Biomedical subjects

N R Saunders

Publications and source records attributed to N R Saunders.

At least 55 records · Page 3Linked to original sources

PubMed1995

Repair and recovery following spinal cord injury in a neonatal marsupial (Monodelphis domestica).

1. Repair and recovery following spinal cord injury (complete spinal cord crush) has been studied in vitro in neonatal opossum (Monodelphis domestica), fetal rat and in vivo in neonatal opossum. 2. Crush injury of the cultured spinal cord of isolated entire central nervous system (CNS) of neonatal opossum (P4-10) or fetal rats (E15-E16) was followed by profuse growth of fibres and recovery of conduction of impulses through the crush. Previous studies of injured immature mammalian spinal cord have described fibre growth occurring only around the lesion, unless implanted with fetal CNS. 3. The period during which successful growth occurred in response to a crush is developmentally regulated. No such growth was obtained after P12 in spinal cords crushed in vitro at the level of C7-8. 4. In vivo, in the neonatal (P4-8) marsupial opossum, growth of fibres through, and restoration of, impulse conduction across the crush was apparent 1-2 weeks after injury. With longer periods of time after crushing a considerable degree of normal locomotor function developed. 5. By the time the operated animals reached adulthood, the morphological structure of the spinal cord, both in the region of the crush and on either side of the site of the lesion, appeared grossly normal. 6. The results are discussed in relation to the eventual longterm possibility of devising effective treatments for patients with spinal cord injuries.

Animals↗

PubMed1995

Randomised trial spacer v nebuliser for acute asthma.

Sixty hospitalised children with asthma aged 1-5 years were randomised to spacer or nebuliser. A clinical score was measured at baseline and every 12 hours. There were no differences between groups in the score over time, or secondary outcome measures. The spacer is an effective delivery method for young hospitalised asthmatic children.

Administration, Inhalation↗

PubMed1995

Innocent heart murmurs in children. Taking a diagnostic approach.

Nearly all pediatric murmurs are heard in normal hearts and are not due to cardiac disorders. These murmurs usually can be classified by distinctive features and distinguished from organic murmurs by skillful clinical examination. This article reviews the various types of innocent heart murmurs in children, discusses their differential diagnoses, and suggests an approach to sorting out pediatric murmurs.

Child, Preschool↗

PubMed1994

Expression and distribution of fetuin in the developing sheep fetus.

Tissue distribution and developmental expression of fetuin were studied in the sheep fetus from embryonic day (E) 30 to adult (gestational period is 150 days). The presence of fetuin was demonstrated immunocytochemically using anti-fetuin antibodies; in situ hybridisation using short anti-sense oligonucleotide probes labelled with digoxigenin was used to study the ability of the developing tissue to synthesise fetuin, and reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate the level of fetuin mRNA in selected tissues. Tissue distribution of fetuin was widespread in the younger fetuses (E30 to E40). The most prominent presence due to in situ synthesis was demonstrated in the liver, central nervous system (CNS) including anterior horn cells, dorsal root ganglia and in skeletal muscle cells. Other developing tissues and organs that showed evidence of fetuin synthesis and presence of the protein included mesenchyme, kidney, adrenal, developing bone, gut, lung and heart. In the immature liver (E30-40) there was a strong signal for fetuin mRNA in hepatocytes and also in numerous haemopoietic cells; the proportion of these latter cells that was positive for fetuin mRNA increased between E30 and E40. Only some hepatocytes and a proportion of the haemopoietic stem cells were immunoreactive for fetuin itself at E30-40; immunoreactive hepatocytes were more frequently observed in the more mature outer regions of the developing liver. Lung and gut contained scattered fetuin-positive epithelial cells, especially at E30; a weak fetuin mRNA signal could be detected above background in many of these cells up to E40, but not at E60-E115 or in the adult. Particularly at E30 to E40, mesenchymal tissue both within organs such as the gut and lung and around forming bone and skeletal muscle contained cells that were positive for fetuin mRNA. Mesenchyme at these ages was also very strongly stained for fetuin protein, much of which may reflect fetuin in tissue extracellular spaces and be derived from the high concentration in plasma. By E80 fetuin mRNA was mainly present in the liver and the CNS; staining of the muscle tissue was becoming less pronounced. However in developing bone tissue, staining of chondrocytes for fetuin mRNA was still prominent in older (E80) fetuses; there was also fetuin protein staining of chondrocytes at the growing surfaces of bones and in bone marrow at this age. In the adult, weak immunocytochemical staining for fetuin itself was present in hepatocytes, but the mRNA signal was barely above the threshold limit of detection.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Development of spinal cord in the isolated CNS of a neonatal mammal (the opossum Monodelphis domestica) maintained in longterm culture.

