Impaired air-liquid settling during swallowing in gastroesophageal reflux disease. A digital videofluoroscopic study.

We hypothesize that the surface of the zone of air-liquid mixture in the esophagus after swallowing is the result of the esophageal gastric junction (EGJ) function or dysfunction. The aim of this study was to quantify the air-liquid components of the bolus in the esophagus and across the EGJ by means of digital videofluoroscopy sequences recorded in patients with gastroesophageal reflux disease (GERD). The patients were allocated to a Normo or a Hypo group, according to basal lower esophageal sphincter (LES) pressure. Two types of analysis were undertaken from the video sequences. For static analysis, maximal opening diameter of the LES and surfaces of air, air-barium mixture, and barium suspension were measured on two images extracted from each sequence. For dynamic analysis, transit times across the EGJ of the total bolus, air, mixture, and barium suspension were evaluated on a video sequence. For static analysis, the maximal opening diameter of the LES, air, and mixture surfaces were higher in the Hypo group. For dynamic analysis, transit time of total bolus, air, and mixture were longer in the Hypo group. The increase in mixture can be attributed to a defect in settling of both air and liquid phases in the esophagus in patients with low LES pressure and/or esophageal hypotonicity. Thus, these evaluations should provide information on the passage modalities of the bolus in esophagus and across the EGJ to assess differential diagnosis of GERD and hence to better select the most appropriate antireflux surgical procedure.

[Swallowing sound signal: description in normal and laryngectomized subjects]. / Le signal acoustique de la déglutition pharyngée: description chez les sujets normaux et chez les patients laryngectomisés.

OBJECTIVES: Recently, we described three sound components in the pharyngeal swallowing sound. The aim of the present study was to identify the origin of these components using modern techniques providing numeric, synchronized acoustic-radiological data in a normal population and in a partial supracricoid laryngectomized population (SCL group) and a total laryngectomized (TL group) population in pre- and postoperative situations. PATIENTS AND METHODS: We enrolled 15 normal subjects (10 men and five women; mean age, 29.5+/-8 years), 11 patients in the SCL group (11 men; mean age, 62; range, 45-75 years), and nine patients in the TL group (three women, six men; mean age, 56; range, 39-73). An X-ray camera was connected to a video acquisition card to obtain acoustic-radiological data (2 images/s). The microphone was attached to each subject's skin overlying the lateral border of the cricoid. The subjects were asked to swallow 10 ml of a barium suspension. We performed the acoustic-radiological analysis using Visualisation and Cool Edit Pro software. Each sound component was associated with a specific position of the bolus and the moving anatomic structure. Three sound components were identified: the laryngeal ascension sound (LAS), the upper sphincter opening sound (USOS), and the laryngeal release sound (LRS). We quantified the total duration of the pharyngeal sound and its components, as well as the duration of the interval. RESULTS: The average duration of the normal pharyngeal sound was 690+/-162 ms and was significantly decreased in the TL group (296+/-105 ms) and increased in the SCL group (701+/-186 ms). The USOS was present in 100% of the recordings. A typical profile of the swallowing sound for each group was obtained. CONCLUSION: This study allowed us to determine the origin of the three main sound components of the pharyngeal swallowing sound with respect to movements in anatomic structures and the different positions of the bolus, and to describe the main variations induced by a partial and a total laryngectomy.

Predominant expression of circulating CD3+ lymphocytes bearing gamma T cell receptor in a prolonged immunodeficiency after allogeneic bone marrow transplantation.

The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells.

[Experimental study of the influence of the segmental transverse colic reversion on the intestinal transit time]. / Etude experimentale de l'impact de l'inversion d'un segment colique transverse sur le transit intestinal.

