Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results

OBJECTIVE: Prolactinomas are frequently treated primarily with dopamine agonists; however, these agents have disadvantages and require life-long therapy. We therefore reassessed transsphenoidal microsurgery as an alternative therapy. METHODS: We reviewed the data for 121 female patients treated surgically for prolactinomas between 1976 and 1979 (Group 1) and 98 patients treated between 1988 and 1992 (Group 2). RESULTS: Of 219 women, 92% with preoperative prolactin (PRL) values of < or = 100 ng/ml and 91% with intrasellar microadenomas experienced initial remission; 80 to 88% of patients with intrasellar macroadenomas or macroadenomas showing moderate suprasellar extension or focal sphenoid sinus invasion experienced remission. Women with PRL values of > 200 ng/ml and those with larger and more invasive adenomas experienced poorer outcomes (37-41% remission). Lower preoperative PRL values and adenoma stage were the best predictors of initial surgical outcomes. At the most recent evaluations, 89% of women who experienced initial remission continued to experience clinical remission; 85% exhibited normal PRL values, and 5% demonstrated mild, asymptomatic, recurrent hyperprolactinemia (PRL values of < 34 ng/ml). In Group 1, 84% of patients continued to experience remission (82% with normal PRL values) after a median follow-up period of 15.6 years. In Group 2, 97% of patients continued to experience remission (88% with normal PRL values) after a median follow-up period of 3.2 years. Lower postoperative PRL values were the best predictors of long-term remission. CONCLUSION: Transsphenoidal microsurgery is an effective alternative to long-term medical therapy for selected patients with prolactinomas. Successful outcomes and long-term remission were achieved in patients with microadenomas and noninvasive macroadenomas.     

Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone

Bone resorption is initiated by osteoclast attachment to the mineralized matrix, cytoskeletal reorganization, cellular polarization, and the formation of the sealing zone. The present study examines the interaction between PYK2 and p130(Cas) (Crk-associated substrate), suggested to be part of the signaling pathway initiated by osteoclast adhesion. Using murine osteoclast-like cells (OCLs) and their mononuclear precursors (pOCs), generated in a co-culture of bone marrow and osteoblastic MB1.8 cells, we show that: 1) p130(Cas) is tyrosine-phosphorylated upon adhesion of pOCs to vitronectin or ligation of beta3 integrins; 2) p130(Cas) colocalizes with PYK2 and the cytoskeletal proteins F-actin, vinculin, and paxillin in the podosomal-rich ring-like structures of OCLs plated on glass and in the sealing zone in actively resorbing OCLs on bone; 3) p130(Cas) and PYK2 form a stable complex in pOCs, independent of tyrosine phosphorylation of either molecule, and this complex is present in Src (-/-) OCLs, in which neither protein is phosphorylated or associated with the osteoclast adhesion structure; 4) the association of p130(Cas) and PYK2 is mediated by the SH3 domain of p130(Cas) and the C-terminal domain of PYK2. These findings suggest that p130(Cas) and its association with PYK2 may play an important role in the adhesion-dependent signaling that leads to cytoskeletal reorganization and formation of the sealing zone during osteoclast activation.     

Heavily loaded bonded composite structure: design, manufacture and test of ‘I'' beam specimens

The use of adhesive bonding in advanced composite structures offers the potential for considerable weight and cost saving compared to the use of mechanical fasteners. However, confidence must be developed in the ability to design and analyse such structures and in their manufacture to suitable quality standards. The programme of work described here was carried out as a step towards building such confidence. Secondarily bonded ‘I' beams were designed to carry an ultimate shear flow of 1712 Nm m⁻¹. They were manufactured under factory conditions and predictions were made of their failure loads and modes. The beams were then tested in three- and four-point bending and the outcomes of these tests were compared to predictions. The beams failed at loads comfortably in excess of the target, a shear flow of 2828 Nm m⁻¹ being carried in four-point bending. Failure was a very energetic process leading to a great deal of damage within the test structures. Despite this an attempt was made to inspect the failed beams in an attempt to determine the quality of the bondlines and identify the site of failure.     

