Clinical efficacy of conservative laser therapy for early-stage cervical cancer

The objective of this study was to evaluate the clinical efficacy of conservative laser therapy for early-stage cervical cancer. Seven hundred fifty-two and 271 patients with carcinoma in situ (CIS) and microinvasive squamous cell carcinoma (MIC), respectively, were treated by laser conization with vaporization. One hundred eighty-four patients with preclinical invasive diseases underwent radical surgery without conization. Their postoperative histologic findings and clinical outcomes were evaluated retrospectively. The cone specimens of 1023 cases were reported as showing that 54 had dysplasia, 663 had CIS, 239 had stage Ia1 without lymph vascular space invasion (LVSI), 14 had stage Ia1 with LVSI, 14 had stage Ia2, and 39 had stage Ib1 diseases. Incomplete excision occurred in 4 (7.4%) of 54 dysplasia, 48 (7.2%) of 663 CIS, and 16 (6.7%) of 239 stage Ia1 cases, but failure rates were only 1 (1.9%), 8 (1.2%), and 4 (1.7%), respectively. The other 67 of 1023 cases underwent abdominal operation. Final pathology results were analyzed for 67 and 184 cases with stages Ia1 to Ib1 receiving radical surgery with or without initial laser therapy. Lymph node metastasis was not observed in 154 Ia1 and 30 Ia2 with stromal invasion of under 4 mm in depth regardless of LVSI, but was detected in 2 of 16 Ia2 with stromal invasion of over 4 mm in depth and in 9 of 51 Ib1 cases. CIS and Ia1 disease without LVSI can be treated only by laser therapy. The limit of stromal invasion for conservative laser therapy in stage Ia cancer may be 4 mm in depth regardless of LVSI.     

Alteration of DNA methylation levels in MRL lupus mice

Recent reports suggest that DNA methylation is involved in the cause of autoimmune disease. We investigated the alteration of DNA methylation levels in lupus strains of mice, MRL/lpr as a model, which develop an age-dependent lymphadenopathy and autoimmune disease. DNA methylation levels of thymus and axillary lymph nodes in 20-week-old MRL/lpr mice, which are in an autoimmune disease state, were lower than those of 4-week-old MRL/lpr mice with no symptoms as yet. No significant changes were observed in MRL/4- strain mice, which seemed normal at least 20 weeks, while DNA methylation levels in the spleen of both strains of mice increased significantly from the age of 4 to 20 weeks. However, no significant changes of DNA methylation levels in peripheral blood were observed with ageing in MRL strains. Moreover, we clarified that administration of 5-azacytidine had a strong effect on longer survival of MRL/lpr mice and reduced DNA methylation levels in the axillary lymph nodes and spleen. The possible relevance of DNA methylation levels to the progression of autoimmune disease is discussed.     

Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting enzyme inhibitor-induced cough

The role of genetic factors was reviewed with respect to the pathophysiology of bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme (ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked to atopy but is associated with serum IgE levels. The β 2-adrenergic receptor gene on 5q32–33 was found to have polymorphism by Ban I and to be related to β 2-receptor function; a defect of a 2.3 kb allele is related to lowered sensitivity to β 2-agonists. This defect is also related to higher prevalence on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to Gly) of β 2-receptors was lower and G1n27 to Glu mutation is extremely rare in the Japanese population compared with Caucasians. There is polymorphism of ACE genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The genotype is a significant determinant of serum ACE activity and may determine the prognosis of sarcoid patients. Genotype II has a higher incidence of coughing induced by ACE inhibitors.     

Genetic factors in lung disease: Atopy and bronchial asthma

Abstract Atopy defined as high IgE responsiveness has now been subject to genetic studies at the molecular level owing to the development of a great number of DNA markers over the human genome. Either by linkage analysis or by association study strong candidate genes of atopy have been proposed to be located on chromosomes 11q13 and 5q31 where high-affinity IgE Fc receptor β subunit and allergy-associated cytokines, respectively, have been mapped. Meanwhile, we found a novel association between one of alleles of D11S97, an anonymous DNA marker on 11g13, and high total serum IgE in a large number of Japanese general population and atopic family members. However, failure to replicate linkage or association studies by different investigators suggest polygenic nature of atopy. In addition to the genes regulating IgE synthesis, the requirement of local (pulmonary) genetic factors in the development of bronchial asthma have been speculated. Linkage analysis suggested possible existence of gene(s) regulating susceptibility and/or clinical characteristics of bronchial asthma also on chromosome 5q. One of the candidate is β2-adrenergic receptor gene polymorphism. Mutated gene transfection studies suggested functional significance of some polymorphisms and clinical evaluations have revealed their contribution to airway responsiveness and severity of asthma.     

