Biomedical subjects
Publications and source records attributed to J Padilla.
Otocephaly is a rare lethal malformation of the first and second branchial arches. We report two infants with otocephaly and failed resuscitation. Both infants had pulmonary malformations: pulmonary hypoplasia and two-lobed right lung. We report these rare associations with a brief review of the literature.
OBJECTIVE: To determine the prognostic factors for the survival in a group of patients operated on for a non-small cell lung cancer classified as T2N1M0. PATIENTS AND METHODS: Two hundred sixteen patients treated exclusively with surgery were studied. Kaplan-Meier survival and Cox multivariable regression analyses were used. RESULTS: The overall survival rate was 39.8% at 5 years and 29.9% at 10 years. Sex, age, presence or absence of symptoms, type of resection, number, and location of affected lymph nodes had no effect on survival. Tumor size (P=.04) and histologic type (P=.03) did significantly affect prognosis. Both variables entered into the Cox multivariable regression model. CONCLUSIONS: Patients operated on for non-small cell lung cancer classified as T2N1M0 have an overall probability of 5-year survival of approximately 40%. However, the prognosis for this group of patients is heterogeneous: in our study it was affected by the histologic type (45.5% for squamous cell and 25% for non-squamous cell cancers) and tumor size (53% for tumors with a diameter of 5 cm).
OBJECTIVE: Retrospective study on the relation between the use of blood products and survival rates in patients treated surgically for stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The study included 856 patients who underwent surgical resection from 1969 to 2000 for stage I NSCLC, classified histologically according to the current guidelines of the Spanish Society of Pulmonary and Thoracic Surgery (SEPAR). Patients who died in the postoperative period were excluded from the study. A series of clinicopathological variables were recorded, including the perioperative use or not of blood products. Descriptive, univariate, and multivariate statistical analyses were performed. Follow up concluded in December of 2003. RESULTS: One hundred twenty-five patients (14.6%) underwent a perioperative transfusion. A significant association was found between the use of blood products and tumor size (P<.001), pneumectomy (P<.001), and cell type (P<.05). The respective 2, 5, and 10-year survival rates were 78%, 63%, and 54% for the nontransfusion group, and 73%, 59%, and 46% for the transfusion group. Both survival curves were compared and no significant differences were found (P=.23). Multivariate regression analysis included tumor size, patient age, and histologic cell type (squamous cell carcinoma or not); no relation between transfusion and survival was found. CONCLUSIONS: In our series, we found no difference in survival rates for patients with stage I NSCLC after perioperative blood transfusion.
OBJECTIVE: To determine the incidence and causes of perioperative mortality following lung transplant for cystic fibrosis. PATIENTS AND METHODS: We analyzed the cases of 57 patients. Fifty-five patients received double lung transplants, 1 received a heart-double lung transplant, and 1 received a combined double lung and liver transplant. Information related to the organ donor, recipient, lung graft, and early postoperative period was gathered. Perioperative mortality was defined as death resulting from anesthesia or surgery regardless of how many days had passed. The Kaplan-Meier method was used to analyze survival. A Cox logistic regression model was used to determine variables affecting mortality. RESULTS: Survival was 83.7% at 1 year after transplantation, 77.3% at 2 years, and 66.9% at 5 years. Five (8.7%) patients died as a result of anesthesia or surgery. A ratio of PaO2 to inspired oxygen fraction (FiO2) less than 200 mm Hg in the early postoperative period was observed in 8 (14%) patients. Primary graft failure occurred in 4 patients, due to pneumonia in 2 and to biventricular dysfunction in 2. Three of those patients died. Two patients with PaO2/FiO2 greater than 200 mm Hg died after surgery, one from septic shock due to Pseudomonas cepacia and the other from massive cerebral infarction. PaO2/FiO2 upon admission to the recovery care unit was the only variable significantly associated with perioperative mortality in the logistic regression model (P=.0034). CONCLUSIONS: The only factor significantly related to perioperative mortality in patients receiving transplants for cystic fibrosis was PaO2/FiO2 upon admission to the recovery unit.
