Biomedical subjects
Publications and source records attributed to H Pujol.
Body dysmorphic disorder (B.D.D.) consists of a preoccupation with an imagined or slight physical defect. This study is the first European report on prevalence and several clinical and functional characteristics of patients with B.D.D. in a cosmetic surgery setting. Comparisons with defect- and severity-matched subjects without B.D.D. were also performed.
OBJECTIVE: This study investigated the personality traits of social phobics using the Temperament and Character Inventory (TCI). METHOD: A sample of 178 social phobics was assessed with the TCI, and compared with controls. The patients were classified into two groups, according to the absence (SP group) or to the presence (SP+D group) of depression. RESULTS: We found significant elevated scores for harm avoidance (HA) in social phobics when compared with controls (16.2 +/- 2.7), in both the SP (26.2 +/- 3.5), and the SP+D (28.9 +/- 4.7), groups. Lower self-directedness scores were found in the SP and in the SP+D groups when compared with the controls. Patients with the generalized type of social phobia had higher HA scores as compared with other social phobics. CONCLUSION: The personality profile obtained in these social phobics, whatever their depressive symptomatology, reflects a dramatically anxious and avoidant temperament associated to an immature character.
The population with Down's syndrome has a different cancer profile compared to the general population, even after taking into account issues of survival and ageing. Several solid tumours are unusually rare, whereas in contrast leukaemias are increased. In addition, few studies are available on this topic. We therefore decided to conduct a mortality study based on the INSERM national mortality statistics in France comparing over a 24 year period deaths from female breast cancer in the general French population with the cancer deaths in women with Down's syndrome. Only 5 deaths with Down's syndrome could be found compared to 68.98 expected based on national statistics. This clear reduction in risk agrees with other studies available in Down's syndrome patients. This observation could be partly explained by over expression of genes linked to gene dosage effects on chromosome 21, playing a role in cell growth, differentiation, survival and death. An additional protective effect could come from the marked and continued decreased exposure to oestrogens, starting in utero for women with trisomy 21 and lasting all over life.
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BACKGROUND: Unknown primary tumors are highly malignant diseases which portend a dire prognosis. We designed a prospective high dose-intensity policy with the aim of improving the results obtained with conventional chemotherapy. PATIENTS AND METHODS: Chemotherapy regimens were determined according to clinical features. In patients younger than 61 years with an ECOG performance status of 0 or 1, poorly differentiated adenocarcinoma or poorly differentiated carcinoma, and no evidence of brain or bone marrow involvement (group A), the treatment plan included four sequential high-dose courses with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 micrograms/kg/d) was given until engraftment. It was planned that cycles would be delivered every three weeks. The remaining patients (group B) received alternative cycles of AC (doxorubicin 50 mg/m2, cyclophosphamide 1000 mg/m2) and EP (etoposide 300 mg/m2, cisplatin 100 mg/m2). Cycles were given at two-week intervals with GM-CSF support (5 micrograms/kg/d) from day 4 to day 10. Patients without measurable lesions were included, since the major endpoint was survival. RESULTS: Sixty patients entered the study. Twenty patients were assigned to group A and 40 patients to group B. In group A, 5 of 12 patients with measurable lesions (42%; 95% confidence interval (95% CI): 22%-62%) achieved major responses to chemotherapy, including one complete response. The duration of the overall median survival was 11 months. In group B, a major response was observed in 12 (39%; 95% CI: 28%-50%) of 31 patients with measurable lesions, including three complete responses. The overall median survival was 8 months. Hematological toxicities were noteworthy in both groups. Two toxic deaths occurred in group B. CONCLUSION: Using these doses and schedules of chemotherapy, a high-dose intensity policy does not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with new drugs are required.
We report the discovery of a unique renal-cell carcinoma operated 9 years earlier on a thyroidectomy operative specimen. Intra-thyroid metastasis from kidney cancer is uncommon. The average delay to discovery as a painless thyroid nodule is estimated around 6 years following nephrectomy. Pre-operative fine needle aspiration and cytology provide the diagnosis. Prognosis of unique thyroid metastasis of kidney cancer is good despite the distant spread. Surgery is the most common therapeutic attitude.
