ABSTRACT
Volcanic tremor is key to our understanding of active magmatic systems, but due to its complexity, there is still a debate concerning its origins and how it can be used to characterize eruptive dynamics. In this study we leverage machine learning techniques using 6 years of continuous seismic data from the Piton de la Fournaise volcano (La Réunion island) to describe specific patterns of seismic signals recorded during eruptions. These results unveil what we interpret as signals associated with various eruptive dynamics of the volcano, including the effusion of a large volume of lava during the August-October 2015 eruption as well as the closing of the eruptive vent during the September-November 2018 eruption. The machine learning workflow we describe can easily be applied to other active volcanoes, potentially leading to an enhanced understanding of the temporal and spatial evolution of volcanic eruptions.
ABSTRACT
BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5-fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin-cyclophosphamide (EC) and locoregional treatment in IBC patients. PATIENTS AND METHODS: PEGASE 07 was a national randomized phase III open-label study involving 14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2) every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (arm A) or the same treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750 mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered postradiotherapy (arm B). Patients with hormone receptor-positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary end point. Secondary end points included tolerance, pathological complete response (pCR) rate, and overall survival (OS). RESULTS: Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and 60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in arm B [HR = 0.93 (0.55-1.60); P = 0.814]. Following DI EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. CONCLUSION: The addition of D-5FU after preoperative DI EC and standard local therapy did not improve DFS in IBC. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier: NCT02324088.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Inflammatory Breast Neoplasms/drug therapy , Mastectomy , Neoadjuvant Therapy/methods , Adult , Antineoplastic Agents, Hormonal/administration & dosage , Axilla , Chemoradiotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/methods , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Inflammatory Breast Neoplasms/metabolism , Lymph Node Excision , Middle Aged , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Taxoids/administration & dosageABSTRACT
PURPOSE: To assess the benefits of magnetic resonance imaging (MRI) in the dosimetric treatment planning for prostate radiotherapy. PATIENTS AND METHODS: Ten consecutive patients have been enrolled. They were treated for a low risk prostate adenocarcinoma. A rigid superimposition was performed between MRI and scan slides obtained at time of virtual simulation, then prostate volume was delineated by four to five physicians, on TDM slides and on MRI/TDM superimposition. For each treatment plan, we assessed the impact of MRI in terms of planned treatment volume (PTV) position, individual variability of prostate delineation and doses delivered to the critical organs. The prescribed dose was 74 Gy in 37 fractions to the PTV. RESULTS: PTV delineated on TDM (V(TDM)) were 1.15 (SD 3.71) larger than volumes delineated on MRI. Prostate apex was 4.6 mm (SD 2.87) lower on TDM than on MRI. Posterior limit of the prostate was in mean 4 mm more posterior on TDM. The variability between physicians in terms of prostate delineation was lower using MRI. For apex, these variations were 6.8 mm using TDM, versus 3.3 mm using MRI. Mean rectal dose was 8 % lower with MRI, compared to delineation using TDM. CONCLUSION: Superimposition TDM/MRI improves accuracy, decreases delineation variability, and allows to spare anterior part of the rectum from irradiation. It remains unknown whether this strategy translates into clinical benefit.
Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Magnetic Resonance Imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Humans , Male , Radiotherapy Planning, Computer-AssistedABSTRACT
PURPOSE: In 1986, The Fédération Nationale desCentres de Lutte Contre le Cancer Breast Group initiated a multicenter randomized trial to assess the usefulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tamoxifen treatment was to be compared with life long adjuvant tamoxifen treatment. PATIENTS AND METHODS: Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 1986 to May 1995, 3,793 patients were randomized from France, Belgium, and Argentina. A total of 1,882 patients stopped tamoxifen (short-term group), and 1,911 patients were to continue tamoxifen for life (long-term group) at the same dose as previously prescribed. The protocol was modified in February 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year treatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group. RESULTS: Overall, longer tamoxifen treatment induced a 23% reduction in relapse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in both groups. This improvement in disease-free survival could be observed in node-positive patients (P: =.001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant increase in disease-free survival in estrogen receptor-positive patients (P: =.03) as well as in estrogen receptor-negative patients (P: =.05). Furthermore, longer treatment reduced contralateral breast cancers and did not increase the number of endometrial cancers. CONCLUSION: Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better disease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in the long-term group are still receiving treatment. Comparison of results as time passes will enable conclusions to be made on the value of long-term treatment over 5 years compared with 2 to 3 years.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/drug therapy , Tamoxifen/administration & dosage , Axilla , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Endometrial Neoplasms/chemically induced , Estrogen Receptor Modulators/administration & dosage , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasms, Second Primary/chemically induced , Receptors, Estrogen/physiology , Survival AnalysisABSTRACT
The French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) conducted a multicenter phase II study of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to evaluate the efficacy and side effects of this combination in pretreated advanced ovarian cancer. Patients with progressive ovarian carcinoma during or after platinum-based chemotherapy received paclitaxel 175 mg/m2 intravenously over 3 hours followed by intravenous carboplatin over 30 minutes every 4 weeks. The dose of carboplatin was calculated using a projected area under the concentration-time curve of 5 mg/mL x min. Of the 50 patients entered, 50 were evaluable for toxicity and 42 for response. There were eight complete and 10 partial responses, for an overall response rate of 43% (95% confidence interval, 28% to 56%). Overall response rates in platinum refractory patients and in those with early (> or = 3 and < 12 months) and late (> or = 12 months) relapse was 28%, 33%, and 71%, respectively. Median response duration, progression-free survival, and overall survivals were 8, 6, and 14 months, respectively. The most frequent and severe toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 30% and 23% of cycles, and granulocyte colony-stimulating factor was administered in 6%. Only one case of neutropenic fever was observed. Grades 3 and 4 thrombocytopenia occurred in 3% and 1% of cycles, respectively. Alopecia and moderate nausea or vomiting were frequent. Transitory peripheral neuropathy was present in 45% of patients but was severe in only one patient. One early death was observed due to progressive disease and possibly to therapy. The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma/drug therapy , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Adolescent , Adult , Aged , Alopecia/chemically induced , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Area Under Curve , Carboplatin/adverse effects , Carcinoma/pathology , Cisplatin/administration & dosage , Confidence Intervals , Disease Progression , Female , France , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Injections, Intravenous , Middle Aged , Nausea/chemically induced , Neoplasm Recurrence, Local/drug therapy , Neoplasm Staging , Neutropenia/chemically induced , Ovarian Neoplasms/pathology , Paclitaxel/adverse effects , Peripheral Nervous System Diseases/chemically induced , Remission Induction , Safety , Survival Rate , Thrombocytopenia/chemically induced , Treatment OutcomeABSTRACT
BACKGROUND: The effect of mycophenolate mofetil (MMF) and sirolimus (rapamycin, RAPA) mono- and combination-therapy was examined in prevention of acute heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat. METHODS: Both drugs were administered orally for up to 30 days. Eleven groups (n=6) were involved in the first part of the heart allografting model. Brown Norway (RT1n) to Lewis (RT1(1)) combination was used in the heart and pancreas transplantation models, whereas Buffalo (RT1b) to Wistar Furth (RT1u) was used in the kidney transplantation model. RESULTS: The naive control group showed a mean survival time of 6.5+/-0.6 days. There were graded dose-responses to monotherapy of MMF 10 and 20 mg(kg/ day (12.5+/-2.6 days; 19.3+/-9.0 days) and RAPA 0.2, 0.4, 0.8, and 1.8 mg/kg/day (19.2+/-2.0 days; 30.0+/-7.3 days; 50.8+/-12.5 days; 51.2+/-2.6 days), respectively (P=0.001). Results with the combined use of drugs indicate that a synergistic or very strong synergistic interaction was produced when compared with monotherapy of MMF or RAPA: MMF 10 mg(kg/day+RAPA 0.2 mg/kg(day (52.7+/-5.7 days, combination index [CI] =0.189), MMF 20 mg(kg/day+RAPA 0.2 mg/kg/day (57.7+/-5.7 days, CI=0.084), MMF 10 mg/kg/day+RAPA 0.4 mg(kg/day (50.2+/-13.5 days, CI=0.453), and MMF 20 mg/kg(day+ RAPA 0.4 mg/kg(day (51.5+/-6.8 days, CI=0.439), respectively. These results were repeatable in the prevention of acute pancreas and kidney allograft rejection in the rat. In the second part of the study of reversal of ongoing acute heart allograft rejection model, the combined treatment of MMF 10 mg/kg(day+RAPA 0.2 mg/ kg(day (35.5+/-16.0 days, CI=0.794) and MMF 20 mg/kg day+RAPA 0.2 mg(kg/day (57.2+/-4.7 days, CI=0.310) represented synergistic interaction compared with monotherapy of MMF or RAPA. CONCLUSIONS: Concomitant therapy of MMF and RAPA produces a synergistic effect in prevention of heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat.