OBJECTIVE: To determine the causes of death in patients treated surgically for nonsmall cell lung cancer (NSCLC) in stage IA and to evaluate the impact on survival of not performing systematic lymph node dissection and of the number of nodes resected. PATIENTS AND METHODS: The study sample consisted of 156 patients operated on for NSCLC and classified in stage IA according to TNM staging. Only palpable or visible lymph nodes were dissected. Kaplan-Meier survival curves were compared using a log-rank test. RESULTS: At the end of the study, 85 (54.5%) patients had died, 67 (42.9%) were alive, and 4 (2.5%) were lost to follow up. Twenty-three (14.7%) died from a recurrence of NSCLC: 2 with local tumors (1.2%), 2 with mediastinal node involvement (1.2%), and 19 (12.1%) with distant metastasis. The cause of death was unrelated to NSCLC in 62 (39.7%) cases: 33 (21.1%) had a new tumor, 18 of which were bronchogenic, and 29 (18.5%) had nonmalignant disease. The 5-year survival rate was 81.4%. The rate was 88.9% among patients from whom no lymph nodes were excised and 79.9% among those with node excision, although the difference was not statistically significant (P=.4073). CONCLUSIONS: Our experience suggests that neither the fact of not performing systematic lymph node dissection nor the number of nodes resected has an impact on survival. A substantial number of patients died of causes unrelated to the NSCLC for which they had been treated.
OBJECTIVE: To assess the prognostic value of a series of clinicopathological variables in stage I nonsmall cell lung cancer, for tumors up to 3 cm in diameter. PATIENTS AND METHOD: The study included 271 patients. Survival was analyzed with the Kaplan-Meier method. The Cox model was used for multivariate analysis. RESULTS: Five- and ten-year survival were 78.63% and 67.59%, respectively. Survival did not significantly depend on sex, age, extent of resection, histology, visceral pleural invasion, level of bronchial invasion or T1 versus T2. The decade in which resection was performed did affect survival (P=.0037). Five-year survival was 58% for operations between 1970 and 1980, 77% for operations between 1981 and 1990, and 84% for operations between 1991 and 2000. Tumor size also affected survival (P=.0046), which was 86% for patients with tumors of less than or equal to 2 cm in diameter and 73% for those with tumors of more than 2 cm in diameter. In the multivariate analysis both variables entered into regression, remaining predictive of survival. CONCLUSION: We found evidence for a prognostic stage migration (Will Rogers phenomenon) according to the decade in which resection was performed and that tumor size affected survival in our population. Finally, the current system of TNM staging fails in conforming groups of patients with a homogenous prognosis.
Dual-energy X-ray absorptiometry (DXA) provides an important opportunity for estimating total body skeletal muscle (SM) mass from DXA-measured appendicular lean soft tissue (ALST). A DXA SM prediction model was developed with magnetic resonance imaging as the reference and ALST (i. e., sum of arm plus leg lean soft tissue) as a main predictor variable. In the present study we examined whether ALST estimates are comparable across systems (i. e., penciland fan-beam) and manufacturers. Pencil-beam systems (Lunar DPX and DPX-L) are usually considered more accurate but slower than fan-beam systems (Lunar Prodigy and Hologic Delphi A). In this study we compared ALST estimates in 35 healthy adults across these four systems. The methods gave similar group mean (+/-SD) values and were highly intercorrelated. There was no significant bias detected across the four systems. ALST estimates from the evaluated DXA systems are comparable and thus appear interchangeable as methods for quantifying total body SM in vivo.
