Interobserver variability in neonatal cranial ultrasonography

The reliability of cranial ultrasound diagnosis in the premature neonate was examined using data from an ongoing multicentre study of the epidemiology and long-term consequences of neonatal brain haemorrhage. First week ultrasound films (obtained at 4 hours, 24 hours and 7 days) from 60 study subjects were randomly selected for independent review by two groups of experienced interpreters, and results were recorded separately for observations (i.e. presence or absence of an abnormal echodense area on a film) and interpretations (i.e. presence or absence of haemorrhage or ventricular dilatation) in each hemisphere. Because of deaths in the first week of life, the total number of films examined was 138. Concordance on the presence or absence of an abnormal echodensity was examined for each individual film for three areas of interest: the germinal matrix, the ventricles and the parenchyma. Concordance on the presence or absence of haemorrhage or ventricular dilatation was examined only for the seventh-day film, or the final film prior to death. Finally, concordance was analysed with the diagnostic interpretations grouped into categories thought to differ prognostically for long-term outcome. In general, concordance was poorest for germinal matrix lesions and best for parenchymal lesions. Concordance was lower for observations made on each individual film than it was for interpretation of the final film in each case. Fifty-five of 60 cases (92%) were assigned to the same major prognostic category by both readers. Ultrasound review conferences were held periodically and there was evidence that concordance in ultrasound reading and interpretation improved during the course of the study.     

Development of a reconstructed human skin model for angiogenesis

We have previously shown that reconstructed human skin engineered from autologous keratinocytes, fibroblasts, and sterilized donor allodermis stimulates angiogenesis within 5-7 days when placed on well-vascularized wound beds in nude mice. When this reconstructed skin was used clinically in more demanding wound beds, some grafts were lost, possibly due to delayed vascularization. As this reconstructed skin lacks any endothelial cells, our aim in this study was to develop an angiogenic reconstructed skin model in which to explore strategies to improve angiogenesis both in vitro and in vivo. We report that culture of small-vessel human dermal microvascular endothelial cells (HuDMECs) was achieved using magnetic beads coated with an antibody to platelet cell adhesion molecule as a means of purifying the culture. Keratinocytes, fibroblasts, and HuDMECs could be cultured from the same skin biopsy. Initial studies culturing HuDMECs and other sources of endothelial cells with the tissue-engineered skin showed that these cells were capable of slowly entering the dermis under standard culture conditions in vitro. In conclusion, this provides us with a model in which to explore strategies for improving angiogenesis in vitro and also establishes the culture methodologies for the production of reconstructed skin containing autologous keratinocytes, fibroblasts, and endothelial cells.     

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.     

Tyrosine hydroxylase and serotonin containing cells in embryonic rat rhombencephalon: a whole-mount immunocytochemical study

Rhombencephala from rat embryos were processed as whole-mounts for immunocytochemical detection of monoaminergic cell populations, using antibodies to tyrosine hydroxylase (TH) and serotonin (5-HT). Specific advantages of the whole-mount technique over the classical serial-section method were that even isolated immunoreactive (IR) cells could be detected easily, and three-dimensional relationships could be ascertained without the need for serial reconstruction. Embryos between embryonic days (E) 12 and 16 (the day following nocturnal mating being considered as E1) were used in this study. Both TH and 5-HT immunoreactivities were already detectable at E12, even in the smallest embryos (crown-rump length: 6 mm), but there was a striking difference in the number and regional distribution of these two types of IR cells. TH was expressed in several cell groups located in the rostral rhombencephalon (the presumed anlage of the A4-7 complex) as well as in the caudal rhombencephalon (the presumed anlagen of groups A1-2 and C1-3), whereas 5-HT was expressed in very few cells located near the rostral border of the rhombencephalon (presumed anlage of the B4-9 complex). Although the three-dimensional distribution of the TH-IR cell groups underwent some modifications during the period studied, its general pattern remained relatively stable after E12. This contrasted with the sequential appearance of the 5-HT-IR cell groups and their spatial transformations during this period. Using the rhombencephalic isthmus as a landmark, we found that conspicuous 5-HT-IR fibre bundles penetrated into the mesencephalon from E13 onwards, but that the 5-HT IR cell bodies were exclusively located caudal to the borderline between the mesencephalon and the rhombencephalon (the rhombencephalic isthmus). We therefore suggest the term "rostral rhombencephalic raphe nuclei" for the rostral 5-HT cell groups instead of "mesencephalic raphe nuclei," which is a misnomer. Close spatial association between TH and 5-HT-IR elements was observed mainly in the caudal rhombencephalon, where 5-HT-IR fibres coursed through an area containing numerous TH-IR cell bodies (the presumed anlagen of groups A1-2 and C1-3).     

Bronchial reactivity to methacholine after combined heart-lung transplantation.

The operation of combined heart-lung transplantation results in acute denervation of the heart, lungs, and airways below the level of the trachea. The bronchoconstrictor response to inhaled methacholine of 12 recipients of heart-lung transplants was compared with that of 12 recipients of heart transplants having similar medication and 12 normal subjects. The median dose of methacholine that produced a reduction of at least 20% in the FEV1 (PC20) for the recipients of heart-lung transplants (8 mg/ml) was significantly lower than that for the recipients of heart transplants (64 mg/ml) and normal subjects (greater than 64 mg/ml). The increased airway reactivity may be related to the effects of chronic pulmonary denervation or subclinical inflammation in the airways. The effect of denervation on the response to full inspiration during bronchoconstriction was studied in six patients with heart-lung transplants by means of partial and maximal forced expiratory manoeuvres. Four showed bronchodilation after a deep breath, indicating that this response can occur after extrinsic pulmonary denervation in man. The patients with heart-lung transplants described a "tight" sensation in the anterior chest during bronchoconstriction, indicating that this sensation is not dependent on pulmonary innervation.     

Actions of nitric oxide on the acute gastrointestinal damage induced by PAF in the rat

The actions of nitric oxide (NO) on the acute gastrointestinal damage induced by platelet-activating factor (PAF) have been investigated in the rat.S-nitroso-N-acetyl penicillamine, which spontaneously generates NO, dose-dependently inhibited PAF-induced gastrointestinal plasma leakage, a measure of the initiation of vascular damage. The inhibitor of NO synthase,N^G-monomethyl-l-arginine substantially potentiated gastrointestinal damage and plasma leakage induced byE. coli endotoxin, but had no effect on that induced by intravenous infusion of PAF.Endogenous NO may thus have a protective role in the gastrointestinal vascular that can be mimicked by generators of NO. The protection afforded by endogenous NO may, however, be dependent on the nature of the inflammatory stimulus used to induce gastrointestinal damage.     

A comparison of dementia in Alzheimer's disease and multiple sclerosis

We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.     

Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases

Metrazol enhanced the penetration of two proteins (¹²⁵I human serum albumin and horseradish peroxidase), and the anticancer agent, razoxane, into the central nervous system of anaesthetized rats. Penetration was increased throughout the whole brain. With the exception of the bladder, no peripheral tissue was affected. The increase in brain permeability was temporary and reversed within 4 hours; brain levels of drug and protein were increased by up to three times.[/p]