Subject(s)
Graft Rejection/prevention & control , Heart Transplantation/immunology , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/immunology , Mycophenolic Acid/analogs & derivatives , Pancreas Transplantation/immunology , Sirolimus/administration & dosage , Acute Disease , Animals , Drug Synergism , Male , Mycophenolic Acid/administration & dosage , Rats , Rats, Inbred BN , Rats, Inbred WF , Transplantation, HomologousABSTRACT
We report two female sibs, with severe split-hand/split-foot malformation associated with renal and genital anomalies. The patients also have severe mandibular hypoplasia and some other, minor anomalies. The relationship to the acro-renal "syndrome" in particular and to other phenotypes with similar malformations in general is discussed. Because of consanguinity in the parents, autosomal recessive inheritance seems likely. However, the presence of a septate uterus in the mother and a double collecting system in the only living sib could also suggest possible dominant inheritance with variable expressivity.
Subject(s)
Foot Deformities, Congenital , Hand Deformities, Congenital , Kidney/abnormalities , Mandible/abnormalities , Consanguinity , Female , Genitalia, Female/abnormalities , Humans , Infant, Newborn , Orofaciodigital Syndromes/genetics , PedigreeABSTRACT
Nine volunteers received a 500 mg oral dose of tetracycline hydrochloride in three trials: A: With 180 ml water; B: With 30 gm colestipol in 180 ml water; C: With 30 gm colestipol in 180 ml orange juice. Tetracycline concentrations in multiple urine samples collected during 48 hours after each dose were determined by high pressure liquid chromatography. The three trials did not differ significantly in 48 hour cumulative urine volume (3086 vs 3207 vs 3194 ml for Trials A, B, and C). However, the three trials differed significantly in 48 hour excretion of tetracycline (F = 28.2; P less than .001). During Trial A, mean excretion was 237 mg; this was significantly (P less than .05) reduced to 109 mg in Trial B and 104 mg in Trial C. However, Trials B and C were not different. Thus, coadministration of tetracycline with colestipol significantly impairs tetracycline absorption by more than 50%. Mixing colestipol with orange juice does not alter colestipol-induced impairment of tetracycline absorption.
Subject(s)
Beverages , Citrates/pharmacology , Citrus , Colestipol/pharmacology , Polyamines/pharmacology , Tetracycline/pharmacokinetics , Adult , Biological Availability , Citric Acid , Half-Life , Humans , Intestinal Absorption/drug effects , MaleABSTRACT
The present study tested if a positive modulator of AMPA-type glutamate receptors would counteract the behavioral effects of a drug that enhances the release of dopamine. BDP-29, a compound shown to increase AMPA receptor-mediated synaptic responses in hippocampal slices, markedly attenuated the amount of stereotypic rearings seen in rats after methamphetamine injections. These results suggest that AMPA receptor modulators ameliorate certain aberrant, dopamine-related behaviors and hence may be of interest with regard to schizophrenia.
