2006年 · 第119卷第17期

Cough is the commonest symptom leading patients to consult with their doctor. What is clear is that at some stage, we all suffer from cough and at times, it is distressing and inhibits normal social activities. In a few subjects, chronic cough leads to a severe loss of quality of life。

Abstract：Background Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (VT) while maintaining constant partial arterial CO2 pressure (PaCO2). We hypothesised that TGI limited peak inspiratory pressure (PIP) and VT and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI).Methods ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n=8 for each group), and subsequently ventilated with limited PIP and VT to maintain PaCO2 within 35 to 45 mmHg for 4 hours. Physiological dead space to VT ratio (VD/VT), dynamic respiratory compliance (Cdyn) and partial arterial O2 pressure (PaO2) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (Vv), myeloperoxidase and interleukin (IL)-8.Results TGI resulted in significant (P＜0.05 or P＜0.01) decrease in PIP [(22.4±1.8) cmH2O vs (29.5±1.1) cmH2O], VT [(6.9±1.3) ml/kg vs (9.8±1.11) ml/kg], VD/VT [(32±5)% vs (46±2)%], TP [(109±22) mg/kg vs (187±25) mg/kg], SA/LA (2.5±0.4 vs 5.4±0.7), myeloperoxidase [(6.2±0.5) U/g tissue vs (12.3±0.8) U/g tissue] and IL-8 [(987±106) ng/g tissue vs (24±3) mN/m] of BALF, and significant (P＜0.05) increase in Cdyn [(0.47±0.02) ml ·cmH2O-1 ·kg-1 vs (0.31±0.02) ml ·cmH2O-1 ·kg-1], PaO2 [(175±24) mmHg vs (135±26) mmHg],TPL/TP (52±8 vs 33±11) and Vv (0.65±0.05 vs 0.44±0.07) as compared with CMV.Conclusions In this animal model of ALI, TGI decreased ventilatory requirements (PIP, VT and VD/VT),resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI。

Abstract：Background The number of immunosupressed patients has increased in the past decades. Among them Pseudomonas aeruginosa (P. aeruginosa) is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosupressed patients is not understood completely. Previous reports showed keratinocyte growth factor (KGF) is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P. aeruginosa pneumonia between immunosuppressed and immunocompetent rats.Methods Immunosuppression of male rats was induced by injecting immunosuppressive subcutaneously.Pneumonia was established by instilling P. aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated.Results The survival rate of immunosuppressed group was lower than that of immunocompetent group (33.3%vs 83.3%). After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group.Conclusions Compared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones。

Abstract：Background There has been increasing interest in the research into cytomegalovirus (CMV) pneumonia after liver transplantation (LT). This study was undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT.Methods Six patients with CMV pneumonia after LT from October 2003 to November 2005 were analyzed retrospectively. They were diagnosed according to clinical manifestations, chest X-ray findings and pathogenic changes and given comprehensive therapy including mainly immunomodulation therapy and anti-viral medication. At the early stage of CMV pneumonia, the dose of immunosuppressive agents was decreased or ceased, instead replaced by immunoenhancement therapy. During recovery period from CMV pneumonia, the dose of immunosuppressive agents was given again or enhanced, and immunoenhancement therapy was ceased.The liver function of the patients was monitored closely during the treatment.Results In this series, five patients were survived and one died. The liver function of the six patients remained normal during the treatment, and no episode of acute rejection took place.Conclusions Poor immunity is the pathogenic basis of CMV pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients should be enhanced, and during the recovery period from CMV pneumonia, immunosuppresants shoud be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT。

Abstract：Background Screening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo.Methods The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium (Ⅴ) oxo core [TcO3+] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 99mTc tripeptoid complexes. The radiocombinatorial screening (RCS) in vivo was carried out on SD rats and A549 tumour bearing mice.Results Signals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, 99mTc RPA, 99mTc VIG and 99mTc RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of 99mTc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of 99mTc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. 99mTc DSG was finally identified the most promising agent for renal function studies.Conclusions RCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries。

