Intracoronary autologous bone marrow cell transplantation beneficially modulates heart rate variability

Antegrade femoral artery access is commonly used for percutaneous transluminal revascularization of ipsilateral lower limbs in patients with critical limb ischemia. While hemostasis at the end of the procedure can be achieved by manual compression, this may lead to an increase in local vascular complications. Femoral artery closure devices, such as the Angioseal collagen plug and anchor device, have been approved and shown of benefit after retrograde femoral artery catheterization. To date, there are however no data on the use of such arteriotomy closure device after antegrade femoral access. We hereby report a case series of five patients in whom Angioseal was successfully used after antegrade femoral puncture and below-the-knee percutaneous transluminal angioplasty. In all cases the device enabled immediate and complete hemostasis without major complications, despite the intense antithrombotic regimen, including heparin, aspirin, and clopidogrel in all patients, as well as glycoprotein IIb/IIIa inhibitors (in two patients) and fibrinolytic therapy (in one).     

Enhancing DNA vaccination by sequential injection of lymph nodes with plasmid vectors and peptides

DNA vaccines or peptides are capable of inducing specific immunity; however, their translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein, we demonstrate that a novel immunization strategy, encompassing sequential exposure of the lymph node milieu to plasmid and peptide in a heterologous prime-boost fashion, results in considerable MHC class I-restricted immunity in mice. Plasmid-primed antigen expression was essential for the generation of a population of central memory T cells, expressing CD62L and low in PD-1, with substantial capability to expand and differentiate to peripheral memory and effector cells, following subsequent exposure to peptide. These vaccine-induced T cells dominated the T cell repertoire, were able to produce large amounts of chemokines and pro-inflammatory cytokines, and recognized tumor cells effectively. In addition to outlining a feasible and effective method to transform plasmid DNA vaccination into a potentially viable immunotherapeutic approach for cancer, this study sheds light on the mechanism of heterologous prime-boost and the considerable heterogeneity of MHC class I-restricted T cell responses.     

Pelage insulation, litter size, and ambient temperature impact maternal energy intake and offspring development during lactation

Energy balance during lactation critically influences survival and growth of a mother's offspring, and hence, her reproductive success. Most experiments have investigated the influence of a single factor (e.g., ambient temperature [T_a] or litter size) on the energetics of lactation. Here, we determined the impact of multiple interventions, including increased conductive heat loss consequent to dorsal fur removal, cold exposure (T_a of 5 °C versus 23 °C), and differential lactational load from litters of different sizes (2 or 4 pups), on maternal energy balance and offspring development of Siberian hamsters (Phodopus sungorus). Lower T_a, fur removal, and larger litters were associated with increased maternal food consumption. Females exposed to multiple challenges (e.g., both fur loss and lower T_a) ate substantially more food than those exposed to a single challenge, with no apparent ceiling to elevated food intake (increases up to 538%). Thus, energy intake of dams under these conditions does not appear to be limited by feeding behavior or the size of the digestive tract. Housing at 5 °C attenuated pup weight gain and increased pup mortality to more than 5 times that of litters housed at 23 °C. Increases in the dam's conductive heat loss induced by fur removal did not affect pup weight gain or survival, suggesting that effects of low T_a on pup weight gain and survival reflect limitations in the pups’ ability to ingest or incorporate energy.     

Non-invasive assessment of graft patency using transcutaneous Doppler echocardiography for the validation of functional improvement after PTCA of the LAD via internal thoracic artery graft

Percutaneous transluminal coronary angioplasty (PTCA) of a native coronary artery via internal thoracic artery (ITA) graft after bypass surgery is a relatively rare procedure. Our current study evaluates the flow velocity patterns of the graft before and after PTCA. After intervention the mean diastolic flow velocity increased under rest and stress conditions. In addition, the graft patency was proved not before control angiography after 6 months. It could be verified that the measurement of flow velocity patterns under rest and stress conditions is a useful non-invasive procedure for monitoring long-term patency and PTCA-results of this vessel.     

