Cysteamine-induced depletion of brain somatostatin is associated with up-regulation of cerebrocortical somatostatin receptors

Cysteamine (CSH) administered as a single sc injection to rats produced rapid depletion of cerebrocortical Somatostatin-14 like immunoreactivity (S-14 LI) with a significant 48% reduction occurring within 5 min and maximum (72%) decrease at 4 h. The depletion of S-14 LI was associated with a 1.7 fold increase in Bmax of the cerebrocortical S-14 receptors 5 min after CSH administration and a concomitant but slower increase in the affinity of these receptors [dissociation constant (Kd) being 1.8- and 1.6-fold lower than the control at 30 and 60 min, respectively, post CSH]. Incubation of intact synaptosomes with 1 mM CSH at 37 C in vitro for 60 min also caused a rapid depletion of S-14 LI, but in contrast to the in vivo data, there was no change in the Bmax or Kd of the S-14 receptors for up to 30 min beyond which time a 2.8-fold decrease in the affinity of S-14 receptors was observed. Higher concentrations of CSH (greater than or equal to 10 mM) added during the incubation of synaptosomes in vitro completely abolished the specific binding of these receptors. The pituitary S-14 receptors were studied 30 min after CSH administration and unlike the cerebrocortical S-14 receptors at this time did not exhibit any change in Bmax or affinity. When added at the time of the binding assay CSH (1 mM) was without a direct effect on cerebrocortical as well as pituitary membrane S-14 receptors. Furthermore, addition of CSH at the time of binding assay did not destroy the integrity of [125I-Tyr11]S-14. It is concluded that administration of CSH to rats in vivo depletes brain S-14 LI and up-regulates synaptosomal S-14 receptors. Exposure of synaptosomes to CSH in vitro for 30 min also depletes S-14 LI but has no effect on S-14 receptors suggesting that S-14 receptor regulation by S-14 is an in vivo phenomenon or requires the intact cell. CSH has a direct inhibitory effect on S-14 receptor binding after prolonged in vitro incubation. Pituitary S-14 receptors unlike those in the brain are unaffected by S-14 LI depletion at least acutely.     

Evidence for the presence of glucagon-like immunoreactivity (GLI) in the pancreas.

Glucagon-like immunoreactivity (GLI), which can be separated from glucagon by isoelectric focusing, has been detected in partially purified canine pancreatic extracts. Like gastrointestinal GLI, this insular GLI reacts with crossreacting antiserum 78J but not with glucagon "specific" antiserum 30K and has an isoelectric point (pl) of 9.5, whereas canine pancreatic glucagon has a pl of 6.25. When combined with glucagon, the GLI-glucagon mixture gives 48J assay values between GLI and this crossreacting antiglucagon serum and thus conceals it in glucagon-containing extracts.     

Percutaneous popliteal approach for angioplasty of superficial femoral artery occlusions

Angioplasty using the percutaneous popliteal approach was utilized in 50 patients (PTS) to recanalize 59 occluded superficial femoral arteries which had been unsuccessfully canalized by using the antegrade approach because of either a flush origin occlusion or inability to maintain the guide wire in the true lumen. All PTS had claudication; 8 had rest pain; 3 had non-healing ulcers. The laser Probe was used in 17 cases and the Rotablator in 3 cases. Occlusion length varied between 1 and 40 cm: 7 lesions were less than 10 cm (group 1); 9 were between 10 and 20 cm (group 2); and 43 were greater than 20 cm (group 3). An angiographic success was obtained in 48/59 lesions (81%): 14/16 (87%) in groups 1 and 2 and 34/43 (79%) in group 3. Three PTS needed complementary common femoral endarterectomy and one required percutaneous aspiration of a thromboembolus. Complications included: arterial perforation and/or dissection (without clinical sequelae) in 11 and a popliteal hematoma in 1 PT. One patient with a severely ischemic leg underwent successful emergency vascular surgery, while another limb salvage patient required below-knee amputation. There was no worsening of limb ischemia from any popliteal approach attempt. At discharge, 39 patients (78%) whose outcome would have been unsuccessful with the traditional antegrade approach were clinically improved after utilizing the popliteal approach to achieve a successful angioplasty procedure.     

Identification of novel markers for mouse CD4+ T follicular helper cells

CD4⁺ T follicular helper (T_FH) cells are central for generation of long‐term B‐cell immunity. A defining phenotypic attribute of T_FH cells is the expression of the chemokine R CXCR5, and T_FH cells are typically identified by co‐expression of CXCR5 together with other markers such as PD‐1, ICOS, and Bcl‐6. Herein, we report high‐level expression of the nutrient transporter folate R 4 (FR4) on T_FH cells in acute viral infection. Distinct from the expression profile of conventional T_FH markers, FR4 was highly expressed by naive CD4⁺ T cells, was downregulated after activation and subsequently re‐expressed on T_FH cells. Furthermore, FR4 expression was maintained, albeit at lower levels, on memory T_FH cells. Comparative gene expression profiling of FR4^hi versus FR4^lo Ag‐specific CD4⁺ effector T cells revealed a molecular signature consistent with T_FH and T_H1 subsets, respectively. Interestingly, genes involved in the purine metabolic pathway, including the ecto‐enzyme CD73, were enriched in T_FH cells compared with T_H1 cells, and phenotypic analysis confirmed expression of CD73 on T_FH cells. As there is now considerable interest in developing vaccines that would induce optimal T_FH cell responses, the identification of two novel cell surface markers should be useful in characterization and identification of T_FH cells following vaccination and infection.     

