Biomedical subjects

N R Saunders

Publications and source records attributed to N R Saunders.

At least 19 recordsLinked to original sources

PubMed1996

The expression of fetuin in the development and maturation of the hemopoietic and immune systems.

The distribution and expression of fetuin, a fetal plasma protein that has been shown to have a wide-spread intracellular presence in many developing tissues including the central nervous system, has been studied in the developing immune and hemopoietic organs of fetal and adult sheep. The presence of fetuin was demonstrated using immuno-cytochemistry and expression of fetuin was studied using northern blot analysis and in situ hybridization. In the developing sheep fetus, fetuin was shown to be expressed first in the hemopoietic cells of the fetal liver and subsequently in the forming spleen. The very first stromal, bone marrow-forming cells, also expressed fetuin mRNA. These cells became more numerous during gestation and by embryonic day (E)115 (term is 150 days), fetuin-expressing cells were identified morphologically to be monocytes/macrophages. Fetuin protein, on the other hand, was present in all hemopoietic and immune organs from the earliest age studied (E30) but was confined initially to matrix, mesenchymal tissue. Fetuin-positive cells could be identified in the spleen at E60 as early hemopoietic cells, in the lymph nodes at E60 as stromal cells and macrophages, and at E115 in the thymus as macrophages and squamous cells. In the adult, fetuin mRNA was only detectable by northern blot in the liver and the bone marrow. Using in situ hybridization in adult tissue, fetuin mRNA-positive cells were identified in the bone marrow to be monocytes/macrophages. Additionally, in the spleen germinal centres, fetuin mRNA was identified in cells with the morphology of dendritic cells. Using three separate cellular markers: lysozyme, S-100, and alpha 1-antitrypsin, the cellular identification of fetuin-positive cells was confirmed to be in the monocyte/macrophage lineage.

Animals↗

PubMed1996

Development of a clinical asthma score for use in hospitalized children between 1 and 5 years of age.

The objective of this study was to develop a clinical asthma score (CAS) for use in hospitalized children between 1 and 5 years of age. Formal approaches to item selection and reduction, reliability, discriminatory power, validity, and responsiveness were used. The final CAS consisted of five clinical characteristics: respiratory rate, wheezing, indrawing, observed dyspnea, and inspiratory-to-expiratory ratio. Interrater reliability was high (weighted kappa = 0.82), and the CAS was discriminatory (Ferguson's delta = 0.92). The CAS was valid, with a strong correlation with length of hospital stay (Spearman's correlation = 0.47, p < 0.05) and drug dosing interval (Spearman's correlation = -0.58, p < 0.01). The CAS was responsive, with a significant change in CAS from admission to discharge (Wilcoxon signed rank test, p < 0.01). This score, for use in hospitalized preschool children, is reliable, discriminatory, valid, and responsive.

Asthma↗

PubMed1996

Terbutaline improves efficiency of oxygenation after coronary artery bypass surgery.

OBJECTIVE: To assess the therapeutic role of the betareceptor agonist terbutaline in reducing postoperative pulmonary dysfunction following coronary artery bypass grafting (CABG). DESIGN: Prospective, randomized, open controlled study. SETTING: Cardiac surgical intensive care unit. PATIENTS. 22 consecutive patients undergoing elective CABG. INTERVENTIONS: 11 were randomized to receive terbutaline 0.5 mg subcutaneously 6 hourly for 48 hours following extubation (group T) while 11 controls did not (group C). MEASURES: FVC, FEV1 and PEFR measured pre-operatively and at 30 min, 12 hrs, 36 hrs and 5 days post-extubation. A-aDO2 calculated from arterial blood gas analysis during the first 24 hrs post-CABG. RESULTS: Terbutaline had no effect on spirometric variables which decreased by over 50% after extubation in both groups and increased in similar fashion over the next 5 days. A-aDO2 increased significantly (p<0.01) after extubation in both groups. Treatment with terbutaline eliminated this change in group T at 6 hrs after extubation. CONCLUSIONS: Terbutaline has little effect on the restrictive ventilatory deficit after CABG but does improve the efficiency of oxygenation in the early postoperative period.

Adrenergic beta-Agonists↗

PubMed1995

Mitral valve replacement with the Carpentier-Edwards standard bioprosthesis: performance into the second decade.