INTRODUCTION: Lung donors are scarce and lung transplantation resources limited, leading to a need to look at transplants in terms of efficiency. Because emergency transplants (C-0) are assumed to yield poor results, most countries do not perform them on a regular basis. Spain, however does accept the concept of emergency lung transplantation for patients who are on waiting lists. We assess outcome for our patients who have received scheduled and emergency transplants. MATERIAL AND METHOD: The survival of patients receiving lung transplants in our service from 1992 through 2001 was studied using, Kaplan-Meier, Cox regression and chi-squared statistical analyses. We compared outcome and perioperative mortality (over 30 days) for scheduled versus C-0 procedures, analyzing the influence of certain variables (age, sex, emergency status, type of transplant, mechanical ventilation and use of extracorporeal membrane oxygenation). RESULTS: Eleven of 183 lung transplants were C-0 and 172 were scheduled. Forty-one were single-lung and 142 were double-lung transplants. Perioperative mortality was 36.4% for emergency procedures and 8.7% for scheduled procedures (p = 0.0035). Survival was significantly better for scheduled patients than for C-0 patients (p = 0.0032), although outcome was similar when perioperative mortality was not taken into account (58.16% vs. 57.14% at 5 years for scheduled and C-0 patients, respectively). CONCLUSIONS: Long-term survival after lung transplantation shows that the procedure is effective and efficient in C-0 patients, in spite of perioperative risk, provided the patient has been adequately monitored.
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BACKGROUND: The aim of this work is to estimate the prognostic value of a set of clinical-pathological factors in patients resected for non-small cell lung cancer (NSCLC) and classified as stage IB, in order to create a prognostic model for establishing risk groups, and to validate that model. METHODS: Among 637 patients resected and classified as stage IB, we analyzed sex, age, symptoms, location, type of resection, cell type, histology, and tumor size. The Kaplan-Meier method was used to estimate the survival. The results were compared using the log-rank test. All the significant variables from this univariable method were then included in a multivariable method of estimation of the proportional risk for survival data developed by Cox, using the variables selected, a regression model was developed for accurately predicting survival. To validate the predictive capability of the regression model, we randomly divided our patients into training and test subsets, containing 322 and 315 cases, respectively. RESULTS: The overall 5-year survival rate of the series was 60%. The cell type, the squamous or non-squamous and the tumor size showed a significant influence on survival in the univariable analysis, while, according to the Cox model, only the tumor size and the squamous or non-squamous type entered into regression. Hazard rates were calculated for each patient. The mean risk was 0.87 +/- 0.25 (range 30-1.94). The series was divided into three risk groups (low, intermediate, and high risk) according to the fitted hazard rates, using cut-off points (one standard deviation from the mean). The 5-year survival rates were 85, 59, and 44%, respectively. To validate the model, we repeated the analysis for training and test subsets. Only the tumor size had a significant influence on survival in the univariable analysis. Using the Cox model, also the tumor size entered into regression. The mean risk was 0.79 +/- 0.29 (range 0.09-2.12). Cut-off points were 0.50 and 1.08 for the low, intermediate, and high-risk groups. The 5-year survival rates were 83, 58, and 40%, respectively. We validated the regression model obtained in the training subset by demonstrating its capacity in identifying risk groups in the test subset. The 5-year survival rates were 83, 61, and 49.5% for the low, intermediate, and high-risk groups, respectively (P = 0.0104). CONCLUSIONS: Stage IB does not succeed in configuring a group of patients with a homogeneous prognosis, as there is a wide variability in a 5-year survival. The estimation of prognosis derived from a multivariable analysis can obviate the limitations of the actual staging system for NSCLC.
OBJECTIVE: To quantify primary graft failure (PGF) and its impact on perioperative and early mortality in single-lung transplant (SLT). METHOD: We analyzed 35 SLT procedures performed using similar techniques. PGF was defined as a PaO2/FiO2 coefficient lower than 200 mmHg during the first 72 hours or ventilation assistance lasting longer than 5 days attributable to primary lung dysfunction. We defined perioperative mortality as occurring within 30 days of surgery and early mortality within 90 days. RESULTS: Twenty-five men and 10 women received lungs, 22 for pulmonary fibrosis and 13 for emphysema; the mean age was 53.26 10.77 years. Twenty right SLTs were performed and 15 left SLTs. Twenty-nine donors were men and 6 were women, with a mean age of 29.31 12.33 years. Twenty-six died from cranial trauma, 8 from stroke and 1 from a brain tumor. The mean time of intubation was 1.69 1.35 days. The mean PaO2 was 470.71 70.82 mmHg. The mean time of ischemia was 201.77 62.64 minutes. Four patients (11.42%) developed PGF and 3 died during the perioperative period. Two additional patients died within the early postoperative period. Survival was 91.4% at one month and 85.5% at three months. The cause of donor death was the only variable that influenced the development of PGF. CONCLUSION: We observed a low incidence of PGF and of perioperative and early mortality, with one and three month survival rates similar to those reported internationally.
