Assessment of blood pressures and gradients by automated blood pressure device compared to invasive measurements in patients previously operated on for coarctation of the aorta.

The aim of the study was to compare invasive and non-invasive blood pressure measurements and gradients. Twenty-two children and 16 adults previously operated for coarctation of the aorta were included. Invasive blood pressures were recorded proximally and distally close to the former operation site and non-invasive systolic blood pressures were recorded by an automated sphygmomanometer on right arm and leg. The adults were investigated at rest and during supine exercise. The correlation between invasive and non-invasive measurements of proximal blood pressures in adults at rest and children were the following, r = 0.92, SD 7.6 mmHg (n = 16) and r = 0.85, SD 11 mmHg (n = 22) respectively. The corresponding correlation for the distal blood pressures were the following for adults at rest 0.64, SD 11.9 mmHg and in children r = 0.82, SD 9.2 mmHg. During exercise in adults we found a low correlation when comparing invasive and non-invasive proximal and distal blood pressures and a poor correlation regarding the gradients, r = 0.50, SD 16 mmHg, r = 0.45, SD 15.9 mmHg and r = 0.30, SD 22.9 mmHg respectively (n = 16). We also measured the time interval between cessation of exercise and completion of the blood pressure recordings, which gave a mean interval of 73 sec (range 45-115 sec). During that interval the mean fall in the proximal blood pressure was 37 mmHg (range 20-80 mmHg), and the mean fall of the gradient was from 41 mmHg (range 20-76 mmHg) to 23 mmHg (range 6-56 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissecting eIF4E action in tumorigenesis

Genetically engineered mouse models are powerful tools for studying cancer genes and validating targets for cancer therapy. We previously used a mouse lymphoma model to demonstrate that the translation initiation factor eIF4E is a potent oncogene in vivo. Using the same model, we now show that the oncogenic activity of eIF4E correlates with its ability to activate translation and become phosphorylated on Ser 209. Furthermore, constitutively activated MNK1, an eIF4E Ser 209 kinase, promotes tumorigenesis in a manner similar to eIF4E, and a dominant-negative MNK mutant inhibits the in vivo proliferation of tumor cells driven by mutations that deregulate translation. Phosphorylated eIF4E promotes tumorigenesis primarily by suppressing apoptosis and, accordingly, the anti-apoptotic protein Mcl-1 is one target of both phospho-eIF4E and MNK1 that contributes to tumor formation. Our results provide insight into how eIF4E contributes to tumorigenesis and pinpoint a level of translational control that may be suitable for therapeutic intervention.     

Comparative analysis of real-time PCR assays in the detection of canine visceral leishmaniasis

Parasitology Research - Dogs are important hosts and reservoirs of leishmaniasis, a disease caused by protozoan parasites from the genus Leishmania, affecting ~12 million people worldwide. The...     

Potentiation by granulocyte macrophage colony-stimulating factor of lipopolysaccharide toxicity in mice.

GM-CSF is known to prime leukocytes for inflammatory stimuli in vitro. The objective of this study was to investigate the role of GM-CSF in vivo in a systemic inflammatory reaction syndrome. The results demonstrate a potentiation of LPS toxicity by GM-CSF in a mortality model as well as in a septic liver failure model in mice. Pretreatment of animals with 50 micrograms/kg GM-CSF induced lethality within 24 h in mice challenged with a subtoxic dose of LPS while controls survived > 72 h. A monoclonal anti-GM-CSF antibody significantly protected against a lethal LPS dose. Serum GM-CSF was inducible by LPS and peaked at 2 h. GM-CSF pretreatment dramatically potentiated systemic TNF release and hepatotoxicity induced by a subtoxic dose of LPS in galactosamine-sensitized mice. Potentiation of LPS hepatotoxicity was possible until 30 min after LPS challenge. Polyclonal anti-GM-CSF IgG protected against septic liver failure in this model and attenuated serum TNF concentrations. In vitro an ex vivo experiments revealed that after GM-CSF pretreatment LPS-induced IL-1 release from bone marrow or spleen cells was also enhanced. These findings suggest that GM-CSF represents an endogenous enhancer of LPS-induced organ injury, possibly by potentiating the release of proinflammatory cytokines such as TNF and IL-1.     

Improvement in glycemic control over 11 years in patients monitored for diabetes in one county.

