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Biomedical subjects

C Borel

Publications and source records attributed to C Borel.

At least 19 recordsLinked to original sources

[Treatment of primary cancer of the breast in elderly women. Role of hormone therapy].

About 40 percent of newly diagnosed breast cancers occur in women older than 65. Hormonotherapy plays an important role as adjuvant treatment of primary cancers in post-menopausal women because of their great hormone-dependence. The drug of choice is tamoxifen which is very well tolerated. Its beneficial effect appears to be related to the duration of administration. It also seems to be particularly promising in the initial treatment (neoadjuvant) of elderly women and potentially beneficial in the breast cancers said to be of good prognosis when the axillary nodes are not involved.

Aged

Effects of 9, 12, 15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on platelet aggregation.

An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin) was extracted from Dicranum Scoparium and preincubated with platelets which were then stimulated by exogenous arachidonic acid (20:4 n-6). This molecule at 10(-4) M weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-5) M and with 10(-6) M of dicranin but to a lesser extent. Platelet hydroxylated dicranin metabolites were also found and the structure of the main compound determined by GC-MS was a 13-hydroxy derivative. Its origin has not yet been elucidated. Platelet aggregation induced by 1 microgram/ml of U46619, a structural PGH2 analogue was completely abolished in the presence of dicranin. Platelet aggregation induced either by thrombin or by arachidonic acid was inhibited by 10(-4) M of dicranin only after preincubation. This observation indicates that the formation of metabolites of dicranin are necessary to effect this inhibition. Dicranin is thus a new inhibitor of platelet aggregation and may prove to be useful for elucidating the effects of 12-HETE in biological systems.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Effects of 9,12,15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on the platelet aggregation.

An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin), extracted from Dicranum Scoparium was preincubated with platelets stimulated by exogenous arachidonic acid (20:4 n-6). Dicranin (10(-4) M) weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-6) M of dicranin but to a lesser extent. The main platelet hydroxylated dicranin metabolite determined by GC-MS was a 13-hydroxy derivative Platelet aggregation induced either by thrombin or by arachidonic acid or by U46619, an structural PGH2 analogue was inhibited by 10(-4) M of dicranin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Phase I study of Datelliptium chloride, hydrochloride given by 24-h continuous intravenous infusion.

Datelliptium chloride, hydrochloride (SR 95 156B, NSC 626718X, DHE) was studied in a phase I trial of escalating doses given on a single 24-h continuous intravenous infusion schedule. Doses were escalated from 40 to 500 mg/m2 in 19 patients who received a total of 24 courses. Courses were repeated after a minimal interval of 3 weeks. Local venous toxicity occurred at low doses (less than or equal to 100 mg/m2) and was circumvented by the use of a central venous access for higher doses. Other clinical adverse events occurred (greater than or equal to 330 mg/m2), including moderate nausea and vomiting, mild diarrhea, dry mouth, neuropsychiatric manifestations, and fatigue. All of these side effects were reversible and none was dose-limiting. The dose-limiting toxicity was related to hepatic laboratory-test abnormalities in the form of reversible elevations of levels of serum bilirubin and liver enzymes at doses of greater than or equal to 330 mg/m2. The maximum tolerated dose for this schedule is 500 mg/m2. Hematologic toxicity was minimal and non-dose-limiting. Neither drug-related deaths nor objective complete or partial responses were observed. However, a minor response and a long-term disease stabilization were obtained.

Adult

[Primary chemotherapy in the treatment of breast cancer].

Between 1980 and 1992, 457 consecutive patients with initial breast cancer entered two successive protocols combining neoadjuvant chemotherapy, hormonotherapy (tamoxifen) and locoregional radiotherapy (teleradiotherapy and boost by iridium) as exclusive locoregional treatment. Cytological diagnosis, hormone receptors, cytological grading were provided by fine needle aspiration. Both protocols included velbe, thiotepa, methotrexate, 5FU and adriamycin with some minor differences regarding the schedule of doses and their number during induction and during the consolidation phase. In both studies, over 50% patients had locally advanced breast cancer (IIb, IIIa or IIIb). Chemotherapy induced tumor regression over 50% in 91% patients of the first protocol (30% complete clinical remission CR) and in 94% patients of the 2nd protocol (40% CR): in this protocol 20 poor responders were given a rescue protocol (2 CR; 9 partial remissions). The 5 year actuarial rate of breast preservation is 94% and the 5 year actuarial rate of local relapses is 15%. The cosmetic results according to Danoff are excellent 20%, good 55%, mean 35%. Disease free survival and overall survival compare favorably to published data: they depend on TNM stages, tumor differentiation and chemotherapy induced early tumor regression.

