Deciphering radiological stable disease to immune checkpoint inhibitors.

BACKGROUND: 'Stable disease (SD)' as per RECIST is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs). This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. Understanding SD would facilitate drug development and improve precision in correlative research. PATIENTS AND METHODS: A systematic review was carried out to characterize SD in ICI trials. SD and objective response were compared to proliferation index using The Cancer Genome Atlas gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of non-small-cell lung cancer (NSCLC). Serial cutpoints of two variables, % best overall response and progression-free survival (PFS), were tested to define a subgroup of patients with SD with similar survival as responders. Results were then tested in external validation cohorts. RESULTS: Among trials of ICIs (59 studies, 14 280 patients), SD ranged from 16% to 42% in different tumor types and was associated with disease-specific proliferation index (ρ = -0.75, P = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of NSCLC [1220 patients, 313 (26%) with SD to ICIs], PFS ranged widely in SD (0.2-49 months, median 4.9 months). The subset with PFS >6 months and no tumor growth mirrored partial response (PR) minor (overall survival hazard ratio 1.0) and was proposed as the definition of SD responder. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab and found to apply in tumor types treated with immunotherapy in which depth and duration of benefit were correlated. CONCLUSIONS: RECIST-defined SD to immunotherapy is common, heterogeneous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS >6 months and no tumor growth may be considered 'SD responders'. This definition may improve the efficiency of and insight derivable from clinical and translational research.

Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.

Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

The intake of thermally processed soybean reduces the feedlot period of lambs independently of roughage to concentrate ratio.

The objective of this study was to evaluate the nutrient intake and performance of feedlot lambs using 2 roughage to concentrate ratios and 2 types of soybean, whole (WS) or thermally processed (PS). Twenty male noncastrated market lambs weighting 23.26 ± 2.18 kg were used. The design was completely randomized in a factorial arrangement of 2 × 2. Diets were formulated with 50:50 and 20:80 of roughage to concentrate ratio on DM, and the thermal processing was realized in an autoclave at 120°C during 1 h. The end of the experimental period was determined by animal BCS, that is, the animals were slaughtered with a BCS between 3 and 3.5. The animals fed with 50% of roughage spent more time consuming feed (P < 0.01) and ruminating (P < 0.01). Thermally processed soybean provided more time consuming (P < 0.05) and less leisure time (P < 0.05) compared with WS. Diet with 20% of roughage provided increased ADG (P < 0.01) and better feed conversion (FC; P < 0.01). The utilization of PS resulted in decreased feedlot period (FP; P< 0.01), increased ADG (P < 0.05), decreased DMI (P < 0.01), and consequently better FC (P < 0.01). Diet with PS decreased the intake of ADF (P < 0.01). There was interaction between the roughage to concentrate ratio and soybean, wherein the diet with 50% of roughage and WS provided increased intake of NDF (P < 0.05). The use of thermally processed soybean provided better performance of lambs, and when this feed is associated with higher concentrate proportion, it reduces the intake of fibrous fraction of the diet.

Dental arch size, biting force, bizygomatic width and face height in three Colombian ethnic groups / Tamaño del arco dental, fuerza de mordida, anchura bizigomatica y altura facial en tres grupos étnicos colombianos

The objective of this study was to describe transversal dimensions of the dental arches, bite force and facial index in three ethnic groups representative of Colombia. The sample size included 197 adolescents, 12 to 14 year old, 33% mestizo, 35% of African ancestry and 32% Amazon Indian; 50.3% male and 49.7% female. The comparative analysis to determine differences between ethnic groups was made by the Kruskal Wallis test and then the Principal Component Analysis was used to establish the pattern of measurements identifying ethnic characteristics. All measurements showed statistically significant differences among ethnic groups except facial height (p=0.157). It was evidenced that Amazon indian have a higher bite force (p <0.05) than the other twoethnic groups. Regarding dental arch transversal dimensions, Amazon Indian have a higher arch transversal width with a length average of 44.1 mm. This length was greater than mestizo adolescents (M=36.7 mm) and Afroamerican (M=38.3 mm). In conclusion, the amazon Ticuna Indian ethnia has a significantly higher bite force, higher dental arch transversal width and higher bizygomatic width than the other two ethnic groups considered.

