Role of Gamma Knife Radiosurgery in Acromegaly

Stereotactic radiosurgery with the Gamma Knife allows the delivery of focused radiation in a single session from a Cobalt-60 source to a pituitary tumor with little radiation to surrounding normal brain tissue. At this time the major role for Gamma Knife radiosurgery in acromegaly is for the treatment of failed pituitary surgery although it may also by used as primary treatment for patients unwilling or unsuitable, for medical reasons, to undergo transsphenoidal surgery. The major risk from Gamma Knife radiosurgery appears to be radiation damage to the visual pathways, but this can be obviated by limiting the radiation dose to the optic chiasm under 10 Gy. In contrast, the neuronal and vascular structures running in the cavernous sinus are much less radiosensitive allowing an ablative dose to be administered to tumors showing lateral invasion and impinging on cranial nerves III, IV, V and VI. Gamma Knife radiosurgery appears to produce effects in GH secreting tumors faster than with fractionated radiotherapy without the potential long-term risk of developing a second extrapituitary brain tumor as well as the neuropsychiatric effects associated with conventional radiation administration.     

Histopathology of arterial lesions in LPA transgenic mice on cholesterol-enriched chow

The aortic root from 21 LPA transgenic mice and 18 control litter mates on cholesterol enriched chow were studied histologically for the presence of atherosclerotic lesions. Serial sections were cut and the total area of the lesions was measured by use of computerised image analysis. Lipid staining lesions were found in 17 aortas of the transgenic mice and were five times more common than in the controls. Foam cell lesions were the only type of lesion in 12 of the aortas from transgenic animals, while five animals had developed fibrofatty lesions. Immunostaining revealed monocytes/macrophages on the endothelial surface, and in the subendothelial space of foam cell lesions. In fibrofatty lesions, spindle shaped cells formed a cap around the lipid core. This study supports the view that transgenic mice expressing human apolipoprotein (a) on a high fat and cholesterol diet, are more susceptible to aortic lesions than control mice and develop early atherosclerotic lesions comparable to lesions in man. Aminoguanidin in the drinking water had no effect on the aortic lesions, but lesion size was significantly, negatively correlated with plasma glucose concentration.     

Physician compensation models in medical group practice

This article examines physician compensation models in medical groups and the factors affecting physician compensation and their impact on individual physician behavior and group practice performance. Four categories of physician compensation models are identified: (1) production-based compensation, (2) salary, (3) group-based compensation unrelated to individual physician productivity, and (4) capitation-based compensation. The statistics and the economic incentives of different compensation methods are presented. Finally, the impacts on health resources consumption, charges in medical group procedures for utilization and care management, and quality of care are discussed.     

POLYCHLORINATED NAPHTHALENES AND OTHER ORGANOCHLORINE CONTAMINANTS IN HUMAN ADIPOSE AND LIVER TISSUE

Chlorinated naphthalenes (CNs) and chlorinated biphenyls (CBs), hexachlorobenzene (HCB), and p,p '-DDE were determined in human adipose and liver tissues collected at autopsy of 5 men and 2 women (Swedish), 47-80 yr of age. In paired adipose tissue and liver samples, the differences of the distribution of CNs, CBs, HCB, and p,p '-DDE were small, but the concentrations of the compounds (lipid weight basis) varied between the subjects. Generally, the profiles of the contaminants were similar in the subjects. However, in one of the male subjects (80 yr of age) the concentrations of 1,2,3,5,7/1,2,4,6,7-pentaCN and 1,2,3,4,6,7/1,2,3,5,6,7-hexaCN were much higher in the liver: 6 and 20 times higher than in adipose tissue, respectively. The concentration of the toxic coplanar 3,3',4,4',5-pentaCB (CB-126) was also high in the liver from this individual, three times higher concentration than in adipose tissue. It is suggested that the multiplicity of contaminants found in humans should be taken into consideration in risk assessment and that further studies are needed on the distribution of contaminants in different tissues.     

Distribution of p120 catenin during rat brain development: potential role in regulation of cadherin-mediated adhesion and actin cytoskeleton organization

p120 catenin (p120ctn) is implicated in the regulation of cadherin-mediated adhesion and actin cytoskeleton remodeling. The interaction of cytoplasmic p120ctn with the guanine exchange factor Vav2 is one of the signaling pathways implicated in cytoskeleton dynamics. We show here that p120ctn is regulated during rat brain development and is distributed at the membrane and within the cytoplasm where it associates with N-cadherin and Vav2, respectively. p120ctn shifts progressively from an axonal expression to a punctuate staining localized to a subset of synapses. In cultured hippocampal neurons, p120ctn redistributes from growth cones to synapses, where it partly colocalizes with N-cadherin or Vav2 and filamentous actin. In the adult forebrain, we show that p120ctn and Vav2 are highly expressed by neuroblasts migrating from the lateral subventricular zone to the olfactory bulb. The dynamic expression pattern of p120ctn and the biochemical evidences of its association with N-cadherin and Vav2 strongly suggest that p120ctn plays a major role in neuronal migration, neurite outgrowth and synapse formation, and plasticity.     

GH and ghrelin increase with fasting in a naturally adapted species,the northern elephant seal (Mirounga angustirostris)

After nursing, pups of the northern elephant seal (Mirounga angustirostris) are approximately 46% body fat and rely almost entirely on the oxidation of their large fat stores to sustain their metabolism for the ensuing 8-12 week postweaning fast, which is a natural component of their life history. Thus, fasting pups provide an ideal opportunity to examine the hormonal alterations associated with prolonged food deprivation in a naturally adapted model. Cortisol, ghrelin, glucagon, growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, blood urea nitrogen (BUN), glucose and non-esterified fatty acids (NEFA) were examined in 20 male and 20 female pups blood sampled early (<1 week postweaning) and late (6-8 weeks postweaning) during the fast. Mean cortisol, ghrelin, GH, and glucagon increased 1.8-, 1.8-, 1.4-, and 2.3-fold between early and late periods, while mean IGF-I and insulin decreased 97% and 38%, respectively. NEFA increased 2.3-fold, while BUN and glucose decreased 46% and 11%, respectively. NEFA was significantly and positively correlated with cortisol and GH; individually; however, when the relationship was examined as a multiple regression the correlation improved suggesting that cortisol and GH act synergistically to promote lipolysis during the fast. GH and BUN were negatively and significantly correlated between early and late fasting suggesting that GH may promote protein sparing as well. The decrease in glucose may be responsible for stimulating glucagon, resulting in the maintenance of relative hyperglycemia. The increases in cortisol, ghrelin, glucagon, and GH suggest that these hormones may be integral in mediating the metabolism of seal pups during prolonged fasting.     

Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: Data from Nordic Society for Pediatric Hematology and Oncology (NOPHO‐AML) and review of the literature

The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children <2 years and associated with a poor prognosis. We present the clinical and cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO‐AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present in patients <2 years of age (median age 6 months) but none was diagnosed as newborn. These patients constituted 4.3% of the patients <2 years of age. There was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with t(7;12) and four of seven patients from the NOPHO database suffered from relapse. The patients with t(7;12) had a 3‐year event free survival of 24% (literature) vs. 43% (NOPHO) and a 3‐year overall survival of 42% (literature) vs. 100% (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being associated with +19.