Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine.

BACKGROUND: Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. METHODS: In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. RESULTS: During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). CONCLUSIONS: PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

Quality of life and mental health in Brazilian women treated for invasive carcinoma of the cervix.

OBJECTIVE: The objective of this study was to compare the quality of life (QOL) and mental health (MH) of women surviving at least 2 years after treatment for invasive carcinoma of the cervix by radical hysterectomy (RH), chemotherapy and/or radiotherapy, or by surgery followed by adjuvant therapy (RH + chemotherapy and/or radiotherapy). The QOL/MH of a control group of women with no history of malignancy was also assessed for comparison with the treated groups. METHODS: The levels of QOL and MH were assessed in 114 Brazilian women (57 patients with an average of 4 years since treatment completion and 57 control subjects). The 36-item Medical Outcomes Study Short-Form Health Survey, the State-Trait Anxiety Inventory, the 12-item General Health Questionnaire, the Life Events Inventory, and a general survey for the assessment of sociodemographic data were applied to each participant of the study. RESULTS: No differences were noted among the 3 treatment groups or between these and the control group concerning the levels of QOL (either physical or MH aspects), anxiety, general health, or life events. However, lower levels of anxiety were detected in cancer survivors when compared with the control group (P = 0.035). CONCLUSIONS: After at least 2 years, the QOL and the MH of Brazilian women treated for invasive carcinoma of the cervix were similar to those of women without malignancy and were not affected by the modality of treatment.

Endotoxin tolerance and cross-tolerance in mast cells involves TLR4, TLR2 and FcepsilonR1 interactions and SOCS expression: perspectives on immunomodulation in infectious and allergic diseases.

BACKGROUND: The study of the endotoxin tolerance phenomenon in light of the recently defined roles of mast cells and toll-like receptors as essential components of the innate immune response and as orchestrators of acquired immunity may reveal potentially useful mechanisms of immunomodulation of infectious and allergic inflammatory responses, such as sepsis or asthma. Here we evaluated the phenomenon of direct tolerance of endotoxins, as well as the induction of cross-tolerance and synergism by stimulation with toll-like receptor-2 (TLR2) and FcepsilonR1 agonists, in murine mast cells prestimulated with lipopolysaccharide (LPS). Additionally, we evaluated some stimulatory and inhibitory signaling molecules potentially involved in these phenomena. METHODS: MC/9 cells and primary bone marrow-derived mast cells obtained from C57BL/6 and TLR4-/- knock-out mice were sensitized to DNP-HSA (antigen) by incubation with DNP-IgE and were prestimulated with LPS for 18 hr prior to stimulation. Cultures were stimulated with LPS or Pam3Cys-Ser-(Lys)4 3HCl (P3C), a TLR2 agonist, individually or in combination with antigen. The production of IL-6 and TNFalpha, the phosphorylation of NFkappaB and p38 MAPK, and the expression of TLR4 and SOCS-1 and -3 were analyzed. RESULTS: We found that production of TNFalpha and IL-6 in murine mast cells that have been pretreated with LPS and challenged with TLR4 (LPS) or -2 (P3C) agonists was reduced, phenomena described as endotoxin tolerance (LPS) and cross-tolerance (P3C), respectively. The expression of TLR4 was not affected by LPS pretreatment. Our results show that the FcepsilonR1 agonist DNP-HSA (antigen) interacts synergistically with LPS or P3C to markedly enhance production of cytokines (TNFalpha and IL-6). This synergistic effect with LPS and P3C was also attenuated by LPS pretreatment and was mediated by TLR4. These results may be attributed to the reduction in phosphorylation of the mitogen-activated protein kinase (MAPK), p38, and the transcription factor NFkappaB, as well as to an increase in the expression of the suppressors of cytokine signaling (SOCS)-1 and -3 proteins in LPS-pretreated mast cells. CONCLUSIONS: These findings can be explored with respect to the modulation of inflammatory responses associated with infectious and allergic processes in future studies.

Expression of p53, Ki-67, and CD31 in the vaginal margins of radical hysterectomy in patients with stage IB carcinoma of the cervix.