The CNS of the newly born opossum removed in its entirety survives and maintains its electrical excitability in suitable culture media for up to ten days at 25 degrees C. The structure of the developing neonatal spinal cord has been studied in the intact animal and in the cultured CNS. The differentiation and survival of individual cells and subcellular structures were followed at the light and electron microscopic level. The expression of cell markers in neuronal and glial cells was studied immunocytochemically using commercially available antibodies. Both mono- and polyclonal antibodies raised against antigens from several other species cross-reacted with Monodelphis antigens. The spinal cord of preparations removed from three-day-old-animals showed many neuron specific enolase-positive large neurons in the ventral horn as well as vimentin- and glial fibrillary acidic protein-positive radial glial cells and numerous small diameter unmyelinated axons, abundant dendrites and synaptic structures. From post natal day 5 to post natal day 8 continued differentiation of neurons and differentiation of radial glial cells into astrocytes were apparent. Radial glial fibres and astrocytes reacted positively to antibodies against glial fibrillary acidic protein. Myelin had not appeared at 8 days. A comparison of material obtained from postnatal day 3-postnatal day 4 preparations fixed immediately after dissection and from postnatal day 3-postnatal day 4 preparations fixed after 5 days in culture showed growth with continued mitotic activity of the neuroepithelial cells and further neuronal and glial maturation in the spinal cord especially in the more rostral end. In successful experiments in vitro, the preservation of individual cells, organelles, membranes and synapses was similar in the freshly dissected and cultured preparations apart from a distinct loss of the youngest and some of the oldest neurons in the spinal cord. Also the main fibre tracts (dorsal, lateral and ventromedial funiculus) survived. Virtually all preparations that had not been damaged or injured showed these results. Possible reasons for the death or survival of individual neuronal or glial cell populations in these preparations are discussed.

Animals↗

PubMed1994

Fate of patients with residual tumour at the bronchial resection margin.

The presence of microscopic deposits of tumour cells at the bronchial resection margin (BRM) may adversely affect the prognosis of patients. Residual tumour cells were identified at the BRM in 40 (5.4%) of 735 patients who had been operated on for non-small cell lung carcinoma (NSCLC). The extent of disease was stage I in 7 (17.5%), stage II in 21 (52.5%), stage IIIa in 10 (25%) and stage IIIb in 2 (5%) patients. Malignant cells were found to have infiltrated the submucosal lymphatics in 5 (12.5%) cases and the peribronchial tissue in the remaining 35 (87.5%). Fifteen (37.5%) patients received adjuvant radiotherapy (RT). Recurrence of the disease was diagnosed in 29 (72.5%) patients after a median of 17 months (range 3-111). The recurrence was local in 17 (59%) and distant in 12 (41%). The 5-year overall actuarial survival rate was 21.6% and was not affected by RT (P = NS). Only patients with stage IIIa disease and a positive bronchial stump had a significantly reduced 5-year survival rate compared to those with a negative stump, 0% vs 17% (P < 0.001). Tumour cells at the resection margin did not affect the survival in this cohort except those with stage IIIa disease, and the addition of adjuvant RT did not significantly affect its recurrence in patients with NSCLC.

Aged↗

PubMed1994

Effect of type of resection on plasma granulocyte elastase levels following surgery for non-small cell lung carcinoma.

