[High pressure trap]. / Piège à haute tension.

Pheochromocytoma is a rare tumor potentially life-threatening and associated with non specific and diverse symptomatology. Cardiac symptoms may mislead diagnosis; they could manifest as myocardial sideration concomitant to a hypertensive peak or supraventricular arythmia. We report a case of pheochromocytoma associated with hypokaliemia revealed by a myocardial ischemia with acute cardiac failure and severe left ventricular depression and complete reversal after surgery.

[Uselessness of high-sensitivity cardiac troponins to improve diagnostic accuracy of dobutamine stress echocardiography in high-risk diabetic patients]. / Intérêt du dosage des troponines hypersensibles dans l'amélioration de la précision diagnostique de l'échocardiographie de stress à la dobutamine chez les diabétiques à haut risque.

BACKGROUND AND AIM: Dobutamine stress echocardiography (DSE) is a well-established noninvasive stress modality for the detection and evaluation of coronary artery disease in diabetic patients. High-sensitivity cardiac troponin T recently emerged as a highly sensitive dosage for the detection of ischemia. The aim of the study was to examine whether high-sensitivity cardiac troponin T may improve the diagnostic accuracy of silent ischemia by DSE in high-risk diabetic patients. METHODS AND RESULTS: Twenty-one patients with long-standing (>10years) and/or complicated type II DM but no established CAD were included. In addition to DSE, venous blood samples for measurement of hs-cTnT were collected prior to DSE, 6hours and 24hours after the test. Troponins were deemed positive if>1.5 upper limit for normality. Patients with positive troponins underwent coronary angiography or CT scan regardless of the result of DSE. Among the 21 patients, 7 had positive troponins measured 6hours after stress, (mean peak troponin=44.5). DSE were negative in all of them. Mean age was 64years significantly higher than patients with negative troponins. No differences were noted between the groups in terms of epidemiological, clinical or echocardiographic characteristics. Patients with positive cardiac troponins were evaluated for the presence of coronary lesions but none of them had significant disease. After an 18-month mean follow-up, no adverse cardiac events were noted in either group. CONCLUSION: In high-risk diabetic patients, the measurement of hs-cTnT during DSE does not improve the sensitivity at least in those with negative DSE tests.

Are we turning to more than a first line treatment of metastatic colorectal cancer with high dose irinotecan?: A monocentric institution safety analysis of 46 patients.

PURPOSE: Irinotecan (CPT11) at 180 mg/m(2) with LV5FU2 for metastatic colorectal cancer (MCRC) has response rates (RRs) of 56 and 4% as first- and second-line treatments, respectively [1-2], and higher doses of CPT11 result in higher RRs. The present cohort analysis aimed to evaluate the effect of increasing doses of this combination treatment in clinical practice. METHODS: Chemo-naive and pretreated patients with MCRC received CPT11 and LV5FU2 (5FU 48-h CI 2400 mg/m(2), D1 bolus leucovorin 200 mg/m(2)), followed by 5FU 400 mg/m(2) (cycles d1-d15). CPT11 dose was increased by 20 mg/m(2) at each cycle, from 180 mg/m(2) up to 260 mg/m(2), unless grade 3 toxicities other than alopecia arose. RESULTS: Between March 2002 and September 2005, 46 patients were recruited (median age: 62.3 years). A total of 512 cycles of chemotherapy were administered (median: 9 cycles/patient; range: 3-41). Median follow-up was 16.2 months. Altogether, 27 patients had received prior chemotherapy: 24 with an oxaliplatin-based regimen; seven with CPT11; and five with LV5FU2 or oral 5FU. Doses of 260 mg/m(2) were used in 17 patients, 240 mg/m(2) in seven, 220 mg/m(2) in six and 200 mg/m(2) in five, while 11 remained at 180 mg/m(2); 121 cycles used 260 mg/m(2) (24%), with 76 cycles at 240 mg/m(2) (14%), 78 cycles at 220 mg/m(2) and 58 cycles at 200mg/m(2). The objective response (OR) was 40%, with stable disease (SD) in 45% and disease progression (DP) in 11%. In the first-line therapy group, partial/complete responses were 55%, with SD in 30% and DP in 15%. In pretreated patients, OR was 30.5%, SD was 58.5% and DP was 11%. Nine patients (20%) had a therapeutic break (median: 5.1 months; range: 3-10). Overall median survival was 17 months, with 16.5 months in pretreated patients and 19.6 months in the first-line group. Toxicity grades 3-4 and overall incidence per cycle were: neutropenia, 3-22%; diarrhea, 4-22%; vomiting, 2-20%; alopecia, 20-26%; anemia, 0.2-2%; thrombocytopenia, 0-0%; and mucositis, 0.4-2.2%. CONCLUSION: The toxicity of high-dose CPT11+LV5FU2 chemotherapy was well tolerated when the dose was progressively increased according to individual tolerability, with 37% of patients receiving CPT11 at 260 mg/m(2). Progression-free survival (PFS) increased with higher doses of CPT11. In the chemo-naive and pretreated subgroups, the median PFS was 10.9 and 8.8 months, respectively (P=0.698, NS). Optimization of CPT11 doses in pretreated patients appears to pave the way for new treatment options.