Injury to a large-caliber artery transurethral resection of a bladder tumor is a rare but serious complication. It is important that an anesthesiologist be able to detect such an injury, in order to include it among the many differential etiological diagnoses for shock. A 75-years-old man reported hematuria. An ultrasound image of the bladder showed many neoformations consistent with a diagnosis of multiple bladder neoplasms, and transurethral endoscopy was performed under subarachnoid anesthesia. Acute hypotension, bradycardia and shock developed 30 minutes into the procedure. The diagnosis was hypovolemic shock due to acute intraoperative hemorrhage, and exploratory laparotomy revealed an opening in the common iliac artery. The rupture was sutured. In spite of administration of crystalloids, colloids, blood products and vasoactive agents, a second operation was required due to hemodynamic instability. The patient died in the intensive care unit.
There is no recognized oral treatment for American cutaneous leishmaniasis. A rising-dose, open-label phase I/II trial of the oral agent miltefosine against Colombian cutaneous leishmaniasis was conducted. Seventy-two male Colombian soldiers (mean weight, 67 kg) received miltefosine at 50-100 mg/day for 3 weeks (for 32 evaluable patients) or at 133-150 mg/day for 3-4 weeks (for 32 evaluable patients). The per-protocol cure rate for 50-100 mg/day was 21 (66%) of 32 patients. The per-protocol cure rate for 133-150 mg/day was 30 (94%) of 32 patients (P =.01, by use of Fisher's exact test). The historic per-protocol cure rate for standard injections of antimony is 93%. "Motion sickness" that did not interfere with normal duties was experienced by 40% of patients and was dose related. Vomiting and diarrhea were reported on approximately 2% of treatment days. In this uncontrolled study of oral miltefosine for treatment of patients with American cutaneous leishmaniasis, a dosage of approximately 2.25 mg/kg/day for 3-4 weeks was effective and tolerated.
An increasing number of studies have documented the central role of T cell costimulation in autoimmunity. Here we show that the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, deficient in B7-2 costimulation, is protected from diabetes but develops a spontaneous autoimmune peripheral polyneuropathy. All the female and one third of the male mice exhibited limb paralysis with histologic and electrophysiologic evidence of severe demyelination in the peripheral nerves beginning at 20 wk of age. No central nervous system lesions were apparent. The peripheral nerve tissue was infiltrated with dendritic cells, CD4(+), and CD8(+) T cells. Finally, CD4(+) T cells isolated from affected animals induced the disease in NOD.SCID mice. Thus, the B7-2-deficient NOD mouse constitutes the first model of a spontaneous autoimmune disease of the peripheral nervous system, which has many similarities to the human disease, chronic inflammatory demyelinating polyneuropathy (CIDP). This model demonstrates that NOD mice have "cryptic" autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway.