The lung is the primary focus of complications associated with adult respiratory distress syndrome (ARDS) and increased activation of granulocytes has been implicated in the genesis of ARDS. In the present study, plasma granulocyte elastase levels were measured in 24 patients undergoing lung resection for non-small cell lung carcinoma. Pre-, peri- and post-operative assessments of plasma elastase levels were made of patients who underwent a partial resection (lobectomy, n = 13) and patients who underwent a complete lung resection (pneumonectomy, n = 11). Preoperatively, values were similar for both patient cohorts and did not differ from those of normal volunteers. However, immediately (1 h) post-operation, elastase levels in patients who had undergone pneumonectomy were significantly elevated (300% of baseline value, P < 0.005), whereas levels were unchanged in lobectomy patients. On the 1st post-operative day (POD), elastase levels had returned to normal in pneumonectomy patients, whilst lobectomy patients now exhibited increased plasma elastase levels which remained marginally increased until the time of discharge (P < 0.05). The determinants of granulocyte activation following lung resection remain to be elucidated but may potentially relate to ischemic reperfusion in patients undergoing lobectomy, or alternatively may simply reflect the extent of manipulation, compression and contusion of lung tissue.

Aged↗

PubMed1994

Repair of connections in injured neonatal and embryonic spinal cord in vitro.

A remarkable preparation for studying development and repair is the CNS of the newborn opossum which, removed in its entirety, survives in culture for more than 1 week. In suitable medium, cells continue to divide, mature and reflex activity is maintained. Moreover, nerve fibers grow rapidly, reliably and extensively across lesions made in the spinal cord. Restoration of conduction has been demonstrated by recording electrically; labeled fibres have been observed directly by light and electron microscopy as they traverse the lesion. Similar experiments have also been made in embryonic (E15) rat CNS in culture. Open questions concern the identity of the fibers that traverse the lesion and the specificity of connections that they make with targets. We are now also analysing mechanisms that favor repair in younger opossums and that prevent it in their older siblings. Of particular interest are oligodendrocytes and myelin that start to appear at about 8-9 days after birth.

Animals↗

PubMed1994

Brain growth and neocortical development in the opossum.

General brain growth and differentiation of the neocortex have been studied in the marsupial, Didelphis virginiana from the 10.5 day embryo through adulthood. Didelphis is born after a short gestation period of about 12.5 days, at a time when the telencephalic wall consists only of two layers and is considered to be at an embryonic stage of development. The cortical plate does not appear until late in the first postnatal week, thus neocortical development is totally a postnatal phenomenon in Didelphis as has been shown in other marsupial species examined to date. The general pattern of development and the establishment of the six-layered adult neocortex in Didelphis is similar to that described in eutherian mammals. Signs of cortical lamination can be seen as early as postnatal day 35 and the cytoarchitecture of a typical mammalian neocortex is well defined by postnatal day 60 in Didelphis prior to the onset of weaning.

Animals↗

PubMed1994

Projection of visuotopically organized afferents to the dorsal thalamus in the opossum, Monodelphis domestica.

Retrogradely transported dyes, Fluorogold and Fast Blue were injected into both sides of the dorsal thalamus in the Monodelphis opossum. Projection of the presumed primary visual cortical area, superior colliculus and parabigeminal nucleus to the dorsal lateral geniculate nucleus and the lateral posterior--lateral intermedius nuclear complex were described. They show close similarities to the homologous projections in the North American Opossum, insectivores and some rodents. In comparison with rat, cortico-thalamic and tecto-thalamic projections in the Monodelphis are less numerous. The peculiarity of cytoarchtitectonics of cortical layer 6 is described and discussed.

Animals↗

PubMed1993

Synthesis of the foetal protein fetuin by early developing neurons in the immature neocortex.

