PubMed Health⌕ Search

Biomedical subjects

L Leon

Publications and source records attributed to L Leon.

At least 19 recordsLinked to original sources

Chest wall resection for locally recurrent breast cancer: is it worthwhile?

OBJECTIVE: The effectiveness of chest wall resection for locally recurrent breast cancer as cancer treatment remains poorly defined, possibly because of the general impression that locally recurrent disease is a harbinger of rapidly progressive metastatic disease and that extensive surgical treatment in these patients is inappropriate. Reports to date have focused on technical feasibility, not long-term outcome. METHODS: We reviewed our experience with 38 women who underwent chest wall resection for locally recurrent breast cancer between October 1987 and May 1997. Overall survival was calculated by the Kaplan-Meier method and the significance of prognostic variables evaluated by log-rank and Cox regression analyses. RESULTS: The operative mortality rate was 0%. Overall survival at 1, 3, and 5 years after chest wall resection was 74%, 41%, and 18%, respectively, and the proportion of patients free of local recurrence at 1, 3, and 5 years was 59%, 42%, and 13%, respectively. Regional nodal disease and size of largest tumor nodule (>4 cm) were significant predictors of local re-recurrence (P <.01, P =.04); lymph node metastasis was the only predictor of long-term survival (P <.01). Patients with and without synchronous sites of metastatic disease had near-identical 3-year survivals. CONCLUSIONS: Chest wall resection for locally recurrent breast cancer has a low mortality. However, a significant number of patients have the development of local re-recurrence or metastases, and 5-year survival is limited. It is unlikely that complete resection of all locally recurrent disease improves survival. Future studies should focus on the quality of palliation achieved.

Adult↗

Factors determining outcome after surgical resection of T3 and T4 lung cancers of the superior sulcus.

BACKGROUND: The treatment of superior sulcus lung cancers is evolving and preoperative chemotherapy is increasingly used. To establish a historical benchmark against which new therapies can be assessed, we reviewed our 24-year experience with patients undergoing thoracotomy for lung cancers of the superior sulcus. METHODS: Data were acquired through retrospective chart review. Overall survival was calculated by the method of Kaplan and Meier, and prognostic factors were examined by log rank and Cox proportional hazards modeling. RESULTS: From 1974 to 1998, 225 patients underwent thoracotomy. The patients included 144 men (64%) and 81 women with a median age of 55 years. The majority of patients (55%) received preoperative radiation, but 35% did not have any preoperative treatment. Tumor stages were IIB (T3 N0) in 52%, IIIA in 15%, and IIIB in 27% of patients. Complete resection was achieved in 64% of T3 N0 tumors, 54% of T3 N2 tumors, and 39% of T4 N0 tumors. Operative mortality was 4%. Median survival was 33 months for stage IIB and 12 months for both stages IIIA and IIIB. Actuarial 5-year survivals were 46% for stage IIB, 0% for stage IIIA, and 13% for stage IIIB. By univariate and multivariable analyses, T and N status and complete resection had a significant impact on survival. Locoregional disease was the most common form of relapse. CONCLUSIONS: Our results provide a benchmark against which new treatment regimens can be evaluated. Control of locoregional disease remains the major challenge in treating lung cancers of the superior sulcus. The potential benefit of preoperative chemotherapy or chemoradiotherapy must be assessed by whether it leads to higher rates of complete resection and a lower risk of local relapse.

Adult↗

Lymph node staging in gastric cancer: is location more important than Number? An analysis of 1,038 patients.

