statistical significance of each variable. Actuarial survival without biological progression was calculated using the Kaplan-Meier method (log-rank test). RESULTS: In this series, 44.8% of patients had extracapsular extension with 41.3% PSM. The mean PSA was 12.4 ng/ml. In univariate analysis, LTI (p<0.0001), NPB (p = 0.0023), PSA (p = 0.0039) and Gleason score (p = 0.0136) were the most powerful variables to predict pT stage; however, in logistic regression analysis, LTI was the most predictive feature. For prediction of PSM, some variables (LTI, NPB and PSA) were found to be of statistical value in univariate analysis, and LTI in combination with NPB and PSA in multivariate analysis. For biological progression, statistical analysis (log rank test) showed PSAD and LTI to be significant predictors. CONCLUSION: The pathological report regarding the biopsy contains crucial information influencing the prediction of pT stage, PSM and biological progression after RP. LTI, NPB and PSA are the most useful parameters for this purpose.

Measures of treatment effectiveness on tumour response and survival: a multi-state model approach.

This paper proposes the application of a counting process approach in the analysis of treatment effect on tumour response and survival. It relies on the definition of two transient states between which individuals may move over time, that is, response and non-response, and of one absorbing state, death. Three models are discussed according to the underlying Markov and duration dependence assumptions, as well as a marginal modelling of repeated transitions between the two transient states. We illustrate the proposed methods with data from a randomized clinical trial assessing the effect of fludarabine in patients with advanced chronic lymphocytic leukaemia.

Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients.

OBJECTIVE: To determine the long-term efficacy and safety of a fixed, very-low-dose tablet combining one-half the standard dose of perindopril with one-quarter the standard dose of indapamide as first-line treatment in elderly patients. DESIGN: Double-blind, randomized, placebo-controlled study in an outpatient setting. PATIENTS AND INTERVENTIONS: Following a single-blind, placebo run-in period of 4 weeks, patients [65-85 years, with mild-to-moderate essential hypertension or isolated systolic hypertension (ISH)] were randomized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg (Per/ Ind) (n=193) or placebo (n=190), daily for 12 weeks. After this first 12-week period, all patients on Per/Ind (n=138) and patients responding to placebo (n=61) were maintained on their previous regimen for a further 48 weeks. Patients in the placebo group whose blood pressure was not normalized, were switched to Per/Ind (n=60). MAIN OUTCOME MEASURE: The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60. RESULTS: After 1 year of treatment (intention-to-treat) supine systolic and diastolic blood pressure decreased by 23.0 +/- 15.3 mmHg and 13.3 +/- 94 mmHg with Per/Ind (n=253: 193 from randomized Per/Ind group and 60 from the placebo group switched at week 12). The mean decreases in systolic blood pressure were similar in essential hypertension and ISH (systolic blood pressure 23.2 versus 22.7 mmHg, respectively). Per/Ind treatment (n=253) achieved an initial normalization of blood pressure in 96.2% [95% confidence interval (CI) 93.6-98.9%; Kaplan-Meier estimate] of Per/Ind-treated patients; 79.8% (95% CI 74.1-85.5%) of these maintained a normalized blood pressure throughout the 1 -year follow-up. The incidence of adverse events was similarly low in the placebo and active therapy groups. Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects CONCLUSIONS: The fixed, very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year, and is well-tolerated.

Effects of spinal cord X-irradiation on the recovery of paraplegic rats.

Axonal regrowth is limited in the adult CNS, especially in the spinal cord, one of the major sites of traumatic lesions. Pathophysiological changes occurring after spinal cord injury include complex acute, subacute, and late processes. In this study, we assessed whether X-irradiation interferes with the acute/subacute phases, thereby improving the functional recovery of paraplegic animals. Two days after acute compression of adult rat spinal cords, various doses (0, 2, 5, 10, 20 Gy) of X-rays were administered as one single dose to the compression site. The animals were functionally evaluated over the course of 1 month after injury, using the Tarlov scale and the Rivlin and Tator scale. We also designed a "physiological" scale, including an assessment of urinary function and infection, appropriate for the evaluation of spinal-cord-lesioned animals. Behavioral analysis suggested that the high doses, 20 Gy and, to a lesser extent, 5 and 10 Gy, were toxic, as shown by morbidity rate and "physiological" score. The 2-Gy group showed better motor performances than the lesioned nonirradiated (LNI) animals and the 5- and 20-Gy groups. Motor performance in the 5-, 10-, and 20-Gy groups was poorer than that seen in the LNI group. Gliosis was reduced in the 2-Gy group compared to LNI animals, and there was high levels of gliosis in the highly (>/=5 Gy) irradiated animals. There was a 23% less lesion-induced syringomyelia in the 2-Gy group than in the other groups (LNI and 5-20 Gy). Thus, low doses of X-rays may interfere with the formation of syringomyelia and glial scar, thereby facilitating the recovery of paraplegic animals. These findings suggest that low-dose irradiation of the lesion site, in association with other therapies, is a potentially promising treatment for improving recovery after spinal cord injury.

Efficacy and safety of a fixed low-dose perindopril/indapamide combination in essential hypertension. A randomised controlled study.

