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S Howard

Publications and source records attributed to S Howard.

At least 73 records · Page 4Linked to original sources

An immunocytochemical study of the germinal layer vasculature in the developing fetal brain using Ulex europaeus 1 lectin.

The characteristics of the germinal matrix vasculature were studied in the developing fetal brain using immunocytochemical methods. A preliminary comparative immunocytochemical study was made on six fetal brains to compare endothelial staining by Ulex europaeus I lectin with that of antibody to Factor VIII related antigen. Ulex was found to stain germinal layer vessels better than Factor VIII related antigen. Subsequently, the germinal layers of a further 15 fetal and preterm infant brains ranging from 13 to 35 weeks' gestation were stained with Ulex europaeus I to demonstrate the vasculature. With increasing gestation, there was a gradual increase in vessel density, particularly of capillaries. This was not a uniform process. A plexus of capillaries was prominent immediately beneath the ependyma while the more central parts of the germinal matrix contained fewer, but often larger diameter, vessels. The variation in vessel density which was a feature of the later gestation brains may have implications for local blood flow and may be a factor in haemorrhage at this site.

Antigens↗

Dissolution rate studies from a stationary disk/rotating fluid system.

The dissolution rates for hydrocortisone alcohol and acetate were determined using a stationary disk/rotating fluid system. The hydrocortisone was compressed in a tablet die, and the die placed in a vessel above a rotating magnetic bar. Dissolution rates were evaluated in aqueous media under conditions involving the following independent variables: solubility (Cs), diffusion coefficient (D), viscosity (v), rotational speed (omega), and tablet radius (r). A design equation which relates dissolution rate (R) to these variables was formulated for the system R alpha Cs D2/3 (v) -1/6(omega)1/2(r)3/2 This design equation adequately represents the system, which is related to fluid mechanics and convective diffusion models. The fluid mechanics model assumes that the fluid ideally rotates as solid-body rotation and the momentum layer is initiated at the outside radius of the tablet die. The convective diffusion model is based on the formation of a diffusion layer at the outside radius of the dissolving surface and a predictable relationship between the momentum and the mass transport quantities of bulk viscosity and diffusion coefficient. This configuration, like the rotating disk in a stationary fluid, offers the attractive attribute of being useful to study drug release mechanisms for systems of pharmaceutical interest.

Chemistry, Pharmaceutical↗

Precision of ultrasound diagnosis of pathologically verified lesions in the brains of very preterm infants.

Abnormalities detected by a mechanical sector scanner were compared 'blind' with autopsy findings in the brains of 56 infants born at less than 33 weeks gestation. Intraventricular haemorrhage was found in 53 of 112 hemispheres and had been accurately diagnosed by ultrasound (sensitivity 91 per cent; specificity 81 per cent). Isolated germinal layer haemorrhage was less successfully identified (sensitivity 61 per cent; specificity 78 per cent); false-positive diagnoses were partly due to difficulty in distinguishing haemorrhage from the normal choroid plexus in extremely preterm infants. Haemorrhagic parenchymal lesions were correctly identified in nine infants (sensitivity 82 per cent; specificity 97 per cent). Only 11 of 39 hemispheres with histological evidence of hypoxic-ischaemic injury, without marked bleeding, were correctly identified by ultrasound (sensitivity 28 per cent), mainly because of failure to detect small areas of periventricular leucomalacia and diffuse gliosis. 10 hemispheres with periventricular echodensities thought to represent leucomalacia showed no histological evidence of hypoxic-ischaemic injury (specificity 86 per cent). Ventricular dilatation in seven infants was always associated with evidence of hypoxic-ischaemic injury at autopsy.

Brain↗

Glial differentiation in the germinal layer of fetal and preterm infant brain: an immunocytochemical study.