El objetivo fue describir las dimensiones transversales de los arcos dentales, la fuerza de mordida y el índice facial en tres grupos étnicos de Colombia. El tamaño de la muestra fue de 197 adolescentes, de 12 a 14 años; 33% mestizos, 35% de ascendencia africana y 32% indio amazónico; 50,3% hombres y 49,7% mujeres. El análisis comparativo para determinar las diferencias entre los grupos étnicos se hizo mediante la prueba de Kruskal Wallis y luego el Componente Principal de Análisis se utilizó para establecer el patrón de las mediciones para identificar las características étnicas. Todas las mediciones mostraron diferencias estadísticamente significativas entre los grupos étnicos, excepto la altura facial (p=0,157). Se evidencia que el indio amazónico tiene una mayor fuerza de mordida (p<0,05) que los otros dos grupos étnicos. En cuanto a las dimensiones transversales del arco dental, el indio amazónico se caracterizó por tener un mayor ancho, con una longitud media de 44,1 mm. Esta longitud es mayor que en los adolescentes mestizos (M=36,7 mm) y afroamericanos (M=38,3 mm). En conclusión, la etnia india amazónica Ticuna tiene una fuerza de mordida significativamente mayor, así como mayor ancho del arco dental transversal y ancho bicigomático que los otros dos grupos étnicos considerados.

Impact of human leukocyte antigen molecules E, F, and G on the outcome of transplantation.

BACKGROUND: HLA class I molecules are divided into classic (Ia) and nonclassic (Ib). Nonclassic HLA molecules (E, F, and G) have acquired relevance owing to their immunomodulatory properties and possible repercussions for induction of tolerance in organ transplantation. The objective of this study was to identify the impact of these molecules on transplant success or failure. METHODS: A systematic review of literature was performed with the use of MeSH terms in Pubmed. Clinical trials, randomized clinical trials, case-control studies, and reviews from the past 15 years were included. RESULTS: HLA-E*0103/E*0103 genotype is associated with lower risk of graft-versus-host disease, decreased mortality, and greater disease-free survival after bone marrow transplantation. There were no significant associations between HLA-F and clinical outcomes in any of the studies. Elevated serum levels of HLA-G were associated with a lower incidence of rejection in hepatic and renal transplantation during the 1st year and lower T-cell response after bone marrow, liver, and kidney transplantation. Detection of mRNA of HLA-G1 was also associated with less graft rejection. CONCLUSIONS: Current literature suggests that nonclassic HLA Ib molecules play an important role in immunotolerance in organ transplantation; however, more studies are required to predict outcomes related to specific genotypes.

Diabetes mellitus and renal transplantation in adults: is there enough evidence for diagnosis, treatment, and prevention of new-onset diabetes after renal transplantation?

BACKGROUND: New-onset diabetes after renal transplantation (NODAT) is one of the most frequent metabolic complications after transplantation; it is present in ∼25% of kidney transplant recipients, increasing their cardiovascular risk and inducing graft damage. The medical approach of this entity is still a matter of controversy, so our aim was to review the evidence available and offer a practical approach for diagnosis, treatment, and follow-up. METHODS: A systematic review of the literature in the Medline, Embase, Cochrane, and Lilacs databases was carried out with the use of the terms "Diabetes Mellitus," "Kidney Transplantation," "Drug Therapy," "Prognosis," "Therapeutics," and "Risk Factors." Randomized controlled trials, meta-analyses, and observational studies were included. RESULTS: The main risk factors were elevated body mass index, family history of diabetes, recipient >60 years old, hepatitis C virus infection, and treatment with tacrolimus/corticosteroids or sirolimus. Some small studies suggest that thiazolidinediones, sulfonylureas, glinides, and dipeptidyl peptidase 4 inhibitors could be useful in the treatment of the disease. NODAT constitutes a prognostic factor for the renal transplant. Although there is a higher risk of developing diabetes in kidney transplant recipients than in the general population, both populations share the same diagnostic criteria. CONCLUSIONS: There is no consensus on the treatment regimen for these patients. It is necessary to review the diagnostic criteria and the screening methods for NODAT, given the higher susceptibility of kidney transplant recipients to develop this entity; therefore, an earlier intervention could be implemented to decrease the negative effects that this disease has on the kidney graft and the recipient.