OBJECTIVE: To compare the impact of staging systems on the survival of 1,038 patients with gastric cancer undergoing resection for cure in a North American center. SUMMARY BACKGROUND DATA: In 1997, the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer redefined N stage in gastric cancer. The number of involved nodes rather than their location defines N, and a minimum of 15 examined lymph nodes is recommended for adequate staging. In the 1988 AJCC N-staging system, N1 and N2 node metastases were defined as within 3 cm or more than 3 cm of the primary; the 1997 AJCC N stages were defined as N1 = 1 to 6 positive nodes, N2 = 7 to 15 positive nodes, and N3 = more than 15 positive nodes. METHODS: Between 1985 and 1999, 1,038 patients underwent an R0 resection. Median and 5-year survival rates were compared and the Kaplan-Meier method was used to estimate median survival. RESULTS: The location of positive nodes did not significantly affect median survival when analyzed by the number of positive nodes. In contrast, the number of positive lymph nodes had a profound influence on survival. The new N categories served as a better discriminator of median survival when 15 or more nodes were examined. Survival estimates for stages II, IIIA, and IIIB were significantly influenced by examining 15 or more nodes. CONCLUSION: The number of positive nodes best defines the prognostic influence of metastatic lymph nodes in gastric cancer. Survival estimates based on the number of involved nodes are better represented when at least 15 nodes are examined.

Adult↗

Variation in the use of alternative levels of hospital care for newborns in a managed care organization.

OBJECTIVE(S): To assess the extent to which variation in the use of neonatal intensive care resources in a managed care organization is a consequence of variation in neonatal health risks and/or variation in the organization and delivery of medical care to newborns. STUDY DESIGN: Data were collected on a cohort of all births from four sites in Kaiser Permanente by retrospective medical chart abstraction of the birth admission. Likelihood of admission into a neonatal intensive care unit (NICU) is estimated by logistic regression. Durations of NICU stays and of hospital stay following birth are estimated by Cox proportional hazards regression. RESULTS: The likelihood of admission into NICU and the duration of both NICU care and hospital stay are proportional to the degree of illness and complexity of diagnosis. Adjusting for variation in health risks across sites, however, does not fully account for observed variation in NICU admission rates or for length of hospital stay. One site has a distinct pattern of high rates of NICU admissions; another site has a distinct pattern of low rates of NICU admission but long durations of hospital stay for full-term newborns following NICU admission as well as for all newborns managed in normal care nurseries. CONCLUSIONS: Substantial variations exist among sites in the risk-adjusted likelihood of NICU admission and in durations of NICU stay and hospital stay. Hospital and NICU affiliation (Kaiser Permanente versus contract) or affiliation of the neonatologists (Kaiser Permanente versus contract) could not explain the variation in use of alternative levels of hospital care. The best explanation for these variations in neonatal resource use appears to be the extent to which neonatology and pediatric practices differ in their policies with respect to the management of newborns of minimal to moderate illness.

Health Maintenance Organizations↗

Phase I and pharmacokinetic study of 10-propargyl-10-deazaaminopterin, a new antifolate.

The 10-deazaaminopterins are a new class of rationally designed antifolates demonstrating greater antitumor effects than methotrexate in murine tumor models and human tumor xenografts. Their design was aimed at improving membrane transport and polyglutamylation in tumor cells, resulting in increased intracellular accumulation and enhanced cytotoxicity. Compared with other 4-aminofolate analogues, 10-propargyl-10-deazaaminopterin (PDX) is the most efficient permeant for the RFC-1-mediated internalization and substrate for folylpolyglutamate synthetase. PDX demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate or edatrexate. We undertook a Phase I study with PDX to identify the potential toxicities and define an optimal dose and schedule. Thirty-three patients were enrolled, all of whom had non-small cell lung cancer (NSCLC) and were treated previously with a median of two prior chemotherapy regimens. Initially, PDX was administered weekly for 3 weeks in a 4-week cycle. Mucositis requiring dose reduction and/or delay in the first cycle occurred in four of six patients treated at the initial dose level (30 mg/m2), making this the maximal tolerated dose for PDX given on this schedule. The treatment schedule was then modified to every 2 weeks. Twenty-seven patients were treated twice weekly with a total of 102 four-week cycles (median, 2 cycles/patient). Mucositis was the dose-limiting toxicity, with grade 3 and 4 mucositis occurring in the first two patients treated at the 170 mg/m2 dose level. Other toxicities were mild and reversible. No neutropenia was observed. The recommended Phase II dose is 150 mg/m2 biweekly. At that dose level, the mean area under the curve was 20.6 micromol x h, and the mean terminal half-life was 8 h. Two patients with stage IV NSCLC had major objective responses, and five patients had stable disease for 7 (two patients), 9 (one patient), 10 (one patient), and 13 months (one patient). PDX is a new antifolate with manageable toxicity and evidence of antitumor activity in NSCLC. A Phase II trial in NSCLC and a Phase I trial with paclitaxel are under way. These studies will also quantitate the expression of genes controlling internalization (RFC-1) and polyglutamylation of PDX in tumor cells as correlates of response.