Abstract：Background In recent years, keyhole microsurgery has become an important subject of modem minimally invasive neurosurgery. In this study, minimally invasive techniques avoiding unnecessary tissue injuries were applied to refine traditional approaches for the removal of third ventricular tumors within a limited operative filed.Methods Individualized keyhole approaches were designed according to the characteristics of third ventricular tumors and their growth patterns. A series of keyhole approaches such as supraorbital subfrontal approach,infratentorial supracerebellar approach, interhemispheric transcallosal approach, pterional approach were taken to enter the third ventricle anteriorly, posteriorly, superiorly or laterally, respectively. A total of 34 removed tumors in or extended into the third ventricle included 11 craniopharyngiomas, 10 pituitary adenomas, 2 pinealomas, 1cholesteatoma, 3 germinomas, and 7 gliomas.Results Total tumor resection was done in 27 (79.4%) of the patients, and subtotal resection in 7 patients (20.6%). Residual tumor was due to tight adherence of germinoma to the vein of Galen (1 patient),craniopharyngioma to the pituitary stalk (3), supratentorial extension of pineal region gliomas (1), suprasellar extension of gliomas (1) and giant pituitary adenoma (1). Complications such as brain contusion, postoperative hemorrhage and infection were not associated with keyhole approaches. Extended incision or enlarged bone flap was not made because of episode during operation or inadequate exposure.Conclusions Keyhole approaches are safe, effective and minimally invasive in the surgical treatment of tumors deeply seated in the third ventricle. Individualized keyhole approach ensures a successful treatment. Tumors in the upper middle part of the third ventricle can be exposed by the interhemispheric transcallosal keyhole approach. Tumors of the posterior third ventricle may be well exposed by the infratentorial supracerebellar keyhole approach. Tumors of the anterior third ventricle can be entered by either a supraorbital subfrontal keyhole approach or a pterional keyhole approach。

Abstract：Background Cataracts is considered be formed because of an abnormal glucose metabolic pathway or oxidative stress. We explored the damaging role of ONOO- and antagonism of cholecystokinin octapeptide-8(CCK-8) in diabetic cataractal rat lenses.Methods A diabetic cataractal animal model was established by peritoneal injection of streptozotocine (STZ).Thirty-six normal SD rats were taken as control group; seventy-two were given STZ (45 mg/kg) and then divided into STZ group and CCK-8 group (peritoneal injection CCK-8). STZ induced diabetic rats were treated with CCK-8 for 60 days. Lenses were examined with slit lamp at 20, 40 and 60 days. Immunofluorescent staining and Western blot analysis were used for determining nitrotyrosine (NT, a marker for ONOO-). RT-PCR and gene array analysis were used for determining the expression of inducible nitric oxide synthetase mRNA (iNOS mRNA) in lens epithelium (LEC).Results STZ group rats developed lens opacity by 20 days that reached a high level by 60 days after STZ injection. CCK-8 group rats delayed the cataract formation. There was no distinct expression of NT and iNOS mRNA in control group. In STZ group, there were distinct expression of NT and upregulation of iNOS mRNA;however, CCK-8 group showed weak expression of NT and downregulation of iNOS mRNA.Conclusions NT, which may be a new form of oxidative stress, was expressed in diabetic rat LEC although CCK-8 could reverse NT damage in LEC. The results suggested that CCK-8 might be a useful therapeutic agent against diabetic cataract. The antagonizing mechanism of CCK-8 may be related to direct antagonism of ONOO-as well as its inhibition of the expression of iNOS mRNA for production of NO and therefore decrease in the formation of ONOO-。

Agrowing concern has focused on the recent identification of influenza A H5N1 virus in Asia.Previously thought to infect only wild birds and poultry, H5N1 has now infected humans, cats, pigs,and other mammals in an ongoing outbreak, often with fatal results. According to a report from the World Health Organization (WHO), 217 human H5N1 cases have been confirmed and 123 of them have been fatal as of May 19, 2006.1 But many questions remain unanswered, for example how the H5N1 virus could cross species barriers and acquire the ability to infect humans; when and how the H5N1 virus will transmit effectively between humans and cause an influenza pandemic; and what are the determinants of its high virulence. This article summarizes research progress on the origin of H5N1 virus, factors determining pathogenicity, the contribution of genetic evolution to H5N1 species barrier traversal, human-to-human transmission, and problems in prevention and treatment of H5N1 avian influenza virus。

