[Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma]. / Traitement conservateur dans la prise en charge locorégionale du cancer du sein après lymphome de Hodgkin.

PURPOSE: To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. PATIENTS AND METHODS: Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. RESULTS: Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). CONCLUSIONS: Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.

[Role of lymph node irradiation in breast cancer patients with negative pathologic node status after neoadjuvant chemotherapy: the René-Huguenin Cancer Center experience]. / Rôle de l'irradiation ganglionnaire chez les patientes indemnes d'envahissement ganglionnaire après chimiothérapie néoadjuvante pour un cancer du sein: expérience du centre René-Huguenin.

PURPOSE: Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery. PATIENTS AND MATERIALS: Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival. RESULTS: All 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR]=3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR]=2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival. CONCLUSIONS: Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.

Mycobacterium pinnipedii: transmission from South American sea lion (Otaria byronia) to Bactrian camel (Camelus bactrianus bactrianus) and Malayan tapirs (Tapirus indicus).

Tuberculosis infections caused by Mycobacterium (M.) pinnipedii in a South American sea lion, Bactrian camel, and Malayan tapirs kept in two zoological gardens spanning a time period of 5 years are reported. The zoos were linked by the transfer of one tapir. Conventional bacteriological and molecular methods were applied to detect the pathogen. Spoligotyping and MIRU/VNTR-typing performed to assess the genetic similarity revealed identical molecular characteristics of the isolates from all animals involved. Anti-tuberculosis antibodies were detected using ELISA and a recently developed serological rapid test. The study shows that: (i) using molecular methods, the assessment of the genetic relationship of infectious agents helps to confirm the routes of infection, and that (ii) immunological tests may help to detect tuberculosis infections ante mortem more reliably and early. This would prevent the transfer of tuberculosis by asymptomatic animals.

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience.

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS: Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

Alteration of the synthesis of the Clp ATP-dependent protease affects morphological and physiological differentiation in Streptomyces.

The genes of Streptomyces coelicolor A3(2) encoding catalytic subunits (ClpP) and regulatory subunits (ClpX and ClpC) of the ATP-dependent protease family Clp were cloned, mapped and characterized. S. coelicolor contains at least two clpP genes, clpP1 and clpP2, located in tandem upstream from the clpX gene, and at least two unlinked clpC genes. Disruption of the clpP1 gene in S. lividans and S. coelicolor blocks differentiation at the substrate mycelium step. Overexpression of clpP1 and clpP2 accelerates aerial mycelium formation in S. lividans, S. albus and S. coelicolor. Overproduction of ClpX accelerates actinorhodin production in S. coelicolor and activates its production in S. lividans.

Occurrence and frequency of transmission of naturally occurring simian retroviral infections (SIV, STLV, and SRV) at the CIRMF Primate Center, Gabon.

Among the primates held at the CIRMF Primate Center, Gabon, no serological sign of SIV infection could be demonstrated in 68 cynomolgus monkeys, 60 chimpanzees, nine gorillas, and 12 sun-tailed monkeys, while seven of 102 mandrills and six of 24 vervets were infected with SIV. Six mandrills, seven vervets and ten cynomolgus monkeys exhibited a full HTLV type 1 Western blot profile. The sera of two gorillas and one chimpanzee presented with a positive but not typical HTLV Western blot profile. The sera of the gorillas lacked p24 antibodies, and the chimpanzee had a Western blot profile evocative of HTLV-II. All attempts to amplify viruses from these animals by PCR were unsuccessful. Two other chimpanzees and seven gorillas presented with indeterminate HTLV Western blot profiles. In the mandrill colony, only male animals were STLV seropositive and no sexual transmission to females was observed. SIV infection was also more frequent in male than female mandrills and sexual transmission appeared to be a rare event. No SRV infection was observed in macaques.

Antibodies from immune African donors with a protective effect in Plasmodium falciparum human infection are also able to control asexual blood forms of the parasite in Saimiri monkeys.

