Histologic Study of Acute Vocal Fold Wound Healing After Corticosteroid Injection in a Rabbit Model

Objectives: Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold because of their effects of wound healing, and to ensure better voice quality. We histologically evaluated the effects of dexamethasone sodium phosphate infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically induced injury by quantification of the inflammatory reaction and collagen deposition. Methods: A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 mL dexamethasone sodium phosphate (4 mg/mL) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histologic analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for qunatification of collagen depostion. Results: There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and control vocal folds. However, the rate of collage deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after injury (p = 0.002). Conclusions: The present results suggest that dexamethasone reduces collagen depostion during acute vocal fold wound healing.

Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

Introduction: Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods: ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)approximate to 70 mmHg; 2) normovolemia (MAP approximate to 100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP approximate to 130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H(2)O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est, L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1 beta, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results: We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est, L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic responses. Conclusions: Volemic status should be taken into account during RMs, since in this sepsis-induced ALI model hypervolemia promoted and potentiated lung injury compared to hypo-and normovolemia.

A Graphical Representation Model for Telemedicine and Telehealth Center Sustainability

This study shows the creation of a graphical representation after the application of a questionnaire to evaluate the indicative factors of a sustainable telemedicine and telehealth center in Sao Paulo, Brazil. We categorized the factors into seven domain areas: institutional, functional, economic-financial, renewal, academic-scientific, partnerships, and social welfare, which were plotted into a graphical representation. The developed graph was shown to be useful when used in the same institution over a long period and complemented with secondary information from publications, archives, and administrative documents to support the numerical indicators. Its use may contribute toward monitoring the factors that define telemedicine and telehealth center sustainability. When systematically applied, it may also be useful for identifying the specific characteristics of the telemedicine and telehealth center, to support its organizational development.

Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.

Development of Lifetime Comorbidity in the World Health Organization World Mental Health Surveys

Context: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. Objective: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. Design: Nationally or regionally representative community surveys. Setting: Fourteen countries. Participants: A total of 21 229 survey respondents. Main Outcome Measures: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. Results: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. Conclusions: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study.

Total Pancreatectomy: Porcine Model for Inducing Diabetes - Anatomical Assessment and Surgical Aspects

Background: The swine is an essential model for carrying out preclinical research and for teaching complex surgical procedures. There is a lack of experimental models describing anatomical and surgical aspects of total pancreatectomy in the pig. Materials and Methods: The experiments were performed on 10 white male swine weighing 27-33 kg. The animals were premedicated with midazolam (0.4 mg/kg, i.m.) and ketamine (4 mg/kg, i.m.). Anesthesia was induced with propofol (1-2 mg/kg, i.v.) and was maintained with propofol and fentanyl (0.3 mg and 0.1 mu g/kg/min, respectively, i.v.). The surgical period ranged from 44 to 77 min. The pancreas anatomy, and the main arterial, venous and pancreatic duct anatomy were assessed. Results: The pancreas anatomy was composed of 3 lobes, the `splenic`, `duodenal` and `connecting` lobe which is attached to the anterior portion of the portal vein. The splenic artery and the junction of the splenic vein and portal vein were divided. The left gastric artery was dissected and separated from its origin at the splenic artery. The head of the pancreas is disposed in a C shape. The pancreas was dissected and liberated from the right portion of the portal vein and the infrahepatic vena cava. The pancreas was separated from the duodenum preserving the pancreaticoduodenal artery, then we performed the total pancreatectomy preserving the duodenum, common bile duct and spleen. Conclusion: Total pancreatectomy with duodenum, bile duct and spleen preservation in the pig is feasible and an important instrument for research purposes and teaching surgical technique. Copyright (C) 2010 S. Karger AG, Basel

A Palliative Prognostic Score for Terminally Ill Children and Adolescents With Cancer

Background. The loss of a child is considered the hardest moment in a parent`s life. Studies addressing length of survival under pediatric palliative care are rare. The aim of this study was to improve a survival prediction model for children in palliative care, as accurate information positively impacts parent and child preparation for palliative care. Procedure. Sixty-five children referred to a pediatric palliative care team were followed from August 2003 until December 2006. Variables investigated (also included in previous studies) were: diagnosis, home care provider, presence of anemia, and performance status score given by the home care provider. Clinical variables such as symptom number were also used to test the score`s ability to pre-validated using the above variables. The number of symptoms at transition to palliative care does not improve the score`s predictive ability. The sum of the single scores gives an overall score for each patient, dividing the population into three groups by probability of 60-day survival: Group A 80.0%, Group B 38.0%, and Group C 28.5% (P < 0.001). Conclusion. A pediatric palliative care score based on easily accessible variables is statistically significant in multivariate analysis. Factors that increase accuracy of life expectancy prediction enable adequate information to be given to patients and families, contributing to therapeutic decision-making issues. Pediatr Blood Cancer. 2010;55:1167-1171. (C) 2010 Wiley-Liss, Inc.

