Effects of Peak Inspiratory Flow on Development of Ventilator-induced Lung Injury in Rabbits

Background: A lung-protecting strategy is essential when ventilating acute lung injury/acute respiratory distress syndrome patients. Current emphasis is on limiting inspiratory pressure and volume. This study was designed to investigate the effect of peak inspiratory flow on lung injury.

Methods: Twenty-four rabbits were anesthetized, tracheostomized, ventilated with a Siemens Servo 300, and randomly assigned to three groups as follows: 1) the pressure regulated volume control group received pressure-regulated volume control mode with inspiratory time set at 20% of total cycle time, 2) the volume control with 20% inspiratory time group received volume-control mode with inspiratory time of 20% of total cycle time, and 3) the volume control with 50% inspiratory time group received volume-control mode with inspiratory time of 50% of total cycle time. Tidal volume was 30 ml/kg, respiratory rate was 20 breaths/min, and positive end-expiratory pressure was 0 cm H2O. After 6 h mechanical ventilation, the lungs were removed for histologic examination.

Results: When mechanical ventilation started, peak inspiratory flow was 28.8 +/- 1.4 l/min in the pressure regulated volume control group, 7.5 +/- 0.5 l/min in the volume control with 20% inspiratory time group, and 2.6 +/- 0.3 l/min in the volume control with 50% inspiratory time group. Plateau pressure did not differ significantly among the groups. Gradually during 6 h, Pao2 in the pressure regulated volume control group decreased from 688 +/- 39 to a significantly lower 304 +/- 199 mm Hg (P < 0.05) (mean +/- SD). The static compliance of the respiratory system for the pressure regulated volume control group also ended significantly lower after 6 h (P < 0.05). Wet to dry ratio for the pressure regulated volume control group was larger than for other groups (P < 0.05). Macroscopically and histologically, the lungs of the pressure regulated volume control group showed more injury than the other groups.     

Analysis of lymph node metastatic pattern in relation to prognosis and recurrence in pN2 resected lung cancer patients]

Lymph node metastasis was analyzed quantitatively with 4 categories and relation to post surgical survival and recurrence pattern was studied in patients with pN2 primary lung cancer who underwent relatively curative or relatively noncurative resection of the tumors. There was no relation between metastatic coefficient and post surgical survival, however, better survival was observed when the metastatic ratio and metastatic frequency were low and metastatic mode was random or skip pattern rather than sequential pattern. Metastatic coefficient and metastatic frequency were higher in cases with recurrence in lymph nodes but the former was lower and the latter was higher in cases with recurrence in intra-pulmonary dissemination or metastasis. There was no relation between metastatic coefficient and distant metastasis but metastatic frequency was lower in cases with recurrence in distant metastasis. Cases with sequential lymph node metastasis showed a tendency of lymph node recurrence and intrapulmonary metastasis and those with random or skip metastasis of lymph nodes had a tendency of distant metastasis.     

An experimental study on direct revascularization of bronchial circulation by microvascular anastomosis.

The effects of direct revascularization of the bronchial artery after bronchoplasty were estimated by laser Doppler velocimetry and india ink injection in dogs. Bronchoplastic surgery at the right main bronchus was performed in all dogs, and the bronchial artery was reconstructed using the internal thoracic artery in the reconstruction group. The mucosal blood flow was measured at the distal side of the anastomosis. India ink was injected into the aorta in the nonreconstruction group and into the internal thoracic artery in the reconstruction group. The peripheral blood flow had diminished immediately after surgeries to 59% of the baseline value and took 14 days to recover to the baseline value in the nonreconstruction group. However, in the reconstruction group, the blood flow recovered at once to 78% of the baseline value and had returned to that value in 5 days. Statistically significant differences were noted between the groups from just after operation to day 7. India ink data confirmed these findings. In the nonreconstruction group, no ink was observed in the peripheral bronchial vessels on day 3; it was noted in part of the vessels on day 7 and in most on day 14. On the other hand, a relatively large number of vessels were stained just after operation in the reconstruction group. Thus reconstruction of the bronchial artery by means of the anastomosis with the internal thoracic artery can be said to be a useful and effective method for preventing airway ischemia.     