Analysis of dental arch dimensions in three Colombian ethnic groups / Análisis de las dimensiones del arco dental en tres grupos étnicos colombianos

The purpose of this study was to compare dental arch transversal and anteroposterior dimensions in three ethnic groups from Colombia. A digital caliper was used to take 16 transversal and two sagittal measurements, 9 for the upper jaw and 9 for the lower jaw. The sagittal measure determining arch length was drawn from a mesial line traced from first right permanent molar to first left permanent molar, and a perpendicular line from the point of contact between central incisive teeth, both for the upper and lower jaw. The dimensions of upper dental arch in the three ethnic groups showed differences in intercanine distance, as well as between premolar and between molar teeth. The same differences were found for lower dental arches. The populations evaluated show distinctive characteristics in dental arch dimensions, thus the mestizo population had narrow arches while the natives had wide arches.

El propósito de éste estudio fue comparar las dimensiones transversal y anteroposterior del arco dental en tres grupos étnicos de Colombia. Se utilizó un calibrador digital para tomar 16 medidas transversales y dos sagitales, 9 maxilares y 9 mandibulares. La medida sagital para determinar la longitud del arco se elaboró a partir de una línea trazada desde mesial primera molar derecho permanente al primer molar izquierdo permanente, y una línea perpendicular desde el punto de contacto entre los incisivos centrales, tanto para el maxilar y mandíbula. Las dimensiones del arco dental maxilar en los tres grupos étnicos mostraron diferencias en la distancia intercanina, así como entre premolares y molares. Las mismas diferencias se encontraron en la mandíbula. Las poblaciones evaluadas presentan características distintivas en las dimensiones del arco dental, por lo que la población mestiza tuvo arcos estrechos, mientras que los nativos tuvieron arcos anchos.

Perfil de ácidos graxos do leite de cabras leiteiras alimentadas com dieta contendo dois níveis de óleo de arroz / Production and milk composition of dairy goats receiving two levels of rice bran oil in the diet

Foram testados os efeitos de dois níveis de extrato etéreo à base de óleo de arroz no concentrado em 30 cabras Saanen durante a fase inicial de lactação. A alimentação baseou-se na relação 60% de volumoso (feno de alfafa) e 40% de concentrado comercial com dois níveis de extrato etéreo (3% e 5%). As variáveis estudadas foram a quantificação e qualificação do perfil de ácidos graxos do leite total e frente ao tempo de lactação. O acréscimo de óleo de arroz na dieta diminuiu (P<0,05) a concentração de ácidos graxos saturados e aumentou (P<0,05) a concentração de ácidos graxos poli-insaturados no leite caprino. O ácido linoleico conjugado (ALC) também é afetado positivamente pelo acréscimo de óleo de arroz na dieta. A inclusão de óleo de arroz nos níveis de 3% e 5% da matéria seca, na dieta de cabras leiteiras da raça Saanen, influencia o perfil de ácidos graxos do leite, com ênfase no ALC, até a 11ª semana de lactação.

The effects of two levels of ether extract based on rice oil concentrate in 30 Saanen goats during early lactation were evaluated. The feeding was based on the ratio of 60% forage (alfalfa hay) and 40% commercial concentrate with two levels of lipids (3% and 5%). The variables were the quantification and qualification of the fatty acid profile of whole milk and forward to the time of lactation. The addition of rice bran oil in the diet decreased significantly (P<0.05) the concentration of saturated fatty acids and increased (P<0.05) the concentration of polyunsaturated fatty acids in goats' milk. The linoleic acid was also positively affected by the addition of rice bran oil in the diet. The inclusion of rice bran oil at levels of 3% and 5% of dry matter in the diet of Saanen dairy goats influences the fatty acid profile of milk, with emphasis on linoleic acid until the 11th week of lactation.