OBJECTIVES: This study was undertaken to evaluate the expression of p53, Ki-67, and CD31 both in the tumor and in the vaginal margins of radical hysterectomy in patients with stage IB squamous cell carcinoma of the cervix, as an attempt to use these proteins as possible markers for residual tumor in cervical cancer. METHODS: Thirty patients with stage IB squamous cell carcinoma of the cervix were submitted to radical hysterectomy (study group), and thirty patients with uterine myoma were submitted to vaginal hysterectomy (control group) and were prospectively studied from November 2001 to September 2002. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM) and were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. Vaginal samples in which the histological examination showed tumor involvement were excluded from the study. RESULTS: Patient's mean age was 48.7 +/- 10.4 years (27-73 years). The clinical stage was IB1 in 22 patients (73.3%) and IB2 in eight patients (26.7%). The expressions of p53, Ki-67, and CD31 were significantly higher in the tumor than in the benign cervix (P < 0.001). Higher expressions of these markers were noted in the vaginal margins of radical hysterectomy in patients with cervical carcinoma compared to the vaginal margins of control patients. This association was demonstrated for p53 in the AVM proximal (P = 0.045), for Ki-67 in AVM proximal (P < 0.001), AVM distal (P < 0.001), PVM proximal (P = 0.009), and PVM distal (P < 0.001), and for CD31 in AVM proximal (P = 0.003) and AVM distal (P = 0.018). There was no difference in p53, Ki-67, and CD31 expression between the proximal and distal regions of the vaginal margins in patients with carcinoma of the cervix. CONCLUSION: The expressions of p53, Ki-67, and CD31 were significantly higher in both the histologically positive (cervical tumor) and negative (vaginal margins) tissues of patients who had undergone radical hysterectomy for cervical cancer compared to the benign control tissues.

Lung compliance, plasma electrolyte levels and acid-base balance are affected by scorpion envenomation in anesthetized rats under mechanical ventilation.

To determine the effects of Tityus serrulatus scorpion toxin on lung compliance and resistance, ionic equilibrium and acid-base balance over time in anesthetized and mechanically ventilated rats, we measured air flow, tracheal and esophageal pressure. Lung volume was obtained by electronic integration of airflow signal. Arterial blood samples were collected through a catheter at baseline (before) and 5, 15, 30 and 60 min after scorpion toxin injection for arterial blood gases, bicarbonate, and alkali reserve levels as well as for, sodium, potassium, magnesium, glucose, lactate, hematocrit, and osmolality analysis. Injection of the gamma fraction of the T. serrulatus scorpion venom in rats under mechanical ventilatory support leads to a continuous decrease in lung compliance secondary to pulmonary edema, but no change in airway resistance. The changes in arterial blood gases characterizing metabolic acidosis were accompanied by an increase in arterial lactate and glucose values, suggesting a scorpion toxin-induced lactic acidosis, in association with poor tissue perfusion (hypotension and low cardiac output). Moreover, scorpion toxin injection resulted in hyperosmolality, hyperkalemia, hypermagnesemia and an increase in hematocrit. The experiments have shown a clinically relevant animal model to study severe scorpion envenoming and may help to better understand the scorpion envenoming syndrome.

Evidence for a role of capsaicin-sensitive sensory nerves in the lung oedema induced by Tityus serrulatus venom in rats.

In the most severe cases of human envenoming by Tityus serrulatus, pulmonary oedema is a frequent finding and can be the cause of death. We have previously demonstrated a role for neuropeptides acting on tachykinin NK(1) receptors in the development of lung oedema following i.v. injection of T. serrulatus venom (TsV) in experimental animals. The present work was designed to investigate whether capsaicin-sensitive primary afferent neurons were a potential source of NK(1)-acting neuropeptides. To this end, sensory nerves were depleted of neuropeptides by neonatal treatment of rats with capsaicin. The effectiveness of this strategy at depleting sensory nerves was demonstrated by the inhibition of the neuropeptide-dependent response to intraplantar injection of formalin. Pulmonary oedema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was markedly inhibited in capsaicin-treated animals. In contrast, capsaicin treatment failed to alter the increase in arterial blood pressure or the lethality following i.v. injection of TsV. Our results demonstrate an important role for capsaicin-sensitive sensory nerves in the cascade of events leading to lung injury following the i.v. administration of TsV.