Isolated primary aldosteronism in adrenocortical carcinoma: A case report and review of literature

Background Adrenocortical carcinoma synthesizing solely mineralocorticoids is an unusual disorder which has only been reported in literature in 22 other patients. Methods This case report describes a patient presenting with hypokalaemia, hypertension, metabolic acidosis and a left adrenal tumor. Extensive laboratory testing allowed the diagnosis of pure primary hyperaldosteronism without secretion of other steroids. Results The treatment of choice after establishing the diagnosis biochemically is to remove the tumor surgically. Histologically the lesion within the left adrenal was classified as a benign adrenocortical adenoma. After recurrence of, disease 6 months postoperatively, a widespread retroperitoneal tumor was en bloc resected and malignancy was confirmed by the histological features. When extended total histological examination of the first tumor was performed, capsular invasion was detected in one slice and the diagnosis of adrenocortical cancer was established retrospectively not only on the basis of clinical behavior. Despite precise surgical treatment of the recurrence and chemotherapy, the patient died 14 months after the diagnosis of primary hyperaldosteronism. Conclusions Close biochemical and clinical follow-up examinations are necessary in each patient with hormonlly active tumors. Sometimes only the postoperative course discriminates benign and malignant lesions.     

Pharmacokinetic aspects of the combination of interferon-alpha-2b and folic acid with fluorouracil]

The plasma levels of fluorouracil (5-fluorouracil, 5FU; CAS 51-21-8) after intravenous administration have been monitored without, under influence of interferon-alpha-2b (IFN) and under influence of IFN combined with folic acid (FA). IFN causes a highly significant change of the pharmacokinetic parameters of 5FU (p less than 0.001) compared to 5FU administration without IFN. The bioavailability of 5FU (compared as the AUC0-60 values) is elevated to 80%. In contrary, the combination of IFN with FA leads to a non-significant change of the 5FU pharmacokinetics, although the bioavailability is increased to 18%. The higher plasma levels of 5FU under the influence of IFN might be causes by a changed renal clearance, which is indicated by the reduction of the total plasma clearance at about 53%. The combination IFN/FA did not show a similar effect. Yet, in both cases an improvement of the tumor response and of the clinical picture could be observed.     

The effect of insulin treatment on the balance between tissue plasminogen activator and plasminogen activator inhibitor-1 in type 2 diabetic patients.

Beside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)     

Computer-assisted lateralization of unilateral temporal lobe epilepsy using Z-score parametric F-18 FDG PET images

Background

To evaluate the use of unbiased computer-assisted lateralization of temporal lobe epilepsy (TLE) by z-score parametric PET imaging (ZPET).

Methods

38 patients with histologically proven unilateral TLE due to pure hippocampal sclerosis, referred for pre-surgical PET evaluation of intractable seizure over a 5-year period, were included. The F-18 FDG images were oriented along temporal long axis and then transformed into ZPET images on a voxel by voxel basis. Multiple regions of interests (21 in total) were placed on cortical, subcortical and cerebellar structures on twenty-eight out of 38 patients with totally seizure-free (class I) outcome. Paired t-tests with Bonferroni correction were used to determine the location of the most asymmetric regions as variables for subsequent discriminant analysis of the entire group of the patients.

Results

The computer program identified the anterior half of the temporal lobe (p < 0.0005) and thalami (p = 0.021) as the most asymmetric regions in TLE patients with Class I outcome. Discriminant analysis using z-scores from a total of 8 ROIs (in 4 pairs) on these structures correctly lateralized thirty-seven out of 38 (97%) patients (sensitivity = 94%; specificity = 100%). The only false localization came from a patient with equivocal z-scores on the temporal lobes and this patient turned out to have poor outcome.

Conclusion

The computer-assisted lateralization of TLE using ZPET provides an accurate, fast and objective way of seizure evaluation.