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Biomedical subjects

N R Saunders

Publications and source records attributed to N R Saunders.

At least 127 records · Page 7Linked to original sources
PubMed1984

Late outcome of patients with Braunwald-Cutter mitral valve replacement.

Eighty patients who underwent mitral valve replacement (MVR) with Braunwald-Cutter prostheses (54, single valve replacement; 26, multiple valve replacement) between December, 1972, and September, 1975, are discussed. The period of follow-up ranged from 72 to 120 months with a mean of 84.6 months. For the hospital survivors, actuarial survival at ten years was 73 +/- 6.7% for patients with MVR alone and 30 +/- 17.5% for those with multiple valve replacement. The linearized rate of embolic complications in patients with MVR was 3.2% per year and in patients with multiple valve replacement, 1.5% per year. These low rates of embolism allow a favorable comparison of the Braunwald-Cutter valve with other mechanical prostheses. There was no evidence of serious poppet wear or poppet escape after ten years of the valve in the mitral and tricuspid positions. Thus, elective replacement of the Braunwald-Cutter valve from the atrioventricular position because of this potential problem is not considered necessary. In the aortic position, escape of the poppet from the valve has occurred as late as 101 months. The overall morbidity for the group was high. Only 34% of the patients having MVR and 12% of those with multiple valve replacement are expected to be alive and to remain free from any major complication ten years after operation.

Actuarial Analysis↗
PubMed1984

Distribution of alpha-fetoprotein in fetal plasma and in amniotic and allantoic fluids of the pig.

The concentration of AFP in the plasma of fetal pigs was highest in early gestation (Days 15-30) and declined with advancing gestation. This pattern was comparable to those observed in other mammals with similar lengths of gestation. In contrast, allantoic and amniotic fluid AFP concentrations were highest during the middle third of gestation but these concentrations were much lower than those in fetal plasma throughout gestation. The allantois appears to be a significant distribution space for AFP in early gestation.

Allantois↗
PubMed1984

Cyclosporin and bronchial healing in canine lung transplantation.

Long-term bronchial anastomotic healing has been assessed in the canine lung transplant model with cyclosporin as the primary immunosuppressant. Early bronchial revascularization was achieved by wrapping an omental pedicle around the bronchial anastomosis. Ten dogs underwent left lung transplantation and six survived 100 days or more before being put to death. No significant bronchial complications occurred. Late bronchostenosis was not seen, despite four biopsy-proved rejection episodes in three of the dogs surviving past 100 days. Histologically, all anastomoses were well healed at autopsy. Cyclosporin was shown to be an effective immunosuppressant in this model and was associated with prolonged survival and low morbidity. Transplant lung function was assessed at 100 days by contralateral pulmonary artery ligation in five dogs and was satisfactory in the three animals that had not had rejection episodes. The findings support our belief that bronchial anastomotic complications after human lung transplantation are mainly related to the effects of immunosuppression with steroids and to the ischemia resulting from division of the bronchial circulation at the time of transplantation.

Animals↗
PubMed1983

The distribution of plasma proteins during early embryonic development in the sheep.

The distribution of the five plasma proteins that are quantitatively most important during development in the sheep has been studied in embryos of 15 to 21 days gestation. The three primary embryonic layers and tissues that differentiate from them were tested for the presence of alpha-fetoprotein (AFP), fetuin, albumin, transferrin and alpha 1-antitrypsin using the indirect immunoperoxidase method. Fetuin was the most prominent of these proteins particularly in the developing central nervous system. Fetuin and transferrin appeared early in the differentiating mesoderm and, with albumin and AFP, were detected in tissues originating from all three layers during the course of development. alpha 1-Antitrypsin appeared to have a limited distribution. All five plasma proteins were detected before the establishment of a circulatory system. It is suggested that their appearance in embryonic tissue is related to its stage of development and that they play an important part in early differentiation.

Albumins↗
PubMed1983

Comparison of proteins in CSF of lateral and IVth ventricles during early development of fetal sheep.