This work reports the action of one halogenic quaternary ammonium compound on the in-vitro proliferation of different lines of human cancer cells. IC 50 inhibition growth was observed at a concentration of 2.10(-6) mol and T1 growth at 3.10(-6)-5.10(-5) mol. These results seem to indicate that halogenic quaternary ammoniums present a potent growth inhibitory activity on different cancer cells lines. The presence of a quaternary ammonium group, responsible for some alkylating effect, could explain such a result.
The opinion survey "Parcours de femmes" initiated in partnership with Bristol-Myers Squibb was conducted by la Ligue nationale contre le cancer between November 1993 and May 1995 and by Sofres Institute. The aim of the study was to increase knowledge of experience of feminine cancers, both by patients and by different treatment teams. Two thousand eight hundred and seventy-four women treated for one of these diseases answered anonymously on a form with sixty-eight questions. Eighty-one individual interviews gave the opinion of the general practitioners and specialists concerned, as well as nursing and hospital staff, pharmacists, health leaders in the private or public fields. The results of this opinion survey highlight and confirm needs, deficiencies, and aspirations of everyone involved. The data show the importance of information, explanations and dialogue at every stage of the disease. The data specify the lines of support to be developed: calming distress, stimulating hope and the will to recover. They also indicate a need for psychological support outside the family and the medical environment as well as for treatment teams. The necessity to improve the hospital environment as well as access to maternal aid during and after treatment to make reinsertion easier are also demonstrated. Apart from associations and help services (such as home care), institutionals do not all have the same sensitivity expect to this pathology. Many people consider it has nothing specific in comparison to other pathologies or to other women in difficulties. They reject the idea of implementing specific measures and valorize research and prevention actions.
We previously reported on a paradoxical oxidant-antioxidant status in breast cancer patients, more so in pre-menopausal than menopausal women. In this study, measurements were performed on 146 patients with various carcinomas. Vitamin E/total cholesterol increased and plasma malondialdehyde decreased with tumor size and progression. To investigate the difference between young pre-menopausal and aged menopausal breast cancer patients, the same measurements were performed in 365 breast cancer patients according to pathology, tumor size and estrogen receptors. The oxidant-antioxidant status varied with these prognosis factors in the same pattern, and was more pronounced in young than aged women.
Some women with benign breast disease eventually develop breast cancer. The mammary gland undergoes tissue remodelling according to hormonal influences, involving a balance between quiescence, proliferation, and mechanisms of cell death. Proliferation and/or apoptotic events could therefore be investigated to help understand the mechanisms of benign lesion formation and identify mastopathies with a poor prognosis. bcl-2 expression was analysed by immunohistochemistry in 75 benign mastopathies. Protein levels were quantitated with an image analyser in various epithelial structures on frozen sections, including adenoses, fibroadenomas, ductal epithelial hyperplasias, cysts, and apparently normal surrounding lobules and ducts. bcl-2 levels were equivalent in apparently normal lobules and ducts, as well as in cysts and ductal hyperplasias. bcl-2 staining was significantly higher in fibroadenomas, known to be of lobular origin [mean = 10.1, quantitative immunochemistry score (QIC) arbitrary units (AU), n = 19], than in normal lobules (mean = 5.1 AU, n = 43, P = 7 x 10(-5). bcl-2 levels in normal lobules and ducts varied according to the menstrual cycle, being higher during the follicular than the luteal phase (P = 1.8 x 10(-2) and P = 1.7 x 10(-2), respectively). This was further supported by a statistical link (P = 5 x 10(-3) between high levels of circulating progesterone and weak bcl-2 staining in lobules and ducts. This progesterone-dependent variation was absent in fibroadenomas. No statistical correlation was found between bcl-2 expression and circulating levels of oestradiol, and follicle-stimulating or luteotrophic hormones. Although these are only preliminary results, they suggest an influence of progesterone on bcl-2 expression which might be lost in fibroadenomas. A hypothesis is proposed concerning the potential involvement of altered regulation of the apoptotic process in the formation of such benign lesions.