Tityus serrulatus scorpion venom and its toxins as tools for physiological studies

O veneno do escorpião Tityus serralatus é uma importante ferramenta para estudos fisiológicos e fisiopatológicos. O seu mecanismo básico de ação é uma estimulação das terminações nervosas do SNA, por meio da abertura de canais iônicos de membrana com liberação de catecolaminas, acetilcolina, ATP e outros mediadores responsáveis pelos efeitos observados. Esses efeitos incluem arritmias cardíacas e respiratórias, hipertensão arterial, choque, edema pulmonar, hipersecreção salivar, gástrica e pancreática, contração da musculatura lisa, liberação de citocinas e quimiocinas, lesão aguda de mucosa gástrica, pancreatite aguda e crônica e eventualmente morte. O veneno pode reproduzir essas alterações, mimetizando uma estimulação fisiológica do SNA, induzindo uma resposta imune ou ainda, possibilitando estudos da fisiopatologia do choque e seu tratamento, em modelos experimentais. Os mecanismos fisiológicos relacionados à estimulação de canais iônicos, contração da musculatura lisa por estimulação nervosa, reflexos cardiovasculares e respiratórios, secreção exócrina gastrintestinal e a cinética dos mediadores e suas interações com seus receptores específicos, podem ser estudados em interações com seus receptores específicos, podem ser estudados em humanos e animais. O estudo da fisiopatologia da intoxicação escorpiônica pode também, ser útil para a elucidação dos macanismos de edema pulmonar, arritmias cadíacas, choque circulatório, síndrome da resposta inflamatória sistêmica e falência de múltiplos órgãos, pancreatite, lesão aguda da mucosa gástrica e resposta imunológica celular e humoral. Muitos desses aspectos são discutidos nesse artigo baseado em experimentos feitos por um grupo de pesquisadores da Universidade Federal de Minas Gerais

Traumatismos raquimedulares cervicais entre C3 e C7. Análise de 48 casos / C3 and C7 cervical spine injury. A study of 48 cases

Os autores descrevem a experiência adquirida no tratamento de 48 casos de traumatismos raquimedulares do segmento da coluna cervical de C3 a C7, admitidos no período compreendido entre novembro de 1989 e março de 1996, sendo 39 destes (81 por cento) do sexo masculino e 9 (19 por cento) do sexo feminino. Näo foram incluídas as lesöes penetrantes. Os casos estudados foram classificados em 4 subgrupos: 1) com fratura isolada; 2) com fratura-luxaçäo; 3) com luxaçäo isolada e; 4) sem alteraçöes radiológicas (conhecidos na literatura com "SCIWORA" ou "Spinal Cord Injury Without Radiologic Abnormality"). É feita a correlaçäo do tipo de traumatismo com a distribuiçäo por idade, sexo, exame neurológico, evoluçäo e tratamento. Säo analisados os resultados assim como os aspectos relativos às diferentes modalidades de tratamento.

Alteraçöes quantitativas das células neuroendócrinas no megacólon chagásico / Quantitative changes in the neuroendocrine cells of chagasic megacolon

Utilizando-se técnicas histoquímicas pela prata (Masson-Fontana e Sevier-Munger) estudaram-se a distribuiçäo e o número de células enterocromafins (EC) e do conjunto EC mais células argirófilas (ARG) em peças cirúrgicas de megassigmóide chagásico. Observou-se que tanto nos "megas" (n = 16) como nos controles (n = 8), a posiçäo das células EC e ARG na mucosa foi predominantemente basal, com distribuiçäo irregular, principalmente das EC. A análise histológica revelou aparente aumento numérico das EC e do conjunto EC mais ARG. Todavia, contagens sistematizadas mostraram que somente o conjunto dessas células apresentou aumento estatisticamente significativo (P<0,01). Realizou-se tambéjm o estudo morfométrico da mucosa e das musculares que revelou espessamento significativo (P<0,01) dessas camadas em relaçäo aos casos controles