OBJECTIVE: to study the feasibility of the transverse segment colic reversion and to evaluate its impact on the intestinal transit time in the rat Wistar. METHOD: On a test group of the rats Wistar males anaesthetized, we isolated a segment from the transverse colon vascularized by a feeder pedicle. This segment colic was reversed and anastomosed into antiperistaltic out of termino-terminal on its site with polyglactine 6/0. Into post-operative, we studied, the weight, the volume of the ingestats, the intestinal transit time, the survival and the histological lesions of the reversed segment colic. On the group controls, we carried out the anastomosis of a segment of the transverse colon isolated and anastomosed into isoperisaltic. RESULTS: Thirty rats males of 231.5 +/- 8.3g had been operated, 15 for the test group and 15 for the control group. The average weight of the ingestats of the rats of the test group was of 21.87 +/- 3g and of 21.75 +/- 4.8g in the control group without significant difference. The intestinal transit occured at 3 +/- 1 post-operatives days in the test group and at 2 postoperative days in the control group. A mechanical obstruction of the bowels before the 15th post-operative day involved a mortality of 87% in the test group. Thirteen percent of the rats of the test group survived, with a regular catch of weight. The histological analysis showed inflammatory lesions on the proximal portion of the reversed segment and a normal wall without ischaemic injury on its distal portion. No death was observed in the group controls. CONCLUSION: The antiperistaltic anastomosis of a transverse segment colic within the colic in the rat Wistar, causes a stop of the intestinal transit time by mechanical occlusion without ischaemic lesion of the segment colic reversed.

Treatment of severe aplastic anemia with antilymphocyte globulin and androgens.

The etiology of aplastic anemia is unknown. A stem cell lesion caused by a toxin, virus or microenvironment defect is the main hypothesis. An autoimmune origin has been recently suspected. In an attempt to demonstrate the autoimmune origin of the disease, 17 patients with severe aplastic anemia were treated with antilymphocyte globulin (ALG). Nine patients showed no improvement, developed infectious or hemorrhagic complications and died within 1 to 7 months. In contrast, eight patients had a prompt rise of granulocyte and reticulocyte counts. Although the hematological reconstitution is not complete, these eight patients are still alive between 11 months and 24 months after treatment. This study shows that ALG may have a beneficial effect in the treatment of patients with severe aplastic anemia.

Efficient transduction of hemopoietic CD34+ progenitors of human origin using an original retroviral vector derived from Fr-MuLV-FB29: in vitro assessment.

A novel retroviral vector has been designed based on a Friend-murine leukemia virus (Fr-MuLV) FB29 strain. The latter has been selected according to characteristics of pathogenicity in mice where it induces a disease of the haemopoietic system affecting all lineages. Higher infectivity has also been demonstrated as compared to other strains. In accordance with these findings, the amphotropic producer clone used in this study carrying along the neomycine resistance gene (FOCH-Neo), harbors viral titers over 10(7) cfu/ml. To investigate the potential of genetically engineering hematopoietic precursors, CD34+ progenitors were selected from cord blood, bone marrow, and peripheral blood mobilized stem cells (patients + solid tumors) and transduced with FOCH-Neo. High transduction rates were achieved using virus supernatant and minimal doses of hematopoietic growth factors during pretransduction and transduction steps. A polymerase chain reaction (PCR) assay investigating the presence of both neomycin-encoding and viral vector sequences tested positive in 45-90% of granulocyte-macrophage colony-forming units (CFU-GM) generating cells (bone marrow and peripheral blood derived cells) following transduction. An average of 35% colonies showed resistance to G418. Such levels of transduction proved reproducible using only supernatants harboring over 10(7) cfu/ml. In those experiments where long-term in vitro cultures could be maintained over 5 weeks (all cord blood and 5 among 23 PBSC), efficient transduction of long-term culture initiating cell (LTC-IC) hematopoietic progenitors was demonstrated on the basis of both resistance to G418 and virus integration. In the latter case, the PCR assay tested positive in as much as 35-60% of late unselected CFU-colonies. This novel retroviral vector harbors interesting features toward genetic modification of hematopoietic progenitors.

Prognostic significance of chromosomal abnormalities in acute nonlymphocytic leukemia: a study of 343 patients.