The germinal layer in preterm infants is a common site of intracerebral hemorrhage that is associated with increased mortality and morbidity in survivors. This matrix is composed of a mass of immature cells containing many thin-walled blood vessels. A major factor in the occurrence of hemorrhage at this site is the absence of a network of fibers to support these vessels. This immunocytochemical study has examined glial differentiation within the germinal layer of brains from fetuses and preterm infants of gestational ages 18 to 35 weeks. Progressive glial differentiation with gestation is described. This process is not uniform and the more posterior germinal layer, lying over the body of the caudate nucleus, demonstrates more rapid maturation than that lying anteriorly near the head of the caudate nucleus. Anteriorly, even at 35 weeks of gestation, a central core of germinal layer cells remains immature with little evidence of glial differentiation. These changes may be related to the occurrence and distribution of germinal layer hemorrhages in preterm infants of varying gestations.

Brain↗

Periventricular intraparenchymal cerebral haemorrhage in preterm infants: the role of venous infarction.

Haemorrhage into cerebral parenchymal tissue supero-lateral to the angles of the lateral ventricles is a major cause of death and disability in preterm infants. It is frequently associated with germinal layer and intraventricular haemorrhage but the mechanism by which parenchymal haemorrhage occurs is uncertain. Recent studies have suggested that it is due to bleeding into tissue previously damaged by ischaemia following cerebral hypoperfusion. We have studied 68 preterm infant brains, of which four contained early intraparenchymal haemorrhage supero-lateral to the angles of the lateral ventricles which were associated with large germinal layer and intraventricular haemorrhages. The anatomical distribution and histological features of these haemorrhages suggested that they resulted from venous infarction and that the venous drainage of the periventricular tissues had been obstructed by the germinal layer haemorrhages. In these four infants, bleeding into parenchymal tissues could be regarded as a complication of germinal layer and intraventricular haemorrhage rather than of cerebral hypoperfusion.

Brain Ischemia↗

Age-dependent antibody response in mice and humans following oral influenza immunization.

In order to compare the antibody response in serum and secretions from healthy young subjects and the elderly (greater than 60 years), volunteers were immunized with the commercial inactivated influenza virus vaccine, by the usual (parenteral) route or orally. Also, young and old mice (mean age, 20 months) were orally immunized with live influenza virus. The older mice responded with a very slight rise in their serum and respiratory tract antibody levels compared with the young mice but showed no diminution in protection against lethal viral challenge. Elderly volunteers showed only slight serum antibody responses after parenteral immunization compared with the young. Neither group demonstrated a rise in serum antibody following oral immunization. With respect to the secretory IgA (SIgA) antibody response, certain differences were noted between the young and the elderly: the preimmunization levels of antibody to influenza virus were significantly greater in nasal secretions and saliva in the elderly as compared to the young volunteers, and the salivary antibody response was diminished in the elderly. This lack of a salivary antibody response in the elderly was explicable by the inverse relationship between the preimmunization SIgA antibody titers and the response to immunization. Oral immunization led to no more side effects than observed in the placebo control group.

Administration, Oral↗

Evaluation of a tube method for determining diffusion coefficients for sparingly soluble drugs.

Evaluation of a non-steady state method using glass tubes for the determination of diffusion coefficients is the purpose of this study. Unlike capillaries, glass tubes accommodate a larger volume of solution, facilitating assay procedures. Tubes are more susceptible to convection than are capillaries, but this effect is anticipated and accounted for in experimental design and data treatment. Glass tubes, 66 or 90 mm in length and 2 mm outer diameter, were siliconized and then filled with aqueous drug solution and placed in a jacketed flask containing gently stirred solvent at 25 degrees C. Diffusion experiments were run from 140 to 168 hours. At the end of this time period, the tubes were removed from the flask, placed in an ultrasonic vibrator for one minute, and their contents assayed spectrophotometrically. Data collected using potassium chloride as the diffusant showed little tube-to-tube variability, demonstrating the precision of the tube method, while diffusion coefficients determined for benzoic acid and p-aminobenzoic acid using the tube method tested the accuracy of the method by comparing reasonably well with values obtained using standard methods such as the rotating disk, free boundary, and membrane cell. Experiments done with either hydrocortisone or sulfisoxazole as the diffusant demonstrated the appropriateness of the tube method for the study of the diffusion of sparingly soluble pharmaceutical solutes.

