Tritiated Uridine Uptake in the Retinal Ganglion Cell Layer of the Cat during Normal Development and after Visual Cortex Ablation

The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer.     

Radioautographic evidence for slow astrocyte turnover and modest oligodendrocyte production in the corpus callosum of adult mice infused with 3H-thymidine

To find out whether glial cells proliferate in the corpus callosum of adult mice, two series of experiments were carried out. The first one made use of 9-month-old "aged" male mice. Some of them were given 3H-thymidine as a 2-hour pulse to examine which cells became labeled and, therefore, had the ability to divide. Others were sacrificed after a continuous infusion of 3H-thymidine for 30 days to examine whether the label would then appear in different cells. In other aged animals, the 30-day infusion was followed by 60 or 180 days without 3H-thymidine to determine whether cells retained or lost their label with time. A second series of experiments was carried out in 4-month old "young adult" male mice to seek confirmation of the main conclusions. Following the 3H-thymidine pulse given to aged mice, only immature glial cells were labeled. After a 30-day infusion, 12.1% astrocytes and 1.1% oligodendrocytes were labeled, so that the net daily addition rate of astrocytes averaged 0.4% and of oligodendrocytes, 0.04%. In young adult mice, the rate after a 7-day infusion averaged 0.9% for astrocytes and 0.08% for oligodendrocytes. However, when the 30-day infusion into aged mice was followed by 60 and 180 days without 3H-thymidine, the labeled astrocytes decreased to 5.3% and 0%, respectively, whereas the number of labeled oligodendrocytes did not change significantly. The interpretation of the results is that the immature cells present in the corpus callosum of mice continue dividing throughout life and their progeny give rise to astrocytes and oligodendrocytes. In the case of astrocytes, the production of new cells occurs in parallel with a loss, so that the astrocyte population turns over. In the case of oligodendrocytes, there is a small production of new, apparently stable cells.     

Radiographical documentation of direct injury of the intracanalicular segment of the optic nerve in the orbital apex syndrome

In the radiographical evaluation of the orbital apex syndrome, standard radiographs, tomograms, and computed tomographic scans have proved useful in the demonstration of the bony pathology, especially for optic canal fractures. The limitation of these methods, however, remains in their inability to provide accurate delineation of the associated soft tissue pathology, including the presence of optic nerve sheath hematoma. Recent developments in computer technology and graphic imaging are now available to provide an accurate three-dimensional radiographical analysis of the extent of skeletal and soft tissue injury in the orbital apex syndrome. The physician, in essence, can perform a radiographical "living autopsy". The technique was used to evaluate a patient with bilateral apex syndrome. It clearly showed that a severe direct injury to the intracanalicular portion of the optic nerve was responsible for the development of blindness in this patient. The progression of optic nerve injury, from perineural sheath hematoma to the ultimate development of optic nerve atrophy and fibrosis, was radiographically documented.     

Effectiveness of neonatal transport in New York city in neonates less than 2500 grams—A population study

In the past two decades, there has been a gradual trend to regionalization of perinatal care, categorization of hospitals and transport services for neonatal health care. The literature alludes to both beneficial and deleterious effects of neonatal transport (T) but no controls such as a matched nontransport (NT) population have been utilized to date.The major goal of this study was to evaluate the effect of neonatal transport from Level I and II high risk 2500 gm. neonates (born in NYC in one calendar year, 1979) compared to a cohort nontransported population matched for hospital of birth, weight, race, sex and risk. All transported 2500 gm. from Level I and II (n=328) were studied and a stratified random sample of the nontransported (NT) infants 2500 gm. from these same hospitals (n=2042) was used for comparison. The principle outcome variable was survival. The major conclusion of this study is that in Level I and II hospitals the transport group had a significantly increased survival in infants who were sick (Apgar <6) compared to cohorted nontransported controls. Interhospital differences in survival were noted among Level I and II but not seen in the subdivisions of (A) and (B) hospitals.Angelo Ferrara, M.D., Ph.D., is Professor, Pediatrics, NYU Medical Center, New York, N.Y.: Melvin Schwartz, M.D., was Research Professor, Environmental Medicine, NYU Medical Center, New York, N.Y.; Helen Page, R.N., M.P.A., is Quality Assurance Reviewer, Manhattan Eye, Ear, Throat Hospital, New York, N.Y.: Morton Israel, M.A., is Research Scientist, Health Resources Administration, City of N. Y., New York, N.Y.; Yucel Atakent, M.D., M.S., is Clinical Associate Professor, NYU Medical Center, New York, N.Y.; C.E. Smith, Ph.D., is President, Health Policy Analysis & Accountability Network, Inc. (HPAAN), Edgewood, New Mexico; Leon Landovitz, Ph.D., is Vice President, Management Information Systems, Healthways System Inc., Islin, N.J.Supported by NCHSR Grant #5-R018-HSO3832     