BACKGROUND: Despite recent progress in modern chemotherapy, metastatic solid tumors still have a poor outcome. The delivery of increased dose intensities of cytotoxic agents could improve response rates. We assessed the feasibility and safety of a high-dose sequential chemotherapy program in chemotherapy-naive patients with solid tumors. PATIENTS AND METHODS: Thirty patients (14 with carcinoma of unknown primary site, seven with metastatic breast cancer, six with small-cell lung cancer, and three with other diseases) were treated by an induction therapy regimen consisting of four cycles of high-dose chemotherapy with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 microg/kg/d) was given until engraftment. Cycles were scheduled to be delivered every three weeks. RESULTS: A total of 108 cycles of chemotherapy were administered. Six patients went off study before the end of the program (three because of progressive disease, three because of toxicity). After the first cycle, a median number of 10 x 10(6)/kg CD34+ cells (range 8-30) were collected. The median number of apheresis procedures was 1 (range 1-3). From cycle 2 to cycle 4, the median number of days when there was an absolute neutrophil count of less than 500/microl increased from three to five, and the median number of days when the platelet count was less than 25,000/microl increased from three to six. Episodes of febrile neutropenia occurred in 36%, 50% and 46% of cycles during cycles 2, 3 and 4, respectively. The median numbers of days between cycle 1 and cycle 2, cycle 2 and cycle 3, cycle 3 and cycle 4 were 24 (range 20-30), 22 (range 20-36) and 22 (range 18-35), respectively. There were no treatment-related deaths. Non-hematologic toxicity included severe (WHO grades 3 or 4) nausea/vomiting in 19 (18%) cycles, mucositis in 8 (7%) cycles and diarrhea in 7 (6%) cycles. CONCLUSION: Support with hematopoietic progenitor cells and growth factors allows the timely administration of repetitive cycles of high-dose chemotherapy in chemotherapy-naive patients, resulting in a significant increase in dose intensity. Toxicity is noteworthy but manageable and does not compromise further therapy.
We report here 2 cases of breast angiosarcoma observed at Centre Val-d' Aurelle of Montpellier over a period of 14 years (1980 to 1994). Based on a review of literature, we analyze the epidemiological, pathological, clinical, diagnostic and treatment aspects of this rare type of breast cancer. The difficulties of histological diagnosis are underlined. Mastectomy is the treatment of reference. Breast angiosarcoma has the worst prognosis of all mammary malignancies, with a mean survival of 24 months. The low histologic grade and an early diagnosis are the most important factors of good prognosis. The benefit of irradiation and chemotherapy as adjuvant therapy remains to be demonstrated.
The modulation of 5-fluorouracil (5-FU) with folinic acid (leucovorin, LV) is more efficacious than 5-FU alone in the treatment of metastatic colorectal cancer, and the combination of 5-FU with cisplatin is currently one of the most active regimens in advanced gastric cancer. A phase II study was therefore conducted to test the efficacy and toxicity of the combination of 5-FU, LV and cisplatin (FLP) in metastatic gastric cancer. 28 patients entered the study. Metastatic sites were observed in the liver (in 21 patients), the peritoneum (in 8), the lymph nodes (in 7) or the bones (in 1) and a local recurrence was noted in 4 cases. The performance status (using World Health Organisation criteria) was 0 for 13 patients and 1 or 2 for the others. Cycles of treatment were administered every 28 days and consisted of LV 200 mg/m2/day for 5 days followed by 5-FU 400 mg/m2/day for 5 days with cisplatin 100 mg/m2 on day 2. The response rate for the 27 evaluable patients was 51.8% (95% confidence interval (CI), 33-70.6%). There were four complete responses (14.8%) and 10 partial responses (37%). Median survival was 11 months and 4 patients were alive at 2 years. Both response rate and survival were better for patients with a good performance status. The overall toxicity was very low, except for 1 patient who died of dehydration and cardiac failure. In conclusion, the FLP protocol was effective and well tolerated in patients with metastatic gastric cancer.
Severity of prognosis factors in breast cancer cases was found to be associated with an increase in plasma vitamin E and a decrease in plasma malondialdehyde (peroxidability index). The first aim of this study was to determine whether this association is also present in other cancers. Measurements were taken before therapy on 129 patients with various carcinomas. Cholesterol was also investigated, as vitamin E is closely related to this analyte. Patients were classified by tumor size (T < or = 5 cm and T > 5 cm) and by invasion status, assessed by the presence of nodes and/or metastasis. The vitamin E/total cholesterol concentration ratio was higher and the cholesterol and malondialdehyde concentrations were significantly lower in the plasma of patients with large tumors or in whom nodes and/or metastasis were present, whatever the site. The multivariate analysis performed to measure the association of these analyte concentrations with tumor progression showed that the presence of nodes and/or metastases was inversely associated with a low vitamin E/total cholesterol ratio (OR, 0.5; CI, 0.3-1.1) and, directly associated with low plasma concentrations of cholesterol and malondialdehyde (OR, 3.0; CI, 1.3-6.8 and OR, 2.8; CI, 1.2-6.7 respectively). The same types of associations were identified with large tumors, but were less strong. Together these findings supported an alteration of lipid parameters related to the oxidant-antioxidant status in cancer patients. This alteration appears to be associated with tumor growth and progression in patients with various cancer sites.