Biotipo morfológico facial en tres grupos étnicos colombianos: una nueva clasificación por medio del índice facial / Facial biotype in three Colombian ethnic groups: a new classification by facial index

El objetivo de este estudio es evaluar el índice facial de tres poblaciones colombianas y proponer un nuevo método para identificar los biotipos morfológicos faciales teniendo en cuenta el tipo de ascendencia. Para esto, se tomaron las medidas de Nasion a Gnation y la distancia Bicigomática con un calibrador digital en tres grupos étnicos diferentes: 63 niños de la población Ticuna (Amazonas), 68 niños del municipio de Puerto Tejada (Cauca) y 65 niños del municipio de Santiago de Cali (Valle). Por medio de la prueba post hoc T2 de Tamhane se determinó que las poblaciones son distintas y que el índice morfológico facial tradicional no discriminaba esas diferencias. Por tal razón se utilizó el método estadístico de conglomerados difusos con el fin de determinar el número de grupos o biotipos para cada tipo de ascendencia. Se concluyó, que las poblaciones mestizas y afro-descendientes tienen similitudes por lo cual se agruparon juntas y el algoritmo c-medias generó cuatro biotipos característicos, mientras que para la población indígena Ticuna (Amazonas) solo se generaron tres biotipos.

The aim of this study is evaluate the facial index of three Colombian populations and propose a new method to identifythe facial morphological biotypes taking into account the type of ascendancy. For this, measures were taken of Nasion to Gnation and bizygomatic distance with a digital caliper in three ethnic groups: 63 children from Ticuna population (Amazonas), 68 children from municipality of Puerto Tejada (Cauca) and 65 children from municipality Santiago de Cali (Valle). Through the post hoc Tamhane's T2 was determined that the populations are different and the facial morphological index did not discriminate these differences. We used the statistical method of fuzzy clusters to determine the number of groups or biotypes for each type of ascendancy. We concluded that mixed populations and African descent have similarities, therefore they were grouped together and the c-means algorithm generated four biotypes characteristic, while the indigenous population Ticuna (Amazon) only generated three biotypes.

Significance of cytomegalovirus prophylaxis strategies and development of cancer in kidney transplant recipients.

Cytomegalovirus (CMV) infection is one of the most common complications among kidney transplant recipients; two approaches preventing this complication are currently available: universal prophylaxis (UP) and pre-emptive therapy (PT). Despite some differences, similar effectiveness and safety have been proven in several studies for both strategies. However, Spinner et al compared both treatments in 115 renal transplant recipients showing deaths were more likely to occur in patients who received UP. Most of these deaths (2/4 cases) occurred because malignancies developed. This finding is paradoxical because CMV is considered a potentially oncogenic virus and, therefore, UP (a longer therapy compared with the PT) should not be linked with the emergence of a greater number of tumors. New evidence suggests that changes in host immune response triggered by CMV infection may have a mitigating effect on the development of tumors. It is now known CMV infection produces a clonal expansion of gamma delta T lymphocytes which can elicit an aggressive response against neoplastic cells. Currently, UP is the therapy most frequently used in Colombian transplant centers; however, doses administered vary depending on several clinical and laboratory factors. There are no clinical cohorts treated with PT. Reviewing the impact of different length dosing schemes is important for creating an immune response affecting malignancy development in kidney transplant recipients.

Hypertrophy signaling during peripartum cardiac remodeling.

UNLABELLED: Molecular signaling pathways that regulate peripartum cardiac remodeling are not well understood. Our objectives were to study the role of mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) in mediating pregnancy and postpartum (PP) cardiac remodeling. METHODS: Adult female Sprague-Dawley rats were divided into nonpregnant (n = 5), 18 days pregnant (n = 5), 0 days PP (n = 7), and 14 days PP (n = 8). Rats underwent echocardiography under sedation to measure left ventricle (LV) size and function, and Western blots were performed to measure myocardial protein expression of MAPKs (p38, JNK, ERK), Akt, and eNOS. RESULTS: 1) During pregnancy, there was an increase in LV mass (0.62 +/- 0.03 to 1.1 +/- 0.04 g, P < 0.001), mass/volume ratio (0.7 +/- 0.02 to 1.28 +/- 0.02 g/ml, P < 0.0001), and ejection fraction (EF) (64 +/- 3 to 74 +/- 2%). Whereas LV mass and mass/volume ratio returned to prepregnancy values in the PP period, EF remained below normal range (53 +/- 3%, P < 0.05). 2) The expression of anti-hypertrophic factors (p38, JNK, Akt) decreased during pregnancy and normalized PP, except JNK, which increased to higher than normal levels. eNOS also increased to higher than baseline levels PP. 3) Activation of p38 and JNK was directly correlated with lower LV mass/volume ratio (r = -0.81 and -0.71, respectively; P < 0.05). CONCLUSION: Pregnancy is associated with physiological cardiac hypertrophy. There is rapid reversal of hypertrophy in the PP period while recovery of cardiac function is delayed, possibly related to PP upregulation of JNK. A dysregulation of MAPK signaling may be an important determinant of PP cardiac dysfunction.

Plasma nitrate accumulation during the development of pacing-induced dilated cardiac myopathy in conscious dogs is due to renal impairment.

Heart failure is associated with an increase in plasma nitrate and nitrite (NOx). To date there is still some controversy regarding the causes of nitrate accumulation during the development of heart failure. The goal of this study was to analyze the underlying mechanisms that cause accumulation of plasma nitrates during the development of heart failure in dogs. Dogs were chronically instrumented for measurement of hemodynamics and renal function. Hearts were paced initially at 210 bpm for 3 weeks and then at 240 until the development of heart failure. Hemodynamics, renal function, renal blood flow, arterial blood gases, hemoglobin, plasma and urine NOx levels, and creatinine levels were measured weekly. Heart failure was assessed by hemodynamic alterations, physical signs such as lethargy, ascites, cachexia, and postmortem evidence of cardiac hypertrophy. LVSP (from 127 +/- 3 to 106 +/- 3 mmHg), LV dP/dt (from 2658 +/- 173 to 1439 +/- 217 mmHg/s), MAP (from 101 +/- 1.9 to 83 +/- 1.8 mmHg) fell, whereas LVEDP tripled (from 6.4 +/- 0.9 to 20 +/- 2.6 mmHg), and heart rate rose (from 101 +/- 4.2 to 117 +/- 6.3 bpm), all changes P < 0.05. RBF (from 146 +/- 10 to 96 +/- 9.9 ml/min), urine output (V) (from 0.26 +/- 0.02 to 0.16 +/- 0.02 ml/min), GFR (from 63 +/- 1.8 to 49 +/- 2 ml/min), and Na excretion (from 45 +/- 4.5 to 14 +/- 4.6 microEq/min) all decreased (P < 0.05), whereas RVR increased (from 0.68 +/- 0.05 to 0.94 +/- 0.1 mmHg/ml/min). These changes took place during a rise in plasma NOx (from 3.7 +/- 0.5 to 16+/-3.3 microM), a decrease in urine NOx (from 33 +/- 9.9 to 8.1 +/- 4.9 microM), and a concurrent increase in NOx reabsorption (from 221 +/- 31 to 818 +/- 166 nmol/min). There was a direct correlation between the increase in plasma NOx levels and an increase in filtered load (r(2) = 0.97, P = 0.02), a negative correlation between NOx levels and NOx excretion (r(2) = 0.65 P < 0.09), and a direct correlation between plasma NOx levels and NOx reabsorption (r(2) = 0.97, P = 0.02). These results indicate that elevated plasma NOx during heart failure are most likely the result of an impairment of the renal function and not increased NOx production. Furthermore, without knowing changes in renal function the measurement of plasma NOx in and of itself is a meaningless index of NO formation.