We have recently shown that an IgG preparation obtained from immune African donors was able to control Plasmodium falciparum multiplication in the blood of Thai patients, but had no inhibitory activity against the parasite in vitro. The same IgG preparation was passively transferred to Saimiri monkeys acutely infected with two different strains of P. falciparum, one of African origin and the other from French Guyana. A dose-dependent in vivo inhibition of parasite development was observed with both strains. The results justify the use of Saimiri monkeys for malaria vaccine trials and permit the introduction of new techniques for screening of candidate antigens for vaccines.

[Merkel cell carcinoma: primary cutaneous neuroendocrine tumor]. / Carcinome à cellules de Merkel: tumeur neuroendocrine cutanée primitive.

Merkel cell carcinoma is a neuroendocrine primitive tumor of the skin. We report a case who develops node and visceral metastasis, and dead. The clinical presentation, diagnosis, histology, immunocytochemistry, treatment and prognosis of this tumor will be discussed.

The effect of increased salt intake on blood pressure of chimpanzees.

A colony of 26 chimpanzees given a fruit and vegetable diet of very low Na and high K intake were maintained in long-standing, socially stable small groups for three years. Half of them had salt added progressively to their diet during 20 months. This addition of salt within the human dietetic range caused a highly significant rise in systolic, mean and diastolic blood pressure. The change reversed completely by six months after cessation of salt. The effect of salt differed between chimpanzees, some having a large blood pressure rise and others small or no rise. These results in the species phylogenetically closest to humans bear directly on causation of human hypertension, particularly in relation to migration of preliterate people, with low Na diet, to a Western urban lifestyle with increased salt intake. The hedonic liking for salt and avid ingestion was apt during human prehistory involving hunter-gatherer-scavenger existence in the interior of continents with a scarcity of salt, but is maladaptive in urban technological life with salt cheap and freely available.

Filariae from a wild gorilla in Gabon with description of a new species of Mansonella.

A search for filariae was performed on a wild male Gorilla g. gorilla from the Lopé Reserve in Gabon, which had died as a result of injuries inflicted by another male gorilla. A female worm of Loa loa and female worms of two species of Mansonella were recovered from the deep tissues of a wounded thigh. In order to analyze these Mansonella, specimens of M. (E.) perstans, M. (E.) vanhoofi and M. (E.) streptocerca from the Collections of the Museum National d'Histoire Naturelle de Paris have been studied and new important discriminative characters characterised, such as the body-swellings in M. (E.) perstans, due to the presence of coelomocytes as in South-american M. (Tetrapetalonema) spp. One of the Mansonella from this gorilla was not identified, but the body-swellings and the microfilarial morphology suggested a possible similarity with M. (Esslingeria) perstans. The other species is new; M. (E.) lopeensis n. sp. is distinguished by its large size, lack of body-swellings, structure of the tegumental sheath, complex vagina, and a tail with a subterminal constriction, a terminal bend and large lappets. Histological sections of organs of this gorilla also showed a microfilaria of M. (E) leopoldi in the blood vessels of the liver, and a male of Mansonella sp., interestingly situated in an afferent lymphatic vessel of an axillary lymph node.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid peroxidation and protective enzymes during myocardial infarction.

Fasting blood taken from 34 patients with myocardial infarction, 19 with unstable angina and 40 healthy controls, was analysed for malondialdehyde and erythrocyte detoxification enzymes, superoxide dismutase and glutathione peroxidase. Malondialdehyde concentration was raised in the patients with myocardial infarction during the initial 48 h after an attack, and correlated with the severity of the attack. 12 days after the infarct, malondialdehyde concentrations were lower but still raised. Superoxide dismutase activity was below normal during the initial 48 h post infarct and raised twelve days after. Glutathione peroxidase was reduced after 12 days. Similar, but less marked changes were seen in the patients unstable angina.

[Randomized ergometric study of vasodilators combined with betablockaders]. / Etude ergométrique randomisée des vasodilatateurs associés aux bêtabloqueurs.