Clonal chromosome abnormalities of 343 patients with de novo acute nonlymphocytic leukemia (ANLL) have been tentatively correlated with prognosis. All the patients were treated according to therapeutic protocols in the same hospital. The complete remission rate and median survival were generally lower in AA-ANLL (ANLL with only karyotypically abnormal metaphases) when compared with NN- and AN-ANLL. Similarly, AA-ANLL had the poorest prognosis in the majority of the classes of the French-American-British nomenclature. ANLL with inversion and/or deletion of chromosome #16 had the best prognosis, and ANLL with t(8;21) was not particularly favorable, nor was acute promyelocytic leukemia with t(15;17). ANLL with complex chromosomal abnormalities had the poorest prognosis. The conclusion is that chromosomal aberrations do have a prognostic significance in ANLL, but that this significance is dependent on the types of chromosomal aberrations.

Effect of combination chemotherapy, duration of methotrexate administration, and patient's age on methotrexate pharmacokinetics.

The kinetics of methotrexate were studied in a group of 59 patients after infusion of high doses. From the triexponential analysis of the serum concentration curve, rate constants and relative concentrations in non-circulating pools were calculated, using a linear 'mammillary' three-compartment model. No significant variation as a function of dose (300-6,000 mg/m2) was observed. In circumstances the rapidly exchanging pool was a reflection of the circulating pool, suggesting that it is an extravascular, protein-bound pool of methotrexate. Considerable variations of the relative concentration and rate constants of the slowly exchanging pool were observed to be a function of the duration of methotrexate infusion, the presence of other drugs, and the patient's age. If this compartment is assumed to include the target cells for methotrexate, then the large variations observed could be responsible for individual differences in toxicity and/or effectiveness.

Prognosis and treatment of acute lymphoblastic leukemia. Study of 650 patients.

The complete hematological remission (CHR) rate, duration of remission and survival were studied in relation to age, peripheral blast cell (PBC) count, presence or absence of tumor masses, cytological type, and treatment in 650 patients with acute lymphoblastic leukemia. Prognostic factors were considered separately and divided into prognostic classes. Age and PCB count correlated with both the rate and the duration of CHR. This correlation was still observed for more recent treatment schedules though it appears to be becoming progressively less significant. Meningeal relapses were more common in patients less than 1 year old and in those with a high PCB count. It is suggested that stratification of patients according to such factors as age, PCB count, presence or absence of tumor, and cytological type might be necessary for the design of new treatment protocols and for the evaluation of their results.

Chemotherapy of carcinomas of the digestive tract.

Adjuvant chemotherapy trials in gastric and colorectal carcinomas are reviewed and no clear benefit from such treatment could be observed. To improve existing chemotherapy regimens, several pilot studies were performed in 95 gastric cancer and 85 colorectal carcinomas patients. Response rate for gastric carcinomas using the mitomycin C plus adriamycin plus 5-fluorouracil (5-FU) (FAM) regimen was 40% and was not improved by the addition of nitrosoureas. In colorectal carcinomas none of the combinations used gave better results than 5-FU alone. Fourteen patients with esophageal carcinoma were treated with combination CDDP and the response rate was as high as 50%.

Clinical trials with diglycoaldehyde (NSC-118994): review and reasons for withdrawal from clinical trial.

All Phase II studies with diglycoaldehyde with leukemia and solid tumors have been reviewed. The dose schedules employed ranged from 1.5 to 2.0 g/m2/day for 3 to 5 days. The most common side effects have been gastrointestinal (nausea and vomiting), which occurred in 22% of the patients. Renal toxicity (rise in BUN, creatinine, and urinary proteins) was seem in 17% of the patients treated. Other infrequent toxicities include hypocalcemia (9%) and local complications such as phlebitis. Leukopenia, thrombocytopenia, positive Coombs' test and impairment in coagulation profile were also reported. In contrast to the hints of therapeutic efficacy described during Phase I trials, in phase II trials no activity was noted among 96 patients with solid tumors and only minimal antileukemic action among 49 other patients. These disappointing Phase II trials coupled with prominent toxicities have prompted the decision to terminate further clinical testing. This report summarizes all clinical observations as an example of circumstances which curtail clinical testing of anticancer drugs.

