Search PubMed⌕ Search

Biomedical subjects

P Trunet

Publications and source records attributed to P Trunet.

At least 19 recordsLinked to original sources

[New developments in the hormonal treatment of breast cancer in postmenopausal women].

Nowadays the role of the hormonotherapy in the treatment of breast cancer in postmenopausal women is well established. The benefit of tamoxifen is demonstrated in the adjuvant setting as well as in the treatment of advanced breast cancer. After tamoxifen failure the hormonosensitive patients can be offered a second and a third hormonal treatment. The developments of new hormonotherapies recently or shortly put at the disposal of oncologists, such as new antiestrogens or selective estrogen receptors modulators (SERM), new steroidal and nonsteroidal aromatase inhibitors and antiprogestins are reviewed as well as the recent data on the use of tamoxifen in the primary prevention of breast cancer. The principal characteristics and the potential therapeutic uses of these agents are reviewed in the treatment and prevention of breast cancer in postmenopausal patients.

Anticarcinogenic Agents↗

Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5 mg single oral administration.

Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is currently under development for the treatment of postmenopausal women with advanced breast cancer. To investigate the influence of food on the bioavailability of letrozole, 12 healthy male volunteers were treated under fed and fasted conditions with single oral doses of 2.5 mg letrozole in film-coated tablets. Plasma concentration profiles were determined. No significant difference in the extent of absorption (AUC or AUC0-8 h) was observed between the two treatments but the rate of letrozole absorption decreased slightly under fed conditions. However, in view of the half-life of about 2 d this small change in the absorption rate is not considered to be of clinical relevance for treatment with repeated administrations.

Absorption↗

In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer.

Thirteen postmenopausal women with advanced breast cancer were enrolled in an open randomized Phase I trial of a new p.o. active aromatase inhibitor, CGS 20267 (letrozole). The primary aim of the trial was to assess the impact of two doses of letrozole (0.5 and 2. 5 mg/day) on the peripheral aromatization of androstenedione to estrone. An in vivo isotopic technique was used to measure peripheral aromatization in each patient before treatment. The patients were then randomly assigned to one of the two doses, and measurements of aromatization were repeated after 6 weeks. At 0.5 mg and 2.5 mg/day, letrozole inhibited aromatization by 98.4% (97.3 to >99.1) and >98.9% (98.5 to >99.1; geometric means and ranges), respectively. Plasma estrogen levels were also measured before and during treatment. At the dose of 0.5 mg/day estrone and estradiol levels fell by 82.0% and 84.1% (geometric means), respectively. At the dose of 2.5 mg/ day, the estrogens fell by 80.8% and 68.1%, respectively. There were no significant differences between the doses in aromatase inhibition. No formal statistical analysis was performed on the estrogen data. Letrozole is therefore a highly effective inhibitor of aromatase, causing near complete inhibition of the enzyme in peripheral tissues at the doses investigated. The falls in estrogen levels were greater than those seen with earlier generation aromatase inhibitors.

Adult↗

CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer--a phase I study.

Forty-six postmenopausal women with either locally advanced or metastatic breast cancer were treated with the aromatase inhibitor CGS 16949A in three different daily doses (0.3 mg, 0.6 mg and 0.9 mg total daily dose). 41 patients (89%) were pretreated by endocrine treatment for metastatic disease; 30 of these 41 were also pretreated with chemotherapy. Of the remaining 5 patients (11%) 3 were previously treated with chemotherapy alone and 2 were not pretreated. Evaluable sites of disease were: skin and soft tissue (including local recurrence) in 34, bone in 31, lung in 14 and viscera in 13 instances, respectively. 1 PR (3%) and 9 stable diseases (24%) were observed in the 37 patients assessable for response. All but two of these results were observed in the 0.9 mg group. Time to progression was 14 months for the patient showing a PR, and the median time to progression for those with stable disease was 6 months (range 6 to 23 months). Plasma estradiol and estrone levels were measured in patients receiving the daily dose of 0.6 mg (n = 4) and 0.9 mg (n = 15). The estrone levels decreased from a mean of 23.1 pg/mL (SD 17.1) to 10.5 pg/mL (SD 6.6) in the 0.6 mg-group and from 21.2 pg/mL (SD 18.9) to 9.1 pg/mL (SD 5.5) in the 0.9 mg-group within 4 days of drug administration (p less than 0.0001 from baseline in both groups, with no significant difference between doses).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of drug-induced illness in admissions to an intensive care unit.

