Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity

We have determined the plasma level of fibrinopeptide A as a specific index of thrombin activity during the infusion of a thrombolytic agent in patients with acute myocardial infarction. Peripheral venous plasma levels of fibrinopeptide A increased following the initiation of thrombolytic therapy from 2.7 nmol/L to a peak of 13.0 nmol/L at 30 minutes with streptokinase and from 1.1 nmol/L to a peak of 10.7 nmol/L at 90 minutes with tissue plasminogen activator. The amount of fibrinogen converted to fibrin I was determined by integration of the plasma level of fibrinopeptide A over time. The amount of fibrin I formed over the five-hour period from the start of drug infusion was approximately 10 mg/dL in response to either streptokinase or recombinant tissue plasminogen activator. We conclude that activation of coagulation occurs in response to thrombolytic therapy despite heparin administration. This thrombin action, though transient, would be sufficient to cause rethrombosis if localized and incompletely opposed by fibrinolytic activity.     

Sunscreens – what's important to know

The popularity of sunscreens dramatically increased since ultraviolet irradiation was implicated in the pathogenesis of skin cancer and skin ageing. The absorption properties, safety, photostability of different organic and inorganic filters are reviewed: para -aminobenzoic acid, salicylates, cinnamates, benzophenones, butylmethoxydibenzoylmethane (Parsol 1789), drometrizole trisulphonic (Mexoryl XL), terephthalydene dicamphor sulphonic acid (Mexoryl SX), methylene bisbenzotriazol tetramethylbutylphenol (Tinasorb M), anisotriazine (Tinasorb S), titanium dioxide and zinc oxide. Furthermore, this review discusses the optimal methods for measuring the protection that a sunscreen offers, the role of sunscreen use in melanoma prevention and future trends in sunscreen filters development.     

A systematic review and meta-analysis of complications following the posterior and lateral surgical approaches to total hip arthroplasty

IntroductionTotal hip arthroplasty is one of the most commonly performed orthopaedic procedures. Despite this, medical evidence to inform the choice of surgical approach is lacking. Currently in the UK, the two most frequently performed approaches to the hip are the posterior and the direct lateral.MethodsThis systematic review was performed according to Cochrane guidelines following an extensive search for prospective controlled trials published in any language before January 2014. Of the 728 records identified from searches, 6 prospective studies (including 3 randomised controlled trials) involving 517 participants provided data towards this review.FindingsCompared with the lateral approach, the posterior approach conferred a significant reduction in the risk of Trendelenburg gait (odds ratio [OR]: 0.31, p=0.0002) and stem malposition (OR: 0.24, p=0.02), and a non-significant reduction in dislocation (OR: 0.37, p=0.16) and heterotopic ossification (OR: 0.41, p=0.13). Neither approach conferred a functional advantage. We draw attention to the paucity of evidence and the need for a further randomised trial.     

The process of HIV status disclosure to HIV-positive youth in Kinshasa, Democratic Republic of the Congo

As access to HIV/AIDS treatment increases in sub-Saharan Africa, greater attention is being paid to HIV-infected youth. Little is known about how HIV-positive youth are informed of their HIV infection. As part of a larger formative study informing a treatment program in Kinshasa, Democratic Republic of the Congo, semi-structured interviews were conducted with 19 youth (10-21 years) who had previously been told their HIV status and 21 caregivers who had disclosed the youth's HIV status to the youth. Questions explored youth's and caregivers' experiences of and immediate reactions to disclosure. Youth's median age at disclosure was 15 years old, with a range of 10-18 years based on caregiver reports (n=21) and from 10-19 years based on youth reports (n=18). The most common reasons spontaneously given for disclosing were the child's adherence to their treatment regimen (5/16), the need of the child to protect her/himself or stay healthy (5/16), the child's increasing age (4/16) and so that the child would know why they are suffering (3/16). Most youth (16/19) were surprised to learn of their diagnosis; 50% (8/16) wondered about the infection's origins. A large majority felt that it is better for them to know their HIV status (88%; 15/17). HIV care and treatment programs must be prepared to address the psychosocial needs of youth and their caregivers during the disclosure process.     

Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt's lymphoma

A patient with Burkitt's lymphoma in complete remission received myeloablative consolidation treatment with superfractionated total body irradation (1,320 rad) and cyclophosphamide (200 mg/kg) followed by autologous transplantation of previously harvested and cryopreserved blood-derived hemopoietic stem cells. Seven successive leukaphereses were performed to yield a total of 55.2 X 10(9) mononuclear cells (MNC) comprising 15.1 X 10(6) CFU-GM or 4.34 X 10(6) CFU-GEMM. Following autologous blood stem cell transplantation (ABSCT), reconstitution of all cell lines occurred very rapidly, ie, 1,000 leucocytes per microL were reached after nine days, 500 granulocytes and 50,000 platelets per microL after ten days. B cells reached normal values around day 35 post- transplantation. CFU-GM first appeared in the circulating blood exhibiting an enormous overshoot. Some days later CFU-GM also appeared in the marrow. The kinetics and pattern of hemopoietic reconstitution after myeloablative treatment and ABSCT provide clear evidence that blood-derived hemopoietic stem cells are capable of completely restoring hemopoietic function in man. A possible reconstitutive advantage of blood over marrow-derived stem cells is discussed.     

Interleukin 4 in inflammatory bowel disease and mucosal immune reactivity

BACKGROUND & AIMS: Interleukin (IL) 4 has immunoregulatory and anti- inflammatory activities, but little is known about IL-4 in the human gut. We investigated production of IL-4 by isolated lamina propria mononuclear cells (LPMCs) from normal and inflamed intestine and its capacity to modulate local immune responses. METHODS: IL-4 levels were measured by enzyme-linked immunosorbent assay in cultures of control and inflammatory bowel disease LPMCs, and the effect of IL-4 on LPMC proliferation and interaction with IL-2, IL-1 beta, lipopolysaccharide, bacterial antigens, superantigen, and antibodies to various T-cell receptors was investigated. RESULTS: Various stimuli induced LPMCs to produce IL-4, but inflammatory bowel disease cells expressed IL-4 messenger RNA and secreted protein in significantly lower amounts than control cells. IL-4 failed to stimulate proliferation by fresh LPMCs, but a vigorous dose-dependent response was observed after preactivation by phytohemagglutinin, IL-2, or IL-4. When added to fresh LPMCs, IL-4 inhibited IL-2-induced proliferation. IL-4 amplified proliferation to IL-1 beta, lipopolysaccharide, peptidoglycan-polysaccharide complexes, staphylococcus enterotoxin A, and antibodies to the CD3 and CD28 receptors but not to tetanus toxoid. CONCLUSIONS: Decreased production of IL-4 in inflammatory bowel disease may cause defective immunosuppressive and anti-inflammatory mechanisms and may contribute to disease pathogenesis. The ability of IL-4 to differentially modulate LPMC reactivity probably influences mucosal immune homeostasis. (Gastroenterology 1996 Jun;110(6):1683-95)     

Alveolar recruitment strategy and PEEP improve oxygenation,dynamic compliance of respiratory system and end‐expiratory lung volume in pediatric patients undergoing cardiac surgery for congenital heart disease

Objective: Optimizing alveolar recruitment by alveolar recruitment strategy (ARS) and maintaining lung volume with adequate positive end‐expiratory pressure (PEEP) allow preventing ventilator‐induced lung injury (VILI). Knowing that PEEP has its most beneficial effects when dynamic compliance of respiratory system (Crs) is maximized, we hypothesize that the use of 8 cm H₂O PEEP with ARS results in an increase in Crs and end‐expiratory lung volume (EELV) compared to 8 cm H₂O PEEP without ARS and to zero PEEP in pediatric patients undergoing cardiac surgery for congenital heart disease. Methods: Twenty consecutive children were studied. Three different ventilation strategies were applied to each patient in the following order: 0 cm H₂O PEEP, 8 cm H₂O PEEP without an ARS, and 8 cm H₂O PEEP with a standardized ARS. At the end of each ventilation strategy, Crs, EELV, and arterial blood gases were measured. Results: EELV, Crs, and P_aO₂/FiO₂ ratio changed significantly (P < 0.001) with the application of 8 cm H2O + ARS. Mean P_aCO₂– PETCO₂ difference between 0 PEEP and 8 cm H2O PEEP + ARS was also significant (P < 0.05). Conclusion: An alveolar recruitment strategy with relative high PEEP significantly improves Crs, oxygenation, P_aCO₂– PETCO₂ difference, and EELV in pediatric patients undergoing cardiac surgery for congenital heart disease.