Subject(s)
Dopamine Agents/pharmacology , Hippocampus/drug effects , Hyperkinesis/drug therapy , Methamphetamine/antagonists & inhibitors , Piperidines/pharmacology , Receptors, AMPA/drug effects , Animals , Half-Life , Hyperkinesis/chemically induced , In Vitro Techniques , Male , Piperidines/pharmacokinetics , Rats , Rats, Sprague-Dawley , Stereotyped Behavior/drug effects , Synaptic Transmission/drug effectsABSTRACT
OBJECTIVES: To evaluate reactive oxygen species production of semen samples and Percoll-washed spermatozoa from men with spinal cord injuries and to determine if there is a relationship between this reactive oxygen species production and sperm motility. PARTICIPANTS: Semen samples from healthy volunteers and infertile patients were collected by masturbation. INTERVENTIONS: Semen samples from men with a spinal cord injury were obtained by electroejaculation or by masturbation after treatment with physostigmine. MAIN OUTCOME MEASUREMENTS: Motility was measured using the CellSoft computer-assisted analysis system (Cryo Resources Ltd., Montgomery, NY). Luminol-amplified chemiluminescence was used to measure reactive oxygen species production. RESULTS: Semen samples and Percoll-washed spermatozoa from men with a spinal cord injury produced reactive oxygen species at much higher frequency and levels than equivalent preparations from infertile men or healthy volunteers. There was an inverse relationship between the percentage of motility and reactive oxygen species production in Percoll-washed spermatozoa from men with a spinal cord injury. CONCLUSION: Semen samples and Percoll-washed spermatozoa from men with spinal cord injury produce high levels of reactive oxygen species that may be related to the low sperm motility and infertility observed in these men.
Subject(s)
Infertility, Male/physiopathology , Reactive Oxygen Species/analysis , Semen/chemistry , Sperm Motility , Spermatozoa/chemistry , Spinal Cord Injuries/physiopathology , Adult , Biomarkers/analysis , Humans , Male , Povidone , Reference Values , Regression Analysis , Silicon Dioxide , Spermatozoa/physiologyABSTRACT
The nutritional state of 12 patients with quadriplegia, secondary to spinal cord injury, was assessed by determining body composition with a multiple isotope dilution technique. For comparative purposes, similar measurements were obtained in 25 normal volunteers. The mean duration of quadriplegia was 14.8 +/- 8.5 months. All the patients were hospitalized, receiving a regular hospital diet and all were on a similar rehabilitation program. Because skeletal muscle atrophy is extensive in quadriplegics, we had expected a reduced body size, which was otherwise normal in composition, with a comparable decrease in both the body cell mass (BCM) and the extracellular mass (ECM). Instead, a body composition characteristic of malnutrition was observed in an unexpectedly large percentage (58%) of patients. In the normally nourished individual, the BCM and ECM are approximately equal in size. However, in seven of the 12 quadriplegic patients, the body composition was characteristic of malnutrition, with a BCM (13.5 +/- 1.6 kg) which was reduced relative to the ECM (28.7 +/- 1.9 kg). Their body composition was significantly (p less than 0.05) different from the body composition of both the healthy volunteers and the other five quadriplegic patients, whose body composition was normal (BCM = 22.9 +/- 1.5 kg, ECM = 28.5 +/- 1.6 kg). The nutritional state of the quadriplegic patients correlated significantly with the level of spinal cord injury and not with the duration of quadriplegia.
Subject(s)
Body Composition , Quadriplegia/metabolism , Adipose Tissue/metabolism , Adolescent , Adult , Aged , Body Weight , Extracellular Matrix/metabolism , Female , Humans , Male , Middle Aged , Nutrition Disorders/metabolism , Quadriplegia/etiology , Spinal Cord Injuries/complicationsABSTRACT
Uridinediphosphoglucuronosyl transferases (UGTs) are a group of membrane bound proteins which catalyze the transfer of glucuronic acid from UDP-glucuronic acid to a wide variety of xenobiotics and drug molecules enabling them to be eliminated. The major UGT isoforms found in the rat are 1A1, 1A6, 2B1 and 2B12. Conventional methods for the assay of glucuronides (GLs) include TLC, extraction and colorimetry or quantification of the aglycone, liberated after hydrolyzing the GL with beta-glucuronidase. However these techniques cannot distinguish between isomeric GLs or GLs of multiple acceptor site substrates. Therefore the purpose of this study was to develop simple and sensitive HPLC methods for the direct and simultaneous analysis of the GL(s) and their aglycones without the drawbacks of the conventional methods. The three classical substrates we chose were 4-methylumbelliferone (4MU), testosterone (TES) and 8-hydroxyquinoline (8HOQ) representing UGT isoforms 1A6, 2B1 and 2B12 of the rat family, respectively. Here we report the validated HPLC conditions, for the detection and separation of 4-methylumbelliferone glucuronide (4MUG), testosterone glucuronide (TESG) and 8-hydroxyquinoline glucuronide (8HOQG) and their aglycones in incubation media containing male Sprague-Dawley rat liver and intestinal microsomal preparations. The separations were achieved on a Zorbax SB-CN column (150 x 4.6 mm, 5 micron). The analysis time for the separation of TES, 8HOQ and 4MU and their glucuronides were 17, 12 and 30 min, respectively. The methods showed excellent linearity (r2 > 0.99) over the concentration ranges tested (0.25-5.0 nmoles of TESG; 0.125-18.75 nmoles of 8HOQG and 0.125-12.5 nmoles of 4MUG), good precision and accuracy (RSD<2.5%). Inter-day variability studies (n = 3) showed no significant difference between the regression lines obtained on the three days. Recoveries were good ( > 90%) at all three points (low, mid-point, high) of the standard curve. The limits of detection were 0.125, 0.1 and 0.1 nmole for TESG, 8HOQG and 4MUG. respectively. The above methods were used to estimate kinetic parameters such as Vmax and Km for the GLs of the three substrates in both liver and intestinal tissue preparations and the values were comparable with previously reported results. UGT2B1 was found primarily in the liver while UGTs 1A6 and 2B12 were present in comparable amounts in both tissues.
Subject(s)
Chromatography, High Pressure Liquid/methods , Glucuronosyltransferase/pharmacokinetics , Intestinal Mucosa/metabolism , Microsomes, Liver/metabolism , Animals , Glucuronides/analysis , Glucuronides/metabolism , Glucuronosyltransferase/analysis , Glucuronosyltransferase/metabolism , Gonadal Steroid Hormones , Hymecromone , Indicators and Reagents , Male , Microsomes/metabolism , Oxyquinoline , Protein Isoforms , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Substrate Specificity , TestosteroneABSTRACT
BACKGROUND AND PURPOSE: The effect of therapeutic massage on the H-reflex amplitude in persons without neurological impairment has been established. To investigate its effects in a sample of persons with a spinal cord injury (SCI), two independent but interrelated studies were undertaken. Study 1 investigated whether the recorded response (H-reflex amplitude) to massage with the subjects in the supine testing position was similar to that recorded in previous studies in which the subjects were tested in the prone position. This study was undertaken because the prone testing position was considered inappropriate for persons with SCI. In study 2, the therapeutic effect of massage (petrissage) on H-reflex amplitude in persons with SCI was examined. SUBJECTS: Seven persons without neurological impairment volunteered to participate in study 1, and 10 individuals with a traumatic SCI volunteered to participate in study 2. METHODS: The two studies shared many methodological features and involved the recording of 10 H-reflex and M-response peak-to-peak amplitudes from the triceps surae muscle during each of five sequential, 3-minute time periods. Massage treatment (MASS) was given during the third time period, and the premassage time periods (C1, C2) and postmassage time periods (C3, C4) served as control conditions. Study 2, in addition to recording the peak-to-peak amplitudes of the recorded responses, also included the recording of the H-reflex latencies. RESULTS: The results of study 1 showed that massage applied with the subjects in the supine position decreased the H-reflex amplitude during the massage. A 56% decrease in the H-reflex amplitude was recorded. Study 2 demonstrated a 27% mean group decrease in the H-reflex peak-to-peak amplitude during the massage for all subjects, with variations in individual responses ranging from an increase in the H-reflex amplitude of 20% to a decrease of 84%. An analysis of variance revealed that the H-reflex means of the five conditions were significantly different. Newman-Keuls post hoc analyses revealed that the mean of the MASS condition (2.01 mV) was significantly different from the means of C1, C2, and C4 (2.79, 2.81, 2.58 mV). The mean of C3 (2.42 mV) was not found to be statistically different from the means of the other conditions. These changes were noted against a stable M-response. CONCLUSION AND DISCUSSION: The results recorded in study 1 are comparable to those obtained with the subjects in the prone position. Based on these results, the supine position was adopted as the testing position for study 2. Study 2 further showed a decrease in H-reflex amplitude concomitant with massage in persons with SCI, but no long-term effects were noted.