OBJECTIVE: To develop and validate a mortality risk model for patients with resected stage I non-small cell bronchogenic carcinoma (NSCBC). PATIENTS AND METHOD: Tumors from 798 patients with diagnoses of NSCBC were resected and classified in stage I. The Kaplan-Meier method and Cox's proportional hazard model were used to analyze the influence of clinical and pathologic variables on survival. RESULTS: Univariate analysis revealed that age (p = 0.0461), symptoms (p = 0.0383), histology (p = 0.0489) and tumor size (p = 0.0002) and invasion (p = 0.0010) affected survival. Size (p = 0.0000) and age (p = 0.0269) were entered into multivariate analysis. Each patient's risk was estimated by applying the regression equation derived from multivariate analysis; the mean was 1.47 +/- 0.31 (range 0.68 to 2.92). The series was divided into three groups by degree of risk (low, intermediate and high), establishing the cutoff points at 1.16 and 1.78 (standard deviation of the mean). Five-year survival rates were 85%, 62% and 46%, respectively (p = 0.0000). To validate the model's predictive capacity, the series was divided randomly into two groups: the study group with 403 patients and the validation group with 395. Age (p = 0.0295), symptoms (p = 0.0396), tumor size (p = 0.0010) and invasion (p = 0.0010) affected survival in the univariate analysis. Size (p = 0.0000) and age (p = 0.0358) were entered into Cox's model. Mean risk was 1.94 +/- 0.36 (range 0.98 to 3.32). The series was divided into three risk groups, with cut-off points established at 1.58 and 2.30. Five year survival rates were 90%, 62% and 46% for the low, intermediate and high risk groups, respectively (p = 0.0000). The same model proved able to identify risk when applied to the validation group, in which five-year survival rates were 78%, 61% and 48%, respectively (p = 0.0000). CONCLUSIONS: Risk models can identify patient subgroups, potentially influenced by co-adjuvant treatment, as well as facilitate comparison of patient series.
Etidronate and medronate have been labelled with technetium-99m (99mTc-HEDP, 99mTc-MDP) for bone scanning and, with rhenium-188 (188Re-HEDP) to palliate the pain resulting from bone metastases. The objective of this study was to label alendronate, ABP, a new bisphosphonate, with SnF2-reduced-188Re. The reagents for the 5 mg ABP kit were SnF2, KReO4 and gentisic acid at acid pH. The chemical, spectroscopic and microscopic characteristics, quality control, rat bone uptake of [188Re]Re-ABP and similarities with 99mTc-ABP are presented. We conclude that this is a promising new radiopharmaceutical for bone metastases pain palliation.
Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltrates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV- and myelin-specific CD4(+) T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8(+) T cells to the TMEV-induced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that beta2M-deficient SJL mice have similar disease incidence rates to wild-type controls, however beta2M-deficient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid (PLP) epitopes, and significantly higher levels of CNS demyelination and macrophage infiltration at 50 days post-infection. beta2M-deficient mice also displayed a significant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8(+) T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4(+) T cells in this capacity and further emphasize the potential for CD8(+) T cells to contribute to protection from TMEV-induced demyelination.
We compared estimates for the phase 2 time constant (tau) of oxygen uptake (VO2) during moderate- and heavy-intensity exercise, and the slow component of VO2 during heavy-intensity exercise using previously published exponential models. Estimates for tau and the slow component were different (P < 0.05) among models. For moderate-intensity exercise, a two-component exponential model, or a mono-exponential model fitted from 20 s to 3 min were best. For heavy-intensity exercise, a three-component model fitted throughout the entire 6 min bout of exercise, or a two-component model fitted from 20 s were best. When the time delays for the two- and three-component models were equal the best statistical fit was obtained; however, this model produced an inappropriately low DeltaVO2/DeltaWR (WR, work rate) for the projected phase 2 steady state, and the estimate of phase 2 tau was shortened compared with other models. The slow component was quantified as the difference between VO2 at end-exercise (6 min) and at 3 min (DeltaVO2 (6-3 min)); 259 ml x min(-1)), and also using the phase 3 amplitude terms (truncated to end-exercise) from exponential fits (409-833 ml x min(-1)). Onset of the slow component was identified by the phase 3 time delay parameter as being of delayed onset approximately 2 min (vs. arbitrary 3 min). Using this delay DeltaVO2 (6-2 min) was approximately 400 ml x min(-1). Use of valid consistent methods to estimate tau and the slow component in exercise are needed to advance physiological understanding.