Tailoring the hybrid palliation for hypoplastic left heart syndrome: A simulation study using a lumped parameter model.

The results of Hybrid procedure (HP) for the hypoplastic left heart syndrome (HLHS) depend on several variables: pulmonary artery banding tightness (PAB), atrial septal defect size (ASD) and patent ductus arteriosus stent size (PDA). A HP complication could be the aortic coarctaction (CoAo). The reverse Blalock-Taussig shunt (RevBT) placement was proposed to avoid CoAo effects. This work aims at developing a lumped parameter model (LPM) to investigate the effects of the different variables on HP haemodynamics. A preliminary verification was performed collecting measurements on a newborn HLHS patient to calculate LPM input parameters to reproduce patient's baseline. Results suggest that haemodynamics is affected by ASD (ASD: 0.15-0.55 cm, pulmonary to systemic flow ratio Qp/Qs: 0.73-1, cardiac output (CO): 1-1.5 l/min and ventricular stroke work SW: 336-577 ml mmHg) and by the PAB diameter (PAB: 0.07-0.2 cm, Qp/Qs: 0.46-2.1, CO: 1.3-1.6 l/min and SW: 591-535 ml mmHg). Haemodynamics was neither affected by RevBT diameter nor by PDA diameter higher than 0.2 cm. RevBT implantation does not change the HP haemodynamics, but it can make the CoAo effect negligible. LPM could be useful to support clinical decision in complex physiopathology and to calibrate and personalise the parameters that play a role on flow distribution.

A neonate with cyanosis and tortuous great arteries.

This report describes an unusual case with tortuosity of the great vessels in a neonate who presented at birth with cyanosis. The diagnosis was made with magnetic resonance imaging (MRI), then confirmed by genetic analysis.

Drug treatment outcomes: investigating the long-term effects of sexual and physical abuse histories.

Individuals in drug treatment, particularly women, generally report high levels of past sexual and physical abuse. Although histories of sexual and physical abuse are associated with greater prevalence and severity of depression, anxiety, phobias, and interpersonal difficulties for individuals seeking substance-related treatment, several recent studies failed to show that prior sexual or physical abuse compromised short-term drug treatment outcomes. This study examined the possible effects of sexual and physical abuse on a wide array of behavioral domains over a two-year posttreatment period. The findings indicate few differences between those with and without past histories of such abuse in terms of drug use, drug treatment and 12-Step program participation, criminality, income sources, intimate relationships, family functioning, and psychiatric symptoms. There are specific exceptions, but they apply only to men. Overall, the findings indicate that the impact of sexual and physical abuse histories on relatively long-term treatment outcomes is minimal. Addressing the sexual and physical abuse histories of those seeking treatment for drug abuse may be justified on humanistic grounds, but it will not significantly improve the long-term effectiveness of drug treatment, nor will it substantially enhance the lives of those with histories of abuse.

Fetal alcohol exposure attenuates lipopolysaccharide-induced fever in rats.

Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We studied the effects of fetal alcohol exposure (FAE) in rats on the core body temperature response to an exogenous challenge of the immune system with lipopolysaccharide (LPS). We report that FAE rats show markedly decreased LPS-induced fever [i.e., they require a higher dose than control rats to show any LPS-induced hyperthermia (50 micrograms/kg vs. 10 micrograms/kg)], and even with the higher LPS dose they manifest a weaker hyperthermia, which declines faster than in control animals. These results suggest that FAE produces an impairment in the release of endogenous pyrogens and/or in the neural substrate for body temperature regulation. This impairment may account for at least some of the decreased resistance to infections observed in FAE animals and humans.

Selective effects of fetal alcohol exposure on rat thymocyte development.

The thymoproliferative response to concanavalin A (ConA) following fetal alcohol exposure (FAE) is higher than control (149%) on day 44, is lower than control (64%) by day 51, and normalizes by day 69 (88% of controls). The ontogeny of HLA-Dr and transferrin receptor (CD71) expression in response to anti-CD3 stimulation is similar among the groups, but is distinct from that of ConA proliferation. The ontogeny of glucocorticoid cytoplasmic receptor (GCCR) sites per thymocyte is also different from the ontogeny of the ConA response. The number of GCCR sites rises sharply (2.5-fold) in control rat thymocytes between days 30 and 44, and remains at that level at later time points. By contrast, the number of GCCR sites per FAE thymocytes rises nearly linearly and normalizes by day 72. Our data support the notion that prenatal alcohol exposure significantly alters thymic development and indicates that the relationship between the development of thymocyte functional responses and that of GCCR is more complex than initially hypothesized.

The effects of chronic postweaning amphetamine on rats exposed to alcohol in utero: weight gain and behavior.

Offspring of rats fed alcohol, pair-fed, or fed ad lib control diets during pregnancy were administered a dose of amphetamine (0, 2 or 10 mg/kg) daily from postnatal day 22 (PN22) to PN42. Body weight was measured regularly from PN22 to PN60, and behavior was measured on PN22, PN28, PN36 and PN42. Rats exposed to alcohol in utero weighed less than controls at birth and throughout most of the experiment, despite a significantly accelerated weight gain relative to controls. By PN60, prenatal alcohol-exposed rats weighed the same as pair-fed controls. There were dose-dependent reductions in the rate of weight gain during amphetamine administration. After the daily injections stopped, the high-dose (10-mg/kg) amphetamine groups showed a higher growth rate than the 0-mg/kg and 2-mg/kg groups. There were no interactions between prenatal treatment and dose of amphetamine on body weight gain. Rats exposed to alcohol in utero showed a greater locomotor activation than controls given 2 mg/kg amphetamine. The magnitude of the locomotor activation to this dose of amphetamine decreased equivalently over the four test days for all prenatal treatment groups. Male but not female rats exposed prenatally to alcohol showed an apparent sensitization to 10 mg/kg amphetamine not seen in control rats between PN28 and PN42. There were no group differences in amphetamine-induced stereotypy or SCH-23390-induced catalepsy. The results implied that children with Fetal Alcohol Syndrome who may be treated for attentional dysfunction would show different dose-responses for some behavioral effects of CNS stimulants, but not for growth-retarding "side effects."

Apomorphine-induced motor behavior in rats exposed prenatally to alcohol.

We psychopharmacologically examined dopamine function in rats exposed to ethanol prenatally. Pregnant rats received liquid diets of 35% or 0% ethanol-derived calories (EDC), or ad lib lab chow (LC). Twenty-eight-day-old offspring received systemic doses of apomorphine chosen to stimulate predominantly presynaptic (0.02 or 0.1 mg/kg) or postsynaptic dopamine receptors (2.0 or 5.0 mg/kg). Behavior was scored automatically for 60 min in an "open field." For males, prenatal ethanol exposure resulted in a dose-response shift to the left for locomotor activity. Females exposed to the liquid diet, with or without ethanol, showed less of an increase in locomotor activity following the 5.0 mg/kg dose of apomorphine than did LC controls. There were no effects of prenatal treatment on repetitious motor behavior in the automated "open field" or on stereotypy scored by direct observation in separate groups of rats. The results are consistent with an hypothesis that prenatal ethanol exposure alters the sensitivity of postsynaptic (perhaps mesolimbic) dopamine systems important to locomotor activity in young male rats.