BACKGROUND: Hemoglobin A(1c) (HbA(1c)) has been used in controlled trials for the last 10 years but has never been evaluated in clinical practice as an effective parameter for clinical outcome. We investigated the trend for glycemic control over 11 years in one county of 350,000 citizens. METHODS: We studied 226,382 HbA(1c-DCCT-aligned) from 39,455 patients in whom routine monitoring for diabetes was initiated in 1993, 1996, or 2001. The trend in glycemic control was investigated in groups by probit plots, and in individual patients by target plots. RESULTS: From 1993 to 2001, the number of HbA(1c) measurements increased three-fold. The number of new monitoring series increased from 0.22% to 0.27% of the county population, and the number of patients monitored using HbA(1c) as a proxy for diabetes increased from 0.5% to 1.5%. A proportional reduction in high HbA(1c) concentrations of 5% was identified in the 1993 group, compared to 15% in the 1996 group, and 20% in the 2001 group. The percentage of patients with diabetic first HbA(1c) experiencing normalization increased from 8% to 30% for males and from 9% to 24% for females (1993-2001). The percentage of HbA(1c) concentrations that were not normalized decreased from 78% to 53% for males and from 83% to 59% for females (1993-2001). The median HbA(1c) at initiation of monitoring decreased from 8.7% in 1993 to 7.5% in 2001 (p < 10(-5)). The number of normal first HbA(1c) results in monitoring series increased from 7% to 17% for males and from 8% to 22% for females. Up to 10% of subjects developed diabetic concentrations during monitoring. CONCLUSION: On average, patients with diabetic first HbA(1c) concentrations (> or =6.62%) showed an improvement in glycemic control from 5% in 1993 to 20% in 2001. High concentrations were easiest to reduce. In patients with originally diabetic HbA(1c) levels, 66% on average showed improved glycemic control in the 2001 series compared to 50% in the 1993 series. An average of 6% (1993) vs. 9% (2001) with originally normal HbA(1c) levels showed an upward trend inHbA(1c) levels. Median HbA(1c) at initiation of monitoring decreased from 8.7% in 1993 to 7.5% in 2001 (p < 10(-5)). The incidence of new cases was constant.     

Outcomes of Minimally Invasive versus Open Radical Hysterectomy for Early Stage Cervical Cancer Incorporating 2018 FIGO Staging

Study ObjectiveTo compare outcomes after minimally invasive surgery (MIS) vs open radical hysterectomy for early stage cervical cancer incorporating 2018 Federation of Gynecology and Obstetrics (FIGO) staging.DesignA retrospective analysis.SettingA single teaching hospital.PatientsPatients after radical hysterectomy for stage IA1 with lymphovascular invasion, IA2, or IB1 squamous, adenosquamous, or adenocarcinoma of the cervix between 2007 and 2018, mirroring the Laparoscopic Approach to Cervical Cancer trial criteria.InterventionsThe use of MIS surgery for performing radical hysterectomy.Measurements and Main ResultsThe outcomes were compared between patients undergoing MIS vs open approaches. A total of 126 patients met the inclusion criteria. The approach was open in 44 patients (35%) and MIS in 82 patients (65%); 49% were laparoscopic and 51% were robotic. Distribution based on the 2009 FIGO staging showed 1 stage IA1 with lymphovascular invasion, 15 stage IA2, and 110 stage IB1 patients. Although not statistically significant, the 3-year disease-free survival (DFS) was higher in the open compared to the MIS group (95% vs 87%; p = .17), and the overall survival was higher in the open compared to the MIS group (97% vs 92%; p = .25).Fourteen patients whose disease recurred were Stage IB1 by FIGO 2009 staging; 11/14 were reclassified to a higher stage by 2018 FIGO staging (5/5 open, 6/9 MIS). Adjuvant therapy was recommended for all these patients based on the Sedlis criteria (10/14) or other risk factors (4/14). Despite this, only 1/9 of MIS patients whose disease recurred received adjuvant therapy compared with 3/5 patients whose disease recurred in the open group (p = .05).ConclusionIn a cohort of patients similar to that of the Laparoscopic Approach to Cervical Cancer trial, 2018 FIGO staging may be useful to refine indications for MIS radical hysterectomy in early stage cervical cancer. However, disparate outcomes between MIS and open approaches may be explained by differences in compliance with National Comprehensive Cancer Network guidelines for adjuvant therapy.     

Effects of load and type of physical training on resting and postexercise cardiac autonomic control

The aim of the study was to investigate the influence of training load and exercise mode on heart rate variability and heart rate recovery (HRR) in healthy individuals. The subjects were divided into three groups: sedentary (SED), resistance trained (RT) and aerobically trained (RT). Resting and postmaximal exercise RR intervals were recorded on supine and seated position, respectively. The HRV indices calculated in the resting position were RMSSD and LF and HF power densities. The following HRR indices were calculated throughout the 5‐minute postmaximal recovery period: semi‐logarithmic regression analysis of the first 30 s (T30); absolute difference between the peak and 60 s HR (HRR_60s); and mono‐exponential time constant of HRR (HRRτ). The RMSSD on subsequent 30‐s segments (RMSSD_30s) on recovery period was also calculated. Both RT and AT groups presented faster HRR than SED (P<0·05). The aerobic trained group was the only group that presented vagal reactivation, when analysing the RMSSD_30s. There were no correlations between the Baecke sport score and the HRV vagal‐related indices. However, it was significantly correlated with HRR. It was concluded that that the training load positively influences the HRR, but has no effect on the HRV at rest and that the type of exercise, showed a marked influence on HRV recovery.