A significant change of vitamin E and malondialdehyde plasma concentrations was reported in breast cancer patients. This change was unexpected because vitamin E was higher and malondialdehyde lower in cases than in controls, and the difference was more significant in young rather than older women. The first aim of this study was to determine whether these changes were associated only with breast cancer, or with hormone-related cancers, and/or cancers associated with nutritional risk factors or with all types of cancers. Measurements were performed before therapy on 269 hospital-based controls and on 146 patients with various carcinomas. Vitamin E:total cholesterol increased and malondialdehyde plasma concentration decreased with tumor size and progression, without relation to the site. The second aim was to understand the difference in the change observed between young and old breast cancer patients. These analytes were measured in 365 breast cancer patients according to three prognosis factors: pathology, tumor size and estrogen receptors. Vitamin E:total cholesterol significantly decreased with estrogen receptor amount. Malondialdehyde plasma concentration decreased with severity of pathology and tumor size. Together, these data support the association of an altered oxidant-antioxidant profile in cancer patients with tumor growth and progression.
The future of cancer epidemiology remains wide open because of the slow progress in reducing mortality. Currently large scale screening is only conducted for cancer of the breast and cervix. Cancer of the colon is in the research stage. For all the other cancers, progress in prevention should result both from a better understanding of the causes and from more active participation by health care workers and the general population once risk factors have been clearly identified. Finally, it is important not to assess progress in therapeutics on the single criteria of long-term survival since one- or two- year remissions are important in terms of human life and may be the first signs of more durable progress in the future.
4-OH-tamoxifen is an active metabolite of tamoxifen that is detectable in the serum and tumour tissue of patients treated by oral tamoxifen. As this metabolite penetrates through the skin, it is possible to compare percutaneous 4-OH-tamoxifen (4-OH-TAM) and oral tamoxifen treatments. We report herein a randomized study of percutaneous 4-OH-TAM versus oral tamoxifen in women with breast cancer. This pharmacology study was designed to compare the 4-OH-TAM concentration in breast cancer and normal breast tissue according to the route and dose used for administration of tamoxifen after a 3-week period prior to surgery and tissue sampling. Women were randomized into one of the five following groups: group I, oral tamoxifen given at 10 mg twice a day; group II, 4-OH-TAM delivered percutaneously at 0.5 mg day to both breast areas; group III, 4-OH-TAM applied percutaneously at 1 mg/day to both breast areas; group IV, 4-OH-TAM delivered percutaneously at 1 mg/day to a large cutaneous area excluding the breasts; and group V, 4-OH-TAM applied percutaneously at 2 mg/day to a large skin area excluding the breasts. 4-OH-TAM plasma and tissue concentrations were significantly higher in the oral tamoxifen group as compared with either the high- or the low-dose percutaneous 4-OH-TAM group. In group II, percutaneous 4-OH-TAM treatment resulted in tissue concentrations of 1,446 and 352 pg/g in tumour tissue and normal breast tissue, respectively. In group I these concentrations were as follows: tumour tissue, 12, 453 pg/g; and normal tissue, 10,214 pg/g. 4-OH-TAM concentrations in tumour tissue and normal breast tissue did not significantly differ in any group. In the oral group we observed classic effects on coagulation and lipid metabolism when pre- and post-treatment values of these biological variables were compared, whereas no difference was observed in the percutaneous group. Although percutaneous administration of 4-OH-TAM led to a low plasmatic concentration of this active metabolite, the breast tissue concentration remained lower than those observed after oral tamoxifen treatment. Therefore, at the doses described in this study, percutaneous 4-OH-TAM cannot be proposed as an alternative tamoxifen treatment.