A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial

Background  

Because of a high cardiovascular disease (CVD) risk in people with Familial Hypercholesterolemia (FH), early prevention of cardiovascular disease is important for health gain and cost reduction. This project focuses on the development and evaluation of an innovative intervention aiming to reduce CVD risk by promoting a healthy lifestyle among people with FH.     

D-dimer in the diagnostic workup of suspected pulmonary thrombo-embolism at high altitude

Background

Pulmonary thrombo-embolism (PTE) is relatively common in high altitude areas where radiological diagnostic facilities are usually not available. So this study was undertaken to use the results of D-dimer assay to determine the need for imaging studies in patients suspected of having PTE at high altitude.

Methods

A total of 101 patients at an altitude of > 3,000 m suspected of having PTE were evacuated. D-dimer and imaging studies were carried out to confirm the diagnosis.

Results

A total of 101 patients suspected of having PTE underwent D-dimer level estimation and imaging studies for PTE. Sixty-eight of these had negative findings) on D-dimer assay. All these patients with negative findings on D-dimer assay had negative findings on pulmonary imaging studies also. So this test is very sensitive with very high negative predictive value (NPV). Whereas, 17 out of 33 patients positive for D-dimer, had positive findings on imaging studies, indicating a relatively less specific test.

Conclusion

Clinical assessment in combination with D-dimer assay can be used for timely differentiation of PTE from other conditions such as high altitude pulmonary oedema (HAPO) especially at isolated high altitude areas/military posts, so that patients could be evacuated as early as possible by fastest means to save the precious lives and in hospital settings this test identifies patients to whom anticoagulant therapy should not be given or patients who should not be subjected to invasive imaging tests.Key Words: D-dimer test, PTE     

AUTACOID INTERACTIONS IN THE REGULATION OF BLOOD FLOW IN THE HUMAN PLACENTA

1. Interactions between autacoids may play important roles in the regulation of blood flow in the foetal placenta. In order to investigate this aspect of placental haemodynamics, human normal-term placentae were perfused in vitro and the responses of the foetal vessels to various combinations of vasoactive agents were determined. 2. Vasoconstriction responses to 5-hydroxytryptamine (5-HT) were potentiated in the presence of endothelin-1 (ET-1), the thromboxane A₂-mimetic U46619 and a nitric oxide synthase inhibitor, N-nitro-l -arginine (NOLA), but not in the presence of angiotensin II. 3. N-Nitro-l -arginine caused vasoconstriction of the perfused placenta and indomethacin attenuated this effect and blocked the potentiation of the 5-HT response by NOLA. 4. Indomethacin did not affect ET-1-induced pressure increases and infusion of U46619 had no effect on release of ET-Iike immunoreactivity into the foetal placental circulation. 5. The present study provides evidence of interactions between several autacoids in human perfused placentae in vitro. These interactions may play important roles in foetal placental haemodynamics in normal or pathological situations.     

Effects of nicotine on bacterial toxins associated with cot death

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death.     

Elevated sleep arousal thresholds in enuretic boys: clinical implications

Enuretic children are described as difficult to arouse from sleep. We studied auditory sleep arousal thresholds in enuretic boys and report on die clinical implications of these findings. Fifteen enuretic and 18 control subjects (7–12-year-old males) were studied in a sleep laboratory for four consecutive nights using standard polysomnographic recording techniques. Sleep was undisturbed for the initial two nights and waking thresholds were measured on the following two nights. Enuretic children wet most frequently in the first two-thirds of the night. Arousal attempts were successful 39.7% of the time in controls and only 9.3% of the time in enuretics. In conclusion, enuretic males were more difficult to arouse than age-matched controls. The elevated arousal thresholds may be due to delayed maturation. Treatment programmes that rely on awakening should be aware of these features.     

Biologic effects of leukocytes present in transfused cellular blood products

A considerable literature has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens, and the immunomodulatory effects that might influence the prognosis of patients with a malignancy. Moreover, it has become evident that such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV as well as other viruses. An interesting development that has occurred coincidentally in transfusion medicine is that agencies responsible for the provision of blood products are being designated manufacturers of biologicals. The trend among manufacturers of biologicals is to try to produce pure products to provide for the specific therapeutic need of patients. Thus, with the realization that allogeneic leukocytes and their products may have adverse biologic activities, there is increasing pressure from various sources for the reduction of the leukocyte content in allogeneic blood components to minimize the occurrence of their adverse effects. Although the threshold leukocyte number below which these effects might no longer occur is still to be determined, a 2 to 3 log10 leukocyte reduction, provided by the currently available commercial leukocyte filters, has been shown to reduce the frequency of many of such reactions. On the other hand, the immunosuppressive effects produced by the infusion of allogeneic leukocytes might be beneficial for some patients, ie, for the maintenance of kidney allografts, in possibly reducing the relapse rate in patients with inflammatory bowel diseases, and in ameliorating recurrent spontaneous abortion. Moreover, therapeutic granulocyte transfusions may be of benefit in certain well- defined categories of patients infected with bacteria, yeast, and/or fungi. These include neonates with bacterial sepsis associated with bone marrow failure as well as severely neutropenic leukemic patients with an infection unresponsive to appropriate and specific antibiotic therapy. Many of the results obtained with the use of leukocyte depletion filters are tantalizing, but the actual clinical benefit of leukodepletion has not been established in most instances, because much of the available data are retrospective or from uncontrolled clinical trials. Moreover, issues of cost-effectiveness and quality control have not been considered adequately. Properly designed prospective clinical trials are essential to provide data with which to answer such questions and also to help define the optimal conditions required for the preparation of blood components ultimately destined for clinical use. Only with the availability of such data can sound decisions be made about the clinical value of leukodepletion.