Behavioural effects of selective μ-, κ-, and δ-opioid agonists in neonatal rats

The behavioural effects of selective -, - and -opioid agonists in 5-, 10- and 20-day-old rats were investigated by observational analysis. The predominant response to -agonists was behavioural depression. High doses (10 mg/kg IP) of morphine and DAGO (d-Ala², NMe-Phe⁴, Glyol⁵-enkephalin) produced overt sedation in all the age groups and also induced catalepsy which was particularly apparent in the 5- and 10-day-old animals. These compounds did not produce any signs of behavioural activation in the neonatal rats. In contrast, rat pups treated with the -agonists U50,488H and PD 117,302 (1,10 mg/kg IP) exhibited marked hyperactivity with increases in wall-climbing and locomotion. Sedative effects of the highest dose of the -agonists began to emerge, however, as the animals grew older, resulting in significant decreases in behaviours such as gnawing and grooming at 20 days of age. The -agonist (+)-tifluadom (0.1–10 mg/kg), but not its corresponding (-)-isomer, produced an increase in activity in 5-day-old rats, thus extending the observations made with U50,488H and PD 117,302 and establishing the stereoselective nature of the response. The involvement of -receptors in opioid-induced hyperactivity was further substantiated by using a variety of opioid antagonists. In this context, the increase in activity induced by U50,488H (10 mg/kg) in 5-day-old neonates was attenuated by naltrexone (1 mg/kg IP) but not by larger doses (10 mg/kg) of either M8008 (which has low affinity for -receptors) or the selective -receptor antagonist ICI 174,864. Finally, DPDPE (d-Pen², d-Pen⁵-enkephalin) which acts selectively at -opioid receptors, did not exert any behavioural effects in either the 5-, 10- or 20-day-old rat pups at doses of up to 10 mg/kg. These results demonstrate behavioural effects of - and -but not -agonists in neonatal rats. There is a clear differentiation between - and -receptor effects and both - and -mediated behaviours show dissimilarities from the adult profile.     

The random blood glucose level, a risk factor for mortality after acute myocardial infarction, in non-diabetic patients

The Correlation between blood glucose level and cardio-vascular events is well established in diabetic patients. In this study, fifty three non diabetic (M:30F:23), patients after acute myocardial infarction were studied for mortality in the following two years, retrospectively. Every patient had random venous glucose estimated on admission. This glucose level was correlated with all cause mortality. At the end of 2 years, 13 patients died and 40 remained alive. There was a significant difference of blood glucose between those who died and remained alive. The difference between the mean blood glucose level is between 0.6 mmol/L and 3.8 mmol/L higher for patients who died (mean = 8.62); compared with those that were still alive (mean = 6.69). This difference was particularly observed in the group of anterior wall infarction. The subgroup analysis also revealed that the difference between the mean blood glucose levels is 9 mmol/L for female patients with heart failure compared with those who did not suffer from heart failure (mean 6.8). The study concludes that, the higher glucose level is associated with increased all cause mortality in the following 2 years of first acute myocardial infarction.     

Stereospecific monoclonal antibodies to nicotine and cotinine and their use in enzyme-linked immunosorbent assays

Stereospecific monoclonal antibodies (McAb) have been prepared against the tobacco alkaloid (S)-(-)-nicotine and its major metabolite (S)-(-)-cotinine. Nine anti-nicotine and 4 anti-cotinine hybridomas, selected by a screening procedure that utilized immunoprecipitation of the ³H-labeled natural isomers of nicotine or cotinine, were grown in the ascites fluid of pristane-primed syngeneic BALB/c mice. Antibodies in concentrations up to 7.5 mg/ml ascites and with binding affinities that generally exceeded 10⁸ M⁻¹ were obtained. Enzyme-linked immunosorbent assays (ELISAs) were developed in which nicotine or cotinine derivatives bound covalently to poly- -lysine werecoated onto wells of polyvinyl chloride microtiter plates. Coated wells were incubated sequentially with McAb in the presence or absence of inhibitor, rabbit anti-mouse immunoglobulin, then horseradish peroxidase-labeled protein A (HRP-SpA) before addition of substrate. The antibodies are highly specific and show minimal cross-reactivity with several nicotine metabolites and other structurally related compounds. In the respective assays, only 0.25 ng (S)-(-)-nicotine and 0.12 ng (S)-(-)-cotinine are required to give 50% inhibition of antibody binding, and as little as 0.05 ng nicotine and 0.02 ng cotinine give 15% inhibition. These assays are 5–10 times more sensitive than analogous ELISAs developed with rabbit antisera and HRP-SpA or conventional radioimmunoassays (RIAs) that utilize the rabbit antisera and ³H-labeled ligands. There was good correlation between the levels of nicotine (r = 0.967) found in saliva samples from smokers and non-smokers assayed by McAb-based ELISAs and conventional RIAs.     

Capnocytophaga ochracea Septicemia

A case report describing Capnocytophaga ochracea (Bacteroides ochraceus) septicemia in a 21-year-old male patient receiving chemotherapy for acute lymphocytic leukemia is presented. The unusual features of this organism are discussed together with a review of the literature.     

Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis

Chronic papillary conjunctivitis has been described following adenoviral conjunctivitis. It is unknown however, how long adenovirus is able to persist in the tear film and conjunctiva. To determine if adenovirus persists in the ocular surface following adenoviral conjunctivitis, 304 patients with a history of adenovirus conjunctivitis from whom an adenovirus had been isolated 10 years previously were sent a questionnaire regarding persistent or recurrent symptoms and were invited to attend. Patients were examined and samples of tears and conjunctival cells were collected from both eyes using tear film washes, filter paper, and swabs, the latter for virus isolation. Extracted DNA from the ocular samples was amplified using primers for herpes simplex virus (thymidine kinase) and adenovirus (hexon) genes. Adenovirus amplicons were sequenced and compared to original serotype. Thirty patients attended, 19 of whom had persistent papillary conjunctivitis. Evidence of adenovirus DNA was detected in 17 of 30 patients, 15 of whom also had evidence of a chronic papillary conjunctivitis. Adenovirus DNA was significantly associated with papillary conjunctivitis (P = 0.03). Adenovirus amplicons were successfully sequenced from six patients. Four patients harbored type 3 adenovirus, the same serotype with which they were infected originally 10 years previously. Two patients were infected originally with adenovirus serotype 3 but the current serotype was type 4. Infection of the ocular surface with adenovirus may predispose to the development of a persistent or recurrent conjunctivitis, the presence of which, appears to be associated with evidence of long term persistence of adenovirus DNA.