Aminopterin↗

IgG concentration in mammary secretions of goats throughout lactation in healthy and coagulase-negative staphylococci infected udders.

Radial immunodiffusion was used to determine immunoglobulin (Ig)-G concentrations in 16 mammary secretions from uninfected udder halves and in 10-14 secretions from halves subclinically infected with coagulase-negative staphylococci in goats throughout lactation. IgG concentrations in samples from uninfected halves decreased rapidly during the first week after parturition (P < 0.001 ), henceforth falling slowly up to 30 d post-partum (P < 0.001). From 30 d post-partum to 180 d of lactation, IgG concentration showed a continuous decline to the end of the experiment but these changes were not statistically significant until 150 d after kidding (P < 0.01). IgG concentrations in lacteal secretions of halves harbouring coagulase-negative staphylococci showed a similar pattern, from the first month of lactation, to that observed in healthy udder halves, but concentrations were always lower. These differences were significant from 2 months after parturition (P < 0.001). IgG concentrations were compared with somatic cell counts obtained using an automatic counter (Fossomatic).

Animals↗

[The treatment of the tracheobronchial stenosis by extracorporeal circulation].

Six children with tracheobronchial stenosis secondary to cardiovascular ring were operated with extracorporeal surgery. Three of them with pulmonary sling had a tracheobroncoplasty with costal cartilage, one with xiphoides appendix and another with pericardio. One girl 2 years old was operated resecting three tracheal rings and anastomosis end to end. The child that was operated with pericardio died with infection and sepsis three months after the operation. The other five are well five, four and two years after plasty.

Bronchi↗

Comparative study of different immunoserological techniques for the detection of antibodies against transmissible gastroenteritis (TGE) coronavirus.

In order to carry out a sero-epidemiological survey of transmissible gastroenteritis (TGE) infection in a high-density pig-breeding area the Murcia region, Spain), the sensitivity and the specificity of 5 different techniques were compared. Twenty-four sera from non-infected and infected pigs were analyzed by the following tests: in vitro neutralization, indirect ELISA with concentrated virus, indirect ELISA with purified virus, immunocapture ELISA and VELCIA (virus-enzyme linked cell immunoassay). All sera from infected pigs were detected as positive only by seroneutralization, ELISA with purified virus and VELCIA (sensitivity 100%). False-positive sera were detected with several tests (ELISA with purified virus and concentrated virus, ELISA immunocapture with a specificity of 88, 88 and 76% respectively). Only VELCIA provided a specificity as high as that obtained with seroneutralization (100%).

Animals↗

Pathogenicity and antigen detection of the Nouzilly strain of transmissible gastroenteritis coronavirus, in 1-week-old piglets.

We compared the pathogenicity and the sites of multiplication of the attenuated Nouzilly strain, with the highly passaged Purdue-115 and the virulent Gep II strains of transmissible gastroenteritis (TGE) coronavirus, in 1-week-old weaned piglets. The immunohistochemical peroxidase technique, with an antiviral nucleoprotein monoclonal antibody, was used for the localization of the multiplication sites, in the intestine and other organs. The Gep II and the Purdue-115 strains, administered orally to piglets, caused clinical signs and lesions of TGE. These strains multiplied within the intestinal tract in the enterocytes of the jejunum and ileum, Peyer's patches and mesenteric lymph nodes. In view of the small numbers of infected cells in the tonsils, spleen, kidney, liver and lung, these tissues are not considered to be preferential multiplication sites. The attenuated Nouzilly strain multiplies only in the ileum and the mesenteric lymph nodes. The variation in the tropism for particular parts of the intestine (with the preferential localization of the virus in the ileum rather than the jejunum), could be related to the high degree of attenuation of the Nouzilly strain.

