Women's mental health: some directions for research

Some key issues regarding gender differences in the prevalence of mental disorders, the course of mental illness, and the use of services are reviewed, along with their diagnosis and psychopharmacologic treatment. Implications for clinical practice are examined, as are directions for future research that will ensure the presence of women's mental health as a major element in the national agenda on women's health.     

Use of insulin-like growth factor I (IGF-I) and IGF-binding protein measurements to monitor feeding of premature infants

To determine whether peptides of the insulin-like growth factor (IGF) system might be useful indicators of nutritional adequacy in premature infants, we studied 50 premature (25-34 weeks gestation) infants prospectively to define the relationship between nutrient intake and serum concentrations of IGF-I, IGF-binding protein-2 (IGFBP-2), and IGFBP-3. Each infant was monitored for at least 2 weeks. Nutrient intake was quantified from daily logs; weight was determined daily, and measurements of IGF-I, IGFBP-2, and IGFBP-3 in serum were made twice weekly. Serum IGF-I correlated strongly with length of gestation, increasing 4.03 +/- 0.95 ng/mL for each additional week of gestation (P < 0.0001) and 0.36 +/- 0.07 ng/mL day each day since birth (P < 0.0001). A higher intake of calories increased IGF-I by 0.07 +/- 0.01 ng/mL for each calorie per kg ingested over the previous 3 days (P < 0.0001). IGF-I increased quadratically as protein intake increased. For each change of 1% in calories as protein squared, IGF-I increased 0.36 +/- 0.11 ng/mL (P < 0.0001). Serum IGFBP-3 concentrations also correlated with length of gestation, increasing 25.06 +/- 11.83 micrograms/L.wk (P = 0.035) and 4.14 +/- 1.33 micrograms/.day since birth (P = 0.003). Unlike IGF-I, variation in the amount of protein supplied did not change IGFBP-3. As calorie intake increased, IGFBP-3 increased by 0.54 +/- 0.17 microgram/L for each calorie per kg consumed over the previous 3 days (P = 0.0015). In contrast to IGF-I and IGFBP-3, IGFBP-2 declined as the length of gestation increased (56.12 +/- 16.92 ng/mL.week; P = 0.001) and with each additional day of life (7.57 +/- 2.44 ng/mL.day; P = 0.003). Dietary protein, the predominant regulator of IGFBP-2, caused a decrease of 33.22 +/- 9.00 ng/mL with each percent increase in dietary calories as protein (P < 0.0003). Calorie intake had less effect on IGFBP-2 than protein intake. These results indicate that each of the three peptides studied is regulated in premature infants by nutritional intake, and that their regulatory patterns are qualitatively similar to those observed in older individuals. Measurements of these peptides in premature infants may be useful indicators of nutritional status and adequacy of nutrient intake.     

Treatment of complications in primary cementless total hip arthroplasty

Five hundred eight consecutive cases (481 patients) treated with the extensively porous coated Anatomic Medullary Locking prosthesis were followed for an average of 9 years (range, 5-14 years). Thirty-one (6%) hips were lost to followup and 33 (7%) hips had complications that required revision surgery. The indications for revision were symptomatic stem loosening (six cases), symptomatic cup loosening (five cases), asymptomatic periarticular osteolysis (seven cases); trochanteric fracture through an osteolytic cyst (four cases), polyethylene fracture (five cases), sepsis (one case), and heterotopic ossification (one case). The surgical treatment of these complications is described. After these revisions, 11 (33%) cases had additional complications, most commonly a dislocation. Four required a second revision. Questionnaires and physical examinations were used to compare the outcome of the cases requiring revision with the outcome of those that did not. There were no differences in patient satisfaction between cases requiring revision surgery and those that did not (97% and 95% patient satisfaction, respectively). Function was also similar between the two groups, with 93% reporting increased function in each group.     