From March 1978, 196 Carpentier-Edwards standard bioprostheses (stCE) were implanted in 194 patients. There were 154 isolated mitral valve replacements (MVR) and 42 aortic plus mitral valve replacements (AVR/MVR) with a mean follow-up of 7.05 (range 0-15.2) years and 7.15 (range 0-13.8) years, respectively. Freedom from structural valve failure at 10 years was 70.8% +/- 4.9% (MVR) and 59.6% +/- 11.1% (AVR/MVR). The incidence of structural valve failure increased sharply after 7 years. Freedom from thromboembolism was 83.0% +/- 3.8% (MVR) and 89.0 +/- 6.0% (AVR/MVR). Thromboembolic events were related to the presence of atrial fibrillation in patients not receiving anticoagulation. Anticoagulant-related haemorrhage was rare. Freedom from mitral valve prosthetic endocarditis at 10 years was 90.9% +/- 3.1% (MVR) and 86.1% +/- 8.4% (AVR/MVR). Prosthetic valve endocarditis was associated with more than 60% mortality. The probability of event-free survival at 10 years follow-up was 43.6% +/- 4.6% (MVR) and 33.3% +/- 8.6% (AVR/MVR). The performance of the stCE in the mitral position shows a low rate of thromboembolic events and anticoagulant-related haemorrhage, but the long-term performance of the prosthesis is unsatisfactory due to a high rate of structural valve failure. This confirms earlier reports.

Adult↗

PubMed1995

Results of pneumonectomy for cancer in patients with limited ventilatory function.

It is well established that patients with compromised pulmonary function have a greater incidence of morbidity and mortality following lung resection. The prognosis of 36 (9.7%) patients with poor respiratory function (forced expiratory volume in ls (FEV1) and FEV1/FVC (forced vital capacity) ratio were equal to or less than 50% of the predicted value) of a total of 369 patients who underwent pneumonectomy due to non-small cell lung carcinoma over 10 years were reviewed. All but three patients were male with a median age of 62.5 years. Right pneumonectomy was carried out in 12 (33%) and left in 24 (67%) patients. Median FEV1 and FEV1/FVC were 1.51 (46%) and 46.5% respectively. Three (8%) patients died within 30 days of surgery. The postoperative complication rate in patients with poor respiratory function was 44%. Nine (27%) of the hospital survivors died due to non-malignant causes (recurrent chest infection/respiratory failure) and 12 (36%) due to recurrent tumour. The cause of death in one patient was second primary lung tumour and it was unknown in three (9%) patients. Eight (24%) long-term surviving patients did not have severe respiratory symptoms; their FEV1 and FEV1/FVC were remeasured and revealed a median 1.05 l (38%) and 50%, respectively of the predicted value. Actuarial 5-year survival was 29%. Poor respiratory function is associated with postoperative complications and non-malignant deaths arising secondary to respiratory failure. The survival profile demonstrates that patients were successfully treated with pneumonectomy and suggests that surgery should not be withheld from those with limited lung function if detailed investigations predict adequate residual lung function.

Aged↗

PubMed1995

Evaluation of short-course therapy with cefixime or rifampin for eradication of pharyngeally carried group A streptococci. The Ontario GAS Study Group.

Therapy to eradicate pharyngeally carried group A streptococci (GAS) has increasingly been used in the management of institutional outbreaks and is now recommended for household contacts of patients with streptococcal toxic shock syndrome. In this randomized, controlled trial, contacts of patients with GAS infections were screened for pharyngeal GAS colonization. Those whose cultures were positive were randomized to receive either cefixime (8 mg/[kg.d]; maximum 400 mg) or rifampin (20 mg/kg; maximum, 600 mg) once a day for 4 days. Two to five days following completion of therapy, repeated cultures were negative for 13 (38%) of 34 rifampin recipients and 71 (77%; 95% CI, 69%-85%) of 97 cefixime recipients. At 10-14 days after treatment, only 53% of cefixime recipients remained culture-negative. Rates of successful clearance improved with increasing age (P < .01); among 17 adults who received cefixime, the success rate was 94%. Four days of therapy with rifampin is not effective for eradication of pharyngeally carried GAS. Four days of therapy with cefixime may be effective for adults, but further studies are needed.

Adolescent↗

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↗