Do Sacral/Peripheral Lesions Contribute to Detrusor‐Sphincter Dyssynergia?

Objectives: While detrusor‐sphincter dyssynergia (DSD) occurs in conjunction with lesions between the brainstem and the sacral cord, it is not well known whether sacral/peripheral lesions contribute to DSD. We studied the relationship between DSD and sacral/peripheral lesions. Methods: One hundred and forty‐four patients with diverse neurologic etiologies underwent urodynamic study and analysis of motor unit potentials in the external sphincter muscles, 117 of whom were able to void during a urodynamic test. Sacral/peripheral lesion (SPL) is defined as neurogenic change in motor unit potentials. Detrusor overactivity (DO) is defined as involuntary detrusor contractions during the filling phase, which commonly occurs in lesions above the sacral cord. We considered DO as a putative indicator of supra‐sacral lesion. Results: DSD was found in 44 (30.6%), SPL in 71 (49.3%), and DO in 83 (57.6%) of 144 patients, respectively. The incidence of DSD was the same in the SPL positive group (31%) and the SPL negative group (30.1%). By contrast, within the subgroup of patients without DO, the incidence of DSD was significantly more common in the SPL positive group (41.4%) than in the SPL negative group (25.0%) (P < 0.05). In 53 of the SPL positive group who were able to void, postvoid residual >100 mL was more common in patients with DSD (not statistically significant). Conclusion: The results of the present study suggest that not only suprasacral pathology, but also sacral/peripheral lesions can produce DSD. In light of the previous reports, DSD might also result from partial lesions in peripheral branches of the sphincter circuit.     

Desquamative interstitial pneumonia may progress to lung fibrosis as characterized radiologically

Background and objective: In some patients, desquamative interstitial pneumonia may progress to lung fibrosis. The aim of this study was to assess the long‐term radiological follow‐up results in patients with desquamative interstitial pneumonia. Methods: Among 75 patients suspected of having desquamative interstitial pneumonia, 31 who fulfilled the criteria were included in this study. Clinical characteristics at presentation, responses to treatment and long‐term follow‐up were evaluated. Results: The 31 patients were predominantly males (94%), and the mean age was 55 years; 93% (28/30) had a history of smoking. The clinical findings included high serum levels of lactate dehydrogenase and immunoglobulin G. Bronchoalveolar lavage (26 patients, 84% of cases) frequently showed an increased percentage of eosinophils (mean 17%). Computed tomography (CT) or high resolution (HR) CT at presentation showed ground glass opacities and/or consolidation in all patients, with one third of patients also showing thin‐walled cysts within the ground glass opacities. There was no honeycombing on CT or HRCT scans at presentation. Corticosteroid therapy was effective early in the course of the disease; long‐term follow‐up (mean 99 months) of 31 patients showed only one death due to progression of the disease, but long‐term follow‐up of 14 patients (mean 125 months) by HRCT showed the development of new thin‐walled cysts and honeycombing in five and lung cancer in four patients, respectively. Conclusions: In a proportion of patients, desquamative interstitial pneumonia may progress to lung fibrosis with honeycombing on HRCT, despite therapy.     

Intra-His Bundle Block Corresponds with Interruption of the Branching Portion of the His Bundle

We compared His-bundle electrograms with pathological findings of the atrioventricular conduction system in four patients with complete atrioventricular intra-His block with narrow QRS complexes on ECG. Split His electrograms were recorded at the time of electrophysiological study. The patients died from noncardiac causes at 10 days, 1 year, 4 years, and 9 years, respectively, after the pacemaker implantation. Serial sections through the atrioventricular conduction system revealed strictly localized more than 50% reduction of conducting cells replaced by fibrosis at the branching portion of His bundle. The proximal portions of the bundle branches also exhibited decrease of the conducting cells showing a rough positive relation with the patient's age. Therefore, we considered that the H₁ spikes seen on His-bundle electrograms originated from the penetrating portion of His, which was virtually intact in our cases, and that the H₂ spikes originated from the right side of the distal branching portion of His.     

倾向指数方法的蒙特卡罗研究

目的评价由倾向指数方法得到的暴露效果的估计量和统计性质,并探讨其实用性。方法利用计算机模拟对倾向指数方法在无模型误定和有模型误定情况下的偏度和精度进行分析,并与基于模型方法的模拟结果进行比较。结果当存在模型误定时,倾向指数方法比基于模型的方法具有较好的稳健性。结论对于大量、关系复杂的数据,应用倾向指数方法具有较大的灵活性。