Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Minimally Invasive Valve Surgery

Cardiac valve surgery is life saving for many patients. The advent of minimally invasive surgical techniques has historically allowed for improvement in both postoperative convalescence and important clinical outcomes. The development of minimally invasive cardiac valve repair and replacement surgery over the past decade is poised to revolutionize the care of cardiac valve patients. Here, we present a review of the history and current trends in minimally invasive aortic and mitral valve repair and replacement, including the development of sutureless bioprosthetic valves.     

CaseBook Consults: Improving Outcomes in Gout (Multimedia Activity)

Gout is a chronic, potentially debilitating condition characterized by an inflammatory process in the joints or periarticular tissues that results from the deposition of monosodium urate crystals. Underdiagnosis and undertreatment can lead to the development of tophi and chronic arthropathy. A presumptive diagnosis of gout can be made on the basis of the clinical presentation as well as risk factors such as metabolic syndrome. Key conditions to rule out in the differential diagnosis are septic arthritis, calcium pyrophosphate deposition disease (pseudogout), fracture, and rheumatoid arthritis. Acute flares of gout should be managed with nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids. With a diagnosis of gout, if urate-lowering therapy (ULT) is required, prophylaxis should be considered with low-dose colchicine or an NSAID, followed by the addition of ULT. The goal of ULT is to reach a serum uric acid (SUA) level ≤6.0 mg/dL. Measurements of SUA should be obtained after resolution of an acute attack, then periodically to facilitate titration of the ULT dose to achieve the target SUA level. Studies have confirmed significant reductions in gout attacks among patients who have attained SUA levels ≤6.0 mg/dL with ULT. Patient education concerning the disease and its treatment is essential to ensure close adherence with recommended therapies. Patients should also understand that ULT is intended as long-term, and for most patients, lifelong therapy to maximize the prospects for control of the disease. Clinicians should feel confident in making a presumptive diagnosis and choosing a therapeutic regimen for gout while effectively communicating with and educating patients about their disease.     

Starting Off on the Best Foot: A Review of Message Framing and Message Tailoring,and Recommendations for the Comprehensive Messaging Strategy for Sustained Behavior Change

Health promotion programs represent a salient means through which physical activity promoters can cultivate positive health behavior change and maintenance. The messages communicated within these programs serve as an essential component as they are often used to convey valuable information, resources, or tools that facilitate health behavior initiation and sustained engagement. Identifying the most effective way to communicate health promotion information is, therefore, of considerable importance to ensuring that people not only attend to these messages, but also connect with and internalize the information conveyed within them. This paper was written to (1) summarize and evaluate the most prominent reviewed research approaches of message framing and tailoring to message design; and (2) offer a comprehensive messaging strategy to promote sustained health behavior change. A review of the literature demonstrated that a messaging strategy that has consistently led to healthy behavior change has yet to be identified. Furthermore, scholars have articulated that a multi-theoretical approach that places emphasis on facilitating motivation and healthy behavior change needs to be employed. Thus, this paper proposes and provides recommendations for employing the Comprehensive Messaging Strategy for Sustained Behavior Change (CMSSBC), which advocates tailoring messages to peoples’ stage of change and framing them to focus on self-determined motives and intrinsic goals.     

Genetic markers may predict disease behavior in patients with ulcerative colitis

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis. (Gastroenterology 1997 Jun;112(6):1845-53)     

Close association of herpes zoster reactivation and systemic lupus erythematosus (SLE) diagnosis: case-control study of patients with SLE or noninflammatory nusculoskeletal disorders

OBJECTIVE: To investigate the prevalence of infections, particularly the frequency of shingles and the timing of varicella zoster virus (VZV) reactivation, and antibiotic use, vaccinations, and joint trauma prior to and at diagnosis of systemic lupus erythematosus (SLE). METHODS: We sent questionnaires to patients with SLE (n = 93) and controls with noninflammatory musculoskeletal disorders (MSK; n = 353) including osteoarthritis, fibromyalgia, and tendonitis. We matched SLE patients to controls for sex (up to 1:3). RESULTS: The response rate in SLE was 66% and in controls 69% (p < 0.53). Four of 61 SLE patients and 12 of 173 controls were men. The mean disease duration in the SLE group was 8 +/- 1 years compared to 10 +/- 1 years in controls (p < 0.23). SLE patients were significantly younger than controls (mean age of SLE patients 49 +/- 2 vs 57 +/- 1 years for controls; p < 0.0004), and results were adjusted for age. A significantly higher proportion of SLE participants had a history of VZV (shingles) (19% vs 7%, respectively; OR 2.98, p < 0.003), whereas rubella was reported less in SLE (23% vs 42%; OR 0.43, p < 0.03). VZV infections were clustered just prior to or after diagnosis in SLE but were more widely spaced temporally in the controls (1 +/- 4.5 years after the diagnosis of SLE vs -14.7 +/- 4 years before the diagnosis of noninflammatory MSK disorder; p < 0.003). Diagnosis of shingles was observed in 6 of 11 SLE patients within +/- 2 years of SLE diagnosis, whereas only 2 of 15 controls had shingles within +/- 2 years of diagnosis (OR 7.2, p < 0.03). Only 2 patients with SLE were taking immunosuppressive drugs or steroids at time of shingles, so immunosuppressive therapy was not usually concomitant at time of VZV reactivation. Common infections (respiratory, urinary tract, ear, and eye) in the SLE group exceeded controls, but not significantly (23% vs 9%; OR 2.98, p < 0.06) and SLE patients were more likely to have been vaccinated since 18 years of age with any type of vaccine (69% vs 51%; OR 2.21, p < 0.04). SLE patients were less likely than controls to report joint trauma within one year prior to their diagnosis (25% vs 40%; OR 0.49, p < 0.04). There were no differences with respect to streptococcal throat infection (p < 0.96), diarrhea/vomiting (p < 0.84), rash with fever (p < 0.07), parvovirus infection (p < 0.16), infection after surgery (p < 0.58), respiratory tract infection (p < 0.71), or ear (p < 0.09) and eye infection (p < 0.68) one year prior to diagnosis. A higher proportion of SLE patients had a history of urinary tract infections (46% vs 25%), but this was not significant (p < 0.17), nor was it significant one year prior to diagnosis (p < 0.63). Overall, the likelihood of having any infection one year prior to diagnosis was not significantly higher in the SLE group (p < 0.56). There were no differences one year prior to diagnosis in travel history (p < 0.69), hospitalizations (p < 0.47), use of antibiotics (p < 0.54), history of rheumatic fever, positive TB skin test, or hepatitis A, B or C infection. CONCLUSION: Varicella reactivation as shingles is increased in patients with SLE and clusters around diagnosis. Vaccinations are increased in those with SLE compared to controls. Common infections are not significantly increased in SLE patients prior to onset of symptoms. We cannot determine if VZV infections are causally associated with SLE in some people, are from an abnormal immune system response due to the lupus itself or from the use of steroids or other immunosuppressive drugs to control the disease, or are spurious.     

Patients with Ehlers-Danlos syndrome type IV lack type III collagen.

One of the genetically distinct collagens (type III) normally found in skin, aorta, and intestine is missing from the tissues of patients with the Ehlers-Danlos syndrome type IV. While skin fibroblasts from other individuals synthesize both types I and III collagen. Ehlers-Danlos syndrome IV cells synthesize only type I. These results suggest that the fragile skin, blood vessels, and intestines of Ehlers-Danlos syndrome IV patients result from an absence of type III collagen.