Cutaneous reflexes from the foot during gait in hereditary spastic paraparesis.

OBJECTIVE: It is known that P2 cutaneous reflexes from the foot show phase-dependent modulation during gait. The role of the motor cortex and the cortico-spinal tract in these reflexes and their modulation is unknown. Patients with hereditary spastic paraparesis (HSP) have a lesion in the cortico-spinal tract and may show deficits in P2 reflexes and/or their modulation. METHODS: Reflex responses of tibialis anterior and biceps femoris after sural nerve stimulation in 10 HSP-patients were compared with those in 10 healthy subjects. The reflexes were studied at two different moments in the step cycle during walking on a treadmill. RESULTS: Both patients and controls showed a phase-dependent modulation of P2 responses. For the individual muscles, no significant difference in reflex activity was observed between HSP-patients and the controls. However, when all muscles were taken together, the reflex activity for the controls was significantly higher than for the patients. CONCLUSIONS: The results of this study suggest that the cortico-spinal tract is involved in the regulation of the amplitude of the P2 responses and their phase-dependent modulation.

Failed suppression of direct visuomotor activation in Parkinson's disease.

The response times in choice-reaction tasks are faster when the relative spatial positions of stimulus and response match than when they do not match, even when the spatial relation is irrelevant to response choice. This spatial stimulus-response (S--R) compatibility effect (i.e., the Simon effect) is attributed in part to the automatic activation of spatially corresponding responses, which need to be suppressed when the spatial location of stimulus and correct response do not correspond. The present study tested patients with Parkinson's disease and healthy control subjects in a spatial S--R compatibility task in order to investigate whether basal ganglia dysfunction in Parkinson's disease leads to disinhibition of direct visuomotor activation. High-density event-related brain potential recordings were used to chart the cortical activity accompanying attentional orientation and response selection. Response time measures demonstrated a failure to inhibit automatic response activation in Parkinson patients, which was revealed by taking into account a sequence-dependent modulation of the Simon effect. Event-related potential (ERP) recordings demonstrated that visuospatial orientation to target stimuli was accompanied by signal-locked activity above motor areas of the cortex, with similar latencies but an enhanced amplitude in patients compared to control subjects. The results suggest that inhibitory modulation of automatic, stimulus-driven, visuomotor activation occurs after the initial sensory activation of motor cortical areas. The failed inhibition in Parkinson's disease appears therefore related to a disturbance in processes that prevent early attention-related visuomotor activation, within motor areas, from actually evoking a response.

Redundant-signals effects on reaction time, response force, and movement-related potentials in Parkinson's disease.