All patients admitted during a 33-month period to a multidisciplinary intensive care unit were prospectively studied in order to determine the incidence and severity of drug-induced illness leading to the admission. The role of underlying diseases was assessed and the avoidability of drug-induced illness considered. Out of 1651 patients, 97 (5.88%) were admitted because of drug-induced illness; 74 of these had serious underlying diseases. 13 (13.4%) of the 97 patients died, but underlying diseases accounted for 4 of the 13 fatalities. In nearly half of the cases, the drug-induced illness appeared potentially avoidable.

Adolescent↗

[Industrial drug-surveillance. Spontaneous notification: data collection, survey].

The importance of post-marketing drug surveillance has often been stressed. To detect new undesirable side-effects it seems more appropriate to improve spontaneous reporting of such effects. The main stages of spontaneous reporting are listed, with detailed information on his first and second stages: data recording and validation.

Data Collection↗

Pirprofen-induced fulminant hepatitis.

We report the cases of 2 female patients aged 69 and 61 yr, suffering from fulminant hepatitis induced by pirprofen, a new nonsteroidal antiinflammatory drug. The duration of pirprofen administration before the onset of hepatitis was long, 7 and 9 mo, respectively. Hepatitis was not preceded or accompanied by hypersensitivity manifestations. The liver lesion consisted of massive, predominantly centrilobular hepatic cell necrosis and microvesicular steatosis. One patient died of liver failure. Although the risk of fulminant hepatitis is very low, we recommend that, in patients taking pirprofen for more than 2 mo and complaining of asthenia, nausea, or vomiting, serum aminotransferase levels should be measured and administration of the drug should be interrupted as soon as an increased level is noted.

Aged↗

[Acute adult respiratory distress syndrome after lymphography].

Pulmonary complications of lymphography are usually described as radiological infiltrates without clinical symptoms. However, a case is here reported of an adult respiratory distress syndrome occurring after lymphography in a 60 year old female lymphoma patient. Pulmonary oedema developed within 48 h; haemodynamic study showed a normal capillary wedge pressure. The patient died from intractable low cardiac output within 24 h. Post-mortem examination showed pulmonary lymphocytic infiltration and multiple fat emboli. The lack of lymphatic drainage was probably responsible for the intravascular passage of lipid-soluble contrast medium, this giving endothelial lesions. In such patients with preexisting lung disease or pulmonary involvement in haematological disease, lymphography has to be considered carefully.

Embolism, Fat↗

Influence of caloric intake on the respiratory mode during mandatory minute volume ventilation.

Mandatory minute volume ventilation has been proposed as a method for weaning patients from ventilators. The purpose of this study was to delineate the influence of caloric intake on spontaneous ventilation in patients receiving mandatory minute volume ventilation. While the value of such ventilation remained unchanged, eight patients were studied at the following three different levels of daily caloric intake: (1) level A, mean of 223 kcal/sq m; (2) level B, mean of 1,380 kcal/sq m; and (3) level C, mean of 2,100 kcal/sq m. We performed gas exchange measurements and a 24-hour recording of ventilation with a monitoring system providing distinction between spontaneous and mechanical cycles. We found that the ventilatory mode was markedly dependent upon the nutritional intake; the percentage of spontaneous ventilation over 24 hours increased from 11 +/- 7 percent (+/- SE) during diet A to 50 +/- 9 percent during diet B and 79 +/- 8 percent during diet C. This increment paralleled the increase in production of carbon dioxide with caloric intake. We suggest therefore that the patient's ability to breathe spontaneously when receiving mandatory minute volume ventilation should be interpreted according to caloric intake.

Aged↗

Decreased plasma epinephrine concentrations after glucose ingestion in humans.

Plasma levels of norepinephrine (NE), epinephrine (E), immunoreactive insulin (IRI), and glucose were measured in six healthy volunteers after glucose consumption and in six volunteers after a water solution. Ingestion of the glucose (100 g) solution significantly decreased E levels from 46.7 +/- 8.0 to 20.8 +/- 1.9 pg/mL (P less than 0.01). Three hours after the glucose ingestion, plasma E levels nearly returned to basal values. Plasma IRI and glucose levels peaked at 45 minutes after glucose consumption (P less than 0.01), then declined toward basal values. Plasma NE levels were unaffected by glucose consumption. There were no changes in glucose, IRI, NE, or E levels in the control group. These results suggest that E behaves as a counter-regulatory hormone to insulin under stimulation by glucose.