Population pharmacokinetics of sirolimus in kidney transplant patients

OBJECTIVE: To characterize the dose-related pharmacokinetics of the immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use of two-stage and nonlinear mixed-effect model population methods. METHODS: Patients (n = 36) from three centers (Germany, the United Kingdom, and Sweden) who received steady-state oral doses of cyclosporine (ciclosporin) were assessed after single oral administration of sirolimus at doses of 3, 5, 10, and 15 mg/m2. Plasma and whole blood sirolimus samples were analyzed by a high-performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well as first-order absorption (ka) and a lag-time. RESULTS: The nonlinear mixed-effect model method (P-Pharm) provided a better characterization of sirolimus kinetics, especially for the absorption and distribution phases where fewer data were available per patient. Sirolimus distribution between whole blood and plasma was concentration-independent, with a mean blood/plasma ratio (coefficient of variation) of 30.9 (48.5%). Elimination was not influenced by dose, as shown by estimates of the terminal half-life of 63 hours (27.5%) and apparent oral blood clearance of 8.9 L/hr (38.2%). Sirolimus distribution parameters were influenced by body weight and surface area. Sirolimus was rapidly absorbed, as shown by the absorption lag-time of 0.27 hour (35.1%), and ka of 2.77 hr-1 (48.4%). The concomitant administration of sirolimus and cyclosporine did not reveal any pharmacokinetic interactions. CONCLUSION: This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.     

Optical ray tracing using parallel processors

One of the instruments on the sun-synchronous Terra (EOS AM) and Aqua (EOS PM) spacecraft, the Moderate Resolution Spectroradiometer (MODIS), obtains calibration data once during every orbit. Observations of the sun permit corrections to observations of the Earth during the ensuing orbit. Although the instrument was designed to receive uniform sunlight over the entire surface of its detector, the sunlight was in fact not uniform. While this did not adversely affect the calibration, it nonetheless implied a lack of understanding of how the optical system really functioned. To learn what was wrong, NASA used an optical ray-tracing program on a DEC Alpha computer. The results correlated well with the observations made by the instrument itself, but it took nearly two weeks to complete the computer simulation, a discouragingly long time. This paper describes the algorithm and its implementation in a system with multiple digital signal processor (DSP) chips operating in parallel. Timing data show a highly linear relationship between the number of DSPs present and the speed of the computation. Administrative overhead is negligible compared to the time taken to compute ray trajectories. This implies that many more than just four DSPs could be harnessed before administrative overhead would begin to be significant.     

Religiosity buffers effects of some stressors on depression but exacerbates others

Although religiosity is protective for mortality and morbidity, its relationship with depression is unclear. We used the 1994 Alameda County Study survey of 2,537 subjects aged 50-102 to analyze associations between two forms of religiosity and depression as well as the extent to which religiosity buffers relationships between stressors and depression. Non-organizational religiosity included prayer and importance of religious and spiritual beliefs; organizational religiosity included attendance at services and other activities. Non-organizational religiosity had no association with depression; organizational religiosity had a negative relationship that weakened slightly with the addition of health controls. Both forms of religiosity buffered associations with depression for non-family stressors, such as financial and health problems. However, non-organizational religiosity exacerbated associations with depression for child problems, and organizational religiosity exacerbated associations with depression for marital problems, abuse, and caregiving. Religiosity may help those experiencing non-family stressors, but may worsen matters for those facing family crises.     

The 72-kDa component of signal recognition particle is cleaved during apoptosis

Proteins cleaved by apoptotic caspases are commonly recognized by autoantibodies found in the serum of patients with rheumatic disease. We report that the 72-kDa signal recognition particle (SRP) protein, a rare target of autoantibodies found in the serum of patients with dermatomyositis and systemic lupus erythematosus, is rapidly cleaved in Jurkat T cells treated with apoptotic (i.e. Fas ligation, treatment with gamma or ultraviolet radiation, or co-culture with anisomycin or staurosporine) but not proliferative (CD3 cross-linking) stimuli. Cleavage of SRP 72 produces a 66-kDa amino-terminal fragment and a 6-kDa carboxyl-terminal fragment that is selectively phosphorylated on serine residues. Cleavage of SRP 72 is prevented by chemical and peptide caspase inhibitors, and by overexpression of bcl-2, an inhibitor of apoptotic cell death. Analysis of the carboxyl terminus of SRP 72 has identified a putative cleavage site (SELD/A) for group III caspases, and carboxyl-terminal serine residues that are highly conserved in phylogeny. Both serine phosphorylation and caspase cleavage of SRP 72 are observed in cells derived from human, dog, rat, and mouse. Canine SRP 72 is cleaved in vitro by recombinant caspase 3 but retains the ability to mediate transport of a signal peptide-containing protein into the endoplasmic reticulum lumen. The 72-kDa component of the SRP joins a growing list of autoantigens that undergo post-translational modifications during programmed cell death.     

