Indeterminate mediastinal invasion in bronchogenic carcinoma: CT evaluation

The computed tomographic (CT) scans of 80 patients with bronchogenic carcinoma classified as indeterminate for direct mediastinal invasion were retrospectively reviewed after the patients had undergone thoracotomy. Forty-eight (60%) of the masses were resectable, without invasion of the mediastinum, 18 (22%) focally invaded the mediastinum but were technically resectable, and 14 (18%) invaded the mediastinum and were not technically resectable. Although in most circumstances in this relatively small subset of patients CT was not helpful in differentiating masses with and without mediastinal invasion, CT was able to separate a large group of masses that were likely to be technically resectable. Thirty-six (97%) of 37 masses with one or more of these CT findings were considered technically resectable: contact of 3 cm or less with mediastinum, less than 90 degrees of contact with aorta, and mediastinal fat between mass and mediastinal structures. Of these 36 masses, 28 were resectable without mediastinal invasion, and eight were resectable with focal limited mediastinal invasion.     

Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs

To assess the relative infectivity and pathogenicity of variants of hepatitis C virus (HCV) genotypes, the distribution of genotypes in hemophilic patients who had been treated with nonvirally inactivated factor concentrates or cryoprecipitates prepared from local blood donors was compared with those found in the respective blood donor populations. Genotype frequencies differed markedly in the four countries investigated (Scotland, Hungary, South Africa, and Thailand) but in each, the HCV genotype distributions in hemophiliacs and blood donors were similar. In addition, HCV genotypes in recipients of commercially manufactured concentrates were similar to those found in the US general population. These findings provide no evidence that HCV genotypes differ significantly from each other in replication rate, transmissibility, or infectivity.     

Radioisotope studies of purine metabolism during administration of guanine and allopurinol in the pig

In pigs pre-fed guanine, some 33 per cent of [8-¹⁴C]guanine administered orally appeared in the urine in 24 hr, principally in the form of allantoin. Little incorporation (less than 1 per cent) of radioactivity into body tissues occurred and only 5 per cent of the radioactivity could be found in the faeces.When allopurinol was added to the guanine diet the pattern of excretion of [8-¹⁴C]-guanine changed considerably. Only 11 per cent of the radioactivity was recovered from the urine in 24 hr while 83 per cent appeared in the faeces in 3 days. Again, less than 1 per cent of the radioactivity was found in the tissues at slaughter.Intravenous administration of [8-¹⁴C]guanine to a pig on the above mixture resulted in the rapid incorporation of approximately 50 per cent of the radioactivity into body tissues with a slow subsequent daily excretion of approximately 2 per cent of this radioactivity in faeces and urine. The finding of 13 per cent of the radioactivity in the faeces is considered evidence of purine excretion into the gut. The recovery of urinary radioactivity (34 per cent of dose) principally in xanthine, but also in hypoxanthine, showed the existence of a rapid additional route of guanine catabolism via hypoxanthine. Experimental evidence is also presented to demonstrate the existence of a reciprocal relationship between urinary [¹⁴C]hypoxanthine and allopurinol riboside excretion suggesting competitive inhibition of allopurinol riboside formation by hypoxanthine in vivo.In the allopurinol treated pig, orally administered [6-¹⁴C]allopurinol was rapidly absorbed and almost totally excreted in the urine in 24 hr (90 per cent). The remainder of the radioactivity (approximately 7 per cent) was excreted in the faeces in 3 days and no radioactivity could be detected in tissue nucleic acids or in tissues to any extent (less than 0.01 per cent of the dose).The significance of these results in relation to the metabolic studies is discussed.     

Omic techniques in systems biology approaches to traditional Chinese medicine research: present and future

Omic techniques have become key tools in the development of systems biology. As the holistic approaches underlying the practice of traditional Chinese medicine (TCM) and new tendencies in Western medicine towards personalised medicine require in-depth knowledge of mechanisms of action and active compounds, the use of omic techniques is crucial for understanding and interpretation of TCM development, especially in view of its expansion in Western countries. In this short review, omic applications in TCM research are reviewed which has allowed some speculation regarding future perspectives for these approaches in TCM modernisation and standardisation. Guidelines for good practice for the application of omics in TCM research are also proposed.     

