Recovering an endangered frog species through integrative reproductive technologies.

The establishment and management of ex situ breeding and assurance populations around the globe are meant to provide short-term solutions to the formidable loss of amphibian diversity presently occurring. Large multi-scaled facilities, such as zoos and aquariums, can provide the infrastructure to safeguard species and populations. However, often even large, economically viable facilities lack the knowledge to efficiently cater to the plethora of environmentally controlled physiological strategies that amphibians possess. Anurans present a class of amphibians that have often been viewed as easy to maintain ex situ. However, while adult survival may be relatively successful it is rarely accompanied by good reproductive output, health, and fitness. Even more conspicuous is the low survivorship of offspring produced ex situ once they are translocated back into the wild. The mountain yellow-legged frog (R. muscosa) ex situ breeding program EBP is a prime example of the challenges that amphibians EBPs face. Although more research is needed, the R. muscosa program has increased reproductive output and health of its colony by incorporating reproductive technologies and strategic genetic management in conjunction with a greater understanding of the species' natural history, to produce and translocate viable animals each year. This paper highlights the EBPs past decade of research featuring the program's contribution to building empirical, multidisciplinary approaches that boost the robustness of an endangered species, by safeguarding existing genetic diversity and maximizing fitness and survival outcomes.

Economic evaluation of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial.

BACKGROUND: Evidence about the cost-effectiveness and cost utility of computerised cognitive-behavioural therapy (CCBT) is still limited. Recently, we compared the clinical effectiveness of unsupported, online CCBT with treatment as usual (TAU) and a combination of CCBT and TAU (CCBT plus TAU) for depression. The study is registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236). AIMS: To assess the cost-effectiveness of CCBT compared with TAU and CCBT plus TAU. METHOD: Costs, depression severity and quality of life were measured for 12 months. Cost-effectiveness and cost-utility analyses were performed from a societal perspective. Uncertainty was dealt with by bootstrap replications and sensitivity analyses. RESULTS: Costs were lowest for the CCBT group. There are no significant group differences in effectiveness or quality of life. Cost-utility and cost-effectiveness analyses tend to be in favour of CCBT. CONCLUSIONS: On balance, CCBT constitutes the most efficient treatment strategy, although all treatments showed low adherence rates and modest improvements in depression and quality of life.

A novel approach to calculation of mean mitral valve gradient by Doppler echocardiography.

The Doppler-derived mean mitral valve gradient (DeltaP(M)) based on the simplified Bernoulli equation requires computerized integration of the Doppler signal and evaluation by a technician with the use of special equipment. We have noted empirically that the DeltaP(M) can be derived by the equation DeltaP(M) = (P(P) - P(T)) / 3 + P(T). Peak (P(P)) and trough (P(T)) pressures are derived from the simplified Bernoulli equation (P = 4V(2)). This equation can be used by the experienced observer to calculate the mean mitral valve gradient without specialized equipment. The purpose of this study is to validate the above empirically derived equation in patients with mitral stenosis. We retrospectively reviewed 41 consecutive studies done at our institution from October 1, 1997, through September 30, 1998, in which mean mitral valve gradient was assessed. Each study was reviewed and the DeltaP(M), P(P), and P(T) were measured for 3 beats by using the software package on an HP Sonos 2500. DeltaP(M) was also calculated with our formula. A linear regression model was used to compare the results of the measured versus the calculated DeltaP(M). The following sub-categories were also evaluated: transthoracic studies (TTE), transesophageal studies (TEE), native valve gradients (NV), prosthetic valve gradients (PV), sinus rhythm (SR), and atrial fibrillation (AF). The results of the regression analysis of the entire population of mean versus calculated DeltaP(M) are n = 41, r = 0.99, P <.001, and standard error of the estimate (SEE) = 0.67. The regression results for the subgroups are as follows: TTE: n = 30, r = 0.99, P <.001, SEE = 0.51; TEE: n = 11, r = 0.99, P <.001, SEE = 59; NV: n = 26, r = 0.99, P <.001, SEE = 0.59; PV: n = 15, r = 0.98, P <.001, SEE = 0.84; SR: n = 23, r = 0.99, P <.001, SEE = 0.58; and AF: n = 18, r = 0.98, P <.001, SEE = 0.82. In conclusion, the simple formula that we have derived is an accurate method for calculation of mean mitral valve gradient, and it is accurate over multiple subgroups. Furthermore, the formula allows visual verification of mean mitral gradient without specialized software.

Meta-analysis of 143 reported cases of aortic intramural hematoma.