Animals↗

Sero-epidemiological survey of porcine respiratory coronavirus (PRCV) infection in breeding herds in southeastern Spain.

In 1987 we conducted a sero-epidemiological survey in the Murcia Region (South-East Spain) to discover the prevalence and spread of PRCV-infection among breeding pigs and farms and determine the association between herd size and geographical zone with PRCV-infection. The Murcia Region was divided into four geographical zones and the farms classified by size in four categories. The random sample was statistically representative of both the breeding stock and farms in each geographical zone. We analysed 6,000 breeding pigs from 480 farms. The immunological techniques employed were indirect ELISA and blocking ELISA. The prevalence (P +/- IC) of PRCV-seropositive breeding pigs and infected breeding farms was 14.53 +/- 0.89% and 21.87 +/- 7.83% respectively. On 55% of the infected farms, the prevalence of seropositive breeding pigs was 60-100%. PRCV-infection appears spread throughout the four geographical zones of the Murcia Region. However, a significant association (p less than 0.01) was observed between geographical zone and the prevalence of PRCV-infection. A herd size of greater than 50 breeding pigs had a greater risk (p less than 0.01) of PRCV-infection.

Animals↗

Trypanosoma cruzi in the opossum Didelphis marsupialis: parasitological and serological follow-up of the acute infection.

The opossum Didelphis marsupialis is known to be among the most important wild reservoirs of Trypanosoma cruzi and one in which the trypanosome may go through both the usual vertebrate intracellular cycle in its tissues and an extracellular cycle in the lumen of its scent glands. The species is highly resistant to heavy inocula and, depending on the parasite strain, experimental infections may be permanent or self limited. Aiming to understand the mechanisms involved in this parasite-host interaction we made a study of the acute phase of infection with different T. cruzi strains. Strains F, G-49 and G-327 produced durable infections with relatively high parasitemia and invasion of the scent glands, while equivalent inocula of the Y strain resulted in scanty parasitemia of short duration, no invasion of the SG, and no evidence of persistent parasitism. A smaller inoculum of G-49 produced only subpatent though persistent parasitemia and no invasion of the scent glands. The humoral immune response was less marked in the Y group; among the other groups IgM and IgG antibodies increased to high levels, higher in the G-49 group. The increase in IgG coincided with a drop of parasitemia to subpatent levels. Two opossums inoculated directly in the scent glands with culture forms of the Y strain had a short-lived subpatent parasitemia, but the parasites remained in the glands and serum Ig antibodies reached high levels. Immunoblot analysis showed that the sera of the inoculated opossums recognized few T. cruzi antigens (more in the F strain) in comparison with those of mice. However, with the only exception of those subcutaneously inoculated with the Y strain and including two naturally infected specimens, all the opossum's sera recognized a 90-kDa peptide in all T. cruzi strains. Our results confirm that opossums are able to selectively eliminate some strains of T. cruzi and indicate that the mechanism involved in this selection is probably not related to the humoral immune response. In infections by strains that are able to establish a permanent foothold in opossum tissues, there are indications that IgG antibodies participate in the control of the parasite population of the acute phase but are unable to prevent the chronic phase. It was once more demonstrated that the opossum infected scent glands function as diffusion chambers for parasite antigens but that, on the other hand, the parasites are here protected against the mechanisms developed by the host to control their population.

Acute Disease↗

Two years of cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for stage II and III breast carcinoma.

