Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.     

Hypercalcaemia in chronic lymphatic leukaemia

A 75 year old woman with a 13 year history of classical chronic lymphatic leukaemia (CLL) developed hypercalcaemia. Unlike previous reports, this was not associated with blastic transformation, hyperparathyroidism or features of multiple myeloma, but was due to classical CLL per se.     

Axonal domains within shared touch domes in the rat: a comparison of their fate during conditions favoring collateral sprouting and following axonal regeneration

Low-threshold mechanosensory nerves in the adult rat differ both from their counterparts in lower vertebrates and from high-threshold nociceptive nerves in mammals in that they appear not to undergo collateral sprouting into adjacent denervated skin, although they will clearly regenerate into it after they are damaged. We have now studied the growth capabilities of the low-threshold nerves supplying touch domes, the visible mechanosensory structures scattered throughout the hairy skin. Touch domes in the rat are often multiply innervated. A serendipitous observation on such domes allowed us to investigate the possibility that a functional collateral sprouting of their nerves can indeed occur, but only to a spatially very restricted extent, e.g., within the confines of a partially denervated dome. We used a "prodder" with a tip diameter of 16 micron to examine the mechanosensory profile across single domes that were preselected as being supplied by only two axons, one running in each of two adjacent dorsal cutaneous nerves (DCNs). Simultaneous recordings were made of the afferent discharges evoked in these nerves when the prodder was applied at about 17 or more locations on a selected dome; the spatial resolution was better than 55 micron. We found that within such a shared dome, one axon can supply a discrete territory (its "domain"), which may or may not overlap with the corresponding domain of the other axon. In a preliminary electron microscopic study, we found no evidence for a sharing of single Merkel cells, which are the specialized sensory cells in touch domes, even in the regions of a shared dome where two domains overlapped; each innervated Merkel cell appeared to be contacted by a single nerve ending, implying that in a shared dome each axon probably supplies an exclusive subpopulation of the Merkel cells. We tested for functional collateral sprouting by eliminating one nerve to a shared dome, and at a selected time thereafter mapping the domain of the remaining axon to see whether it had enlarged. The result was the same whether the two domains initially had a region of overlap or not; no expansion of the surviving domain occurred over postoperative periods up to 4 months (an expansion of the domain by 55 micron would have been detected). Thus functional collateral sprouting had failed to occur.(ABSTRACT TRUNCATED AT 400 WORDS)     

Variability of ankle and brachial systolic pressures in the measurement of atherosclerotic peripheral arterial disease.

The aim of this study was to determine the variability of measurements of ankle and brachial systolic pressures and ankle brachial ratios in order to assess their suitability for use in epidemiological studies of arterial disease in the lower limbs. Thirty-six subjects had repeat measurements taken by four observers on two separate days using a Doppler probe and random zero sphygmomanometer. The variability in the measurement of ankle systolic pressure was comparable to that for brachial systolic pressure. The 95% confidence limits of one measurement of the ankle brachial ratio was estimated to be +/- 16%, reducing to +/- 10% for the mean of four measurements taken by two observers on two days. Analysis of variance indicated that the variability in the measurement of ankle brachial ratios attributable to observers, days, timing of measurements on the same day, and repeat measurements was considerably less than the "biological" variability between subjects and between legs. These results suggest that repeatability of the ankle brachial ratio is such that a single measurement is suitable for most epidemiological studies of atherosclerotic peripheral arterial disease.     

Application of molecular biology techniques to malignant haematology]

Malignant hemopathies, although heterogeneous in their prognosis and oncogenesis, represent an interesting model for studying cancer genesis mechanisms in man through the recurrent presence of genetic abnormalities involved in oncogenesis and the availability of tumour material. Nowadays, molecular biology techniques are very much used for the diagnosis, the treatment and the follow-up of these diseases. Firstly used for research, the new techniques have completely changed our ability to characterise malignant hemopathies and to understand the cancer-inducing processes, permitting us to perform the biological assessment of patients with malignant hemopathies, the diagnosis, and to estimate and follow the outcome of patients after treatment. At a more fundamental level, the structural and functional analysis of the deregulated genes implied in leukaemia and lymphoma has improved our knowledge and understanding of oncogenic and physiologic mechanisms significantly.     

The Effects of IB4, a Monoclonal Antibody to the CD18 Leukocyte Integrin on Phorbol Myristate Acetate (PMA)-Induced Polymorphonuclear Leukocyte (PMN) Accumulation and Endothelial Injury in Rabbit Lungs

A model of acute lung injury induced by intravenous phorbol myristate acetate (PMA) is described. The model is characterized by the accumulation of polymorphonuclear leukocytes (PMNs) and a hemorrhagic edema in bronchoalveolar lavage (BAL) fluid when measured 6 h following the administration of PMA (60 g/kg, i.v.). It was also determined that PMA induces acute leukopenia and neutropenia which were maximal at 5 min following the injection of PMA and were sustained for at least 6 h, with circulating leukocyte numbers returning to control values by 24 h. The extents to which the inflammatory and systemic changes induced by PMA were dependent on the surface expression on leukocytes of the 2-integrins was assessed by comparing responses to PMA in control animals and animals pretreated with the anti-CD18 monoclonal antibody IB4. The administration of IB4 (1 mg/kg, i.v.) 15 min before PMA did not alter the time course or extent of PMA-induced leukopenia and neutropenia. In contrast IB4 administration (0.1 to 1 mg/kg) produced a dose dependent inhibition of PMN accumulation and plasma extravasation measured in BAL fluid. IB4 (1 mg/kg) completely inhibited PMA evoked increases in plasma extravasation (94.5 ± 1.7%, N = 4) and hemorrhage (95.2 ± 2.1%, N = 4) whereas PMN accumulation in BAL fluid was inhibited by 77.8 ± 3.8% (mean ± SEM, N = 4). Thus, a small, but reproducible, component of the PMA-induced PMN accumulation was not inhibited using this regimen of IB4 administration. If IB4 administration was delayed for 3 h post injection of PMA and bronchoalveolar lavage performed 3 h later, the extents of PMN accumulation and edema formation were similar to those observed 3 h following PMA challenge in control animals not dosed with IB4. This suggests that administration of IB4 during an ongoing inflammatory response is capable of preventing the further development of inflammatory changes and further supports the therapeutic potential of CD18 blockade in conditions such as adult respiratory distress syndrome.     

Do women 'over-report' morbidity? Men's and women's responses to structured prompting on a standard question on long standing illness

It is frequently observed in contemporary industrialised societies that although women live longer than men, they are sicker than men in that they report higher rates of morbidity, disability and health care use. One common element of the explanation for women's higher rates of morbidity is that there are gender differences in the way that symptoms are perceived, evaluated and acted upon. It is widely assumed that women will be more ready to report illness and to seek help and that they have greater flexibility in their lives to accommodate illness. The few studies that have examined men and women with the same conditions or symptoms are contradictory, but lend little support to this hypothesised greater propensity, yet it is still widely believed. Here we compare men's and women's answers to a global, commonly used question about chronic illness and to a series of more specific prompts and classify the conditions reported by an externally defined categorisation of severity and International Classification of Disease chapter. Contrary to the common expectation that women report higher rates of morbidity and are more ready to report mental health problems, we found: no gender differences in the initial reporting of conditions; men reported a higher proportion of their conditions in response to the initial global question; and no evidence that women were more likely to report 'trivial' or mental health conditions in response to the initial question.