Aortic intramural hematoma (IMH) is a clinical condition that has still not been completely defined. We conducted a meta-analysis of reported cases and analyzed the demographic profiles, imaging modalities, pathologic sites, and treatment strategies in relation to outcome in 143 patients with IMH. We performed an English language search of Medline for manuscripts with the keywords "aortic diseases," "aorta AND hematoma," and "intramural hematoma." Data from 143 reported cases were extracted. IMH of the aorta has a reported incidence of 5% to 20% among patients with acute aortic syndromes and a mortality rate of 21%. Most patients were men (61%) and median age was 68 years (range 15 to 88). Hypertension was a predisposing factor in 53% of the patients. Most patients had chest and/or back pain (80%). Transesophageal echocardiography, computer tomographic scan, or magnetic resonance imaging may be effectively used to diagnose this condition. There is no difference in the overall mortality rates in Stanford type A versus type B patients. Patients with Stanford type A IMH who underwent surgery, compared with those who underwent medical management, had a significantly better prognosis (14% vs 36% mortality, respectively, p < 0.02). Patients in Stanford group A who received medical treatment had a higher mortality rate than those in group B who received medical treatment (36% vs 14% mortality respectively, p < 0.02). In type B patients, medical and surgical outcomes were similar.

Cardiac manifestations of acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome is a serious problem worldwide. Recent advances in the knowledge about human immunodeficiency virus (HIV) replication and the treatment of HIV infection have improved survival in HIV patients. Because of the longer survival in HIV patients, the more manifestations of late-stage HIV infection will be seen, including HIV-related cardiac diseases. The common cardiac manifestations in patients with the acquired immunodeficiency virus are pericardial effusion, myocarditis, dilated cardiomyopathy, endocarditis, pulmonary hypertension, malignant neoplasms, and drug-related cardiotoxicity. This review focuses on these cardiac manifestations in patients with the acquired immunodeficiency syndrome.

Clinical predictors of pulmonary hypertension in patients undergoing liver transplant evaluation.

Clinical prediction of portopulmonary hypertension (PPHTN) is critical in the preoperative evaluation of candidates for orthotopic liver transplantation (OLT) because of its association with significant morbidity and mortality. To determine the clinical, laboratory, and echocardiographic predictors of PPHTN, we retrospectively evaluated 55 candidates before OLT. From those, 8 candidates had pulmonary hypertension ([HTN] group A) and 47 candidates did not (group B). Pulmonary HTN was defined as a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater and either elevated pulmonary vascular resistance or normal pulmonary artery wedge pressure. The significant predictors of PPHTN were (1) systemic arterial HTN (63% in group A v 9% in group B; P <.001), (2) loud pulmonary component of the second heart sound (38% v 2%; P =. 001), (3) right ventricular (RV) heave (38% v 4%; P =.002), (4) RV dilatation by echocardiogram (63% v 0%; P <.001), (5) RV hypertrophy by echocardiogram (38% v 0%; P =.001), and (6) echocardiogram-estimated systolic PAP (SPAP) greater than 40 mm Hg (63% v 2%; P <.001). The sensitivity of these variables for the detection of pulmonary HTN ranges from 37% to 63%, and their specificity from 91% to 100%. We conclude that several clinical and echocardiographic features are significantly associated with pulmonary HTN in patients with cirrhosis. In particular, echocardiogram-estimated SPAP greater than 40 mm Hg is strongly associated with pulmonary HTN and is specific. These predictors, however, are not sensitive enough to identify all the patients with PPHTN. Therefore, the evaluation of a combination of these variables may be useful for the preoperative identification of pulmonary HTN in liver transplant candidates.

Incidence of bleeding complications associated with abciximab use in conjunction with thrombolytic therapy in patients requiring percutaneous transluminal coronary angioplasty.

The use of abciximab after full-dose failed thrombolytics within 15 hours of acute myocardial infarction significantly increases the risk of major bleeding complications.

Hypoxia due to patent foramen ovale in the absence of pulmonary hypertension.

In most patients with a patent foramen ovale, blood flows from the left atrium to the right atrium in the absence of pulmonary hypertension. Our report describes a patient with a patent foramen ovale in whom flow occurred from the right atrium to the left atrium in the absence of pulmonary hypertension. We discuss hemodynamic findings and present a brief review of the pertinent medical literature regarding this phenomenon. We also discuss the role of transesophageal echocardiography in the diagnosis of this condition and in the elucidation of the underlying mechanisms, and we suggest several mechanisms that may explain the occurrence of this phenomenon in our patient.

Bacterial lipopolysaccharide binds and stimulates cytokine-producing cells before neutralization by endogenous lipoproteins can occur.