Identification of the regions of the HPV 5 E6 protein involved in Bak degradation and inhibition of apoptosis

UVB induced DNA damage is the major aetiological agent in NMSC development, but mounting evidence suggests a role for human papillomaviruses (HPV) from genus beta, including HPV 5 and HPV 8, in the development of NMSC on sun exposed body sites. We have previously shown that UVB activates Bak, an apoptogenic mitochondrial factor that, following an apoptotic stimulus, undergoes a conformational change that leads to pore formation in the mitochondrial membrane that releases apoptotic factors. The HPV E6 protein effectively inhibits UVB-induced apoptosis and targets Bak for proteolytic degradation. We have now identified the regions of the HPV5 E6 that are required to mediate Bak proteolysis and contribute toward the antiapoptotic activity of the protein. Interestingly, while wild-type HPV5 E6 does not bind or target p53 for proteolysis, we have isolated specific HPV5 E6 mutants that switch target specificity from Bak to p53 in a p53 codon 72 isoform-dependent manner. Furthermore, we demonstrate that the ability of wild-type HPV5 E6 to target Bak or specific E6 mutants to target p53 for proteolysis is not dependent on the E6-AP ubiquitin ligase.     

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject ? and What does the study add? The treatment of younger men with testicular germ cell cancers is well documented with established intensive chemotherapy regimens for those with advanced disease. Although the majority of patients present in the third or fourth decade, men also present in later life. These patients are typically excluded from clinical trials and there are no contemporary published series describing their management. This series describes the management of older patients with testicular germ cell tumours at both early and advanced stages of disease. Patients with stage I seminoma can be safely managed with all recognised treatment strategies and state I non‐seminomas were managed with surveillance. Cure can still be achieved in older patients with advance germ cell tumours however chemotherapy regimens developed in younger patients must be tailored to the presence of co‐morbidity.

OBJECTIVES

? To review the practice of a large referral centre for the management of older patients with testicular germ cell cancer (GCC). ? There are few published data available on the management of testicular GCC in elderly patients, who often have medical comorbidities and have been excluded from clinical trials.

PATIENTS AND METHODS

? We reviewed our prospectively collected database for patients presenting with GCC who were aged ≥60 years. ? Details of presentation, management and outcome were recorded.

RESULTS

? In total, 60 patients aged ≥60 years were identified from 1461 patients treated with GCC from 1979–2005, representing 4% of the total population. ? Median age was 67 years, 44 had seminoma (73%) and 16 had non‐seminoma histology (27%). ? Stage I seminoma patients were managed with surveillance, adjuvant radiotherapy and adjuvant carboplatin. All stage I non‐seminomas underwent surveillance. ? In total, 15 patients received systemic chemotherapy for metastatic disease with modified bleomycin, etoposide and cisplatin; etoposide and cisplatin; carboplatin‐based regimens; or other combinations. Toxicity was manageable, with no toxic deaths. ? In total, four patients (6.7%) died of GCC.

CONCLUSIONS

? In elderly patients, GCC should be managed with curative intent. ? Conventional therapies are tolerable for most men with stage I seminoma. In metastatic disease, comorbidity may necessitate treatment modifications. ? Most patients are cured with manageable toxicity.     

Comparison of stage-matched and unmatched interventions to promote exercise behaviour in the primary care setting.

This study examined the effectiveness of stages of change-based counselling for exercise delivered by nurses in four primary care centres. Two-hundred and ninety-four subjects enrolled, recruited from patients attending 30-min health checks. The average age of participants was 42.4 years (SD = 15.1) and 77% were female. Participants completed a questionnaire assessing stage of exercise adoption, self-efficacy and exercise levels. Each centre was assigned to either one of three experimental conditions or to a control condition. Participants were counselled accordingly, receiving either stage-oriented exercise materials with counselling (stage plus counselling), stage-oriented materials without counselling (stage no counselling), non-staged materials with counselling (counselling only) or the current level of advice (control). Sixty-one percent (n = 180) returned follow-up questionnaires. When baseline differences in self-efficacy, age and gender were controlled for, there was no significant group or interaction effect for stage. There was a significant time effect (F = 3.55, P = 0.031). Post hoc analyses showed that significant differences were between baseline and 2 (t = -3.02, P = 0.003) and 6 months (t = -2.67, P = 0.009). No changes in self-efficacy and exercise levels were observed. Stage-based interventions were not superior to the other interventions. All single-contact interventions, while having no impact on exercise behaviour and self-efficacy, did enhance motivation to change.     

《亚洲男性学杂志》“21世纪精液分析特刊”后序

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