This study examines the relationship between plasma proteins in blood and in CSF in the developing brain of sheep fetuses between 30 and 60 days gestation. Five proteins account for the very high concentration of protein in fetal CSF (over 1000 mg/100 mg/100 ml at 30 days): alpha-feto-protein, fetuin, albumin, alpha 1-antitrypsin and transferrin; the concentration of each protein is similar in lateral and IVth ventricular CSF at 30 days. By 40 days there is considerable decrease in protein concentration in lateral ventricular CSF. At this age in the IVth ventricle the overall total was unchanged, although there were changes in concentration of individual proteins. At 60 days the concentration of each protein in both compartments had fallen below that at 40 days; the marked concentration difference between lateral and IVth ventricular CSF was still present. Experiments using i.v. [125I]- or [3H] labeled plasma proteins in 30-40-day fetuses showed that very little protein penetrated into lateral ventricular CSF by 3-5 h after injection; in the same experiments [125I]albumin reached a CSF/plasma ratio of about 15% in the IVth ventricle (compared with 55% for the natural steady state). Autoradiographic studies carried out on material from the same animals did not give evidence for transfer of labeled protein across the choroid plexuses although any such penetration may have been below the threshold of the method. Other explanations for the high concentration of protein in CSF that were considered include penetration via cerebral vessels and synthesis of plasma proteins by choroid plexus epithelial cells or neurons within the brain.

Albumins↗
PubMed1983

Identification of fetuin in human and rat fetuses and in other species.

The fetal protein, fetuin, has previously only been identified in species belonging to the order Artiodactyla. Samples of fetal, newborn and adult human (Homo sapiens) and rat (Rattus norvegicus) plasma and tissues have been studied using three techniques: (a) crossed immunoelectrophoresis of plasma against each of four different anti-fetuin antisera (two anti-cattle, one anti-pig and one anti-sheep); (b) the peroxidase-antiperoxidase technique applied to agarose gels containing plasma spots; (c) the indirect immunoperoxidase technique applied to human fetal tissue sections. In human fetal samples all three methods gave evidence for the presence of fetuin except late in gestation and in the newborn. Adult plasma was negative. In rat fetuses only plasma was tested, by methods (a) and (b). Positive reactions were obtained for both fetal and adult samples; the fetal samples cross-reacted with several of the anti-fetuins, adult samples reacted with only one. All the fetal and embryonal plasma samples tested with the peroxidase-antiperoxidase method were positive for fetuin except for the chicken. Thus fetuin appears to be distributed in at least five mammalian orders (Artiodactyla, Primates, Rodentia, Carnivora and Perissodactyla).

Animals↗
PubMed1982

Intracellular plasma proteins in human fetal choroid plexus during development. I. Developmental stages in relation to the number of epithelial cells which contain albumin in telencephalic, diencephalic and myelencephalic choroid plexus.

The developmental stages of telencephalic, diencephalic and myelencephalic choroid plexuses in the human fetus and the morphology of choroid plexus epithelial cells in the various plexuses in different development stages were described on basis of PAS- and toluidine blue-stained material. Six different cell types were identified in various combinations in 4 different stages (I-IV). The number and distribution of albumin-containing epithelial cells in various plexuses in the different stages of development were investigated by indirect immunoperoxidase technique. Albumin-containing cells did not belong to a single cell type. The telencephalic plexus exhibited a staining pattern for albumin which was different from that of the diencephalic and myelencephalic plexuses. In the telencephalic plexus positive epithelial cells were frequent in stage I, whereas only a few positive cells were present in stage II and III. In contrast, 30-40% of the epithelial cells in both diencephalic and myelencephalic plexuses in stage I, II and III showed a positive staining reaction. Later in gestation less than 10% were positive. It is suggested that a main function of the diencephalic and myelencephalic plexuses early in gestation is associated with protein transport rather than with glycogen synthesis and storage which might be a major function of the telencephalic plexus.

Cell Differentiation↗
PubMed1982

Intracellular plasma proteins in human fetal choroid plexus during development. II. The distribution of prealbumin, albumin, alpha-fetoprotein, transferrin, IgG, IgA, IgM, and alpha 1-antitrypsin.

