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Biomedical subjects

S Robertson

Publications and source records attributed to S Robertson.

At least 145 records · Page 8Linked to original sources
PubMed1991

Essential fatty acid diet supplementation. Effects on peripheral nerve and skeletal muscle function and capillarization in streptozocin-induced diabetic rats.

Effects of essential fatty acids on nerve conduction, hypoxic resistance, skeletal muscle contractile properties, and capillary density were examined in streptozocin-induced diabetic rats. Nondiabetic and diabetic controls and three diabetic groups treated with 10% supplements of corn oil, evening primrose oil (Efamol), or a mixture of 80% evening primrose oil and 20% fish oil (Efamol Marine) for 2 mo were used. Efamol and Efamol Marine increased plasma gamma-linolenic acid levels, but arachidonic acid was elevated only with Efamol. Diabetes resulted in 15-29% reductions in sciatic motor and sensory saphenous nerve conduction velocity. Efamol prevented conduction deficits more effectively than Efamol Marine, and corn oil had no effect. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for action potential amplitude to decline by 50% with diabetes. Corn oil had no significant effect. With Efamol, hypoxic resistance was within the nondiabetic range. Efamol Marine produced intermediate results. Functional improvements may relate to enhanced vasa nervorum perfusion, because endoneurial capillary density increased by 22% with Efamol, angiogenesis perhaps resulting from eicosanoid production from arachidonic acid. Soleus muscle contractions were prolonged by diabetes. This was partially corrected by treatment, Efamol being most effective. Extensor digitorum longus muscle had reduced tetanic tension with diabetes, and this was prevented by all treatments. Soleus showed a modest increase in capillarization with Efamol, which may have contributed to reduced susceptibility to fatigue. The data suggest involvement of abnormal fatty acid metabolism in the etiology of diabetic neuropathy and myopathy.

Animals↗
PubMed1990

Epidermal growth factor and the onset of epithelial epidermal wound healing.

At 10 days in ovo the embryonic chick epidermis acquires the ability to spread as a cohesive epithelial sheet when wounded. A tissue culture system has been constructed that supports epidermal cell outgrowth consistent with epidermal behaviour in vivo and permits experimental manipulation of the isolated tissue with growth factors and other hormones. This culture system consists of embryonic chick epidermis isolated at days 8, 10, and 12 of development, serum-free, chemically-defined culture medium, and the inner surface of the vitelline membrane of the hen's egg as the culture substratum. At 8 days the cellular outgrowth is mesenchymal in the absence of exogenous EGF. The 8 day tissues responds to added EGF by exhibiting precocious epithelial outgrowth. The results suggest that sensitivity to EGF or EGF-like growth factors is part of the mechanism underlying the developmental onset of epidermal wound healing in skin. The epidermal origin of the outgrowth is determined by antibody staining for specific cytokeratins. The epithelial character of the outgrowth is determined by visualizing actin microfilament distribution. The normal epithelial outgrowth shows apical/basal polarization of the sheet except at the edge. From 10 days on, the isolated epidermis exhibits epithelial outgrowth from explants in culture in the absence of exogenous EGF, suggesting endogenous production of an EGF-like factor. Glucocorticoid and mineralocorticoid hormones both produce a reduced amount of epithelial outgrowth. This retardation of the early outgrowth by glucocorticoids and mineralocorticoids could result from a reduced ability of the cut edge of the epidermis to 'disorganize' and assume the unpolarized migratory form required for rapid epidermal wound healing.

Actin Cytoskeleton↗
PubMed1990

Early randomized intervention with high-frequency jet ventilation in respiratory distress syndrome.

To determine whether early use of high-frequency jet ventilation reduces neonatal mortality or pulmonary morbidity rates, we randomly selected 42 infants with clinical and radiographic evidence of severe respiratory distress syndrome to receive either high-frequency jet ventilation or conventional ventilation. Separate sequential analyses (two-sided, alpha = 0.05, power = 0.95 to detect 85:15 advantage) were performed for mortality rates, air leaks, bronchopulmonary dysplasia, intraventricular hemorrhage, and assignment crossover, and a combined analysis was performed, with death overriding other outcome variables. Enrollment was completed when the combined analysis reached the sequential design boundary indicating no treatment difference. Mortality rates (19% among infants receiving high-frequency jet ventilation vs 24% among infants receiving conventional ventilation), the incidence of air leaks (48% vs 52%), bronchopulmonary dysplasia (39% vs 41%), and intraventricular hemorrhage (33% vs 43%), and assignment crossovers (14% vs 24%) did not differs significantly between the treatment groups. We conclude that early use of high-frequency jet ventilation does not prevent or substantially reduce mortality or morbidity rates associated with assisted ventilation.