4-Aminobenzoic Acid↗

Secretory antibody following oral influenza immunization.

Secretory IgA antibody may be important in protection against respiratory viral infections, and the concept of a common mucosal immune system offers the theoretical basis for the convenient stimulation of this antibody. Therefore, the oral route was compared with intramuscular injection in a double-blind, placebo-controlled study in young healthy volunteers. A killed influenza vaccine, given in enteric-coated capsules (total of 98 ug hemagglutinin of A/Bangkok) led to significant salivary and nasal IgA antibody rises in a 4-week period. The preimmunization titers in secretions were inversely correlated with the antibody rise after immunization. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to reactions following the intramuscular route. The latter route also was without significant effect in regard to a stimulation of secretory antibodies. The observed simultaneous induction of antibodies in saliva and nasal secretions following oral administration of killed vaccine gives further evidence of a common mucosal immune system and its possible clinical use.

Administration, Oral↗

Determination of the chromosomal locations of four Bacillus subtilis genes which code for a family of small, acid-soluble spore proteins.

The chromosomal locations of four genes which code for small, acid-soluble spore proteins (SASP) in Bacillus subtilis have been determined. Although these four genes code for extremely homologous small, acid-soluble spore proteins (greater than 65% sequence identity), the genes are not clustered but are located at 70 degrees (adjacent to glyB [sspB gene]), 115 degrees (between metC and pyr cluster [sspD gene]), 180 degrees (between metB and kauA [sspC gene]), and 260 degrees (between ilvC and aroG [sspA gene]) on the B. subtilis genetic map.

Bacillus subtilis↗

The histopathology of the larynx in the neonate following endotracheal intubation.

Subglottic stenosis is the most common serious complication of endotracheal intubation in the neonate with an incidence of between 1-8 per cent. While considered a complication of traumatic injury to the larynx and possibly associated with prolonged intubation, the pathogenesis is poorly understood and the pathology has not been described in detail. The nature of intubation induced injury has been investigated by examining step-sections of 43 larynges removed from neonates post-mortem who had been intubated for periods ranging from 10 min to 12 weeks. Focal ulceration was identified in the supraglottis and the anterior glottis. Similar injury was seen in the posterior glottis and subglottis but with more prolonged intubation there was full thickness mucosal necrosis, perichondritis and partial destruction of the arytenoid and cricoid cartilages. Although the severity of the injury progressed with time and many of the most severe injuries occurred early, in the second and third weeks of intubation, the larynx usually healed despite the continued presence of the endotracheal tube. Prolonged intubation on its own does not appear to be an important factor in the production of severe laryngeal injury nor, therefore, the subsequent complications such as subglottic stenosis.

Cricoid Cartilage↗

Burns: causes and risk factors.

In a retrospective study of 277 adult patients consecutively hospitalized for burns over a five-year period (1975-1979) patients' characteristics, circumstances of burn injury and prevalence of established predisposing factors were determined. The average age was 44.5 years, 78% were black and 62% were men. Average extent of burn was 19.7% body surface area. Major causes included flames in 44.8%, scalds in 28.5%, and chemicals in 9.7%. Seventy-four percent of all burns occurred at home. Burns resulting from assault accounted for 20.9%. Fifty-six percent of the patients had one or more of the established predisposing factors. Judged to be predisposed to burn injury were all of those who attempted suicide, all who were using self-treatment for some preexisting conditions, 85% of the elderly, 83% of those who died, 81% of those burned in the bathtub and 80% of those assaulted. Other described groups were also at high risk. Living alone increased risk of injury in persons prone to burn. The most common predisposing factors were alcohol and drug abuse, physical and mental illness and advanced age. Mortality rate was 12.6%. This study emphasizes the urgent need for effective burn prevention programs in which all health professionals should play an important role.