The results after 6 years of a prospective clinical trial of adjuvant chemotherapy with a regimen of two drugs--cyclophosphamide and 5-fluorouracil (CF)-- for 2 years in 97 women with stage II or III breast cancer are reported. Eligible patients were free from distant metastases. All patients began adjuvant therapy within 4 weeks of surgery; therapy consisted of radical, modified, or extended radical mastectomy. No postoperative radiotherapy was given. The results are compared with a historical control group from previous consecutive patients treated by surgery alone. Patients were stratified by age (younger than 50 or older than or equal to 50) and nodal status (one to three positive axillary nodes vs. four or more positive nodes). The estimated 6-year survival was 60% for CF patients vs. 31% for control patients (P = 0.001). The estimated 6-year disease-free survival was 53.6 and 30.3% for CF and control, respectively (P = 0.007). There was a trend toward longer disease-free survival (DFS) and survival (S) in patients treated with CF, but this was not significant in all the subgroups. Disease-free survival was statistically significant in the subgroup of women greater than or equal to 50 years old with one to three positive nodes (P = 0.038); survival in the patients less than or equal to 49 years old with four or more positive nodes (P = 0.0036); and in patients greater than or equal to 50 years old with one to three lymph nodes involvement (P = 0.038).

Adult↗

Ambulatory electrocardiographic correlates of ventricular inducibility during programmed electrical stimulation.

To determine the relation between spontaneous and induced ventricular arrhythmias, ambulatory electrocardiographic (Holter) monitoring and programmed electrical stimulation were performed in 48 adult patients with suspected life-threatening ventricular arrhythmias. Nine had no inducible arrhythmia, 11 demonstrated 1 to 2 beats of intraventricular reentry, 19 exhibited non-sustained ventricular tachycardia and 9 exhibited sustained ventricular tachycardia during electrophysiologic studies. Patients without arrhythmia inducibility had a high incidence of multiformity (56%) and bigeminy (44%), but a low incidence of either couplets (11%) or spontaneous ventricular tachycardia (11%) on Holter monitoring. An increasing incidence of all "complex" ectopic features was found with increasing degrees of ventricular inducibility. In patients with inducible sustained ventricular tachycardia, multiformity was present in 100%, bigeminy and couplets in 89% and spontaneous ventricular tachycardia in 78%. Premature ventricular complex frequency, couplet frequency and the repetition index (the ratio of couplets to premature ventricular complexes) were also found to be directly correlated with the degree of ventricular inducibility. Three quantitative arrhythmia variables were identified which predicted ventricular tachycardia inducibility. Seven (78%) of 9 patients with a mean premature ventricular complex frequency of 100 or more/1,000 normal beats, 11 (85%) of 13 with a mean couplet frequency of 1 or more/1,000 normal beats and 19 (83%) of 23 with a mean repetition index value of 15 or more/1,000 premature ventricular complexes proved to have inducible ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Role of iron in jejunal uptake of cadmium in the newborn rat.

There is evidence that suckling animals and children have a greater capacity for intestinal transport of both essential and nonessential metals than do adults of the species. It has also been observed in experiments using adult animals that the intestinal transport of iron and the nonessential metal cadmium interact with one another. In the study reported here, the influence of tissue iron status on jejunal uptake of cadmium was investigated in suckling, adolescent, and young adult rats using an in situ incubation technique. In the presence of 0.4 mM FeSO4, intestinal uptake of cadmium was significantly decreased in 14-d-old pups. Access to an iron-deficient diet reduced tissue iron levels in 28- and 42-d-old but not in 14-d-old rats. Intestinal uptake of cadmium was significantly greater in 28- and 42-d-old rats placed on the iron-deficient diet but did not change in 14-d-old rats compared to controls. In suckling rats injected with iron dextran over a six-d period, a significant decrease in intestinal uptake of both cadmium and iron was observed compared to controls. The results of the present study suggest that intestinal cadmium transport in the suckling, as well as the adolescent and young adult rat, interacts with, at least in part, the pathway responsible for iron transport.

Aging↗