The ergometric effects of different vasodilator drugs in 5 series of 10 patients with stable angina and persistent effort ischaemia despite beta-offckade, were compared two by two in a random, single blind cross-over study under basal conditions on betablocker therapy and at the peak of their action, the second measurement being performed after a 2 to 7 day interval. The principal criteria of assessment were the work required to induce 1 mm ST depression (WST1), and the maximum ST depression (ST max) at comparable work loads. Molsidomine (2 mg), Risordan 20 mg) and Nifedipine (10 mg) significantly improved both parameters (p less than 0.001). Lenitral (7.5 mg), Langoran (40 mg), Trinitrin skin patch (10 mg) did not produce a significant improvement. Corditrine improved WST1 (p less than 0.05) and slow release Trinitrin (2.5 and 5 mg) improved WST1 at 3 hours (p less than 0.05) and ST max at 15 minutes (p less than 0.001) and 3 hours (p less than 0.05). The fall in resting blood pressure was parallel to the ergometric changes. These results suggest that Molsidomine, Nifedipine, Risordan and slow release Trinitrin (2.5 mg) are the most effective vasodilators when used in association with betablockers.

A comparative trial of ordinary metoprolol tablets and metoprolol sustained-release tablets in hypertensive patients at rest and on exercise.

An open, randomized crossover trial was carried out in 10 patients with hypertension to compare the degree and duration of antihypertensive effect of metoprolol given as 100 mg ordinary tablets twice daily and as single daily doses of a 200 mg sustained-release tablet. Blood pressures and heart rate were measured, at rest and during maximum exercise effort, before treatment, at the second hour after the start of each treatment sequence, and at the end of both 14-day treatment periods: after 12 hours in the case of ordinary metoprolol and after 24 hours with sustained-release metoprolol. The results showed that heart rate was greatly reduced (less than 0.001) both at rest and on exercise at all times studied with both treatments. At rest, blood pressure was significantly reduced except by sustained-release metoprolol at 2 hours. On exercise, blood pressure was also significantly reduced except for the 12-hour value for diastolic pressure with ordinary metoprolol. It is concluded that, for similar reductions in heart rate reflecting satisfactory beta-receptor blockade, the antihypertensive effect of metoprolol given at a dosage of 200 mg per day was more rapid in onset after the ordinary tablet formulation but less marked at 12 hours than at 24 hours after the sustained-release formulation.

[Molsidomine in exertion angina]. / La molsidomine dans l'angor d'effort.

Molsidomine (M), a new anti-angina drug, was studied by stress tests in 50 cases of stable angina and clinically in 33 patients not controlled by beta-blockers. One hour after sublingual administration of 2 mg of M. to 10 patients, the work required to cause ST depression of 1 mm (WST1) was increased by 94 per cent (p less than 0.005), the total work was increased by 52 per cent (p less than 0.005) and the maximal ST depression (ST max) was reduced by 45 per cent (p less than 0.01). The resting heart rate was unchanged and the blood pressure dropped mildly. In 4 of the 10 patients with exertional angina even while taking beta-blockers, the synergistic effect of M was remarkable. With a sublingual dose of 1 mg, the WST1 and the ST max are very significantly improved. The effect is even more marked at a dose of 2 mg. With a sublingual or oral of 2 mg, WST1 and ST max are very significantly improved at 1 hour and at 3 hours (p less than 0.005). Data from the literature show a significant anti-ischaemic effect until the 6th hour. In two series of 10 patients, 2 mg of M administered orally were compared to 20 mg of isosorbide dinitrate and to 10 mg of nifedipine at the 2nd hour. The WST1 and ST max were very significantly improved by all three drugs to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ergometric study of a new vasodilator agent in angina: molsidomine. Value of combination with beta-blockaders]. / Etude ergométrique dans l'angor d'un nouveau vasodilatateir : la molsidomine. Intérêt de l'association aux bêta-bloqueurs.

