The behavioral risks and life circumstances of adolescent mothers involved with older adult partners.

OBJECTIVE: To investigate behavioral risks and life circumstances of adolescent mothers with older (> or =5 years) adult (> or =20 years old) vs. similar-aged (+/-2 years) male partners at 12 months' postpartum. METHODS: Nine hundred thirty-one adolescent females were interviewed after delivery and were mailed surveys to complete at 12 months' postpartum. Analysis by chi(2) and t test was used to identify differences in behavioral risks (planned repeated pregnancy, substance use, and intimate partner violence) and life circumstances (financial status, school enrollment, and social support) for adolescent mothers with older adult vs similar-aged partners. Additional stratified analyses were conducted to evaluate the extent to which living with an adult authority figure or being with the father of her infant born 12 months previously might alter observed relationships. RESULTS: At 12 months following delivery, 184 adolescent mothers (20%) reported having an older adult partner, whereas 312 (34%) had a similar-aged partner. The remaining adolescent mothers (n = 239) were excluded from further analyses. Adolescent mothers with older adult partners were significantly less likely to be employed or enrolled in school and were more likely to report planned repeated pregnancies. These adolescent mothers also received less social support. No differences were observed in intimate partner violence or the mother's substance use. Adolescent mothers with older adult partners who did not live with an adult authority figure seemed to be at greatest risk. CONCLUSIONS: The negative educational and financial impact of coupling with an older vs. similar-aged partner seems greater for those mothers who no longer reside with an adult authority figure. These adolescent mothers are also at greater risk of planned rapid repeated pregnancy. Given their limited educational attainment and family support, a subsequent pregnancy may place these young women at considerable financial and educational disadvantage.     

Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist.

The pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist, was investigated in four independent studies including 36 healthy male volunteers. Using the model of exercise-induced tachycardia (ET) the beta-adrenoceptor blocking properties of bisoprolol (2.5-40 mg) were examined in comparison to metoprolol (50 and 100 mg), propranolol (40 and 80 mg) and atenolol (50 and 100 mg). The maximal reduction of ET was achieved between 1 and 4 h following single oral administration. The dose-response relationship using individual maximal reduction of ET showed, on a molar basis, that bisoprolol is about 5, 7 and 10 times more effective than propranolol, atenolol and metoprolol, respectively. In the model of insulin-induced hypoglycaemia bisoprolol behaved as a beta 1-selective adrenoceptor antagonist. There was a good correlation (r = 0.94) between the log bisoprolol concentration and the reduction in exercise-induced tachycardia. Bisoprolol is a potent new cardioselective beta-adrenoceptor antagonist with a competitive action at beta 1-adrenoceptors.     

Effects of Calcium on Gap Junctions Between Osteoblast-Like Cells in Culture

The present study investigated the effects of elevated cytoplasmic free calcium concentrations ([Ca²⁺]_i) on the permeability of gap junctions between cultured osteoblast-like (OB) cells derived from calvarial and periosteal fragments of newborn rats. This was studied using the double whole cell patch clamp technique and intracellular dye injections. To increase [Ca²⁺]_i, patch pipette solutions contained 100 μmol/liter Ca²⁺. About 1–2 minutes after whole cell modes had been attained, the total number of gap junction channels was reduced from an average of 400 in normal Ca²⁺ to 20 in high Ca²⁺. Thereafter, remaining gap junction channels were active for up to 8 minutes. In normal rat kidney (NRK) cells, gap junction channels were closed by high Ca²⁺ within 1 minute, pointing to a similar sensitivity of Connexin43 gap junction channels in OB and NRK cells. To study the effects of elevated [Ca²⁺]_i on the dye permeability of gap junctions between extended OB cells, the spread of Lucifer Yellow to neighboring cells was evaluated. [Ca²⁺]_i was gradually increased from 1.5- to 14-fold the normal value by application of either ouabain, Na⁺-free/ouabain, or A23187. Reduced dye spread correlated with the increase of [Ca²⁺]_i measured by analyzing the fluorescence of fura-2. These data show that gap junctions in OB cells are sensitive to Ca²⁺. Received: 15 August 1995 / Accepted: 12 February 1996     

Ventrolateral neurons of medullary organotypic cultures: intracellular pH regulation and bioelectric activity.