Individual choroid plexuses of human fetal brain at different developmental stages were investigated by an indirect immunoperoxidase technique. The number and distribution of prealbumin-, albumin-, alpha-fetoprotein-, transferrin-, IgG-, IgA-, IgM- and alpha 1-antitrypsin-containing choroid plexus epithelial cells were recorded. The distribution of prealbumin in choroid plexus epithelial cells differed from that of other plasma proteins identified in these cells. Prealbumin was present in more than 90% of the cells at all ages examined in contrast to albumin, alpha-fetoprotein, transferrin and IgG, which were found in less than 40% of the cells, and this proportion declined later in gestation to only a few per cent. The telencephalic plexus exhibited a staining pattern for the proteins, except for prealbumin, which was different from that of the diencephalic and myelencephalic plexuses. Double-staining and staining with polyvalent antiserum indicated that the same epithelial cells showed positive reaction for albumin, alpha-fetoprotein, transferrin and IgG. The results are related to the observation of a high concentration of plasma protein in fetal CSF which may result from transcellular transfer from blood to CSF across the choroid plexus epithelial cells.

Blood Proteins↗
PubMed1982

Transferrin in fetal sheep cerebrospinal fluid and plasma during gestation.

1. Transferrin concentrations in fetal sheep CSF and plasma have been estimated between 31 and 125 days gestation and in the adult, using a radial immunodiffusion assay. 2. The plasma concentration was lowest (183 +/- 35 mg/100 ml) in the earliest fetuses examined (31 days). It increased to over 350 mg/100 ml by 35 days; thereafter it was around the adult value (580 mg/100 ml). 3. In CSF the transferrin concentration increased from 43 +/- 10 mg/100 ml at 31 days to a maximum of 163 +/- 14 mg/100 ml at 40 days gestation after which it decreased considerably to 6.1 +/- 0.7 mg/100 ml at 125 days and was even lower in the adult (1.1 +/- 0.2 mg/100 ml). 4. CSF: plasma ratios for transferrin especially when compared with those of other plasma proteins, are not compatible with passive leakage of protein from blood to CSF in the developing brain. The results may be explained by specific transfer of proteins into CSF but synthesis by the choroid plexus or brain has not been excluded.

Animals↗
PubMed1982

The management of neonatal posterolateral diaphragmatic hernia.

Between March, 1978, and August, 1980, 7 neonates with a left posterolateral diaphragmatic hernia were seen in respiratory distress within 12 hours of birth. Each had severe acidosis and hypoxia. They were immediately intubated and ventilated. Arterial and central venous lines were inserted, the acidosis was partially corrected, and a dopamine infusion of 5 microgram/kg/min was begun immediately. Continuous monitoring of arterial and venous pressures, core, and skin temperatures, blood gases, and pH was instituted. Diaphragmatic defects were repaired by direct suture in 5 neonates and by Gore-Tex patches in the other 2. The left lung in all patients was hypoplastic. Ventilation and inotropic support were continued for 4 to 5 days post-operatively, and close control of acid-base balance was maintained. All the patients are doing well. We consider the key to survival to be management of the dangerous combination of acidosis (by enhancing peripheral and renal perfusion with dopamine) and hypoxia (by prolonged assisted ventilation).

Dopamine↗
PubMed1982

Proteins in cerebrospinal fluid and plasma of fetal pigs during development.

