Transmission electron microscopy with a liquid flow cell.

The imaging of microscopic structures at nanometre-scale spatial resolution in a liquid environment is of interest for a wide range of studies. Recently, a liquid flow transmission electron microscopy (TEM) holder equipped with a microfluidic cell has been developed and shown to exhibit flow of nanoparticles through an electron transparent viewing window. Here we demonstrate the application of the flow cell system for both scanning and conventional transmission electron microscopy imaging of immobilized nanoparticles with a resolution of a few nanometres in liquid water of micrometre thickness. The spatial resolution of conventional TEM bright field imaging is shown to be limited by chromatic aberration due to multiple inelastic scattering in the water, and we demonstrate that the liquid in the cell can be displaced by a gas phase that forms under intense electron irradiation. Our data suggest that under appropriate conditions, TEM imaging with a liquid flow cell is a promising method for understanding the in situ behaviour of nanoscale structures in a prescribed and dynamically changing chemical environment.

Formation of ultrasharp vertically aligned Cu-Si nanocones by a DC plasma process.

We report an effective method for the production of ultrasharp vertically oriented silicon nanocones with tip radii as small as 5 nm. These silicon nanostructures were shaped by a high-temperature acetylene and ammonia dc plasma reactive ion etch (RIE) process. Thin-film copper deposited onto Si substrates forms a copper silicide (Cu3Si) during plasma processing, which subsequently acts as a seed material masking the single-crystal cones while the exposed silicon areas are reactive ion etched. In this process, the cone angle is sharpened continually as the structure becomes taller. Furthermore, by lithographically defining the seed material as well as employing an etch barrier material such as titanium, the cone location and substrate topography can be controlled effectively.

The CBCL as a screen for psychiatric comorbidity in paediatric patients with ADHD.

AIMS: To examine the informativeness of the Child Behavior Checklist (CBCL) as a screening tool to identify comorbid and non-comorbid cases of attention deficit hyperactivity disorder (ADHD) in a paediatrically referred population. It was hypothesised that specific scales of the CBCL would help identify specific comorbidities within ADHD cases in the primary care setting. METHODS: The sample consisted of children and adolescents 6-17 years old of both genders with ADHD (n = 121). A receiver operating curve (ROC) approach was used to determine which CBCL scales best differentiated between ADHD cases with and without its comorbidities with conduct, anxiety, and mood disorders. RESULTS: ROC analysis showed that the CBCL Delinquent Behavior and Aggressive Behavior scales predicted the structured interview derived diagnoses of conduct and bipolar disorder, the Anxious/Depressed and Aggressive Behavior scales predicted major depression, and the Anxious/Depressed and Attention problems scales predicted anxiety disorders. CONCLUSIONS: These results extend to a paediatrically referred population with previously reported findings in psychiatric samples documenting good convergence between structured interview diagnoses and syndrome congruent CBCL scales. These findings support the utility of the CBCL as a screening tool for the identification of psychiatric comorbidity in ADHD youth in the primary care setting.

Equal effectiveness of very-low-intensity anticoagulation and standard low-intensity anticoagulation: a pilot study.

We compared the efficacy of very-low-intensity oral anticoagulation (OA) with that of the recommended standard low-intensity oral anticoagulation, using international normalized ratios (INRs). We enrolled 101 patients into a pilot study--51 patients in the very-low-intensity anticoagulation arm (INR 1.4 to 2.0) and 50 in the standard low-intensity anticoagulation arm (INR 2.0 to 3.0). They were monitored for thrombotic/embolic and hemorrhagic complications for an average follow-up of 1.5 years. Two thrombotic/embolic events occurred in the very-low-intensity group; no thrombotic/embolic events occurred in the standard low-intensity group. No major bleeding occurred in the very-low-intensity group; one major hemorrhagic event occurred in the standard low-intensity group. These findings did not achieve a statistically significant difference in major complications between the two groups. It appears that very-low-intensity OA (INR 1.4 to 2.0) is as effective in preventing thromboses as standard low-intensity OA (INR 2.0 to 3.0).

Face perception and within-category discrimination in prosopagnosia.

