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.     

Adulthood functioning: the joint effects of parental alcoholism, gender and childhood socio-economic stress

The popular literature has publicized the adjustment difficulties of adult children of an alcohol-dependent parent (ACOAs); however, empirical studies do not provide consistent support. We examined the impact of parental alcoholism, degree of childhood socio-economic stress and gender on three broad categories of adulthood functioning (psychopathology, socio-economic attainment and marital stability). These effects were investigated with a heterogeneous sample of 400 men and 226 women participating in studies at the University of Michigan Alcohol Research Center. Parental alcoholism and childhood socio-economic stress exerted significant independent effects on most adulthood functioning measures. Men and women differed substantially only on socio-economic attainment measures, and effects of parental alcoholism and childhood economic stress on men and women were generally similar. For marital stability, parental alcoholism and childhood socio-economic stress interacted. These results suggest that researchers who study the impact of family history for alcoholism on psychological functioning should consider other aspects of the family of origin that promote wellbeing. In addition, results of this study point to the need for more research on gender differences, protective factors that promote good adjustment and outcome measures reflecting general life adaptation.     

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.     

Unfolding and inactivation of Penaeus penicillatus acid phosphatase during denaturation by guanidine hydrochloride

Neuromuscular terminals of a single motoneuron to four muscles (CPV7a, GM5a, CV2, and CV3) in the stomach of the blue crab Callinectes sapidus showed structural evidence for the exocytotic release of dense-core vesicles exclusively at synapses. The primary evidence was the appearance of dense cores in the synaptic cleft, accompanied by indentations of the presynaptic or postsynaptic membrane. In their simplest form, these consisted of an omega-shaped figure of the presynaptic membrane enclosing one dense core, denoting release of a single dense-core vesicle. A larger indentation of the presynaptic membrane enclosing several dense cores denoted multiple release. A more complex form of multiple release was where the presynaptic membrane was normal, but the postsynaptic membrane elaborated into a sac projecting into the granular sarcoplasm and filled with dense cores. The postsynaptic sac in some instances was compressed into a thin, fingerlike extension, which lacked dense cores and, at its distal end, separated into small cisternae, suggesting a mechanism for membrane recycling. Profiles depicting single and multiple releases of dense-core vesicles were found more frequently at neuromuscular terminals that release relatively large amounts of transmitter with a single stimulus, such as CV2 and CV3, compared to those releasing smaller amounts, such as CPV7a and GM5a. The disparity in release sites among the four muscles of this single motor unit and the fact that many of the multiple-release figures were closely adjacent to the active zones for transmitter release suggest a possible modulatory role for dense-core vesicles in synaptic transmission. Such modulation may be long lasting, as implied by the postsynaptic sacs, which may permit prolonged release of the contents of their dense cores into the synaptic cleft. This is in keeping with the functional role of these stomach muscles, which is to be continuously active for long periods of time.