[Oncornaviruses and human leukemias]. / Oncornavirus et leucémies humaines

This is a brief review on current progresses which appeared recently on the isolation of a putative human oncornavirus from human leukemic cells. There are strong arguments in favor of the existence of such an oncornavirus, both indirect (existence of viral nucleotide sequences and viral proteins in human leukemic cells), and direct (isolation of a Type-C virus from in vitro cultures of human leukemic cells).

Indications for bone marrow grafting.

Bone marrow transplantation has found during the last decade his major indications which are severe aplastic anemia and acute leukemia in complete remission. For the time being, bone marrow transplant is feasible only if the patient has an HLA identical sibling. Efforts are being made to improve the prognosis of complications such as graft versus host disease and interstitial pneumonitis. The long term survival currently obtained is over 50 per cent.

[Hodgkin's disease in children: long-term therapeutic results (author's transl)]. / Maladie de Hodgkin de l'enfant résultats à long terme du traitement.

Between 1965 and 1976, 83 previously untreated children aged 15 years and under, with biopsy-confirmed Hodgkin's disease were assessed, treated, and followed-up at Hoôpital Saint-Louis, Paris. Clinical stages were IA-IIA for 59, IB-IIB for 19, and III-IV for 5 patients. Two main types of treatment were used: - monochemotherapy-radiotherapy in 26 patients who received mantle field irradiation followed by monthly vinblastine injections for 3 years; - 57 patients received a combination of MOPP and radiotherapy. The MOPP-radiotherapy treated patients have a significantly better survival and relapse-free survival than the monochemotherapy-radiotherapy treated patients (86.9 p. cent vs 76.1 p. cent and 83.5 p. cent vs 65.4 p. cent). Thirteen relapses were observed after a median complete remission period of 30 months: 6 patients are now free from disease and one is still under treatment. Ten patients died after a 55 months median survival: 7 died from Hodgkin's Disease and 3 from treatment toxicity. No secondary cancer or leukemia has been observed. The main long-term complications of therapy were sterility in male patients, after chemotherapy, and growth defects and disturbances of thyroid functions after radiotherapy.

[Characterization of the viral-type nucleotide sequences detected in the RNA of human leukaemic cells by probes of murine and simian origins (author's transl)]. / Caractérisation des séquences nucléotidiques de type viral détectées dans le RNA des cellules leucémiques humaines par des sondes d'origine murine et simienne.

Molecular hybridization techniques were used for searching nucleic acid sequences homologous to murine and simian oncornaviral genomes in the RNA of various categories of human leukaemic cells. We report attempts to characterize the sequences that were detected in defined categories of leukemias. It is shown that: i) although there is some correlation between the two probes used in our study with regard to the positivity or the negativity of the tests for the same leukaemic cases, there are also some discrepancies since some of the cases are positive with one probe and negative with the other; ii) the common sequences of the two probes when isolated, were ineffective to detect any complementary sequences in leukemic cases which were scored as positive when the entire probes were used; iii) the complementary sequences detected in three positive cases of acute myelogenous leukemias by a recycled probe are additive and therefore most probably distributed along the viral genome.

Bone marrow transplantation in 65 patients with severe aplastic anemia.

This articles summarizes the experience of the Hospital Saint-Louis Bone Marrow Transplantation Team of bone marrow transplantation in severe aplastic anemia. Sixty-five consecutive patients have been transplanted with an HLA identical sibling marrow. Various conditioning regimen have been used. Conditioning regimen using high dose Cyclophosphamide alone or associated with Procarbazine and anti-thymocyte globulin gave a high number of bone marrow graft rejection. Therefore, a conditioning regimen using Cyclophosphamide and total body irradiation with lung shielding has been used for the last three years. This regimen suppressed bone marrow graft rejection. The main problems remain graft versus host disease and intercurrent infections. Despite these complications, 50 per cent of the patients become long term survivors and are apparently cured of their initial disease.

[Acute leukemia in childhood: present status of 100 cases after 7 years of complete remission (author's transl)]. / Leucémie aiguë. Bilan de 100 enfants en rémission depuis plus de 7 ans.