Prosopagnosics are impaired at face recognition, but unimpaired, or relatively less impaired, at common object recognition. It has been suggested that this dissociation results simply from the greater difficulty of face recognition compared to object recognition, or from the greater need to discriminate visually similar members of a single category in face recognition compared to object recognition. We tested these hypotheses using the performance of normal subjects in an 'old/new' recognition paradigm to establish the true relative difficulty of face and object recognition, and required both normal subjects and a prosopagnosic subject to discriminate both faces and visually similar exemplars of nonface object categories. In two different experiments, the prosopagnosic patient performed disproportionately poorly with faces. These results disconfirm the hypotheses described above, and imply that prosopagnosia is an impairment of a specialized form of visual recognition that is necessary for face recognition and is not necessary, or less necessary, for the recognition of common objects.

Tissue plasminogen activator for treatment of livedoid vasculitis.

Livedoid vasculitis, a hyalinizing vasculopathy, is characterized by extensive formation of microthrombi and deposition of fibrin in the middermal vessels, which result in epidermal infarction, ulceration, and formation of stellate scars. In a prospective study of nonhealing ulcers in patients with livedoid vasculitis, we found a high incidence of anticardiolipin antibodies, lupus anticoagulants, increased levels of plasminogen activator inhibitor, and low levels of endogenous tissue plasminogen activator (t-PA) activity. This procoagulant tendency and decreased fibrinolysis may provide an explanation for the occlusive vasculopathy often noted in biopsy specimens from these patients. On the basis of these findings, we proposed that fibrinolysis with recombinant t-PA would lyse microvascular thrombi, restore circulation, and promote wound healing. In six patients who had nonhealing ulcers caused by livedoid vasculitis and in whom numerous conventional therapies had failed, low-dose t-PA (10 mg) was administered intravenously during a 4-hour period daily for 14 days. Five of the six patients had dramatic improvement; almost complete healing of the ulcers occurred during hospitalization, and tissue oxygenation, as measured by transcutaneous oximetry, increased. The one treatment failure was due to rethrombosis of the microvasculature; this patient was subsequently re-treated but with concurrent anticoagulation, and her leg ulcers healed. We conclude that daily administration of a low dose of t-PA is safe and effective treatment for nonhealing ulcers due to occlusive vasculopathy.

Embryology and morphology of microphthalmia in transgenic mice expressing a gamma F-crystallin/diphtheria toxin A hybrid gene.

BACKGROUND: Transgenic mice in which elongating lens fiber cells were ablated resulting in microphthalmia have been reported, however, their embryology and detailed morphology have not. EXPERIMENTAL DESIGN: The morphology of homozygous and hemizygous CDI, transgenic mice carrying the gamma FDT-A gene was studied by light microscopy on different days of gestation as well as postpartum. The findings were compared with normal CD-1 wild type controls. RESULTS: The earliest changes in mouse embryos transgenic for the gamma F-crystallin/diphtheria toxin A transgene are seen on day 12, when apoptotic cells appear in the area of elongation. In hemizygous embryos, ocular development is relatively normal until day 17 when the lens and eye are slightly smaller than normal and the lens vesicle is filled with abnormal lens material. At this time, the posterior capsule of the lens may rupture, releasing abnormal lens material which disperses throughout the eye, perturbing growth and other ocular structures. Additional breaks may subsequently occur and the ultimate morphology of the hemizygotes correlates with when the posterior capsule ruptures, how much lens material is released, and where it disperses. In homozygous embryos, due to extensive ablation of lens fiber cells, the "lens" becomes a diminutive mass of abnormal lens material, posteriorly located within the eye, and otherwise unable to fulfill its mechanical or inductive role in the development of the cornea, anterior chamber, iris, ciliary epithelium, and zonules with the result that all of these structures are markedly abnormal or absent. In addition, the lens is necessary for the accumulation of vitreous which in turn is required for the growth of the eye as a whole. In homozygous animals, vitreous does not accumulate and severe microphthalmia results. CONCLUSIONS: This study confirms and extends previous observations and conclusions on the central, orchestrating role of the lens in the development of the eye and illustrates the power of transgenic technology to elucidate the finer points of mammalian ocular development.

Acute coronary artery thrombosis in paroxysmal nocturnal hemoglobinuria.

We have reported a case of coronary artery thrombosis in a 36-year-old man with paroxysmal nocturnal hemoglobinuria (PNH), a potentially lethal thrombotic complication not previously documented in this unique patient population. Although the etiology of PNH remains unknown, the pathogenesis appears to be related to the deficiency of a specific membrane complement-regulatory protein, decay accelerating factor. Coronary artery thrombosis must now be added to the list of potential life-threatening thrombotic complications.

