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.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.     

A case of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy) with Notch 3 (Arg169Cys) mutation and typical granular osmiophilic materials in peripheral small arteries]

We report a 64-year-old Japanese woman with recurrent ischemic strokes and progressive dementia without any cardiovascular risk factors. Her first stroke was at 45 years old, and she has a family history of ischemic strokes compatible with an autosomal dominant trait. Marked leukoaraiosis and multiple lacunar infarcts were shown on brain MR images, and no atherosclerotic changes were observed in her extra- and intra-cranial arteries by cervical arterial echography and intracranial MR angiography. Excluded other inherited or metabolic diseases causing leukodystrophy by examination of her blood samples, her disease was diagnosed as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy). We demonstrated granular osmiophilic materials (GOM) on the wall of small arteries from a biopsied peripheral nerve tissue specimen and detected a mutation Arg169Cys of Notch 3 gene. Many CADASIL patients have been reported and over 28 kinds of mutations of the Notch 3 were identified in western countries, while few CADASIL patients have been reported in Japanese people. Among them, eleven CADASIL families have been reported and only five mutations (Arg133Cys, Cys174Phe, Arg213Lys, Arg90Cys and Arg141Cys) have been determined so far. The mutation of Notch 3 in our patient was determined as Arg169Cys, and this is the first report on a Japanese patient with CADASIL due to this mutation.     

A Quantitative Study of Specific Immunoglobulins to Mosquito Salivary Gland Antigen in Hypersensitive and Common Types of Mosquito Bite Reaction

This study was designed with two purposes: first, to elucidate immunologic mechanisms in different cutaneous reactions, particularly in hypersensitivity to mosquito bites, and, second, to develop a more reliable and safer method of identifying the causative species of mosquito in severe cases. The amounts of IgG, IgG₄ and IgE specific to the mosquito salivary gland extract of Aedes albopictus were determined in the sera of 116 volunteers with normal reactions, either immediate or delayed, and 4 patients with severe systemic symptoms caused by mosquito bites. Titers of IgG and IgE in the severe cases were considerably higher than in volunteers with normal reactions, but there were no differences in IgG, titers between the two groups. These results indicate that high titers of IgG and IgE may be involved in development of systemic symptoms in severe cases and verify the possibility of in vitro tests to identify causative species of the mosquito.     

Surgical treatment of infected intralobar pulmonary sequestration: a collective review of patients older than 50 years reported in the literature.

We report on the rare and surgical treatment of a senile patient of infected intralobar pulmonary sequestration. A 56-year-old male who had complained of headache, vomiting, cough, sputum production, and high fever was admitted to our hospital. Chest computed tomography (CT) showed an infected intralobar pulmonary sequestration as an 8x6 cm cystic mass with multiple air-fluid cavities in the left lower basal segment and severe pneumonia in the left upper and lower lobes around the mass. A 3-D CT showed an aberrant artery entering the consolidation from the descending aorta. A standard lower lobectomy was performed with a ligation of the aberrant artery with a diameter of 1 cm supplying the posterior segment of the left lower lobe. A histological examination of the lung revealed acute and chronic broncho-bronchiolitis with cystic dilatation consistent with intralobar pulmonary sequestration. We discuss the characters of senile patients compared with juvenile patients, with reference to a collective review of patients older than 50 reported in the literature.     

Dynamic Interaction of Craniofacial Structures during Head Positioning and Direct Laryngoscopy in Anesthetized Patients with and without Difficult Laryngoscopy

Background: We lack fundamental knowledge of the mechanisms of difficult laryngoscopy despite its clinical significance. The aim of this study was to examine how head positioning and direct laryngoscopy alter arrangements of craniofacial structures.

Methods: Digital photographs of the lateral view of the head and neck were taken at each step of head positioning and direct laryngoscopy in age- and body mass index-matched patients with (n = 13) and without (n = 13) difficult laryngoscopy during general anesthesia with muscle paralysis. The images were used for measurements of various craniofacial dimensions.

Results: Both simple neck extension and the sniffing position produced a caudal shift of the mandible and a downward shift of the larynx, resulting in an increase of the submandibular space. Direct laryngoscopy during the sniffing position displaced the mandible and tongue base upward and caudally, and the larynx downward and caudally, increasing the submandibular space and facilitating vertical arrangement of the mandible, tongue base, and larynx to the facial line. These structural arrangements in response to direct laryngoscopy were not observed in patients with difficult laryngoscopy, whereas head positioning produced similar structural arrangements in patients with and without difficult laryngoscopy.     

Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.

OBJECTIVE: NKH477 was recently identified as a water-soluble forskolin derivative and was reported to prolong survival of murine cardiac allografts. However, the mechanism of the efficacy is not clear in vivo. The aim of this study was to investigate the immunosuppressive effects of NKH477 on acute lung allograft rejection in the rat model and its mechanism of action in vivo. METHODS: Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. Grafts were excised on Day 3 or Day 5 to determine histopathological rejection and expressions of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma by enzyme-linked immunosorbent assay. The cytokine expression at Day 3 or Day 5 was also evaluated in recipient spleens by immunohistochemistry. Furthermore, mesenteric lymph node cells from recipients at Day 5 were cultured alone or stimulated with donor antigens for 72 hours to determine cell proliferation by means of thymidine incorporation. RESULTS: NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Expression of IL-2 and IL-10 also increased in the spleen of untreated allorecipients. NKH477 suppressed expression of both cytokines in the spleen. In addition, lymphocyte proliferation was inhibited in NKH477-treated recipients as compared with untreated recipients. CONCLUSION: These results suggest that NKH477 exerts an antiproliferative effect on lymphocytes in vivo with an altered cytokine profile in rat recipients of lung allografts.     

A case of primary malignant lymphoma of the uterine body]

A 70-year-old female was found to have class V cytology on an endometrial smear, and a histological diagnosis of malignant lymphoma was made by endometrial biopsy. The pathological diagnosis was malignant lymphoma, diffuse large cell-type according to the Working Formulation classification. Immunohistochemical staining showed lymphoma cells to be positive for CD 20 (B 1), indicating B cell lineage. Two cervical lymph nodes were palpable, and swelling of a para-aortic lymph node was also found by abdominal CT scan. The clinical stage was determined to be III according to the Ann Arbor classification. After three courses of CHOP chemotherapy, lymphoma cells could no longer be detected by endometrial biopsy, and the para-aortic and cervical lymphadenopathy also disappeared. Primary malignant lymphoma of the uterus, especially of the uterine body, is very rare. Only eight cases of primary malignant lymphoma of the uterine body were reported in the literature. The cell lineage was decided in only one case, which was B cell type.