The concentrations of total protein, alpha-fetoprotein, fetuin, transferrin and albumin have been measured in cerebrospinal fluid (CSF) and plasma of fetal pigs from 26 to 109 days gestation. Plasma total protein concentration was lowest in the youngest fetuses but thereafter it was between 1,500 and 2,200 mg/100 ml. alpha-Fetoprotein was the predominant plasma protein early in development but its concentration declined throughout the fetal period. alpha-Fetoprotein, fetuin and transferrin accounted for over 65% of the total protein concentration at all fetal ages. Albumin was not detectable in either plasma or CSF at 26 days and did not account for more than 10% of total plasma protein concentration at later stages of gestation; in contrast fetuin was the major protein in plasma (and CSF) later in fetal development. In CSF the concentration of fetuin was highest (178 +/- 8 mg/100 ml) at 26 days. The concentrations of total protein (961 +/- 95 mg/100 ml), alpha-fetoprotein (406 +/- 77 mg/100 ml) and transferrin (195 +/- 19 mg/100 ml) were highest at 31 days after which the concentration of all the main proteins fell very considerably. Albumin was first detected in CSF at 38 days and contributed less than 10% of total protein concentration at later fetal ages. Possible origins of plasma proteins in fetal CSF are discussed. Differences in CSF: plasma ratios for different proteins are consistent with a specific transfer mechanism between their two compartments; but synthesis by fetal choroid plexus or brain has not been excluded.

Animals↗
PubMed1981

Plasma proteins in fetal sheep brain: blood-brain barrier and intracerebral distribution.

1. Plasma proteins have been demonstrated to be present in early fetal sheep brain in amounts which cannot be accounted for by blood contamination. 2. The distribution of alpha-fetoprotein, albumin, fetuin, alpha 1-antitrypsin and transferrin has been studied by immunoassay of extracts from brain homogenates and by immunoperoxidase histochemistry of fetal brains between 37 and 125 days gestation (term is 150 days). 3. At 35 days gestation fetuin and albumin were quantitatively the most important proteins in fetal brain, both as estimated by extraction and by immunohistochemistry. Both of these proteins, and also alpha-fetoprotein and alpha 1-antitrypsin, declined considerably in amount by 60 days gestation. After 60 days the concentrations of albumin and alpha-fetoprotein were not significantly different from that due to blood contamination and only occasional cells could be demonstrated by immunohistochemistry. Fetuin and alpha 1-antitrypsin were present in reduced but significant amounts at least up to 125 days gestation. 4. The immunohistochemical results showed that considerable numbers of immature neurones were stained for some plasma proteins. Fetuin positive cells predominated both in terms of the larger number of cells which stained at 35-40 days gestation and in the persistence of positive cells up to 125 days gestation. Numerous cells in the neuroependymal layer and in several layers of the developing cortical plate were positive, especially early in gestation. Only a few transferrin or alpha 1-antitrypsin positive cells were observed. 5. Permeability of the blood-brain barrier to sheep or human serum albumin (labelled with 125I) was tested in 60 day fetal sheep by intravenous injection and estimation of brain radioactivity at 3 or 6 hr with allowance for blood contamination. Only a very small (but significant) penetration of protein was detected. Unlike penetration of protein into c.s.f. at the same age, it did not reach its natural steady state in brain. 6. It is concluded that the blood-brain barrier to protein is well developed in the immature fetal sheep but that developing neurones probably acquire certain plasma proteins directly from the c.s.f. when they are differentiating in the neuroependyma. The subsequent distribution of plasma protein positive cells in different brain regions is suggested to be due to the migration of developing neurones for the neuroependyma although the possibility of local synthesis of plasma proteins has not been excluded.

Albumins↗
PubMed1980

Proteins in cerebrospinal fluid and plasma of fetal sheep during development.