The hypothesized role of the intracellular pH (pH(i)) as a proximate stimulus for central chemosensitive neurons is reviewed on the basis of data obtained from organotypic cultures of the medulla oblongata (obex level) of new born rats (OMC). Within OMC a subset of neurons responds to hypercapnia as do neurons in the same (or similar) brain areas in vivo. Maneuvers altering intra- and/or extracellular pH (pH(o)) such as hypercapnia, bicarbonate-withdrawal, or ammonium pre-pulses, evoked well defined changes of the neuronal pH(i). During hypercapnia (pH(o) 7.0) or bicarbonate-withdrawal (pH(o) 7.4) most ventrolateral neurons adopted a pH(i) which was < or = 0.2 pH units below the steady state pH(i), while signs of pH(i)-regulation occurred only in a small fraction of neurons. During all treatments leading to intracellular acidosis, bioelectric activity of chemosensitive neurons increased and was often indistinguishable from the response to hypercapnia, regardless of whether pH(o) was unchanged, decreased or increased during the treatment. These data strongly suggest that the pH(i) acts as proximate stimulus. The mode of acid extrusion of chemosensitive neurons is, therefore, of major importance for the control of central chemosensitivity. Immunocytochemical data, pH(i) measurements and neuropharmacological studies with novel drugs pointed to the Na(+)/H(+) exchanger subtype 3 (NHE3) as a main acid extruder in ventrolateral chemosensitive neurons. Possible functions and neuropharmacological strategies arising from this very local NHE3 expression are discussed.     

Valproate acidifies hippocampal CA3-neurons--a novel mode of action.

Various hypotheses try to explain the anticonvulsive and mood stabilizing effects of valproate. Among them, amplification of GABAergic inhibition and reduction of membrane excitability is favored. Here we show that superfusion with 0.1-1 mM valproate induced a moderate intracellular acidification of BCECF-AM-loaded CA3-neurons (hippocampal slices, guinea pig) which was measured as the difference between intracellular pH before (baseline pH(i)) and during valproate treatment (deltapH(i)). In two groups of neurons treated with 1 mM and 0.1-0.5 mM, deltapH(i) values amounted to 0.20 +/- 0.10 and 0.10 +/- 0.04 (deltapH(i) +/- S.D.), respectively, suggesting a dependence on the used valproate-concentration. DeltapH(i) did not correlate with the baseline pH(i). Furthermore, the acidification seems to be independent from an activation of postsynaptic GABA-A receptors, as it was not influenced by 0.1 mM picrotoxin. Since our previous studies clearly demonstrated a reduction of membrane excitability during moderate intracellular acidification, we suggest that the valproate-mediated intracellular acidification may substantially contribute to its anticonvulsive and mood stabilizing properties.     

What Staging Surgery Should Be Performed on Patients with Uterine Papillary Serous Carcinoma?

OBJECTIVE: While uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype, it fortunately is not as common as some other histologic subtypes. Overall, patients with UPSC have a poor survival rate. Since the optimal surgical procedure to perform on patients with this tumor is unknown, the authors wanted to determine what the optimal surgical management of patients with UPSC should be. METHODS: All patients with the preoperative or frozen section intraoperative diagnosis of UPSC were treated with a staging or cytoreductive procedure analogous to patients with serous carcinoma of the ovary. Patients analyzed underwent surgery from March 1983 to September 1995. RESULTS: Sixty-five patients with UPSC were found. Twenty patients had FIGO stage I tumors, 6 stage II tumors, 8 stage III tumors, and 31 stage IV tumors. Twenty-nine patients had upper abdominal disease (17 gross disease and 12 microscopic disease only). Forty-eight patients underwent pelvic and paraaortic lymphadenectomy, with 6 of 48 having positive lymph nodes. All 14 patients with lymphovascular space invasion had stage IV disease. Thirty-one of sixty-five patients had positive cytology at the time of surgery. CONCLUSION: Based on the clinical experience of these investigators, patients with UPSC should undergo a staging laparotomy similar to the procedure undertaken for patients with ovarian carcinoma. The surgery should include at least partial omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal washings, peritoneal biopsies, and pelvic and paraaortic lymphadenectomy similar to an ovarian cancer staging procedure if no gross disease > or =2 cm is found at time of surgery. If disease > or =2 cm is found, cytoreduction should be undertaken when feasible.