Temperature Dependence of the Thermal Diffusivity/Conductivity of Aluminum Nitride

The temperature dependence of the thermal conductivity of a polycrystalline AIN was measured using the flash-diffusivity technique over a range of experimental conditions. Thermal conductivity data from room temperature to 300°C, obtained with attenuated laser pulse energies to minimize the specimen temperature increase, were found to be inversely proportional to the absolute temperature, as expected from theory. For high pulse energies, the experimental data deviated significantly from expected behavior. This latter effect is offered as an explanation for the anomalously low temperature dependence for the thermal conductivity reported in the literature.     

Further evidence for a deficit in switching attention in schizophrenia.

In this study, sustained, selective, divided, and switching attention, and reloading of working memory were investigated in schizophrenia by using a newly developed Visual Attention Battery (VAB). Twenty-four outpatients with schizophrenia and 24 control participants were studied using the VAB. Performance on VAB components was correlated with performance of standard tests. Patients with schizophrenia were significantly impaired on VAB tasks that required switching of attention and reloading of working memory but had normal performance on tasks involving sustained attention or attention to multiple stimulus features. Switching attention and reloading of working memory were highly correlated with Trails (B–A) score for patients. The decline in performance on the switching-attention task in patients with schizophrenia met criteria for a differential deficit in switching attention. Future research should examine the neurophysiological basis of the switching deficit and its sensitivity and specificity to schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychostimulant users are sensitive to the stimulant properties of alcohol as indexed by alcohol-induced cardiac reactivity.

One indicator of increased sensitivity to alcohol-induced reward is a heightened heart rate (HR) increase following alcohol intoxication, a characteristic associated with increased alcohol-induced dopamine (DA) release. The goal of this study was to determine whether users of drugs known to induce DA release have higher HR increases after alcohol intoxication than never users have. Sixty-four men with known drug-use histories participated in an alcohol challenge in which HR was measured. Stimulant users had significantly higher ethanol-induced HR increases than never users had, although use of marijuana or hallucinogens was not associated with this marker. Stimulant users obtained superior Sensitivity to Reward scores (R. Torrubia, C. ávila, J. Moltó, & X. Caseras, 2001) compared with never users. Stimulant drug users may be more sensitive to the stimulating properties of alcohol, and this appears to be mediated by superior activity in the Behavioral Approach System (J. A. Gray, 1991). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The stability of children's physical activity as measured by accelerometry and self-report

The Computer Science Application (CSA) accelerometer uses integrated circuitry and memory to provide a continuous recording of minute-by-minute movement counts. It has been previously validated as an objective monitor of children's physical activity in field and laboratory settings. Our purpose was to derive accelerometry summary variables reflective of different physical activity intensity levels, evaluate the stability of these summary variables, and define the number of days needed to adequately measure usual physical activity. A secondary study purpose was to compare three self-report questionnaires to accelerometry. Thirty children (7-15 yr) wore accelerometers for 12 h.d-1 for 6 d. Daily summary variables of average movement count (total physical activity) and daily frequency of sedentary through vigorous activity were constructed. Intraclass correlation coefficients (R) and 95% confidence intervals (CI) were used to analyze the data. Accelerometry stability using 1 monitored day to represent usual physical activity was R = 0.42-0.47. When 6 d were used, stability increased to R = 0.81-0.84. Acceptable intraclass correlations and CI were achieved with 4 d of monitoring (R = 0.75-0.78, CI = 0.60-0.88). The self-report questionnaires were poorly to moderately correlated to accelerometry variables (r = -0.03-0.51). Data indicate that in field settings: 1) accelerometry can be used to assess the intensity of children's activity and 2) 4 or more days of activity monitoring are needed to achieve satisfactory reliability.