Effects of estrus cycle on thermoregulatory responses during exercise in rats

Summary In female rats, rectal temperature (T _re), tail vasomotor response, oxygen uptake , and carbon dioxide production were measured in proestrus and estrus stages during treadmill running at two different speeds at an ambient temperature (T _a) of 24° C. Experiments were performed at 2.00–6.00 a.m., when the difference inT _re was greatest between the two stages;T _re at rest in the estrus stage was 0.54° C higher than in the proestrus stage. In a mild warm environment, thresholdT _re for a rise in tail skin temperature (T _tail) was also higher in the estrus stage than in the proestrus stage. In contrast, no difference was seen in the thresholdT _re and steady stateT _re at the end of exercise between proestrus and estrus stages. These values were higher at the higher work intensity. was also similar between the two stages, except in the second 5 min after the beginning of exercise, when was greater andT _re rose more steeply in the proestrus stage. These data indicate that deep body temperature during exercise is regulated at a certain level depending on the work intensity and is not influenced by the estrus cycle.This study was supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (Grant No. 62480114)     

Lipopolysaccharide Induces CD25-Positive, IL-10-Producing Lymphocytes Without Secretion of Proinflammatory Cytokines in the Human Colon: Low MD-2 mRNA Expression in Colonic Macrophages

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.     

Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.     

Effect of malnutritional rehabilitation on tuberculin reactivity and complement level in rats

The purpose of this study was to clarify the effect of differing nutritional states on various components of the immune system, especially on the interplay of the complement system and cell-mediated immunity. Malnutrition was induced in Sprague—Dawley rats by feeding them diets containing 5% protein or 0.5% protein as compared with 18% protein in the diet of the controls. Nutritional rehabilitation was achieved in some experimental groups by transferring those fed 0.5% protein diet to the 18% protein diet. Malnutrition was confirmed by weight changes, biochemical findings in the sera, haematological observations and histological observation of the liver, and rehabilitation was confirmed by body weight increase and changes in other measurements. In rats suffering malnutrition, the tuberculin skin reactivity was suppressed. After feeding the 0.5% protein diet for 8 weeks, all the rats showed negative tuberculin skin reactions. In the malnourished rats, including those fed with 0.5% protein, the serum complement level decreased but did not show any significant differences as compared with the well nourished control group. After 1 week of nutritional rehabilitation, the tuberculin reactivity of six out of ten rats remained negative and after 2 weeks, all rats showed positive tuberculin reactions. After 1 week of nutritional rehabilitation, all the rats showed a normal or higher serum complement level. At this stage, two of the tuberculin-negative rats showed significantly higher titre of serum complement than even the controls.     

Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo

Summary: Components of the type 2 immune response may mediate host protection against both helminthic parasites and harmful allergic responses. A central player in this response is the T‐helper 2 (Th2) effector cell, which produces interleukin (IL)‐4, IL‐5, IL‐13, and other Th2 cytokines during the primary and memory response. Specific aspects of the parasite that trigger Th2‐cell differentiation are not yet defined. Furthermore, the cell types and cell surface and secreted molecules that provide the immune milieu required for the development of Th2 effector cells and also Th2 memory cells are not well understood. They will probably vary with the particular helminth or other antigen inducing the Th2 response. We have used third stage larvae of intestinal nematode parasites as adjuvants to promote naïve nonparasite antigen‐specific T cells to differentiate into Th2 cells. This model system avoids possible parasite antigen‐specific T‐cell clones or cross‐reactive memory T cells that may preferentially differentiate into Th2 effector cells during the course of infection and confound the stereotypical components of parasite‐induced Th2 cell differentiation. We have found that these parasites have a potent adjuvant effect and have used our model system to begin to investigate the events that lead to the development of polarized Th2 cells in vivo.