Adult

Fotemustine (S 10036) in the intra-arterial treatment of liver metastasis from malignant melanoma. A phase II Study.

Fotemustine is a new nitrosourea which has shown some efficacy on disseminated malignant melanoma (DMM) (24.2% response rate (RR) among 153 patients in a Phase II trial) but little activity on hepatic metastasis (8.8% RR). In order to improve those poor results, hepatic intra-arterial infusion (HIAI) of fotemustine was performed. After two years, thirteen patients, all in good general condition, were evaluable. Seven were pretreated and six had extrahepatic metastasis on entry into the study. All patients had a surgically implanted intra-arterial catheter. The induction cycle consisted of 100 mg/m2/week for 3-4 weeks, followed by 5 weeks rest and maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Two complete responses (CR) (72+ and 145+ weeks) and six partial responses (PR) (7-18.5 weeks) were observed. The hepatic RR reached 61.5%. A RR of 42.8% was registered on preexisting EHM (one CR and one PR on cerebral lesions). Nevertheless, this treatment is limited by the high progression rate of 46.1% in extrahepatic disease. Toxicity was mainly hematologic (grade III-IV), comprising 36% neutropenia and 15% thrombopenia. Hepatic intra-arterial infusion of fotemustine is efficient therapy for liver metastases of DMM, but combination schedules (IV + HIA) are warranted.

Adult

[Tumor regression as a prognostic factor in breast cancer].

Two hundred and fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (m) and 5-fluorouracil (f) (VTMF) with or without Adriamycin (A) (Doxorubicin; Adria Laboratories, Colombus, OH USA), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients, 130 post menopausal and 65 pre-menopausal, and was omitted in 55 patients (31 postmenopausal and 24 pre-menopausal). There were 19 stage I, 86 IIa, 51 IIB, 36 IIIA and 58 IIIB. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5 years DFS rates were 100% for stage I, 82% for stage IIA, 61% for stage IIB, 46% for stage IIIA and 52% for stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases, 6 locoregional and distant metastasis and 27 isolated locoregional metastases. The actuarial rate of locoregional recurrence is 13% for T2, 18% for T3, 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results are excellent or good for most patients. The 5 years overall survival (OS) were 95% for stage I, 94% for stage IA, 80% for stage IIB, 60% for stage IIIA and 58% for stage IIIB. In multivariate analysis tumor regression appears as an independent and significant factor. This parameter should be preserved in many patients with infiltrative breast cancer.

Actuarial Analysis

Results of neoadjuvant chemotherapy and radiation therapy in the breast-conserving treatment of 250 patients with all stages of infiltrative breast cancer.

Two hundred fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (M), and 5-fluorouracil (F) (VTMF), with or without Adriamycin (A) (doxorubicin; Adria Laboratories, Columbus, OH), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients (130 postmenopausal and 65 premenopausal) and was omitted in 55 patients (31 postmenopausal and 24 premenopausal). There were 19 Stage I, 86 Stage IIA, 51 Stage IIB, 36 Stage IIIA, and 58 Stage IIIB patients. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5-year disease-free survival (DFS) rates were 100% for Stage I, 82% for Stage IIA, 61% for Stage IIB, 46% for Stage IIIA, and 52% for Stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases. The actuarial rate of locoregional recurrence was 13% for T2, 18% for T3, and 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results were excellent or good for most patients. The 5-year overall survival (OS) rates were 95% for Stage I, 94% for Stage IIA, 80% for Stage IIB, 60% for Stage IIIA, and 58% for Stage IIIB. Most patients with breast cancer should be given the option of breast-preserving treatment.