Amongst 1,200 leukemie children treated between 1958 and 1971, 60 are in complete remission for more than 10 years and 100 for more than 7 years. There were 96 acute lymphoid and 4 acute myeloid leukemias. Ten patients who have relapsed in the past have not done so lately. The F/M sex ratio is 1.5. Poor prognostic features were initially absent in 2/3 of cases. In 1/3 there was associated hyperleucocytosis and/or tumours. 93 children are in remission, their treatment having been stopped for 1 to 12 years. Five children relapsed and 4 are in a second remission for more than 2 years. Two children died in remission: one from a hepatocarcinoma and one from cardiac failure. These patients have been shown to have the following: 1) normal growth; 2) normal puberty: 8 patients have been able to reproduce, giving 10 children, one with multiple malformations; 3) school achievement and later socioprofessional behaviour has been normal. The patients have often sought a medical or paramedical career. Sequelae are minimal, psychological problems being minimal in the child. With the protocols used, mean remission curve shows a plateau after 9 years and complete definitive care is achieved in 92 per cent of patients surviving at 7 years. The very distant future outlook is not known. No other malignant haematological disease has occurred but one child died from a carcinoma.

Erythromycin elicits opposite effects on antro-bulbar and duodenal motility: analysis in diabetics by cineradiography.

We have previously demonstrated by cineradiography analysis that erythromycin (Ery) increases antral contractility and antropyloric coordination in diabetics. The aim of this study was to further characterize antro-bulbar and duodenal motility after Ery i.v. administration. Fourteen diabetic patients (mean age 61.2 years) were randomly allocated to receive either 100 or 500 mg of Ery intravenously 4 hours after a standard solid liquid meal. After ingestion of a barium sulfate suspension, a series of 15 fluorographic plates (one every two seconds) was performed. the same procedure was repeated twice for each subject with a delay of 3 days once before and once after Ery. Antral, bulbar and duodenal areas and evolution diagrams were calculated in baseline conditions and after Ery administration using a graphic table connected to a microcomputer. No differences were found between the two doses of the drug. Ery significantly decreased antral (1284 +/- 268 mm2 vs 704 +/- 181 mm2; P < 0.01) and bulbar areas (127 +/- 26 mm2 vs 73 +/- 21 mm2; P < 0.01). In contrast, duodenal areas were significantly increased after Ery (875 +/- 112 mm2 vs 575 +/- 112 mm2; P < 0.01). This study suggests that the known prokinetic effect of Ery on gastric emptying seen in diabetic patients could be related to an increase of motility in the antrum and in the bulb simultaneously with a relaxation in the duodenum.

[Gastric peristalsis and dyspepsia: value of cineradiographic analysis in men]. / Péristaltisme gastrique et dyspepsie: intérêt de l'analyse cinéradiographique chez l'homme.

Gastric peristalsis has not been studied extensively in patients with dyspepsia. The aim of our study was to further characterize gastric peristalsis in such patients using a newly described fluorographic method. Thirty-two patients with dyspepsia and 18 healthy volunteers were included in our study. Four hours after a standard solid-liquid meal, the subject swallowed 250 ml of a baryum sulfate solution and (100 mm x 100 mm) fluoroscopy of the stomach was performed every 2 s during 30 s. Spot films were analyzed using a graphic table and a amateur microcomputer program. For each subject, the instant velocity, vi, and mean velocity, V, of gastric peristalsis were calculated and used to generate a time-space diagram of contractions, a velocity histogram and an index of propagation, Ip. These parameters were compared to normal values (V = 2.2 +/- 0.2 mm/s; Ip = 2.2 +/- 0.4). When compared with normal values, 3 different motility patterns appeared in dyspeptic patients with a high correlation between V and Ip (P less than 0.01): normoperistalsis (n = 8; 1.8 less than V less than 2.6 mm/s); 1.4 less than Ip less than 30); hypoperistalsis (n = 7; V less than 1.8 mm/s; Ip greater than 3.0) and hyperperistalsis (n = 7; V greater than 2.6 mm/s; Ip less than 1.4). In a 4th group (n = 5), a retroperistalsis was effect observed with Ip less than 0. For 5 other patients, Ip or V was abnormal with atypical motor activity detected on the time-space diagram.(ABSTRACT TRUNCATED AT 250 WORDS)