The presence of the foetal protein fetuin has previously been demonstrated by immunocytochemistry to be specifically confined to the primordial plexiform layer, the early cortical plate and subplate zone cells in the developing neocortex of a number of species. In order to investigate its origin there, we have applied in situ hybridization in paraffin sections of Bouin's fixed foetal sheep brain, using a short anti-sense oligonucleotide probe. The distribution of fetuin mRNA has been compared with that of the protein by using anti-fetuin antibodies and immunocytochemistry. This allowed us to confirm that fetuin is synthesised initially in cells of the primordial plexiform layer and subsequently cortical plate and subplate cells. On the other hand, cells in the ventricular zone that are fetuin (protein) positive do not contain detectable fetuin mRNA. The time course of fetuin mRNA expression in the developing neocortex follows closely the previously described pattern of fetuin (protein) distribution in the sheep brain, apart from its absence from the ventricular zone where its origin is probably by uptake from cerebrospinal fluid.

Animals↗

PubMed1993

Bovine internal mammary artery as a conduit for coronary revascularization: long-term results.

Graft patency after coronary artery bypass grafting depends largely on the choice of conduit. Because an increasing number of patients have insufficient or poor-quality autologous material, there is a need for a suitable synthetic graft that is readily available and easy to handle and that has good long-term patency. Early results suggest that the bovine internal mammary artery graft may meet these criteria. We have used a total of 26 such grafts in 18 patients. Postoperative angiography has been performed in 19 grafts in 14 patients, 3 to 23 months after operation; of these grafts, 3 are currently patent (15.8%, compared with 85.7% and 75.0% patency for native internal mammary artery and saphenous vein grafts in the same patients). We report the results of clotting studies and an analysis of lipid status. These patients do not, however, appear to represent any atypical group, either in terms of coagulopathy, native coronary artery size, or the type of vessel disease. Nevertheless, our poor results contrast markedly with the early enthusiasm reported from other centers.

Aged↗

PubMed1993

Noncardiogenic pulmonary edema complicating lung resection.

Postresectional pulmonary edema is a rare but potentially fatal complication of thoracic operations. In a retrospective study of 402 lung resections we have identified 11 cases of postresectional, noncardiogenic pulmonary edema. We have analyzed the individual data to test recognized hypotheses regarding this condition. Pulmonary edema occurred in 5.1% of right pneumonectomies, 4.0% of left pneumonectomies, and 1% of all lobectomies. In 2 patients the symptoms occurred immediately after operation; in the other 9 the mean interval to diagnosis was 43.4 hours. All 11 patients were in a positive fluid balance in the first 24 hours after operation (mean, 20.8 +/- 9.1 mL/kg). However, there was no significant difference between this value and the respective values for control groups of 20 patients having pneumonectomies and 20 patients having lobectomies in whom pulmonary edema did not develop. Our findings differ from other reported series in that perioperative fluid overload was not found to be a significant contributory factor in the development of postresectional pulmonary edema. We discuss other possible mechanisms for this phenomenon.

Aged↗

PubMed1993

Neuraminic acid specific lectins as markers of early cortical plate neurons.

Early cortical plate and subplate cells in the developing neocortex of many animal species and humans contain one specific plasma protein, fetuin. Fetuin is heavily glycosylated and it is possible that due to the large amount of sugars, this molecule may play a part in cellular recognition during brain development. Cellular and extracellular carbohydrates in the developing brain of the sheep were studied histochemically using a battery of fluorescein-labelled lectins. Two neuraminic acid specific lectins, Sambucus nigra and Maackia amurensis, labelled consistently the fetuin-positive cells as demonstrated by double labelling with lectins and antifetuin antibodies. Brain sections from other species, known to contain fetuin-positive cells (fetal cow, postnatal tammar wallaby) showed a similar lectin staining pattern to that of the sheep fetus. Additionally, sections from species thought to contain fetuin in their developing brains that failed to cross-react with available antifetuin antibodies (postnatal Monodelphis, fetal cat) also demonstrated lectin-positive staining in the same neuronal cell population. Thus, neuraminic acid is a common and well conserved terminal carbohydrate in cortical plate and subplate neurons of the developing brain. Neuraminic-specific lectins are useful markers for these neurons in addition to the more traditional use of immunocytochemical methods in studies of formation of the neocortex.

Animals↗

PubMed1993

Long-term results in the elderly following pulmonary resection for non-small cell lung carcinoma.