Differential expression of presynaptic genes in a rat model of postnatal hypoxia: relevance to schizophrenia

Obstetric complications play a role in the pathophysiology of schizophrenia. However, the biological consequences during neurodevelopment until adulthood are unknown. Microarrays have been used for expression profiling in four brain regions of a rat model of neonatal hypoxia as a common factor of obstetric complications. Animals were repeatedly exposed to chronic hypoxia from postnatal (PD) day 4 through day 8 and killed at the age of 150 days. Additional groups of rats were treated with clozapine from PD 120-150. Self-spotted chips containing 340 cDNAs related to the glutamate system (""glutamate chips"") were used. The data show differential (up and down) regulations of numerous genes in frontal (FR), temporal (TE) and parietal cortex (PAR), and in caudate putamen (CPU), but evidently many more genes are upregulated in frontal and temporal cortex, whereas in parietal cortex the majority of genes are downregulated. Because of their primary presynaptic occurrence, five differentially expressed genes (CPX1, NPY, NRXN1, SNAP-25, and STX1A) have been selected for comparisons with clozapine-treated animals by qRT-PCR. Complexin 1 is upregulated in FR and TE cortex but unchanged in PAR by hypoxic treatment. Clozapine downregulates it in FR but upregulates it in PAR cortex. Similarly, syntaxin 1A was upregulated in FR, but downregulated in TE and unchanged in PAR cortex, whereas clozapine downregulated it in FR but upregulated it in PAR cortex. Hence, hypoxia alters gene expression regionally specific, which is in agreement with reports on differentially expressed presynaptic genes in schizophrenia. Chronic clozapine treatment may contribute to normalize synaptic connectivity.

(18)F-FDG PET After 2 Cycles of ABVD Predicts Event-Free Survival in Early and Advanced Hodgkin Lymphoma

Our objective was to assess the prognostic value of (18)F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). Methods: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. Results: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. Conclusion: PET2 is an accurate and independent predictor of EFS in HL. A negative interim (18)F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

Survival in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Objectives The objective of this study was to evaluate the natural history of untreated schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) patients as compared to idiopathic pulmonary arterial hypertension (IPAH) with respect to hemodynamics recorded at presentation and 36 months survival. Background Schistossomiasis (Sch) is one of the most prevalent chronic infectious diseases in the world. Nevertheless data regarding one of its most severe clinical complications, pulmonary arterial hypertension (PAH), is scarce. Methods We retrospectively analyzed case notes of all consecutive patients diagnosed of Sch-PAH and IPAH referred to the Heart Institute in Sao Paulo, Brazil, between 2004 and 2008. None of the Sch-PAH received PAH specific treatment whereas all IPAH patients did. Results Sch-PH patients (n = 54) had less severe pulmonary hypertension as evidenced by lower levels of pulmonary vascular resistance (11.3 +/- 11.3 W vs. 16.7 +/- 10.6 W; p = 0.002) and mean pulmonary artery pressure (56.7 +/- 18.7 mm Hg vs. 64.6 +/- 17.4 mm Hg; p = 0.01) and higher cardiac output (4.62 +/- 1.5 l/min vs. 3.87 +/- 1.5 l/min; p = 0.009) at presentation than IPAH patients (n = 95). None of the Sch-PAH patients demonstrated a positive response to acute vasodilator testing, whereas 16.2% of IPAH patients did (p = 0.015). Survival rates at 1, 2, and 3 years were 95.1%, 95.1%, and 85.9% and 95%, 86%, and 82%, for Sch-PAH and IPAH, respectively (p = 0.49). Both groups had a higher survival rate when compared to IPAH survival as estimated by the NIH equation (71%, 61%, and 52%, respectively). Conclusions Sch-PAH has a more benign clinical course than IPAH despite a lack of demonstrable acute vasoreactivity at hemodynamic evaluation. (J Am Coll Cardiol 2010; 56: 715-20) (C) 2010 by the American College of Cardiology Foundation

Trisomy 16q21 -> qter: Seven-Year Follow-Up of a Girl With Unusually Long Survival

The 16q21 -> qter duplication is a chromosomal abnormality rarely found in liveborn infants, with only four published cases. We report here on the 7-year follow-up of a female patient with trisomy 16q21 -> qter due to a maternal balanced translocation t(4;16)(q35.2;q21). The patient shows severe mental retardation, congenital heart malformations, nephropathy, and other congenital anomalies. The derivative chromosome was characterized by GTG banding, fluorescent in situ hybridization (FISH) with different BAG probes and the array technique, in order to map the breakpoints. The patient has a 16q21 -> qter duplication, with a 4q35 -> qter monosomy, which we assume does not contribute to the abnormal phenotype. This is the first reported case of postnatal survival to the age of 7 years, an unusually long time in this chromosomal syndrome. (C) 2010 Wiley-Liss, Inc.