Adult

Acute management of intracranial hemorrhage in patients receiving thrombolytic therapy: case reports.

Intracranial hemorrhage is an uncommon complication of antithrombotic therapy. We present two patients who suffered life-threatening intracranial bleeding as a complication of thrombolytic/anticoagulant treatment. Early diagnosis and treatment appear to be crucial factors for survival. We suggest an approach to perioperative management for intracranial hemorrhage resulting from antithrombotic therapy.

Aged

Cerebrospinal fluid atrial natriuretic factor in intracranial disease.

We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor

Intensive management of severe head injury.

Intensive management of patients with severe head injury offers the best hope of minimizing death and functional disability in a young, working population. Secondary neurologic insult can be decreased by cardiorespiratory support and ICP control from the outset. Rapid neurologic assessment, airway management, and support of circulation are the basis of emergency management for head injury. Patients with severe head injury require intensive care management for two major reasons: management of ICP and management of organ system dysfunction. Care should not be withheld because of initially grim (and inaccurate) prognostic assessment. Newer techniques for assessing the adequacy of cerebral circulation may allow refinement of management strategies in the future.

Craniocerebral Trauma

[Expectations and defeat in the treatment of epithelial cancer of the ovary].

One hundred and thirty-nine patients were treated between 1980 and 1988 for epithelial cancer of the ovary: 35 stage I, 30 stage II, 66 stage III and 8 stage IV (according to the IFGO classification). For stage I and II patients, who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy followed by combination chemotherapy, the 5 year survival rate without relapse was 91%. For those classified as stage III, the 5 year survival rate was 36%. When the tumor was completely removed surgically, the 5 year survival rate was 82%, but the disease-free (without relapse) rate was only 47%. When the malignancy could not be completely excised, the 5 year survival rate was only 15%. The only chance these patients had to survive was if chemotherapy effectively controlled the residual mass (verified during an exploratory laparotomy). In our experience, the combination of cisplatin, doxorubicin and cyclophosphamide, in spite of a 78% response rate, only histologically eliminated the residual tumor in 15% of the patients.

Antineoplastic Combined Chemotherapy Protocols

Sodium and water regulation in a patient with cerebral salt wasting.

Hyponatremia, in patients with central nervous system disease, can be attributable to impaired free water excretion (syndrome of inappropriate secretion of antidiuretic hormone) or to excessive sodium excretion (cerebral salt wasting). We present a patient with a parietal glioma and hyponatremia characterized by salt wasting and dehydration. Rehydration and sodium repletion corrected the sodium and volume deficits; withdrawal of supplemental sodium resulted in recurrence of dehydration and hyponatremia. We determined sodium and water balance and measured plasma atriopeptin, antidiuretic hormone, and aldosterone. Plasma atriopeptin ranged from 8 to 44 pg/mL (normal, less than 45 pg/mL); antidiuretic hormone was not elevated at 4 to 5 pg/mL, and aldosterone was slightly elevated at 1040.25 pmol/L. The concentrations of these hormones could not directly explain the natriuresis; interactions with neural or other humoral factors may be involved. In evaluating such patients, careful attention to sodium and water balance is important to guide appropriate therapy.

Adult

Cardiovascular autonomic dysfunction in Guillain-Barré syndrome. Therapeutic implications of Swan-Ganz monitoring.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy that may lead to quadriparesis, ventilatory failure, and autonomic dysfunction. While significant mortality due to ventilatory failure has been associated with this syndrome, this complication can now be readily managed. However, an estimated mortality of 5% to 20% remains attributable to medical complications (pulmonary embolus, sepsis) and to acute cardiovascular collapse due to autonomic failure. In this report, detailed sequential changes in hemodynamic parameters, as measured by Swan-Ganz catheter, associated with severe autonomic cardiovascular instability in a patient with GBS are described. Knowledge of changes in these hemodynamic parameters led to optimal therapy. Long-term Swan-Ganz monitoring in an intensive care setting may dramatically benefit the critically ill patient with GBS and cardiovascular autonomic dysfunction, and may help to eliminate the residual morbidity and mortality associated with this disease.

Aged