This multicenter, double-blind, parallel-group study was designed to assess the efficacy and the safety of fixed low dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) versus atenolol 50 mg (Ate). After a 4-week placebo run-in, 446 hypertensive patients (mean age : 55.8 +/- 11.0 years) were randomised to receive Per/Ind or Ate for 12 weeks. The primary outcome measures were the changes in trough supine systolic and diastolic blood pressure (sSBP, sDBP) between baseline and the last observation. Equivalence was assessed in an intention-to-treat analysis using a two one-sided tests procedure. Per/Ind and Ate decreased sSBP by -20.5 mmHg and -20.1 mmHg, respectively; the 90% confidence interval [-2.3; 1.5] of the intertreatment difference (-0.4 mmHg) fell within the predefined equivalence interval [-8; +8 mmHg]. Similarly, the sDBP decreased by -15.1 mmHg (Per/Ind) and -16.2 mmHg (Ate) with an intertreatment difference of 1.1 mmHg whose 90% confidence interval [-0.1; 2.2 mmHg] fell within the predefined equivalence interval [-4; +4 mmHg]; thus antihypertensive efficacy of Per/Ind and Ate were equivalent (P <0.001). In patients older than 65, Per/Ind induces a statistically greater decrease in sSBP than Ate (P <0.05). Per/Ind was well tolerated. Further controlled studies are needed to confirm these results on a long-term period.

Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study.

BACKGROUND/AIMS: A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma. METHODS: Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed. RESULTS: 130 patients had detectable iron at enrollment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002). CONCLUSIONS: These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.

White blood cell count: a prognostic factor and possible subset indicator of optimal treatment with low-dose adjuvant interferon in primary melanoma.

AlphaIFN has recently been recognized as an adjuvant therapy to surgery in melanoma patients. A major issue is to select patients who will benefit from this therapy and to avoid toxicity in those who will not respond. The aim of this exploratory analysis was to identify the predictive factors of response to alphaIFN. The French cooperative group has recently shown that adjuvant therapy of melanoma patients with low-dose alphaIFN provides a benefit on disease-free interval (DFI). Using this database, predictors of DFI were investigated using Cox models and treatment-covariate interactions were sought. Gender, age, Breslow thickness, and baseline WBC count, given an alphaIFN-WBC interaction, were independent predictors of DFI. Baseline WBC count was the only variable for which there was an interaction with alphaIFN, whatever the Breslow: patients with low WBC count (<6.8 x 10(9)/liter = median) did not benefit from alphaIFN (HR=1.27 (95%CI: 0.84-1.91); P = 0.26) whereas the DFI of patients with high WBC was prolonged (P = 0.0001) with a hazard ratio of 0.50 (95% confidence interval, 0.35-0.71). The estimated values of WBC count for which IFN was significantly superior to no-treatment were those > or = 7.2 x 10(9)/liter. The baseline WBC count was correlated to baseline neutrophils but not to Breslow thickness or to time since last melanoma surgery. AlphaIFN prolonged DFI in patients with a high WBC count but not in those with a low WBC count. The results of this exploratory analysis, if confirmed by other studies, may help to identify patients who are most likely to benefit from alphaIFN.

Short therapy with amoxicillin-clavulanate and corticosteroids in acute sinusitis: results of a multicentre study in adults.

Evolution of bacterial resistance shortens antibiotic treatment in ENT infections. The efficacy and tolerance of amoxicillin-clavulanate (ACA), with and without associated short steroid therapy, was evaluated in acute sinusitis of adults at a dosage of 1.5 g/d for 5 d vs. 10 d. This multicentre, randomized, double-blind, placebo-controlled study included 433 patients, 417 of whom were suitable for intent-to-treat (ITT) analysis. The therapeutic success rate in the ITT population, assessed according to strict clinical and radiological criteria, was respectively, 80% and 85% in the 5-d and 10-d treatment groups. Due to the statistical risks that were evidenced, the 2 durations of treatment could not be considered equivalent. The analysis of medical history shows that some risk factors (recurrence of sinusitis, previous surgical sinus drainage) seem to promote therapeutic failure and that 5-d treatment is inappropriate in these patients. The persistence of therapeutic success on day 30 was not influenced by the initial duration of treatment. The efficacy and good tolerance of ACA in acute sinusitis in adults were confirmed. Further studies will be needed to define the indications of short treatments better, which seem to be indicated in the absence of specific risk factors.

Prognostic relevance of a scoring system based on clinical and biological parameters in early chronic lymphocytic leukemia.

INTRODUCTION: Among patients with indolent form of B-cell chronic lymphocytic leukemia, some of them will progress into more advanced stages. To better define this subpopulation of patients, we attempted to define some parameters capable of predicting a pejorative clinical outcome. MATERIALS AND METHODS: Eighty-eight previously untreated patients with B-cell chronic lymphocytic leukemia in Binet stage A were analysed to study the prognostic value of simple serological variables: soluble CD23 (sCD23), beta2 microglobulin (beta2m), lactate-dehydrogenase activities and albumin level. Results were compared to other conventional clinical and biological parameters by univariate and multivariate statistical analysis. RESULTS: Our data show that: (1) among those studied, sCD23 >50 u/ml was the only serological significant parameter clearly correlated with disease progression and (2) stage A" patients (hemoglobin level between 100 and 120 g/l and/or lymphocytosis >30.10(9)/l), axillary lymph nodes and hypogammaglobulinemia were found to be other variables associated with a pejorative outcome. These four variables enabled the establishment of a scoring system, capable of predicting disease progression since 66% of the patients with a score < or =2 are going to evolve into advanced stages vs 12% with a score <2. Furthermore, the time to progression is shortened when the score is increasing. CONCLUSION: Our findings show the prognostic relevance of a scoring system including sCD23 level. This score could be taken into account in the treatment strategy of B-cell chronic lymphocytic leukemia.