Alterations of medial preoptic area neurons following pregnancy and pregnancy-like steroidal treatment in the rat.

There is a marked increase in the maternal behavior displayed by a female rat following pregnancy-due primarily to exposure to the gonadal hormones progesterone and estradiol (P and E(2), respectively). We examined Golgi-Cox silver-stained, Vibratome-sectioned neurons visualized and traced using computerized microscopy and image analysis. In Part One, we examined the hormonal-neural concomitants in the medial preoptic area (mPOA), an area of the brain that regulates maternal behavior, by comparing cell body size (area in microm(2); also referred to as soma and perikaryon) in the mPOA and cortex of five groups (n = 4-6/group) of ovariectomized (OVX-minus), diestrous, sequential P and E(2)-treated (P+E(2)), late-pregnant, and lactating rats; for Part Two, we examined a subset of mPOA neurons, which were traced in their entirety, from these same subjects. In Part One, whereas there was no difference between OVX-minus and diestrous females, both had smaller somal areas compared to OVX+P+E(2)-treated and late-pregnant females. The area of the soma returned to diestrous/OVX-minus levels in the lactating females. We found no change among the five groups in area of cell body in cortical neurons, which generally lack steroid receptors. In Part Two, which included a more detailed morphometric analysis of mPOA neurons, we examined several additional measures of dendritic structure, including number of proximal dendritic branches (the largest proximal dendrite was defined as the one with the largest diameter leaving the soma); cumulative length of the largest proximal dendrite; area of the cell body; number of basal dendrites; cumulative basal dendritic length; number of basal dendritic branches; and branch-point (distance from cell body to first branch of largest proximal dendrite). Again, we found similar effects on cell body size as in Part One, together with effects on number of basal dendritic branches and cumulative basal dendritic length in pregnant and P+E(2)-treated groups compared to OVX, diestrous, and lactating. An increase in somal area denotes increased cellular activity, and stimulatory effects on additional neuronal variables represents modifications in information processing capacity. Pregnancy and its attendant hormonal exposure, therefore, may stimulate neurons in the mPOA, which then contribute (in an as yet undetermined manner) to the display of maternal behavior. During the postpartum lactational period, when cues from pups primarily maintain maternal attention, the neuronal soma appears to return to a pre-pregnancy, non-hormonally dependent state, whereas other aspects of the dendrite remain altered. Collectively, these data demonstrate a striking plasticity in the brains of females that may be reflected in modifications in behavior.

Group therapy for schizophrenia: combining and expanding the psychoeducational model with supportive psychotherapy.

Combining psychoeducation and supportive psychotherapy resulted in a successful group experience for schizophrenics in a long-term care setting within a Veterans Administration Medical Center. This article describes the two approaches and discusses the ways in which they were combined and enhanced in a structured manner. A case study is presented and practice implications are explored. Important accomplishments and behavioral changes were observed in group members participating in this group. Schizophrenics with problematic behavioral histories and recurrent active psychoses were able to participate productively, work toward greater independence and achieve community living.

Left ventricular function during lethal and sublethal endotoxemia in swine.

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.

Depression of left ventricular performance during canine splanchnic artery occlusion shock.

We studied canine left ventricular contractile performance following splanchnic artery occlusion (SAO) shock. We evaluated contractile performance by analyzing the left ventricular end systolic pressure-diameter relationship (sigma ES) because we have previously shown that sigma ES is independent of large changes in preload, afterload, and heart rate but sensitive to changes in ventricular contractility. Following release from 2 hours of SAO, seven dogs survived, five expired immediately, and ten expired between 0.5 and 3.5 hours (termed nonsurvivors, [NS]). The NS dogs exhibited slight tachycardia, slight increase in total peripheral resistance, marked decreases in +dP/dt, cardiac output, arterial blood pressure, stroke volume, and stroke work. Ventricular performance (sigma ES) declined with time following SAO release in the nonsurviving dogs; in contrast, surviving animals exhibited an augmentation of sigma ES during SAO and following SAO release. Sham dogs exhibited no time-dependent changes in sigma ES. The dogs that expired immediately following SAO release exhibited a precipitous decline in sigma ES from 43.0 +/- 9.0 to 23.0 +/- 4.8 mm Hg/mm within minutes of SAO release. We analyzed these data by Cox multiple regression analysis to determine the major covariates of survivability. The analysis revealed that sigma ES at the midpoint in time between SAO release and death was best correlated with the survival function. These results suggest that cardiovascular collapse of SAO shock is associated with an early and sustained loss of ventricular contractility.

Canine left ventricular function during experimental pancreatitis.

Left ventricular contractility following induction of experimental pancreatitis (EP) was studied. Contractility was evaluated by analyzing the left ventricular end systolic pressure-diameter relationship (sigma ES). Sigma ES is independent of large changes in preload, afterload, and heart rate, but sensitive to changes in ventricular contractility. Following injection of 100,000 IU trypsin in 4% taurocholate into the pancreas to induce EP, seven of eight dogs survived 5 hr. These dogs exhibited an initial significant reduction in mean arterial pressure (MABP) which stabilized at 90% of control at 3-5 hr post-EP. Cardiac output (CO) dropped slowly after EP induction (from 3.08 +/- 0.43 to 2.22 +/- 0.22 liters/min) associated with no significant change in peripheral resistance. Stroke work and stroke volume were markedly depressed reflecting the changes in MABP and CO. No consistent changes in +dP/dt or -dP/dt were observed. The ratio of endo/epicardial blood flow was unchanged as was blood Ca2+ levels throughout the experiment. Ventricular contractility as reflected by sigma ES tended to improve (from 49.7 to 69.6 mm Hg/mm at 4 hr following EP). Therefore, it was concluded that these animals exhibited no loss of ventricular contractility during EP.

Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcgamma receptors (FcgammaR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, lambdas > 10, purported linkage at 1q41-42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14-23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26-27, and 12p12-11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcgammaRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects.