Convection-enhanced delivery of macromolecules in the brain.

For many compounds (neurotrophic factors, antibodies, growth factors, genetic vectors, enzymes) slow diffusion in the brain severely limits drug distribution and effect after direct drug administration into brain parenchyma. We investigated convection as a means to enhance the distribution of the large and small molecules 111In-labeled transferrin (111In-Tf; M(r), 80,000) and [14C]sucrose (M(r), 359) over centimeter distances by maintaining a pressure gradient during interstitial infusion into white matter to generate bulk flow through the brain interstitium. The volume of distribution (Vd) containing > or = 1% concentration of infusion solution increased linearly with the infusion volume (Vi) for 111In-Tf(Vd/Vi, 6:1) and [14C]sucrose (Vd/Vi, 13:1). Twenty-four hours after infusion, the distribution of 111In-Tf was increased and more homogeneous, and penetration into gray matter had occurred. By using convection to supplement simple diffusion, enhanced distribution of large and small molecules can be obtained in the brain while achieving drug concentrations orders of magnitude greater than systemic levels.     

Drug mixture which improves survival of ischemic rabbit epigastric skin flaps

The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl₂ (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes. © 1994 Wiley-Liss, Inc.     

Children With Chronic Physical Disorders: Maternal Reports of Their Psychological Adjustment

Advances in biomedical science have resulted in dramatic improvementsin the medical care of chronically ill and handicapped children.Past measurement problems have resulted in a lack of clarityregarding the psychological adjustment of these children. Themothers of 270 chronically ill and handicapped children wereadministered the Child Behavior Checklist in an attempt to identifypatterns of behavioral functioning across six pediatric chronicdisorders: juvenile diabetes, spina bifida, hemophilia, chronicobesity, juvenile rheumatoid arthritis, and cerebral palsy.In general, it was found that children in all chronic disordergroups were perceived by their mothers as evidencing on theaverage more behavioral and social competence problems thanexpected based on norms for children in general. However, theirbehavioral and social adjustment was reported as better thanthat of a normative sample of children referred to mental healthclinics. There were essentially no differences between childrenwith different chronic disorders in terms of behavior problemsand social competence. The results were taken to support theview that these children were as a group at risk for adjustmentproblems. They were also discussed in terms of the noncategorialapproach, which suggests that similar psychosocial challengesare faced across pediatric chronic physical disorders.     

Aerobiology of the Colorado Rockies: pollen count comparisons between Vail and Denver, Colorado.

Pollen patterns were compared between Vail, CO (8,200 feet elevation), Aspen, CO (7,900 feet) and Denver, CO (5,280 feet) from 1984 through 1988. Counts were obtained at all sites with a volumetric intermittent cycling rotating impaction sampler. Aspen and Denver were compared in 1984, and Vail and Denver from 1985 through 1988. While counts were generally lower in the mountain sites than Denver, certain pollens, especially trees, were quite high. Ragweed was essentially absent from Aspen and Vail, and chenopod-amaranth counts were very low. Cedar, pine, and aspen frequently pollinated despite active snowfall.     

Detection of intra-amniotic infection by gas-liquid chromatography.

The use of gas-liquid chromatography to detect short-chain organic acids in the amniotic fluid of patients with amnionitis has been previously described. Most of the studies describe patients in the early third trimester with such infections. The purpose of the current study was to confirm the correlation of infection with increased production of organic acids and to assess the effect of gestational age on the presence of these short-chain fatty acids in the amniotic fluid. Six patients with confirmed chorioamnionitis were used as positive control subjects. Seventy-two patients at various gestational ages from 18 to 42 weeks with negative Gram's stain and culture results from the amniotic fluid were used as negative control subjects. The data revealed an increased production of organic acids, particularly pyruvic, oxalic and succinic, in patients with amnionitis regardless of gestational age. Interestingly, patients with noninfected amniotic fluid also revealed an increase in the concentrations of volatile organic acids between 27 and 32 weeks' gestation. It appears from this study that previous results correlating chorioamnionitis with an increased production of organic acids in the amniotic fluid may have been confounded by gestational age.     

Psychotherapist perceptions of self and patients in the treatment of borderline personality disorder.

Psychotherapists' reactions to patients with borderline personality disorder were assessed by semantic differential ratings in an analogue study. Vignettes presented one of two patients who enacted the Rewarding and Withdrawing object relations units in two separate therapy sessions. In response to the Rewarding object relations unit therapists evaluated themselves more positively and perceived themselves as more active and more potent than in response to the Withdrawing object relations unit (p less than .01). They also evaluated the patients more positively and perceived them as less active (p less than .01). These patterns were modified by some order effects and some differences in response to the two vignettes, which represented a lower and higher functioning borderline patient.     

Hematologic disorders in pregnancy.

Hematologic disorders in pregnancy are relatively common and encompass a wide spectrum of clinical conditions. The treatment and obstetric management of the majority of these diseases are well established, although controversy exists in areas such as sickle cell disease and ITP. Once the diagnosis of a specific disorder is confirmed, therapy is directed toward improved perinatal outcome. Recent advances in prenatal diagnostic techniques make in utero diagnosis feasible for most of the inherited disorders and aid in genetic counseling.     

Release of heat-loss responses in paradoxical sleep by thermal loads and by pontine tegmental lesions in cats

Thermoregulatory heat-loss responses at high ambient temperatures were studied in intact cats and those with bilateral electrolytic lesions in the pontine tegmentum during wakefulness (W), slow-wave sleep (SWS), paradoxical sleep (PS) and PS without atonia induced by the lesions. Panting (respiratory rate 90/min) was present W, SWS, and in some cases, during PS. The percentage of the PS episodes with panting was directly related ambient temperature. In intact cats at 30 °C, panting occurred in 8% of the PS episodes; at 35 °C, in 52%, and at 40 °C, in 77%. The percentage of PS episodes with panting higher in the pontine-lesioned cats (90% at 35 °C), probably another indication of the altered thermoregulation of such animals. Thermoregulatory responses to heat load, and thermoregulation in general, have previously been shown to be suppressed in PS. Because hypothalamic thermosensitive neurons lack thermal responses during PS, the partial activation of heat-loss responses observed here may depend upon the function of extrahypothalamic brainstem areas.     

Bilateral cerebellopontine angle tumors in neurofibromatosis type 2

In a series of over 500 cases of cerebellopontine angle tumors, 19 patients had bilateral neurinomas. Four of these tumors arose from the facial rather than the acoustic nerve. A conservative policy regarding surgery had been adopted in an effort to prevent hearing loss for as long as possible. Nevertheless, all patients operated on in this series are now totally deaf. The results of managing these patients surgically and conservatively are discussed.