Surgical experience with diseases of the tricuspid valve. Cross-sectional and Doppler echocardiographic evaluation following DeVega's repair

Seventy-eight patients undergoing mitral valve surgery with or without replacement of the aortic valve also underwent procedures on the tricuspid valve over a period of 10 years. All patients were in functional class III or IV preoperatively. The procedures were performed in all patients with organic disease of the tricuspid valve (N = 44) and in those with moderate or severe functional tricuspid valvar regurgitation (N = 34). Seventy-one patients underwent DeVega's annuloplasty with or without commissurotomy. The overall mortality was 11.5%. 65 long-term survivors were followed up for a period of 6 months to 10 years (mean 5.3 years). Sixty-three patients were in functional class I or II at the last follow-up. Six patients had clinical evidence of mild to moderate tricuspid regurgitation. Regression of cardiomegaly (as judged by the chest radiograph and right ventricular hypertrophy seen in the electrocardiogram) was evident in most cases. Fifty-one of 54 patients evaluated by cross-sectional echocardiography were reported to have a functionally normal tricuspid valve. Doppler echocardiography in 28 patients showed no significant tricuspid regurgitation or stenosis in 26 patients. Eleven consecutive patients undergoing DeVega's annuloplasty were studied prospectively with pre- and postoperative Doppler echocardiography. Good correlation existed between right ventricular systolic pressures predicted by Doppler with those obtained preoperatively at cardiac catheterization. Postoperative Doppler echocardiography in these 11 patients showed complete restoration of competence of the tricuspid valve as well as normalisation of the right ventricular systolic pressure in 10 patients.     

Do Current Recommendations for Upper Instrumented Vertebra Predict Shoulder Imbalance? An Attempted Validation of Level Selection for Adolescent Idiopathic Scoliosis

Background

Shoulder balance for adolescent idiopathic scoliosis (AIS) patients is associated with patient satisfaction and self-image. However, few validated systems exist for selecting the upper instrumented vertebra (UIV) post-surgical shoulder balance.

Questions/Purposes

The purpose is to examine the existing UIV selection criteria and correlate with post-surgical shoulder balance in AIS patients.

Methods

Patients who underwent spinal fusion at age 10–18 years for AIS over a 6-year period were reviewed. All patients with a minimum of 1-year radiographic follow-up were included. Imbalance was determined to be radiographic shoulder height |RSH| ≥ 15 mm at latest follow-up. Three UIV selection methods were considered: Lenke, Ilharreborde, and Trobisch. A recommended UIV was determined using each method from pre-surgical radiographs. The recommended UIV for each method was compared to the actual UIV instrumented for all three methods; concordance between these levels was defined as “Correct” UIV selection, and discordance was defined as “Incorrect” selection.

Results

One hundred seventy-one patients were included with 2.3 ± 1.1 year follow-up. For all methods, “Correct” UIV selection resulted in more shoulder imbalance than “Incorrect” UIV selection. Overall shoulder imbalance incidence was improved from 31.0% (53/171) to 15.2% (26/171). New shoulder imbalance incidence for patients with previously level shoulders was 8.8%.

Conclusions

We could not identify a set of UIV selection criteria that accurately predicted post-surgical shoulder balance. Further validated measures are needed in this area. The complexity of proximal thoracic curve correction is underscored in a case example, where shoulder imbalance occurred despite “Correct” UIV selection by all methods.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9451-y) contains supplementary material, which is available to authorized users.     

Correlation between peripheral arterial disease and coronary artery disease using ankle brachial index-a study in Indian population

ObjectiveTo study the prevalence of peripheral arterial disease (PAD) of the lower limbs in a high-risk population and its correlation with coronary artery disease (CAD), using the ankle brachial index (ABI).MethodsThe present study was conducted in randomly selected indoor patients >45 years of age with one or more risk factors for PAD admitted in the cardiology and medicine wards in a tertiary care institute.ResultsBased on ABI <0.9, PAD was diagnosed in 32 of the 182 (18%) patients. Coronary artery disease was present in 15 cases of PAD which was statistically significant.ConclusionThere is a definite and strong correlation between PAD and CAD. Correct diagnosis and supervision of patients with PAD is important for preventing the local progression of the disease and effective secondary prevention of future coronary and cerebrovascular events.