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.     

Mammography using an ultrahigh-strip-density, stationary, focused grid

A 1-mm-thick, stationary, ultrahigh-strip-density, focused grid was evaluated with respect to patient radiation dose and mammographic image quality as it affected the resolution of microcalcifications and masses. Radiographic technique was varied to determine the most useful alteration to improve image quality with the grid. Results from 89 patients demonstrated that no improvement in diagnostic ability was found in women with fatty breasts. As breast density increased, the advantage of the grid technique became more apparent. Grid mammography also often solved the problem of questionable microcalcifications with improved visualization of their number and geometry.     

安心酮注射剂研制及其稳定性研究

以正交设计筛选处方,研制了安心酮注射剂,考察了制剂的稳定性,有效期为２．８５年。采用酸性染料比色法测定注射剂中安心酮的含量,平均回收率为９８．７％（ＲＳＤ＝０．４４％）。本品对离体灌流豚鼠心脏的作用与原药相似。     

Pregnancy management and successful outcome of Ehlers-Danlos syndrome type IV

Ehlers-Danlos syndrome type IV (EDS IV) is a rare but serious disorder of connective tissue that is characterized by the abnormal production or secretion of type III collagen. Experience with pregnant patients exhibiting this syndrome is limited. This report describes the successful management of a pregnancy in a woman with EDS IV that included activity restriction and complete bed rest after 32 weeks, use of 1-desamino-8-D-arginine vasopressin (DDAVP) before delivery to improve coagulation, and cesarean section before the onset of labor. The possibility of prenatal diagnosis based on genetic linkage studies also is discussed.     

Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low- molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.      

Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia.

We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all-trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d-dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor 1 (PAI-1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin-1 beta (IL-1 beta). The mean plasma levels of fibrin d-dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL-1 beta gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL-1 beta) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.     

Winning the battle but losing the war: methicillin-resistant Staphylococcus aureus (MRSA) infection at a teaching hospital

A methicillin-resistant Staphylococcus aureus (MRSA) control policy, aimed at eradication, was established at a 1000-bed hospital in 1985, applied consistently for 10.5 years, and then relaxed. Its components included screening of high-risk patients, transfer of carriers to exhaust-ventilated isolation rooms, closure of wards to new admissions when local transmission was detected, MRSA screening during outbreaks, and prospective collection of clinical and epidemiological information. During the eradication policy period, every 6 months, a mean of 5.1 patients (range 1-12) already carrying MRSA were admitted, and a mean of 3.6 (range 0-16) acquired carriage in the hospital. The largest outbreak comprised 11 patients despite epidemic MRSA strain EMRSA-16 being introduced six times, and MRSA did not become endemic. MRSA- positive admissions increased progressively from 1993; nursing staff workload increased, areas available for alternative patient accommodation were reduced, the resulting ward closures interfered with clinical services, and hence the control policy was relaxed in mid- 1995. Isolation facilities were overwhelmed with 622 new patient- isolates in the next 18 months, and there were 67 clinical infections in 1996. The proportion of blood cultures positive for MRSA rose nearly sevenfold by 1996 and 27-fold by 1997. Thus, repeated eradication of MRSA, even epidemic strains, by use of a stringent policy, is possible given sufficient resources, whereas flexible national guidelines designed to control, but not eradicate, epidemic staphylococci, are currently unlikely to be successful. The costs of eradication policies need to be weighed against those of endemicity.      

The effects of epinephrine infusion in patients with von Willebrand''s disease.

Epinephrine infusion causes variable increases in the components of the Factor VIII (antihemophilic factor) complex in patients with von Willebrand's disease. The increase in antihemophilic factor procoagulant activity was greater than that of Factor VIII-related antigen and von Willebrand factor activity in two patients with von Willebrand's disease. Similar increases in the three individual factors were demonstrated in two other patients. A 4-10-fold increase in Factor VIII-related properties was identified in each of these individuals after infusion. One patient has been studied with very severe von Willebrand's disease; none of the Factor VIII-related properties increased despite two infusions of epinephrine. Bleeding times were normalized or remained normal in the two patients whose von Willebrand factor activity was greater than 25 U/100 ml. It remained prolonged in those three patients whose von Willebrand factor activity levels remained below that concentration. The increase in procoagulant activity was transient in all patients and t 1/2 values were estimated to be between 0.8 and 3.4 h.