Studies using transcranial magnetic stimulation have established that patients with Parkinson's disease have increased motor cortex excitability. Relying on current evidence that the redundant-signals effect has its source in the motor system, we investigated whether, as a result of cortical hyperexcitability, Parkinson's disease patients demonstrate an enhancement of this effect. Eight patients with moderately severe Parkinson's disease and nine healthy control subjects participated in a task requiring simple manual responses to visual, auditory, and combined auditory-visual signals. During the task, motor cortex activation was recorded by means of movement-related EEG potentials, while responses were measured via isometric force recordings. The movement-related potentials and the force measures both yielded support for the view that the redundant-signals effect is partially caused in the motor system. However, the facilitatory effect of bimodal as compared to unimodal stimulation (i.e. the redundant-signals effect) was of the same size in Parkinson's disease patients and control subjects, as expressed in latency measures of the movement-related potentials and the force signals. We conclude that the redundant-signals effect is not enhanced in Parkinson's disease and that the mechanisms underlying this effect are probably not influenced by the increased motor cortex excitability found in this disease.

[Conservative treatment of anal canal carcinoma with external radiotherapy and interstitial brachytherapy, with or without chemotherapy: long-term results]. / Traitement conservateur des cancers du canal anal par irradiation suivie de curiethérapie interstitielle, avec ou sans chimiothérapie: résultats à long terme.

PURPOSE: A retrospective analysis of conservative treatment of anal canal cancers with external radiation therapy and interstitial brachytherapy with or without chemotherapy. PATIENTS AND METHODS: From 1986 to 1996, 69 patients were treated with external radiotherapy (40 Gy/20 fractions) and interstitial brachytherapy (20 Gy) after a mean interval of six weeks for a localized epidermoid carcinoma of the anal canal. Patients who did not complete the whole therapeutic sequence were not included. Forty-five patients received additional 5-fluorouracil- and/or mitomycin C-based chemotherapy regimen. RESULTS: Acute toxicity was acceptable. Complete response rate was 81%. Actuarial local control rate was at two and five years, 65% and 59% respectively (median follow-up: eight years). At two, five and ten years, actuarial colostomy rate was 26%, 33% and 33% respectively, and colostomy-free survival rates 61%, 47% and 37%. Overall survival at two, five and ten years was 81%, 65% and 53% respectively. Distant metastases occurred in 11 patients (16%). Prognostic factors for overall survival were performance status (PS) (79% survival at five years for patients with PS 0 versus 50% for patients with PS 1-3, P = 0.04) and tumor stage (80% at five years for T1-T2 versus 53% for T3-T4, P = 0.03). Overall treatment time less than 12 weeks and time interval between external radiotherapy and brachytherapy inferior than six weeks were associated with a better local control (P = 0.05). In multivariate analysis, these prognostic factors were not significant. CONCLUSION: These results confirm the efficacy of external radiotherapy and brachytherapy in the treatment of small anal canal cancers, and point out the need for improving treatment outcome of larger tumors.

Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators.

OBJECTIVES: To investigate the efficacy and safety of fosinopril in the treatment of chronic heart failure (CHF), patients with mild to moderate CHF and left ventricular ejection fractions <40% were randomly assigned in a double-blind manner to receive fosinopril 5 to 20 mg every day (n = 122) or enalapril 5 to 20 mg every day (n = 132) for 1 year. RESULTS: The event-free survival time was longer (1.6 vs 1.0 months, P= .032) and the total rate of hospitalizations plus deaths was smaller with fosinopril than with enalapril (19.7% vs 25.0%, P= .028). There was consistently better symptom improvement with fosinopril (P< .05). The incidence of orthostatic hypotension was lower in the fosinopril group (1.6% vs 7.6%, P< .05). CONCLUSIONS: Fosinopril 5 to 20 mg every day was more effective in improving symptoms and delaying events related to worsening of CHF and produced less orthostatic hypotension than enalapril 5 to 20 mg every day.

Management of hypertension: the role of combination therapy.

