Metabolic studies in human obesity during overnutrition and undernutrition: thermogenic and hormonal responses to norepinephrine

Overfeeding increases the thermogenic response of norepinephrine (NE) in normal but not in certain genetically obese rodents. It has been suggested that human obesity may be associated with a similar thermogenic defect. To determine whether there are differences in the thermogenic sensitivity to NE in human obesity, energy expenditure in response to graded infusions of NE (0.05, 0.10, 0.15, 0.20 micrograms/min/kg fat-free mass) was measured in six lean and six obese subjects (9.5 +/- 1.8 v 36.3 +/- 3.8% body fat P less than 0.005). Resting metabolic rate (RMR), thermogenic response to NE, and thermogenic response to exercise were measured during weight maintenance and during the third week of feeding 1000 extra Kcal/d in the lean and obese subjects. These components of energy expenditure were also measured in the obese subjects during the third week of a 589 Kcal/d diet. Resting metabolic rate increased during overfeeding in lean (6.6%, P less than 0.05) but not in the obese subjects (2.7%, P = NS) and fell during underfeeding in the obese (-9.1%, P less than 0.02). There was a logarithmic increment above baseline in VO2 v plasma NE concentration during the NE infusions (r = 0.75, P less than 0.005) in lean subjects which was unaltered by overfeeding. The obese exhibited equivalent VO2 responses to NE to that measured in the lean. Supine plasma NE concentrations were lower but metabolic clearance rates (MCR) of NE were similar in the obese compared to lean subjects during both weight maintenance and overfeeding. Overfeeding minimally increased plasma concentration but not MCR of NE in both groups. The thermogenic response to exercise was similar in the lean and obese subjects and was unaltered by overfeeding or underfeeding. The increments in plasma glycerol and free fatty acid in response to the NE infusions were proportional to the total fat mass of each individual and were greater in the obese subjects. Overfeeding partially suppressed the lipolytic response to NE in both groups and underfeeding increased the lipolytic response in the obese. There are no differences in thermogenic responses to NE in human obesity to account for excessive fat deposition. Overfeeding does not increase the thermogenetic responses to NE in humans as has been reported in small mammals.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.     

Perceived professional support and the use of blocking behaviours by hospice nurses

A prospective study of the impact of training 41 hospice nurses in assessment skills was used to test hypotheses that blocking behaviours would be used more when patients disclosed feelings and used less when nurses perceived that they had satisfactory professional support Each nurse was asked to assess a patient's current problems before and after feedback training and 8 months later Audiotape recordings of these interviews were rated by trained raters They determined the frequency of nurses' responses which had the function of blocking patient disclosure and the emotional level of patient disclosure Before each patient assessment each nurse was interviewed and questionnaires administered to measure her perceptions of the support she received Blocking behaviours were most evident when patients disclosed their feelings (Kendalls r=0 36, P < 0 001) In interviews containing most patient disclosure of feeling, blocking was significantly less (r= - 0 24, P < 0 5) when the nurse felt that practical help would be available if needed and when the nurse felt that her direct supervisor was concerned about the nurse's own welfare (r= -0 37, P < 0 005)     

HDAC6 inhibition results in tau acetylation and modulates tau phosphorylation and degradation in oligodendrocytes

Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family. It is localized within the cytoplasm and has unique substrate specificities for nonhistone proteins, such as α‐tubulin. Furthermore, it plays a major role in protein aggregate formation and recently was demonstrated to interact with the microtubule associated protein tau and tau was identified as a possible substrate for HDAC6 in neurons. This study was undertaken to investigate whether HDAC6 is present in oligodendrocytes and whether it is involved in tubulin and tau acetylation in these cells. We show for the first time that HDAC6 is expressed in cultured rat brain oligodendrocytes. Its inhibition by the specific HDAC6 inhibitor tubastatin A (TST) leads to morphological alterations, microtubule bundling, and tubulin acetylation, and changes in tau‐isoform expression and phosphorylation. Furthermore, the microtubule binding activity of tau was reduced. Using the oligodendroglial cell lines OLN‐t40 and OLN‐t44, which were genetically engineered to express either the longest human tau isoform with four microtubule binding repeats (4R‐tau), or the shortest tau isoform with three repeats (3R‐tau), respectively, we demonstrate that tau is acetylated by HDAC6 within the 4R‐binding domain. Tau acetylation reduced its turnover rate and acetylated tau was degraded slower in these cells. TST and shRNA‐mediated knockdown of HDAC6 in oligodendroglia cells caused an increase in pathological hyperphosphorylated tau detectable with the 12E8 antibody. Hence HDAC6 and dysregulation of the deacetylation and acetylation process in oligodendrocytes may contribute to diseases with oligodendroglial pathology. GLIA 2014;62:535–547     

Elective paratracheal neck dissection for lateral metastases from papillary carcinoma of the thyroid: Is it indicated?

BACKGROUND: Therapeutic paratracheal neck dissection for patients with papillary carcinoma of the thyroid is standard treatment. Its use as an elective procedure is controversial. METHODS: Thirty-seven patients with papillary carcinoma of the thyroid and evidence of positive adenopathy at levels II-V underwent selective neck dissection and elective/therapeutic paratracheal neck dissection. Results of preoperative ultrasonography of the neck were compared with the dissection specimens. RESULTS: Morbidity of the surgical procedure was minimal (1 permanent hypocalcemia). All specimens showed metastases from papillary thyroid carcinoma: 100% (37/37) in the jugular chain of lymphatics and 83.7% (31/37) in the paratracheal region. The rate of occult (negative physical examination and ultrasonography) metastases in the paratracheal region in the presence of metastases in the ipsilateral jugular chain was 83.3% (20/24). CONCLUSION: The high rate of occult metastases in the paratracheal region and the low rate of surgical morbidity speak in favor of elective paratracheal neck dissection in patients with metastatic papillary carcinoma of the thyroid.     

Uterine artery embolization for symptomatic fibroids with imaging follow up

The aim of this study was to determine the effectiveness of uterine artery embolization (UAE) as a primary treatment method in treatment of symptomatic fibroids, whether there are any preembolization MRI characteristics of fibroid predictive of reduction in volume and assess reduction in uterine and dominant fibroid volumes using ultrasound (US) and MRI. Study was carried out in total of 32 patients aged 25–49 years (mean 40.9 years). Uterine and dominant fibroid volume were determined using US and MRI before UAE, MRI and US at 3 months and US alone at 6 and 12 months post‐UAE, supplemented by clinical evaluation at interval of 3, 6 and 12 months. Procedure was carried out through unilateral femoral puncture using poly vinyl alcohol (PVA) particles 355–500 μm in size. All 32 patients had successful procedures. Overall, 25 patients responded, giving a clinical success rate of 78.12%. Mean reduction in volume of uterus and fibroid was 33 and 59.7% and 48.9 and 75.5% on US at 3 and 12 months respectively, and 33.3 and 58.6% on MRI at 3 months. Volume reduction on US and MRI at 3 months was highly correlative. There was no statistical difference in size reduction in volume of fibroids, which were hypointense or hyperintense on T2‐weighted image (T2WI) on pre‐UAE MRI. Uterine artery embolization leads to good technical success and fibroid volume reduction. Ultrasound alone may be used for follow up of patients post‐UAE. Preprocedure signal characteristics on T2WI are not predictors of volume reduction after UAE.