The long-term results of 647 patients undergoing pulmonary resection for non-small cell lung carcinoma (NSCLC) between 1980-1988 were reviewed. One hundred forty-five (22%) were elderly patients (70 years or more, group 1), with a mean age of 72.3 years (70-81) and the other 502 (18%) were younger (69 years or less, group 2) with a mean age of 61.4 (40-69) years. The male to female ratio was 4:1 in group 1 and 3:1 in group 2. The number of patients in group 2 (n = 234, 47%) who underwent pneumonectomy was significantly greater (P < 0.01), compared to group 1 (n = 47, 32%). Cardiopulmonary complications were more frequently observed in group 1 (19.3%) than in group 2 (7.4%), P < 0.05. Although cardiac complications (i.e. arrhythmias) were more common in the elderly group, pulmonary complications (retained secretions, atelectasis) occurred more commonly in the younger group. The overall hospital mortality in group 1 and group 2 was 8.9% and 5.3%, respectively (NS), and mortality following pneumonectomy in group 1 (10.6%) was similar to that of group 2 (7.6%) (NS). The 2- and 5-year overall actuarial survival rates were 61% and 30% in group 1 and 57% and 37% in group 2 (NS). Superior survival was achieved in patients in stage I of the disease in both groups. Cell type was not a determinant of long-term survival differences between the groups whereas type of operation (lobectomy) and sex (female) were.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1993

Recurrence of rectal carcinoma in the mediastinum.

Mediastinal metastases arising from a primary gastrointestinal neoplasm usually follow extensive subdiaphragmatic spread. However, we have reported the rare recurrence of rectal carcinoma in the mediastinum. In addition to emphasizing the systemic metastatic spread of rectal carcinoma, this case demonstrates the need to consider metastases arising from abdominal tumors as a cause of mediastinal masses.

Adenocarcinoma↗

PubMed1993

Zn-binding globulin in human fetal brain and liver: a marker for passive blood/CSF transfer of protein.

The presence of Zn-binding globulin (ZnbG) during human fetal development was studied in cerebrospinal fluid (CSF) and plasma with immunodiffusion methods and in brain, CSF, plasma and liver using immunocytochemical methods. At the earliest stages examined with immunocytochemistry (5-6 weeks gestation) no staining for ZnbG was visible in liver, plasma, CSF or brain. However, the primitive mesenchyme exhibited a prominent staining reaction. In late embryonic and early fetal stages, staining for the protein was most prominent in the spinal cord, brain stem and diencephalon and in the choroid plexuses and marginal and subplate zones in the telencephalon. At the cellular level, synaptic strata and territories were most strongly stained. The distribution of ZnbG in the early developing central nervous system suggests that this protein may be involved in the initial establishment of CNS circuitry. Embryonic brain was positive for ZnbG well before the protein could be detected in CSF, plasma or liver. The early occurrence of ZnbG in brain tissue prior to its presence in liver or plasma also suggests that the protein is synthesized in early fetal brain. At the time when CSF first became positive (17 weeks gestation), the brain staining had largely disappeared. ZnbG in plasma increased throughout gestation to reach 2.6 +/- 0.4 mg/100 ml at term and subsequently increased to an adult value of 6.8 +/- 1.5 mg/100 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

The nature of the decrease in blood-cerebrospinal fluid barrier exchange during postnatal brain development in the rat.

1. The blood-cerebrospinal fluid (CSF) exchange of a wide range of passively transported lipid insoluble compounds (0.43-5.4 nm molecular radius) has been investigated in rats at different stages of postnatal development (2 days old to adult). A novel 'litter-based' model for investigating blood-CSF barrier exchange in immature animals is described. 2. At each age investigated there was a clear inverse correlation between molecular radius and blood-CSF barrier exchange, in addition to an overall decrease in blood-CSF barrier exchange with increasing age. 3. The decrease in blood-CSF barrier exchange with age was not consistent with a reduction in pore diameters, nor does it appear to be due to an increase in the CSF sink effect with age. It seems likely to be due to a relative decrease in the number of a population of large diameter pores.

Animals↗