The complementary action of angiotensin converting enzyme inhibitors and diuretics in the treatment of hypertension has been demonstrated in a number of studies of fosinopril and hydrochlorothiazide (HCTZ). The combination provides a clinically significant reduction in blood pressure while minimizing the dose-dependent adverse effects of HCTZ, such as hypotension and its metabolic effects on plasma lipoproteins, by keeping the dose of each agent to the minimum. Fosinopril has a unique dual mechanism of elimination and can therefore be used in patients with renal impairment. The efficacy of the combination of fosinopril and hydrochlorothiazide compared with placebo and other agents is reviewed in this article. Studies have demonstrated that the combination is effective in the elderly and in renally impaired patients, regardless of severity. In addition, in non-insulin dependent diabetes, antihypertensive effect is achieved without further affecting carbohydrate and lipid metabolism, which is often the case when thiazide diuretics alone are used. A matrix study was performed to evaluate the optimum dose combination to produce blood pressure normalization and minimize side effects. This study evaluated 17 different dose combinations and demonstrated that the lowest dose combination to produce a clinically significant effect was fosinopril 10 mg and HCTZ 12.5 mg. However, a dose-related antihypertensive effect can be seen, giving the option for the use of 20 mg fosinopril for moderately hypertensive patients. Both combination therapy and fosinopril were significantly more effective than HCTZ alone or placebo. The fosinopril/HCTZ combination has also been shown to have a comparable effect to sustained-release nifedipine and propanolol + HCTZ. The studies reviewed here demonstrate that fosinopril/HCTZ combination treatment has a number of advantages over either agent used alone, providing blood pressure normalization in a broad range of hypertensive patients, including diabetic patients and the elderly.

Postmenopausal patients with node-positive resectable breast cancer. Tamoxifen vs FEC 50 (6 cycles) vs FEC 50 (6 cycles) plus tamoxifen vs control--preliminary results of a 4-arm randomised trial. The French Adjuvant Study Group.

In 1986 the true benefit of adjuvant medical treatment in postmenopausal patients with pathological node-positive breast adenocarcinoma was still controversial. The French Adjuvant Study Group (FASG) initiated a randomised trial to elucidate the respective roles of adjuvant chemo-and/or hormonotherapy in this group of patients. Of the 776 patients who have been included between 1986 and 1990, 741 were fully eligible for evaluation. Inclusion criteria were postmenopausal patients aged between 50 and 70 years with adenocarcinoma of the breast, positive pathological nodes and no distant metastasis. Patients were randomised to 1 of 4 treatment arms: Group A (n = 192) received tamoxifen 30 mg/day orally for 3 years; Group B (n = 183) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) for 6 cycles; Group C (n = 182) received tamoxifen 30 mg/day orally for 3 years plus FEC 50 for 6 cycles; Group D (n = 184) received no medical adjuvant treatment. Surgery was either modified radical mastectomy (n = 363) or tumorectomy (n = 378), and postoperative irradiation was given to all patients. All major prognostic factors were well balanced between the 4 patient groups. Toxicity was evaluated in 348 patients in Groups B and C who received a total of 1983 chemotherapy cycles. Median epirubicin dose intensity (mg/m2/week) was 15.8 in Group B and 15.7 in Group C. Grade 3 to 4 neutropenia was observed in 4.7% of cycles for Group B and 3.7% for Group C. Grade 3 to 4 nausea/vomiting were seen in 18% of treatment cycles in Group B and 15% in Group C.(ABSTRACT TRUNCATED AT 250 WORDS)

[Methodology of phase II clinical trials of hypocholesteremic drugs: which criteria?]. / Méthodologies des essais cliniques d'hypocholestérolémiants en phase II: quels critères?