[Inhibition of invasion and multiplication of Toxoplasma gondii in human colonic epithelial cells by a monoclonal antibody against protein SAG2]. / Inhibición de la invasión y multiplicación de Toxoplasma gondii en células epiteliales de colon humano por un anticuerpo monoclonal contra la proteína SAG2.

By an bromodeoxyuridine (BrdU) incorporation assay, it was proved hat an IgG 1 subclass, murine monoclonal antibody to surface protein SAG2 of Toxoplasma gondii is capable of reducing the invasion and multiplication of the parasites in highly differentiated mucine secretory HT29-18N2 line cells from a human colon adenocarcinoma. This result shows the importance of surface protein SAG2 of T.gondii in invasion and further multiplication of parasites in the host cell.

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in colombian patients with acute and chronic ocular toxoplasmosis.

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35%) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10%). In group 2 (recurrences) in 1/7 (14%) we found IgM and IgA test positives and in 1/7 (14%) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18%). These results show that serum IgM or IgA or IgE can be present during recurrences.

Bovine polymerized hemoglobin increases cardiac oxygen consumption and alters myocardial substrate metabolism in conscious dogs: role of nitric oxide.

We investigated the effect of bovine polymerized hemoglobin-based oxygen carrying (HBOC) solution on myocardial oxygen consumption (MVO2) and substrate use. At 15 min after the end of HBOC infusion (20% blood volume, i.v.) in nine permanently instrumented conscious dogs, mean arterial pressure and coronary blood flow were both increased by 41+/-5% and 93+/-20% (p<0.01) without affecting late diastolic coronary resistance and left ventricular dP/dtmax. Administration of HBOC did not affect arterial PO2 or O2 content, but significantly decreased coronary sinus PO2 and O2 content by 21+/-3% and 36+/-3%, respectively. MVO2 was increased from 7.2+/-0.8 to 15+/-1.8 ml O2/min (p<0.01). Despite an increase in triple product from 44+/-2 to 56+/-3 (p<0.01) 15 min after HBOC, the ratio of MVO2 and triple product was markedly elevated by 62+/-19%. Myocardial free fatty acid consumption was decreased from 14+/-1 to 4.5+/-2.2 microEq/min, whereas consumption of lactate increased from 19+/-6 to 69+/-10 micromol/ min and that of glucose increased from 1.0+/-0.5 to 10+/-3 mg/min (all p values, <0.05). These metabolic changes were not observed in dogs that received angiotensin II at a dose used (20-40 ng/kg/min, i.v.) to match those hemodynamic effects of HBOC. These results suggest that administration of HBOC increases coronary blood flow and MVO2 and shifts cardiac metabolism from using free fatty acid to using lactate and glucose in conscious dogs at rest. These metabolic changes are independent of the HBOC-induced change in hemodynamics.

A maternal screening program for congenital toxoplasmosis in Quindio, Colombia and application of mathematical models to estimate incidences using age-stratified data.

We studied 937 pregnant women from Quindio, Colombia for the presence of specific anti-Toxoplasma gondii IgG antibodies using the indirect immunofluorescence antibody technique (IFAT-IgG). Specific anti-T. gondii IgM antibodies detected using the immunosorbent agglutination assay (ISAgA-IgM) were investigated in patients with high titers in the IFAT-IgG (dilutions > or = 1:1,024). We used mathematical models based on the age prevalence results of the IFAT-IgG to estimate the number of seroconversions and these were compared with the results predicted by the IgM based-incidence results. We found 15 positive cases by ISAgA-IgM and we were able to follow the children of six mothers from this group in which we found one case of congenital toxoplasmosis with the development of a retinal scar despite prenatal and postnatal treatment. The estimation of new cases for the annual total of pregnancies (approximately 8,000) in the Quindio region was 30-120 according to the ISAgA-IgM results and 57-85 using mathematical models. Thus, mathematical models based on age prevalence can give useful estimations of the magnitude of the problem.