1. The concentration of total protein in c.s.f. and plasma has been measured in fetal sheep of different gestational ages and in the adult. In c.s.f. it was highest (approximately 840 mg/100 ml.) in the youngest fetuses (35 days) and declined steeply by 60 days (260 mg/100 ml.). It decreased less markedly in the last half of gestation to reach about 50 mg/100 ml. at 125 days which is twice the adult value. Protein concentration in plasma was lowest in the youngest fetuses and did not rise much until the second half of gestation during which time it doubled. There was a further rather larger increase between the late fetal (125 days) stage and the adult.2. Albumin, fetuin, alpha-fetoprotein (AFP), transferrin and lipoprotein were identified in c.s.f. and plasma.3. The concentrations of albumin, AFP and fetuin in c.s.f. and plasma at different gestational ages were measured using immunodiffusion and radioimmuno-assays.4. Albumin was the major protein in plasma at all ages studied (35-128 days gestation and adult). Its concentration increased throughout gestation whereas that of fetuin was similar at all fetal ages and that of AFP declined markedly during the second half of gestation. In the adult, fetuin was only about 0.1% of the total protein in plasma and AFP was not detectable.5. In 35-40 day fetuses albumin, AFP and fetuin accounted for 90% of the total protein concentration in plasma and for about 70-80% of the total protein concentration of c.s.f. As gestation progressed the concentration of all three proteins in c.s.f. declined. But the concentration of AFP and fetuin fell more rapidly and to a greater extent than that of albumin; neither AFP nor fetuin could be detected in adult c.s.f.6. The c.s.f.: Plasma ratio was above 50% for AFP and above 60% for fetuin at 35 days compared with about 25% for albumin at the same fetal age. The c.s.f.: plasma ratios for all three proteins declined with increasing fetal age and were not significantly different from each other by about mid gestation.

Albumins↗
PubMed1980

Blood-cerebrospinal fluid transfer of plasma proteins during fetal development in the sheep.

1. The penetration of human and sheep plasma proteins from blood into c.s.f. of sheep fetuses (57-86 days gestation) has been studied. The proteins were injected intravenously via cotyledonary vessels. After different time periods the c.s.f. concentrations of marker proteins were estimated by radioactive counting of iodinated human or sheep proteins or by immunoassay of human proteins.2. Several proteins of similar molecular size penetrated into c.s.f. to a different extent in 60 day fetuses. The steady-state c.s.f.: plasma ratios were about 15% for human AFP, 10% for human transferrin and sheep albumin, 7% for human alpha(1)-antitrypsin, and 5% for human albumin. In older fetuses the penetration of protein from blood into c.s.f. was much reduced and no evidence for differential penetration of different proteins was found.3. The penetration of human AFP, transferrin and sheep albumin from blood into c.s.f. was greater than can be accounted for by passive diffusion.4. The results of this paper are discussed in relation to those of the preceding paper on the identification and quantification of proteins in fetal c.s.f. and plasma. The hypothesis is put forward that the choroid plexus of the immature (60 days and less) sheep fetus contains a mechanism for the transcellular transfer of plasma proteins which may be selective in nature and of importance for some aspects of brain development.

Albumins↗
PubMed1980

Rapid effect of nerve injury upon axonal transport of phospholipids.

1. Axonal transport of phospholipids labelled by lumbosacral spinal cord injection of [3H]choline has been studied in normal and injured sciatic nerves of the rat. 2. The appearance of labelled material in progressively increasing amounts in the sciatic nerve following spinal cord injection was consistent with a maximum velocity of axonal transport of about 20 mm/hr. There was also evidence of substantial amounts of labelled phospholipids being transported at much slower velocities. 3. In sciatic nerves injured by crushing there was an accumulation of labelled phospholipid immediately proximal to the crush. The accumulation was progressive with time. There was also an increase of labelled phospholipid in all the more proximal segments of the crushed nerves; this reached a maximum of about twice that in uncrushed nerves at 10 hr. after spinal cord injection. 4. The labelled phospholipid was shown to be about 80-90% phosphatidylcholine both in uncrushed and crushed nerves. 5. The nature of the mechanism of this very rapid response of neurones to peripheral injury did not appear to be due to loss of 'information' from the periphery or action potentials initiated at the site of injury. The phenomenon has been further investigated by injection of drugs into the injured or control nerves. KCl injected at (but not proximal to) the site of injury was effective in blocking the injury response providing it was injected between a few minutes before or up to 30 min after the time of injury. Injection of either tetrodotoxin or local anaesthetic was as effective as injury in increasing the amount of labelled phospholipid transport. 6. These results suggest that the occurrence of an injury in a distant process of a neuron can be signalled retrogradely to the cell body by a mechanism involving a signal velocity of at least 140 mm/hr.

Animals↗