Phase II is crucial in drug trials: during this period the first patients are exposed to the drug and the results influence the continuation of the development and the success of later trials. This stage is fundamental in lipid lowering drugs considering the costs of development and potential benefits for public health. The choice of pertinent criteria for the design of a lipid lowering drug trial depends on the analysis of data acquired during previous large scale trials. These criteria should demonstrate the potential of the tested drug and the best conditions of its administration. It is especially at this stage that the drug dosage optimising the efficacy/tolerance ratio should be determined. Analysis of large scale prevention trials indicates LDL-cholesterol as the principal criterion. It is related to coronary risk in the major trials of lipid lowering drugs. A reduction of LDL-cholesterol gives a good numerical estimate of the expected reduction of cardiovascular risk. It is then possible to formulate the hypotheses required for the design of these trials, in particular to calculate the size of the treatment group required. The total cholesterol should also be measured above all because of the large amount of data correlating it with cardiovascular risk. The HDL-cholesterol and triglycerides should also be taken into account even though some of the data concerning these parameters is controversial. The discrimination obtained by measuring HDL-cholesterol is without any doubt crude, and future criteria should enable more accurate and rapid evaluation of lipid lowering activity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Combination radiotherapy and chemotherapy in cancer of the pancreas. Review of the literature and prospects]. / Les associations radio-chimiothérapiques dans le cancer du pancréas. Revue de la littérature et perspectives.

Overall prognosis of pancreatic adenocarcinoma is still very poor with median survival around 10 months after radical surgery in operable patients, or after full-dose radiation therapy in non-surgical candidates. In metastatic disease, multidrug chemotherapy regimens give a response rate of around 30% with median survival of 10 months. Random trials conducted by the GITSG in inoperable cases have shown improved results for chemoradiation with 5-FU for radiotherapy alone and a doubling of median survival with a 1-year survival of 40% vs 10%. Incorporation of Adriamycin in these combined modality protocols does not improve the results in terms of survival. Chemoradiation also shows improved results compared with chemotherapy alone. In patients amenable to radical surgery, adjuvant post-operative treatment with chemoradiation gave superior results over surgery alone with a doubling of median survival and a significant improvement of a two-year survival rate (42% versus 15%). Intra-operative radiation therapy leads to better local control but without a significant improvement in survival. With a better understanding of radio-chemotherapy interactions and mechanisms of radiosensitization through continuous infusion of fluorouracil and/or cisplatinum, these encouraging results should be confirmed within the next few years.

Influence of training on blood lipids and coagulation.

Even if the effects of physical training on secondary prevention are controversial, it is known that exercise may influence several of the risk factors for coronary heart disease (CHD). One of the most important is cholesterol. Studies conducted to determine the influence of training on lipid profile have shown in normals, as well as in CHD patients, a favourable influence: a small decrease in total cholesterol and low-density lipoprotein cholesterol, and an increase in high-density lipoprotein cholesterol. These results are obtained after prolonged and intensive training. The influence of training on coagulation is more controversial and less well known. During short bouts of exercise the following changes are generally observed: an increase in platelet count and platelet aggregation (the effects on platelet adhesiveness and activation are controversial), potentiation of coagulation with an increase in factor VIII, and an increase in fibrinolytic activity due to an increase in plasminogen activator level. The effects of training have been less well studied. It is supposed that training could diminish the clotting potentiation observed during short exercise. Fibrinolysis is also increased in these conditions. If the influence of training on blood lipid profile may be considered as favourable in secondary prevention, no study has yet assessed the role of training on coagulation factors in secondary prevention.

Prognostic significance of angina pectoris recurring soon after myocardial infarction.

The prognostic significance of an early occurrence, or recurrence, of angina pectoris after myocardial infarction was studied in 254 patients (221 male, 33 female; mean age 58 +/- 11 years). During the in-hospital rehabilitation program, 41 patients (16%) had anginal pain. The mean follow-up was 21 months (range 12-33 months). Among the 254 patients, 21 died, five had recurrent myocardial infarction, 13 had unstable angina, and 22 underwent aortocoronary bypass surgery. An early recurrence of angina pectoris was predictive of combined (medical + surgical) events (21 patients, P less than 0.05), medical events (11 patients, P less than 0.05) and surgical events (10 patients, P less than 0.001), but failed to predict individual death (six patients), recurrent myocardial infarction (two patients) or unstable angina (three patients). Of the events that occurred in the 254 patients, 34% were predicted by the early recurrence of angina pectoris. Early post-infarction angina was observed more frequently in older patients and patients with previous history of angina pectoris. This represents an important prognostic factor after myocardial infarction, which defines a high-risk group of patients requiring further investigation and appropriate therapeutic approaches.