Molsidomine, a new venous vasodilator, was studied in 40 cases of stable angina by ergometric stress testing. 1. In 10 patients, one hour after 2 mg molsidomine sublingually, the work inducing a 1 mm ST depression (WST 1) increased by 94% (p less than 0,05), the total work by 52% (p less than 0,005) and the maximum ST depression (ST max) fell by 45% (p less than 0,01). Resting heart rate was unchanged. There was a mild fall in systemic blood pressure. 2. Molsidomine had a significant synergic effect in 3 groups of 10 patients on betablocker therapy but with ischaemic changes on exercise: a) Molsidomine 1 mg sublingually increased WST 1 by 36% (p less than 0,05); at a 2 mg dosage, by 55% (p less than 0,001). ST max decreased from 2,4 +/- 0,4 mm to 1,3 +/- 0,3 (p less than 0,005) and 1,2 +/- 0,33 (p less than 0,001) respectively. The maximal effect was obtained with 1 mg in 5 out of 10 patients. b) One and three hours after 2 mg Molsidomine sublingually or orally: WST 1 increased from 97% to 110% (p less than 0,005): ST max decreased in similar proportions (p less than 0,005). c) 2 mg Molsidomine and 230 mg isosorbide dinitrate orally were compared after two hours: WST 1 increased by 130% after Molsidomine (p less than 0,005) and by 112% after isosorbide (p less than 0,005). ST max decreased in similar proportions (p less than 0,005). The blood pressure fell less with molsidomine. Molsidomine appeared to be better tolerated than isosorbide. (5 cases of mild headache in 40 patients compared to 4 cases out of 10 patients). The results of a preliminary clinical trial are reported. The association of molsidomine (2 mg per os three times daily) reduced the number of anginal attacks by over 50% in 16 out of 17 patients inadequately controlled by betablockade alone. 3 patients complained of headache at the onset of therapy. The efficacity was comparable and the tolerance better than in 28 patients with isosorbide dinitrate and betablockade, and in 10 patients with nifedipine and betablockade. In conclusion, molsidomine is a venous vasodilator with useful pharmacokinetic properties. It seems to be effective and well tolerated in the treatment of angina whether used alone or in association with betablockers.

Fibrinolytic treatment of thrombus on prosthetic heart valves.

Fibrinolytic agents were administered for 13 episodes of thrombus formation on mitral or aortic valvar prostheses in 12 patients. The most common presenting features were pulmonary oedema (six cases) or arterial emboli (six cases). The diagnosis of thrombus formation was made by phonocardiography on the following criteria: (a) modifications of the prosthetic sounds (12 cases), (b) appearance of a valvar obstructive syndrome (10 cases). The treatment consisted of streptokinase (100 000 units/h after a loading dose, seven cases) or urokinase using either low doses (75 000 or 112 500 units/h, three cases) or moderate doses (150 000 units/h, three cases) for one to four days. Immediate complete regression of clinical and phonocardiographic anomalies was seen in eight cases. Incomplete improvement was seen in two patients, leading to operation: this was unsuccessful in one patient who had surgery on the third day, and was successful in the other on the 75th day. There were three failures leading to successful reoperative procedures in two patients and to an early death in the third patient suffering from acute myocardial infarction. One non-fatal haemopericardium was observed in a patient treated with streptokinase. No important side effect was noted during delivery in a pregnant woman. During subsequent follow-up, a recurrent episode of thrombus formation was observed in one patient, treated by fibrinolytic therapy with success. One patient had an operation for a valve replacement six months after fibrinolytic treatment because of non-thrombotic valvar dysfunction; the outcome was fatal. Six patients are alive and in good condition, with a follow-up of six months to five years.

[Evolution of serum lipids during the first hours of an acute myocardial infarction (author's transl)]. / Evolution du taux des lipides sériques pendant les premières heures suivant la survenue d'un infarctus du myocarde.

The evolution of serum lipids is investigated in 26 patients admitted in a coronary care unit less than 9 hours after the onset of an acute myocardial infarction. Blood samplings are made every 3 hours until the 15th hour after the onset of the infarction. The decrease of total serum lipids concentration is significant at the 9th hour (3rd hour : 8,45 +/- 0,58 g/l ; 9th hour : 7,74 +/- 0,36 g/l) ; that of triglycerides, at the 6th hour (3rd hour : 1,33 +/- 0,17 g/l ; 6th hour : 1,18 +/- 0,21 g/l) ; that of cholesterol is more delayed, at the 9th hour (3rd hour : 2,98 +/- 0,18 g/l ; 9th hour : 2,83 +/- 0,11 g/l). The proportion of alphalipoproteins increases, that of prebetalipoproteins decreases, that of betalipoproteins remains unchanged. There is no difference between the patients who received heparin and those who did not. Total lipids and triglycerides concentrations are lower in the group of patients with complications than in the group without complications.