Subject(s)
H-Reflex/physiology , Massage , Spinal Cord Injuries/physiopathology , Adult , Female , Humans , Male , Prone Position , Reaction Time , Supine PositionABSTRACT
Conductance measurements were used to determine the bacterial concentrations in the blood of mice receiving a suspension of Escherichia coli by the intravenous route. The study was also carried out on animals that had been treated with a drug (RU 41740) that stimulates the reticuloendothelial system. The intensity of the in vivo phagocytosis was assessed by calculating the difference between the mean detection times of the treated and control groups (ΔDT). The results obtained by conductance measurements were not statistically different from those obtained by the standard method of counting on Petri dishes. The conductance measurement method was also compared with the carbon clearance test, the reference test for studying in vivo phagocytosis. The two clearance tests revealed a major stimulation of the reticuloendothelial system by RU 41740. The coefficient of variation was lowest in the case of the bacterial clearance test.
ABSTRACT
The aim of this report is to draw the attention of clinicians to the possible occurrence of endometrial cancers of rare histological type among women currently undergoing or having in the past undergone tamoxifen therapy, in particular for breast cancer. We report a case of heterologous mixed malignant müller tumor occurring in an 80-year-old woman. At 69, she had been diagnosed with breast cancer and received tamoxifen for a total of 55 months over a 6-year period. In the 5th year after cessation of tamoxifen therapy, an endometrial carcinosarcoma was diagnosed. Although the association between tamoxifen use and endometrial cancer is recognized, only a few reports of occurrence long after cessation of therapy exist. We believe ours is the second for this particular histological type. Tamoxifen may have played a role in the occurrence of this tumor although it is also known that this type of tumor may arise de novo in elderly women. The etiologic hypothesis obtained from this case description will now be tested in a formal epidemiological investigation which hopefully will provide more definitive evidence.
Subject(s)
Adenocarcinoma/drug therapy , Breast Neoplasms/drug therapy , Carcinosarcoma/etiology , Endometrial Neoplasms/etiology , Mixed Tumor, Mullerian/etiology , Neoplasms, Second Primary/etiology , Tamoxifen/therapeutic use , Aged , Aged, 80 and over , Female , Humans , Tamoxifen/adverse effects , Time FactorsABSTRACT
Seventy-two consecutive patients with totally implanted catheters for administration of chemotherapy for solid tumours or lymphomas were studied prospectively to assess the prevalence of venous thrombosis. During the follow-up period of 343 (6-1,177) days, 11 cases of venous thrombosis (15.2%), of which 45% were partial and only 36% symptomatic were observed. Venous thrombosis was an early complication, 6/11 cases being observed within 1 month of implantation. No clinical or biological predisposing factor, apart from the presence of malignant disease, could be identified. Doppler ultrasonography is a good method of following-up these patients. This method should become an essential diagnostic tool in this field.
Subject(s)
Brachiocephalic Veins , Infusion Pumps, Implantable/adverse effects , Jugular Veins , Subclavian Vein , Thrombosis/etiology , Adult , Aged , Antineoplastic Agents/therapeutic use , Female , Humans , Male , Middle Aged , Neoplasms/drug therapy , Prevalence , Prospective Studies , Thrombosis/diagnostic imaging , Thrombosis/epidemiology , UltrasonographyABSTRACT
The main complication of totally implantable venous access devices is deep venous thrombosis on catheter. It may dramatically reduce the already limited venous capacity of patients undergoing chemotherapy and obturate catheters, causing pulmonary embolism or functional disorders. These thromboses usually involve veins of the superior vena cava system where the catheters are implanted. Generally, they occur early, are extensive and often asymptomatic. Doppler ultrasonography is the diagnostic investigation of choice, phlebography being reserved for particular cases or to specify the limits of the thrombus. In a series of 412 vein access devices implanted and systematically monitored by Doppler ultrasonography, we found 57 thromboses (13.8%), 15 partial and 42 complete. The lowest thrombosis rate was observed in the right internal jugular vein (10% vs 20 to 23%, p = 0.006). Thirty-two patients received a systemic fibrinolytic treatment, 16 with streptokinase (SK), five with urokinase (UK), four with tissue plasminogen activator (rt-PA) and seven with SK/UK association. No serious side effects were observed. Sixteen repermeabilizations (50% of fibrinolysis) were obtained. There were no significant differences with respect to the fibrinolytic, the initial characteristics of thrombosis or the patients. Patients without fibrinolysis received 3 weeks of low molecular weight heparin (curative doses) then warfarin. Only one patient was repermeabilized with this treatment (significative difference with fibrinolysis: p = 0.009). Fibrinolysis is indicated in symptomatic thrombosis and/or in cases of extension to the innominate vein or the superior vena cava. Systematic monitoring by Doppler ultrasonography and prophylactic anti-thrombotic treatment are recommended in patients with implantable venous access devices in order to decrease the occurrence of thromboses, to detect asymptomatic patients at an early stage and to increase the effectiveness of fibrinolysis.