Accidents, Home↗

Immunization against influenza in humans using an oral enteric-coated killed virus vaccine.

By ingestion of subunit-killed influenza virus vaccine in the form of enteric-coated capsules, local synthesis of secretory IgA (sIgA) antibody was stimulated in human nasal secretions. A fairly equal antibody response initiated by oral and intramuscular administration was demonstrated in the nasal secretions, although a systemic immune response was not elicited from ingestion of the vaccine. If the secretory antibody response resulted from absorption of antigen and transport to the respiratory mucosa, systemic (serum) antibody would be expected. Therefore these findings support the hypothesis that specialized collections of lymphoid cells in the small intestines have IgA precursor cells which circulate and populate distant mucosal sites. A number of studies have suggested that protection against mucosal infection by a variety of respiratory viruses correlates better with the presence and level of sIgA antibody than with serum antibody. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to the intramuscular route. Thus, the oral method of influenza vaccination could prove to be superior in providing for immunological protection due to equal secretory antibody stimulation, improved convenience and less toxicity.

Administration, Oral↗

The effect of amniocentesis and drainage of amniotic fluid on lung development in Macaca fascicularis.

Amniocentesis and withdrawal of amniotic fluid was performed on pregnant monkeys (Macaca fascicularis) at two stages in development, either between 47 and 64, or between 85 and 95 days gestation. After birth the lungs of each infant monkey were studied using precise morphometric techniques, and compared with those in a control group of animals. The lungs after amniocentesis had alveoli of normal maturity but reduced in number and increased in size, features which both reduce the relative area for gas exchange. There was also a reduction in the number of respiratory airways. These changes occurred regardless of the time of amniocentesis, the amount of fluid removed and even if the membranes were simply punctured with no fluid removal. There is some evidence to suggest that similar sublethal effects may be present in human infants after maternal amniocentesis.

Amniocentesis↗

The influence of in situ repair systems on survival of several irradiated parenchymal cell types.

Radiation survival curves are presented for several normal parenchymal cell types irradiated in situ or in vitro. The data presented indicate that the in situ survival parameters for a specific cell type cannot be simply extrapolated from the results of either in vitro assays or rapid in vivo clonal transplantation assays. The data suggest that the D0 and terminal slope of in vitro survival curves can reflect those parameters for cells left in situ, but the shoulder width and the n value cannot. This appears to be due to the inability of the in vitro environment to support two major forms of repair that occur in situ, i.e. the "contact effect" and in situ repair (ISR). ISR is a form of potentially lethal damage repair (PLDR) that occurs when certain cells are allowed to remain in situ following irradiation. ISR is characterized by an increased shoulder in the survival curve without a change in slope and it has been observed in rat mammary, thyroid and liver epithelia.

Adolescent↗

Morphometric studies on the structural development of the lung in Macaca fascicularis during fetal and postnatal life.

The structural development of the normal monkey lung (Macaca fascicularis) from 61 days of gestation to 14 days postnatal age has been described using quantitative morphometric techniques. The lung of the adult monkey has also been studied. The airway and arterial branching pattern has been traced using serial sections. The alveolar number and size have been estimated and the structure of the arteries after postmortem arterial injection has been assessed. Comparison of lung morphology in monkey and man shows that there are similarities in segmental arrangement, structure and branching pattern of airways, in arterial structure and in changes in the arteries after birth. Although there are differences in the number of lobes, the number of generations of different types of airways and the number and size of alveoli, the overall structure in the monkey is more similar to that in man than is the structure of the lung in species such as sheep, pig or rat. During fetal life the monkey lung passes through the same stages of development as the human fetus but at birth the monkey has a full complement of airways and mature alveoli. Postnatal growth of airways and alveoli is due to increase in size rather than to multiplication. In man there is an increase in the number of alveoli and alveolar ducts after birth as well as an increase in size. Despite the differences between the species it seems appropriate to use the monkey in experimental studies on the lung.

Animals↗