Volume acceleration as an index of neuromuscular output

At the transition from expiration to inspiration, when flow and volume changes are small, changes in the respiratory system driving pressure could determine the degree of volume acceleration (AI), which, in turn, could reflect the degree of respiratory center output. To test this hypothesis, we calculated AI occurring in each respiratory cycle at the transition from expiration to inspiration during CO2 rebreathing in 4 healthy supine subjects. To minimize the flow and volume change over the measurement interval, we measured AI just prior to inspiration within the limits of an expiratory flow of 0.2 L . sec -1 to zero flow using digital differentiation. We also measured mouth pressure 100 msec after the onset of inspiration (P0.1) during intermittent transient inspiratory airway occlusions. During CO2 rebreathing AI increased significantly with both increasing PCO2 and P0.1. We also compared pairs of rebreathing studies, performed without and with an alinear (16 cm H2O . L -1 . sec -1) inspiratory resistor (IR), repeated twice in the 4 subjects. IR markedly decreased delta VE/delta PCO2 and the slope of the increase in mean inspiratory flow rate with PCO2 (delta VT/TI/delta PCO2) but did not significantly alter either delta AI/delta PCO2 or the increase in P0.1 with PCO2 (delta P0.1/delta PCO2). However, the effects of IR on AI and P0.1 differed between the early and late phases of each rebreathing run; early in the rebreathing runs (PCO2 = 55 Torr) IR increased both AI and P0.1 by a similar amount, but near the end of rebreathing (PCO2 = 60 Torr) IR increased P0.1 but not AI. Our results are consistent with the possibility that AI reflects neuromuscular output under the conditions of the study. Hence this approach justifies further evaluation to determine its general applicability.     

Evaluation of a computerised test for the assessment of peripheral vascular disease

This paper reports a study carried out in 200 patients to assess the effectiveness of a clinical vascular laboratory in the routine assessment of peripheral vascular disease (PVD) of the lower limb. Laboratory assessments involved a computer based hierarchical testing system incorporating pedal pressure indices, maximum walking distances and principal component analysis of the common femoral artery blood velocity waveform. The study fell into two parts. In the first, the laboratory assessments of 100 patients referred six years ago were compared retrospectively with their eventual clinical outcome. In this comparison, the laboratory provided a "diagnosis" which was 79% correct. In the second, a double blind prospective study was carried out in 100 patients to compare the vascular laboratory "diagnosis" with the diagnosis and prognosis of a skilled clinician, the outcome being compared one year after the initial assessment. In this study the laboratory proved to be correct in 78% of cases, the clinician in 70%. With a slightly modified computer protocol for the non vascular diagnosis, the computer would have been correct in 85% of cases. This test provides a quantitative and objective assessment of PVD which can assist in the patient's clinical diagnosis and management.     

The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncog-ene results in persistent mitogenic signalling. Upregul-ated c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retino-blastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cyto-toxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.     

Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.