Flank-marking behavior and the neural distribution of vasopressin innervation in golden hamsters with suprachiasmatic lesions

In golden hamsters, microinjections of arginine-vasopressin (AVP) within the anterior hypothalamus trigger a stereotyped scent-marking behavior, flank marking. Our experiment was carried out to test the contribution of AVP neurons within the suprachiasmatic nucleus (SCN) in the control of this behavior. Our results suggest that the SCN does not contribute to flank-marking behavior. Whereas SCN lesions disrupted circadian rhythms of wheel running, the same lesions did not disrupt flank-marking. The results also suggest that neurons located outside the SCN contribute significantly to the vasopressinergic innervation of the brain and the expression of AVP-dependent behaviors, such as flank-marking behavior. Although AVP-immunoreactive fibers were severely (ca. 95%) depleted from several forebrain areas in SCN-lesioned hamsters, the effect of the lesions was much more limited within the forebrain areas involved in flank-marking behavior as well as within the midbrain and hindbrain.     

Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men

Effects of a 10-week progressive strength training program composed of a mixture of exercises for increasing muscle mass, maximal peak force, and explosive strength (rapid force production) were examined in 8 young (YM) (29+/-5 yrs) and 10 old (OM) (61+/-4 yrs) men. Electromyographic activity, maximal bilateral isometric peak force, and maximal rate of force development (RFD) of the knee extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF), muscle fiber proportion, and fiber areas of types I, IIa, IIb, and IIab of the vastus lateralis were evaluated. Maximal and explosive strength values remained unaltered in both groups during a 3-week control period with no training preceding the strength training. After the 10-week training period, maximal isometric peak force increased from 1311+/-123 N by 15.6% (p <.05) in YM and from 976+/-168 N by 16.5% (p <.01) in OM. The pretraining RFD values of 4049+/-791 N*s(-1) in YM and 2526+/-1197 N*s(-1) in OM remained unaltered. Both groups showed significant increases (p < .05) in the averaged maximum IEMGs of the vastus muscles. The CSA of the QF increased from 90.3+/-7.9 cm2 in YM by 12.2% (p <.05) and from 74.7+/-7.8 cm2 in OM by 8.5% (p <.001). No changes occurred in the muscle fiber distribution of type I during the training, whereas the proportion of subtype IIab increased from 2% to 6% (p < .05) in YM and that of type IIb decreased in both YM from 25% to 16% (p < .01) and in OM from 15% to 6% (p < .05). The mean fiber area of type I increased after the 10-week training in YM (p < .001) and OM (p < .05) as well as that of type IIa in both YM (p < .01) and OM (p < .01). The individual percentage values for type I fibers were inversely correlated with the individual changes recorded during the training in the muscle CSA of the QF (r=-.56, p < .05). The present results suggest that both neural adaptations and the capacity of the skeletal muscle to undergo training-induced hypertrophy even in older people explain the gains observed in maximal force in older men, while rapid force production capacity recorded during the isometric knee extension action remained unaltered during the present mixed strength training program.     

Evaluation of lacticin 3147 and a teat seal containing this bacteriocin for inhibition of mastitis pathogens

Lacticin 3147 is a broad-spectrum bacteriocin produced by Lactococcus lactis subsp. lactis DPC3147 which is bactericidal against a range of mastitis-causing streptococci and staphylococci. In this study, both lacticin 3147 and the lantibiotic nisin were separately incorporated into an intramammary teat seal product. The seal containing lacticin 3147 exhibited excellent antimicrobial activity and might form the basis of an improved treatment for the prevention of mastitis in dry cows.