Adult↗

[Prospective evaluation of the complications of anticoagulants in an intensive care unit].

A prospective study was undertaken in a multidisciplinary intensive care unit to determine the proportion of complications due to anticoagulant therapy, to evaluate their severity and to estimate what proportion was potentially avoidable. Among 1911 hospitalized patients over a 3 year period, 30 patients had a complication of anticoagulant therapy (1,57 p. 100). The causality was definite in 14 cases, probable in 14 and possible in 2 cases. Nineteen p. 100 were hemorrhagic complications. These iatrogenic illnesses were fatal in 5 cases, life-threatening in 6, moderate in 15 and minor in 4 cases. Potentially avoidable complications accounted for 60 p. 100 of the cases and were due to biological overdosage or interaction between drugs. Our results indicate that some complications of anticoagulant therapy could be reduced or eliminated by medical education and increased information.

Anticoagulants↗

[Increase in partial arterial carbon dioxide pressure due to parenteral nutrition during artificial ventilation].

The influence of increased enteral caloric intakes on respiratory gas exchanges was evaluated in 6 patients (5 men, 1 woman; mean-age: 54 years) in steady state and requiring continuous ventilatory support. Oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (R), determined using an open circuit indirect calorimetric method, and arterial blood gases were measured on two consecutive days while ventilation conditions were unchanged. On the first day, the patients received a water diet only and on the following day an enteral caloric load (1491 +/- 65 Kcal/m2/24 h). The results showed a significant increase in VO2 (p less than 0.05) and R (p less than 0.001) and a rise in VCO2 from 106 +/- 4 to 139 +/- 9 ml/mn/m2 (p less than 0.01). The rise in VCO2 induced an increase of arterial carbon dioxide tension (PaCO2) from 26.3 +/- 1.6 to 34.4 +/- 2.4 mmHg (p less than 0.001). This study showed that because of the constancy of alveolar ventilation, the enteral nutrition-related increase of VCO2 is responsible for a PaCO2 increase and emphasized the need for adjusting artificial ventilation to any change in caloric intake in patients supported with mechanical ventilation.

Carbon Dioxide↗

[Hyperthermia during parenteral nutrition].

In a woman with caustic burn of the oesophagus total parenteral nutrition (3000 calories, 16 g nitrogen daily) resulted in a rise in body temperature from 37 to 39 degrees C. Temperature returned to normal when nutrition was discontinued to rise again when it was resumed. No infection or other cause of fever was detected. This case suggests that high calorie and nitrogen parenteral nutrition may induce hyperthermia, the possible mechanisms of which are discussed.

Adult↗

[Suppurating splenic infarction originating from endocarditis].

Three cases of splenic infarction complicated by abscess formation during bacterial endocarditis are reported. In all three cases there were associated clinical abdominal signs and, in one case, there was persistently positive hemocultures. The diagnosis was made by CAT scanning. The three patients underwent splenectomy and one patient also underwent valve replacement the same day. The methods of early diagnosis of splenic complications during endocarditis and the indications of splenectomy are discussed. Ultrasonography and abdominal CAT scanning are the most sensitive diagnostic methods for splenic lesions. As splenic rupture is associated with a high mortality and this complication may occur at any time during infarction complicated by abscess formation, early splenectomy is justified when abdominal clinical signs are elicited associated with a persistent, infectious syndrome with or without positive blood cultures, under appropriate antibiotic therapy. Splenectomy should also be considered if valve replacement is carried out in the same circumstances to avoid infection of the prosthesis.

Abscess↗

[Denutrition of cancer patients].

Denutrition of cancer patients is a complex phenomenon involving inadequate calorie uptake from anorexia and metabolic disorders. The malignancy itself is the source of excessive energetic expenditure secondary to little known biological disturbances. Several effects of cytostatic drugs also contribute to nutritional imbalance. The need for re-establishing nutritional balance becomes obvious when the detrimental consequences of denutrition (particularly as regards immune defence mechanisms) are borne in mind. Nutritional requirements can be accurately determined by means of repeated simultaneous analysis of simple data. When oral feeding, even supplemented, appears insufficient, artificial feeding is capable of reducing, at least partly, the nutritional deficiency, improving the patient's comfort, lowering the incidence of infections and improving tolerance of cytostatic drugs. The effects of artificial feeding on response to these drugs have not yet been clearly established. Continuous enteral feeding deserves to be revalorized; it should be preferred to parenteral feeding when digestive functions remain satisfactory.

Anorexia↗