Human temperature regulation during cycling with moderate leg ischaemia

The effect of graded ischaemia in the legs on the regulation of body temperature during steady-state exercise was investigated in seven healthy males. It was hypothesised that graded ischaemia in the working muscles increases heat storage within the muscles, which in turn potentiates sweat secretion during exercise. Blood perfusion in the working muscles was reduced by applying a supra-atmospheric pressure (+6.6 kPa) around the legs, which reduced maximal working capacity by 29%. Each subject conducted three separate test trials comprising 30 min of steady-state cycling in a supine position. Exercise with unrestricted blood flow (Control trial) was compared to ischaemic exercise conducted at an identical relative work rate (Relative trial), as well as at an identical absolute work rate (Absolute trial); the latter corresponding to a 20% increase in relative workload. The average (SD) increases in both the rectal and oesophageal temperatures during steady-state cycling was 0.3 (0.2)°C and did not significantly differ between the three trials. The increase in muscle temperature was similar in the Control (2.7 (0.3)°C) and Absolute (2.4 (0.7)°C) trials, but was substantially lower (P<0.01) in the Relative trial (1.4 (0.8)°C). Ischaemia potentiated (P<0.01) sweating on the forehead in the Absolute trial (24.2 (7.3) g m^–2 min^–1) compared to the Control trial (13.4 (6.2) g m^–2 min^–1), concomitant with an attenuated (P<0.05) vasodilatation in the skin during exercise. It is concluded that graded ischaemia in working muscles potentiates the exercise sweating response and attenuates vasodilatation in the skin initiated by increased core temperature, effects which may be attributed to an augmented muscle metaboreflex.     

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Heterogeneous sensitivity of cerebral and muscle tissues to acute normobaric hyperoxia at rest

The purpose was to investigate the effects of acute normobaric hyperoxia at rest on cerebral, respiratory and leg muscle oxygenation. Ten healthy men were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air and on the other 100% normobaric O(2) for a 2-hour time period. Oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total (Δ[tHb]) hemoglobin in the cerebral frontal cortex, and in the intercostal and vastus lateralis muscles were simultaneously monitored with near-infrared spectroscopy. The hyperoxic stimulus promptly increased Δ[O(2)Hb] (~2 μM) and decreased Δ[HHb] (~3.6 μM) in the frontal cortex. These cerebral responses were directly and fully countered by resumption of normoxic air breathing. In contrast, Δ[HHb] significantly decreased due to the acute hyperoxic stimulus in both intercostal and vastus lateralis muscles. The temporal changes in muscle oxygenation were slower compared to those in the cerebral area; and they only partially recovered during the 15-min normoxic-recovery period. Acute supplementation of normobaric O(2) at rest influences cerebral, leg and respiratory muscle oxygenation of healthy individuals, but not in the same manner. Namely, the frontal cortex seems to be more sensitive to hyperoxia than are the skeletal muscle regions.     

Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non‐small cell lung cancer

Urokinase plasminogen activator (uPA) cleaves its three‐domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II‐III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non‐small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time‐resolved fluoroimmunoassays (TR‐FIAs) measuring intact uPAR(I‐III) (TR‐FIA 1), uPAR(I‐III) + uPAR(II‐III) (TR‐FIA 2) and uPAR(I) (TR‐FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I‐III), uPAR(I‐III) + uPAR(II‐III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I‐III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.     

A clinical and epidemiologic study morsicatio buccarum/labiorum

abstract – A study of habitual self mutilation of the buccal and/or labial mucosa by biting was conducted on 8,589 persons attending the Royal Dental College, Copenhagen. Forty-two cases were found. The youngest patient was 5 years old and the oldest was 47. The condition occurred most frequently (1.77%) among persons aged 15–19 years. There was no difference in prevalence between males and females. Combined mutilation of cheek(s) and lip(s) was more frequent (62%) than isolated mutilation of the cheek(s) (24%) or isolated mutilation of the lip(s) (14%). Bilateral biting of the cheeks was more frequent than unilateral biting, and biting of the lower lip was more frequent than biting of the upper lip. Ninety-three per cent of the patients were aware of their habit, and most of them stated that they had been biting for years. Twenty patients were re-examined; in all but one patients the biting persisted but in 7 patients the location of the lesions had changed. In several cases a link could be traced to personal problems and mental stress. It was further noticed that many patients were students and white-collar workers, suggesting that "intellectual" work may predispose for the habit.     

PSYCHOLOGICAL EFFECTS OF AN EPIDEMIOLOGICAL STUDY OF BENIGN PROSTATIC HYPERTROPHY

SUMMARY The psychological impact of an epidemiological study of benign prostatic hypertrophy (BPH) was assessed in a representative sample of practice list patients. Of the 889 men completing a general health self-report questionnaire previously validated in a screening programme, 75% knew nothing of problems of the prostate, and 84.5% were not at all worried about prostate problems prior to commencement of the study. Receiving the letter of invitation and the procedures neither increased nor reduced anxiety levels for 69% and 70% respectively. In the 227 men referred to hospital for further investigation the procedure increased anxiety in 28%, decreased anxiety in 20%, and had no effect on the remainder. The sample of 137 (16%) men who, prior to interview, were in some way worried about problems of the prostate had significantly more urinary tract symptoms than those who were not at all worried about prostatic problems. Despite being worried about prostatic problems and having significant urinary symptoms, this group was no more likely to have attended a GP for investigation and/or treatment. Results are discussed in relation to the possible psychological effects of general health screening and the reluctance of men to attend for consultation despite awareness and concern regarding urinary symptomatology.