alpha-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Model

Purpose: alpha-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of a-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates. Materials and Methods: We performed a prospective, blinded, randomized, placebo controlled study in 26 pigs. Laparoscopic technique was used for left nephrectomy and to induce complete warm ischemia in the right kidney for 120 minutes. AP214 (200 mu g/kg intravenously) was administered daily on the day of surgery and for 5 days thereafter. Kidney function was measured for 9 days. We measured changes in serum creatinine, estimated glomerular filtration rate, serum C-reactive protein and urine interleukin-18. Results: In the placebo control and AP214 groups mean peak serum creatinine was 10.2 vs 3.92 mg/dl and the estimated glomerular filtration rate nadir was 22.9 vs 62.6 ml per minute per kg (each p = 0.001). Functional nadir occurred at 72 vs 24 hours in the control vs AP214 groups. Estimated glomerular filtration rate outcome on postoperative day 9 was 118 vs 156 ml per minute per kg in the control vs AP214 groups (p = 0.04). Conclusions: We noted a robust renoprotective effect of AP214. A similar AP214 effect may be observed in humans. Future research includes mechanistic studies in pigs and a phase II human clinical trial of AP214 in kidney transplant and partial nephrectomy populations.

Assessment of disease-free survival in patients with laryngeal squamous cell carcinoma treated with radiotherapy associated or not with chemotherapy

In early stage (I and II) laryngeal squamous cell carcinoma, both surgery and radiotherapy results in significant local and regional control. In advanced tumors (III and IV), radiotherapy alone has local-regional control rates of 32-43%. Aim: To assess disease-free survival in SCC laryngeal carcinoma patients submitted to radiotherapy alone and/or associated with chemotherapy. Materials and Methods: Retrospective study involving 84 cases of laryngeal SCC treated with radiotherapy or chemotherapy together with radiotherapy. Fifty-three cases were treated with intension to cure and 31 because of impossibility to resect the disease. As to clinical stage (CS), 12 were CS I, 15 II, 21 III and 5 IV. In the second group, 11 cases were EC III and 20 IV. Results: Mean age was 60 years, 84.5% were men. Fifty-eight (69.1%) cases had complete response and 26 (30.9%) had persistent or residual disease. Five-year disease-free survival was of 42.5%; 62.5% of the patients with organ preservation indication and 9.75 in the group of irressecable disease. Conclusion: disease-free survival of those patients submitted to radiotherapy because of laryngeal SCC was of 62.5%

Short- and long-term survival of patients with metastatic solid cancer admitted to the intensive care unit: prognostic factors

Decisions for intensive care unit (ICU) admissions in patients with advanced cancer are complex, and the knowledge of survival rates and prognostic factors are essential to these decisions. Ours objectives were to describe the short- and long-term survival of patients with metastatic solid cancer admitted to an ICU due to emergencies and to study the prognostic factors presented at ICU admission that could be associated with hospital mortality. We retrospectively analysed the charts of all patients with metastatic solid cancer admitted over a 1-year period. This gave a study sample of 83 patients. The ICU, hospital, 1-year and 2-year survival rates were 55.4%, 28.9%, 12.0% and 2.4% respectively. Thrombocytopenia (odds ratio 26.2; P = 0.006) and simplified acute physiology score (SAPS II) (odds ratio 1.09; P = 0.026) were independent factors associated with higher hospital mortality. In conclusion, the survival rates of patients with metastatic solid cancer admitted to the ICU due to emergencies were low, but of the same magnitude as other groups of cancer patients admitted to the ICU. The SAPS II score and thrombocytopenia on admission were associated with higher hospital mortality. The characteristics of the metastatic disease, such as number of organs with metastasis and central nervous system metastasis were not associated with the hospital mortality.

CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD

Obstructive sleep apnoea syndrome (OSAS) often coexists in patients with chronic obstructive pulmonary disease (COPD). The present prospective cohort study tested the effect of OSAS treatment with continuous positive airway pressure (CPAP) on the survival of hypoxaemic COPD patients. It was hypothesised that CPAP treatment would be associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving long-term oxygen therapy (LTOT). Prospective study participants attended two outpatient advanced lung disease LTOT clinics in Sao Paulo, Brazil, between January 1996 and July 2006. Of 603 hypoxaemic COPD patients receiving LTOT, 95 were diagnosed with moderate-to-severe OSAS. Of this OSAS group, 61 (64%) patients accepted and were adherent to CPAP treatment, and 34 did not accept or were not adherent and were considered not treated. The 5-yr survival estimate was 71% (95% confidence interval 53-83%) and 26% (12-43%) in the CPAP-treated and nontreated groups, respectively (p<0.01). After adjusting for several confounders, patients treated with CPAP showed a significantly lower risk of death (hazard ratio of death versus nontreated 0.19 (0.08-0.48)). The present study found that CPAP treatment was associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving LTOT.