Lipoproteins are able to bind to lipopolysaccharide (LPS) and neutralize its deleterious effects. However, it is not clear why the LPS-binding capacity of circulating lipoproteins, which is 10- to 10 000-fold above the maximal LPS concentrations found in septic patients, is not sufficient to inhibit the effects of LPS during an infection, whereas infusion of exogenous lipoproteins has a potent inhibitory action. In this study, the kinetics of LPS-neutralization by VLDL, LDL, and HDL were investigated, at lipoprotein-to-LPS ratios found in severe Gram-negative sepsis. At least 4-8-h preincubation of LPS with either LDL or HDL were necessary to inhibit 50% of the LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMC), whereas after 24 h of preincubation LDL or HDL strongly inhibited the TNF-alpha synthesis (70-90%, P<0.01). VLDL was the least effective lipoprotein fraction. In contrast, FITC-LPS bound to PBMC much more rapidly, with 70% of the total binding after 30 min, and 90% after 1-h incubation. The increase of LDL or HDL concentrations up to 10-fold (as in experimental models of hyperlipoproteinaemia) was able not only to further decrease TNF-alpha production after long LPS-lipoproteins preincubation periods, but also to improve the kinetics of LPS neutralization. In conclusion, LPS binds and stimulates the mononuclear cells in circulation before neutralization by endogenous lipoproteins can occur. Additional increase in the lipoprotein-to-LPS molar ratio (e.g. by infusion of exogenous lipoproteins) accelerates the kinetics of LPS neutralization, and may be useful as adjunctive therapy in severe Gram-negative infections.

Evaluation of hemolysis in patients with prosthetic heart valves.

The primary mechanism and most common cause of hemolytic disease in patients with prosthetic heart valves are mechanical trauma to red blood cells and paraprosthetic valvular regurgitation, respectively. Presenting features in patients with this condition include anemia, congestive heart failure, fatigue, jaundice, dark urine, and a regurgitant murmur. Various laboratory studies can be utilized to diagnose hemolytic anemia and to assess the severity of hemolysis. Transthoracic echocardiography, transesophageal echocardiography, and Doppler studies including color Doppler are useful imaging methods to assess valve function. Treatment is usually medical (oral iron); however, in patients with paravalvular regurgitation, surgery is often required to correct the anemia.

Lipoprotein(a) inhibits lipopolysaccharide-induced tumor necrosis factor alpha production by human mononuclear cells.

Lipoproteins can bind lipopolysaccharide (LPS) and decrease LPS-stimulated cytokine production. Lipoprotein(a) [Lp(a)] was as potent as low-density lipoproteins (LDL) in inhibiting LPS-stimulated tumor necrosis factor synthesis by human mononuclear cells. The kinetics of LPS inhibition by Lp(a) was similar to that of LDL. This suggests that circulating Lp(a) may be an important factor determining the amplitude of the response to LPS in humans.

Glutathione homeostasis is disturbed in CD4-positive lymphocytes of HIV-seropositive individuals.

BACKGROUND: Numerous in vitro tests have suggested that a disturbed cellular glutathione homeostasis plays an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. METHODS: Using validated high-performance liquid chromatography (HPLC) methods, glutathione concentrations were determined in plasma and in cytosol of CD4+ lymphocytes and CD14+ cells of HIV-seropositive individuals and healthy control subjects. We measured concentrations of total glutathione, which is the sum of reduced (GSH) and oxidised (GSSG) glutathione and mixed disulphides of which there are two fractions: soluble mixed disulphides (GSSR) and protein bound glutathione (ProSSG). Also, non-protein-bound glutathione was measured, which is the sum of GSH, GSSG and GSSR. Thirty-five healthy control subjects and 35 HIV-infected individuals participated in the study. RESULTS: We found that in CD4+ lymphocytes from HIV-seropositive individuals, total glutathione levels were significantly higher than in healthy control subjects, whereas the fraction of non-protein-bound glutathione was not different. This can only be explained by an increase in the protein-bound fraction of glutathione indicating the presence of oxidative stress in CD4+ lymphocytes of HIV-seropositive individuals. Glutathione measurements of cytosol of CD14+ cells and plasma were, however, not compatible with significant increased oxidation. Glutathione precursors (cysteine, cysteinylglycine, glutamylcysteine and homocysteine) and products of lipid peroxidation (thiobarbituric acid-reactive substances) were also measured in plasma and did not differ between healthy control subjects and HIV-seropositive individuals. CONCLUSION: We conclude that the glutathione homeostasis is disturbed in CD4+ lymphocytes of HIV-seropositive individuals. The glutathione redox dysbalance in CD4+ lymphocytes could be important in the pathogenesis of HIV infection and have implications for therapy.

Mycotic aneurysm of the descending thoracic aorta: the role of transesophageal echocardiography.

Mycotic aneurysms of the aorta are prone to rupture. Thus rapid and accurate diagnosis is essential so that surgical repair can be undertaken. We report a case of mycotic aortic aneurysm caused by mitral valve endocarditis. The aneurysm situated at the junction of the thoracoabdominal aorta was readily detected by transesophageal echocardiography. Computed tomography and aortography were complementary to transesophageal echocardiography in establishing the diagnosis. The patient underwent successful repair and acute inflammation of the aneurysm was present at histologic examination.