Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits

Introduction

Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties.

Methods

The PEEP level (8 cmH₂O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA.

Results

PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated.

Conclusions

Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.     

G蛋白偶联受体激酶的研究进展

G蛋白偶联受体激酶(GRKs)属丝氨酸／酪氨酸蛋白激酶家族,其亚型广泛存在于各种组织, 能特异地使活化的G蛋白偶联受体(GPCR)发生磷酸化及脱敏化,从而终止后者介导的信号转导通路．现就G蛋白偶联受体激酶的结构、种类及分布、生物学功能及与疾病关系的新进展进行总结与概括,并对其发展进行了展望．     

The effect of chemotherapy on the kinetics and proliferative capacity of normal and tumorous tissues in vivo

The proliferative state of a given tissue is a major determinant of its sensitivity to both phase-specific and cycle-specific chemotherapeutic agents. To study the extent of injury induced by antitumor agents to normal and tumorous tissues, a technique for following DNA synthesis as reflected in the incorporation of tritiated thymidine (3H-TdR) into DNA was compared to the conventional radioautographic technique of the labeling index (LI) and to the functional kinetic technique of granulocyte colony formation in vitro. Alterations in DNA synthesis induced by a single dose of cyclophosphamide in normal and tumorous tissues in vivo paralleled in many respects the changes seen when the more time-consuming techniques of the LI or granulocyte colony formation were employed. However, the recovery of granulocyte colony formation after cyclophosphamide therapy lagged behind the recovery of DNA synthesis in the bone marrow, obscuring a kinetic event of potential therapeutic significance. The determination of DNA synthesis simultaneously in normal and tumorous tissues in vivo was easy to perform and supplied therapeutically pertinent results comparatively quickly.     

A clonally distinct recurrence of Burkitt's lymphoma at 15 years

A human immunodeficiency virus-negative male was successfully treated for two occurrences of Burkitt's lymphoma, 15 years apart. As consolidation of his second remission, he underwent high-dose chemotherapy with peripheral blood stem cell transplantation. In an effort to prove whether the second lymphoma was a relapse of the first or a second primary lymphoma, we obtained paraffin-embedded material from both lymphomas. DNA was extracted from this material and amplified by polymerase chain reaction (PCR) using consensus JH and VH region primers. Analysis of the PCR products, which mostly reflects VDJ joints, showed two sharp bands of different molecular size, proving the monoclonal nature of the lymphomas and suggesting that each had different Ig gene rearrangements. Sequencing of both PCR products showed a marked dissimilarity in nucleotide sequence in the clonally unique VDJ joint region, providing strong evidence for the separate cellular genesis of each lymphoma. These results suggest that late relapses of Burkitt's lymphoma should be examined for clonal distinctiveness. If the second lymphoma is distinct from the primary one, it might be treated as a primary lymphoma rather than as recurrent disease.     

Transferring AAC intervention to the home

Purpose: To evaluate the acquisition of AAC skills during an initial clinical trial and assess subsequent transfer of the training to the home setting. Method: A 12-year-old male with autism was first seen in a clinical setting to establish the use of a voice-output communication device. After learning to use the device to request access to preferred objects in the clinical trial, the intervention was transferred to the home. Follow-up with the parent was conducted via e-mail and telephone. Videotapes were made of initial home-based sessions to enable evaluation of the participant's progress. Results: The programme was successful in teaching the participant to use a portable AAC device to make requests during the clinical trial and then in two home-based activities. Conclusion: An initial clinical trial with follow-up support for parents may be an efficient method for beginning AAC intervention and transferring the training procedures to the home setting.     

Mucosal vulval lichen planus: outcome, clinical and laboratory features

BACKGROUND: Mucosal lichen planus of the vulva is a rare but increasingly recognized condition. It has potentially severe complications such as fusion of the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be increased. An association between hepatitis B and C infection and skin or oral lichen planus appears to exist in certain geographical areas. OBJECTIVE: To investigate the course of mucosal vulval lichen planus, its response to treatment and associated laboratory features. SUBJECTS AND METHODS: Forty-four women with mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory data were collected. RESULTS: Thirty of 44 patients had additional oral lesions, only nine had cutaneous findings compatible with lichen planus. We did not find an association with antibodies to hepatitis B or C virus in this British study population. All women were treated with potent to very potent topical corticosteroids; however, in the majority of patients symptoms persisted. In seven (16%) patients vulval lichen planus was in remission after a disease duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval SCC. CONCLUSIONS: Screening for hepatitis B and C in women with mucosal vulval lichen planus in the UK seems unnecessary. We recommend long-term follow-up, and that all non-healing ulcerative and papular lesions should be biopsied.     

原位PCR技术及其应用

目的：阐述原位PCR技术的基本原理，进展，应用及存在问题。方法：通过检索国内，外相关文献，归纳整理，结合实践操作经验，展开分析，结果：原位PCR技术是一种特异性，敏感性较高的靶序列检测定位技术，作为研究基因信息和细胞，染色体等的形态信息的有力工具，尤其是专用原位PCR仪在医学研究（医学检验，病理学领域）上的广泛应用，结论：原位PCR技术的应用推广及研究深入，也存在其技术应用不完善之处。     

Experiences of special gynaecological services for children and adolescents: a descriptive study

Gynaecological examination of girls during childhood is undertaken somewhat infrequently. These genital examinations should not be taboo or a frightening experience for the girl, for her parents or for the physician. Studies of children suspected of sexual abuse have paid attention to the wide variety of gynaecological conditions already present in childhood. In 1988 we founded a special gynaecological outpatient clinic for girls under 16 y of age at a university hospital to develop the special knowledge and skills needed in children's gynaecology. In this gynaecological clinic for children and adolescents we were able to gain and offer expert knowledge of the problems of this age group. In this special clinic for children, gynaecological examination by special techniques and sonography led to a diagnosis in 71% of the patients without any instrumentation. Children and adolescent girls in need of special gynaecological care should be recognized specifically. Particular attention should be paid to the gynaecological care of victims of child sexual abuse and mentally or physically handicapped girls. In good co-operation with the girl, a gynaecological examination can become a positive experience during the development of female identity.