Cardiac transplantation: University of South Florida--Tampa General Hospital experience.

Cardiac transplantation has evolved from an experimental procedure to an accepted mode of therapy that prolongs life in patients with severe heart failure. The University of South Florida-Tampa General Hospital began performing cardiac transplantation for the treatment of end-stage cardiac disease in June 1985. Since then 42 heart transplantations have been performed and 30 patients are alive and well. The one-year actuarial survival is 78.73% and the two-year actuarial survival is 72.15%. Multiple complications have been encountered most notably rejection and infection. The recent approval of the USF/TGH program as a Medicare funded cardiac transplantation center is expected to greatly expand the number of potential recipients and will provide the residents of Florida, and the Southeastern United States, with an additional health care resource.

Lipoxygenases in rat embryo tissue.

It has previously been reported that rat embryonic tissue produces various prostanoids. This report demonstrates that rat embryo homogenates synthesized various lipoxygenase metabolites, including 12-hydroxyeicosatetraenoic acid (12-HETE) as the major metabolite, 5-HETE, and 15-HETE. The cyclooxygenase product 11-HETE was also formed. Product identification was based on radioimmunoassay and comparison of reverse-phase- and straight-phase-high-pressure liquid chromatography retention times with authentic standards. Additional evidence was the observation that the lipoxygenase inhibitor nordihydroguaiaretic acid inhibited HETE formation. It appears that, under the same (though not necessarily optimal) experimental conditions, lipoxygenase metabolites predominate quantitatively over cyclooxygenase pathway products and that 11-day embryonic tissue produces more HETEs than either 12-day or 13-day embryo homogenates.

Renal osteodystrophy.

Patients with chronic renal failure often suffer from severe metabolic bone disease. This is usually either osteitis fibrosa cystica or osteomalacia. While parathyroidectomy is indicated in osteitis fibrosa cystica, desferrioxamine is an exciting new development in the treatment of osteomalacia.

Prostaglandin synthesis in rat embryo tissue: the effect of non-steroidal anti-inflammatory drugs in vivo and ex vivo.

Aspirin and salicylate are well-known but poorly understood teratogens in laboratory animals. Because aspirin inhibits PG synthesis, we systematically examined PG synthesis in rat embryo homogenates, the inhibition of PG synthesis in vivo and ex vivo by various non-steroidal anti-inflammatory drugs, and tested the hypothesis that the inhibition of PG synthesis is responsible for aspirin-induced limb defects in rats. We report that embryonic rat homogenates synthesize 6-keto-PGF1alpha, PGE, and PGF in large amounts from endogenous substrate, that aspirin and other non-steroidal anti-inflammatory drugs inhibit PG synthesis in vitro but not necessarily in vivo, and that contrary to our original hypothesis, the inhibition of PG synthesis is likely not responsible for aspirin-induced limb defects in rats.

Aspirin-induced psychoteratogenesis in rats as a function of embryonic age.

Gravid Wistar rats were treated with either 625 mg/kg of aspirin (acetylsalicylic acid) or vehicle alone on either gestational Day 11 or 12, and their progeny were evaluated postnatally using a standardized series of neurobehavioral tests and physical measurements. The results showed that aspirin given on Day 11 produced maternal and offspring growth deficits not seen when given on Day 12. In addition, aspirin on Day 11 reduced behavioral performance in the progeny on tests of pivoting locomotion, negative geotaxis orientation, home scent (olfactory) orientation, and swimming performance. Further analysis revealed that some of the behavioral effects of aspirin on Day 11 significantly covaried with the body weight reductions noted in this group, such as negative geotaxis, whereas other results showed only minor associations with weight, such as pivoting and swimming. Interestingly, the olfactory orientation results were more apparent after body weight differences were factored out. These data demonstrate that (1) aspirin causes marked differences both in behavior and postnatal growth with only a 24-hr difference in embryonic age at the time of treatment; (2) behavioral tests are differentially affected by differences in body weight; and (3) behavioral tests appear to be measuring phenomena not reflected by growth, survival, or physical landmarks of development and, as such, add significant information about the toxicological effects of aspirin.