Subject(s)
Catheters, Indwelling/adverse effects , Infusion Pumps, Implantable/adverse effects , Thrombolytic Therapy , Thrombosis/drug therapy , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Drug Administration Schedule , Female , Fibrinolytic Agents/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Middle Aged , Neoplasms/drug therapy , Phlebography , Retrospective Studies , Thrombosis/diagnosis , Thrombosis/etiology , Thrombosis/prevention & control , Treatment Outcome , Ultrasonography , Vena Cava, Superior/diagnostic imaging , Vena Cava, Superior/pathologyABSTRACT
Tamoxifen is widely used nowadays in the management of breast cancer, having established its efficacy in this indication, especially for postmenopausal patients with ER-positive breast tumours. However, tamoxifen has recently been recognized as carcinogenic for the human endometrium, probably with an effect of duration of treatment. Moreover, this drug may be associated with the occurrence of endometrial cancers of unusual histological types and/or of a more aggressive nature. We describe a case series of 11 patients who developed such cancers after having previously received tamoxifen for breast cancer. Several assumptions on the mechanisms underlying the attributed carcinogenic properties of tamoxifen, for the endometrium and potentially for other organs, are discussed on the basis of current knowledge.
Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/drug therapy , Endometrial Neoplasms/chemically induced , Tamoxifen/adverse effects , Adult , Aged , Breast Neoplasms/mortality , Drug Administration Schedule , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Endometrial Neoplasms/therapy , Female , Follow-Up Studies , France/epidemiology , Humans , Middle Aged , Ovarian Neoplasms/etiology , Ovarian Neoplasms/therapy , Prognosis , Risk Factors , Survival AnalysisABSTRACT
Colonic transit time (CTT) was measured with abdominal radiographs using Chaussade's technique in 30 spinal cord injured patients (ASIA A and B) following ingestion of 20 radiomarkers per day for three days. A significant increase in total CTT (p = 0.0001) and segmental CTT of the right colon (p = 0.0004) and of the left colon (p = 0.0001) was shown. While using on the average only 2.3 films of the abdomen per patient, we obtained results comparable with other radiologic techniques which use radiomarkers to measure CTT. The clinical relevance of these results is not clear and their correlation with intestinal symptoms remains to be investigated.
Subject(s)
Colon/physiopathology , Gastrointestinal Transit/physiology , Spinal Cord Injuries/physiopathology , Adolescent , Adult , Colon/diagnostic imaging , Female , Humans , Male , Middle Aged , Radiography, Abdominal , Reference Values , Spinal Cord Injuries/diagnostic imagingABSTRACT
We studied the effect of a fractionated heparin, Dalteparine Sodium, on the prevention of thrombosis of veins of the superior vena cava system catheterized by implantable infusion devices. Forty-six patients with solid or lympho-proliferative tumors, whose clinical condition required installation of a such device, were successively included into the study in 1991. The anticoagulant was administered for one month following implantation at the dosage of 2,500 anti-Xa units per day. The development of deep vein thrombosis was investigated by systematic Doppler ultrasound before the first and third months and at 1 year. Three early (D9, D12 and D16) and asymptomatic thrombosis were diagnosed (6.5%). This rate, although clearly more favourable, was not significantly different (p = 0.254) from the rate of 15.2% previously reported in a group of 72 comparable patients, but who did not receive preventive treatment. These results demonstrate the necessity and feasibility of a randomized study on a larger number of patients testing several protocols, before concluding on the efficacy of this type of preventive treatment.