Fractalkine (FKN) is the only known chemokine that fulfils the dual functions of an adhesive molecule and a soluble chemoattractant.1 FKN expression was reported increase in lungs of patients with severe pulmonary arterial hypertension,2 suggesting that FKN may participate in pathogenesis of pulmonary hypertension.Breviscapine is a flavonoid extracted from Erigeron breviscapus (Vant.) Hand. Mazz. Breviscapine can prevent the development of hypoxic pulmonary hypertension3 but the mechanism is unknown. This study evaluated the role of FKN in the pathogenesis of hypoxic pulmonary hypertension and the effect of breviscapine on FKN in hypoxic pulmonary hypertension。

Lung cancer is the leading cause of cancer related death in the world and its mortality could be greatly reduced by diagnosis and treatment in its early stages. Effective tools for the early detection of lung cancer and its high risk factors remain a major challenge. Biomarkers that detect lung cancer in its early stages or identify its pretumour lesions,enabling early therapeutic intervention, would be invaluable to improve its dismal prognosis。

Nowadays, despite the high prevalence of hypertension, the awareness rate and control rate of this disease are still very low. In addition, the prevalence of hypertension in old population is very high, and most of cases are isolated systolic hypertension (ISH). We investigated people ranging in age from 80 to 99 years in 28 cadre retirement centers in Beijing to study the prevalence and incidence of target organ injury and analyze the relative factors of ISH。

Tumoural hypoxia can influence response to radiotherapy and other treatments, and oxygenation status has proved to be a prognostic indicator of the outcome of radiotherapy.1Therefore, it is important to assess tumoural hypoxia and reoxygenation before selection of treatment protocols. During the last two decades, much attention has been paid to noninvasive imaging techniques using radiolabelled markers for the detection of hypoxic cells in solid tumours.2Technetium (99mTc) is a very convenient isotope for use with such imaging because it is readily available and suited to routine clinical use. 99mTc labelled ligands containing 2-nitroimidazole have been recently developed. 99nTc labelled 4, 9-diaza-3, 3, 10,10-tetramethyldodecan-2, 11 -dione dioxime (99mTc-HL91), which lacks the nitroimidazole group,showed even greater hypoxic selectivity.3

We report a rare case of a patient who died suddenly, in whom bilateral pulmonary artery thrombosis with multiple myeloma was found at autopsy. An estimate of the incidence of pulmonary embolism in myeloma patients based on postmortem examinations is about 3.2%. Hypercoagulability and decreased fibrinolytic capacity due to multiple myeloma were the probable causes of multiple thromboses。

Berry Syndrome is a rare combination of congenital cardiac abnormalities firstly reported in 1982.1 It consists of aortopulmonary window, anomalous origin of the right pulmonary artery (RPA) from ascending aorta, intact ventricular septum,interruption of the aortic arch with patent ductus arteriosus(PDA). This is the 26th case reported in literature2 and the first report in Hong Kong. Delayed recognition can result in potential lethal condition.This report demonstrated the importance of prompt clinical recognition, timely echocardiography and early operation in the management of this rare cardiac anomaly。

Cord blood transplantation (CBT) from unrelated donors has increasingly been performed worldwide during the last decade. The immaturity of lymphocytes in cord blood permits HLA-mismatching between donors and recipients and reduces the severity of graft-versus-host disease (GVHD).However, the relatively small dose of the cord blood nucleated cells is associated with a high frequency of engraftment failure.1-5 But re-transplantation with stem cells from the original donor is impossible。

To the Editor: Pulmonary embolism (PE) used to be thought to be rare in China.1 Traditional teaching by such authorities as Snapper, who was highly regarded in old China as one of the most astute diagnosticians, was that PE was uncommon in China.2 As a matter of fact, he did not even mention it in his book "Chinese lessons to western medicine",3 published in 1941. The rarity of pulmonary embolism was even more remarkable when one considered the widespread use of birth control pills among the Chinese women of child-bearing age.1

To the Editor: We read with great interest the article by Gao and his colleagues1 proposing a new schema and hypothesis regarding pleural fluid turnover. In the proposed hypothesis, the visceral pleura possesses a more active role in humans than what was believed. The authors support the notion that in humans the pulmonary lymphatic vessels originate directly from the mesothelium of the visceral pleura and that it has an effect on both infiltration and reabsorption of pleural fluid in human beings。

To the Editor: We are pleased to respond to the letter of Zarogiannis and his colleagues1 for their interest in our study,2 emphasizing the role of human visceral pleura in pleura fluid turnover. We definitely agree to Zarogiannis and colleagues'comments that the absence of many cuboidal cells in the visceral pleura does not favor the existence of visceral lymphatic stomata。