Age Factors↗
PubMed1990

Further development of a morphine hydrogel suppository.

1. A sustained release monolithic morphine hydrogel suppository (MHS) was developed and administered to five volunteers. 2. The MHS delivered a mean of 55 mg morphine over 12 h. The mean plasma morphine concentration was 15 ng ml-1 from 2 to 12 h after administration. 3. Plasma morphine concentrations were comparable with those reported for the same dose given orally over the same time period. 4. The morphine hydrogel suppository appears to be an effective means of delivering morphine and may be of value in the management of chronic pain.

Administration, Rectal↗
PubMed1990

Changes in skeletal muscle contractile properties in streptozocin-induced diabetic rats and role of polyol pathway and hypoinsulinemia.

Functional changes in slow-twitch soleus and fast-twitch extensor digitorum longus muscles were assessed after 2 mo of streptozocin-induced diabetes in rats. For soleus, there was a slowing of twitch times both for contraction and relaxation and a reduction of maximum tetanic relaxation rate. There was little effect on strength performance assessed by maximal tetanic tension production. Treatment with the aldose reductase inhibitor ponalrestat largely prevented relaxation defects but had little effect on contraction. For the fast muscle, twitch times were relatively unaffected, but maximum tetanic relaxation rate was reduced. In addition, tetanic tension output decreased. These changes were largely prevented by ponalrestat treatment. The effects of partial insulin therapy were also investigated. This regimen reduced hypoinsulinemia, but sufficient hyperglycemia remained to stimulate the polyol pathway. It prevented the slowing of soleus twitch contraction but had no effect on relaxation. For extensor digitorum longus, insulin produced further deleterious effects on tetanic tension and maximum relaxation rate, which were antagonized by ponalrestat. A 1% dietary myo-inositol supplement had little effect on contractile function in slow or fast muscles. It was concluded that polyol-pathway activity is an important factor underlying skeletal muscle functional changes in diabetes, probably acting through disruption of Ca2+ handling. Hypoinsulinemia was considered a secondary factor causing atrophy, particularly of fast muscles. There was no evidence of effects dependent on neuropathy.

Aldehyde Reductase↗
PubMed1990

S-antigen: preparation and characterization of site-specific monoclonal antibodies.

Previous attempts to prepare monoclonal antibodies (MAbs) against S-antigen, a photoreceptor cell protein involved in the visual process and a potent autoantigen for the induction of experimental autoimmune uveitis (EAU), have yielded MAbs which define only carboxyl terminal epitopes. In this study we devised alternate strategies to prepare five MAbs directed to other regions of the molecule. MAbC10C10 and MAbH11-A2 were prepared against synthetic peptides known to be uveitopathogenic and they were selected for more detailed studies. MAbC10C10 was generated against synthetic peptide BSA281-302 which contains a predictive consensus sequence for defined T cell epitopes (GIALD) as well as a consensus sequence for GTP-binding proteins. One human adenosine deaminase synthetic peptide containing an extensive amino acid sequence homology to BSA281-302 was a potent inhibitor of MAbC10C10 binding in a competitive inhibition radioimmunoassay. MAbH11-A2 was generated against peptide BSA303-332 which also contains a uveitopathogenic site. The binding site of MAbH11-A2 was determined to be within amino acid positions 305 to 314 (NLASSTIIKE) in S-antigen. This binding site corresponded closely to the binding site of an affinity-purified rat polyclonal antibody raised to human S-antigen. MAb5C6.47 was isolated from a mouse hyperimmunized with bovine S-antigen and was specific for a highly conserved sequence near the amino terminus, amino acid residues 42 to 48 (DGVVLVD). Both MAbC10C10 and MAb5C.47 were useful in screening gt11 cDNA libraries expressing S-antigen polypeptides as fusion proteins. Our results demonstrate the feasibility of producing site-specific MAbs potentially useful in the study of T cell-mediated immune mechanisms in EAU as well as in the phototransduction of vision.

Amino Acid Sequence↗
PubMed1990

The distribution and utilization of CNSs on Long Island.

The present study provides a data base concerning the professional characteristics and various roles and functions of the CNS. Data for this survey research were collected by questionnaire and compared to the literature and ANA's National Survey of Clinical Nurse Specialists which was done in 1984. Results obtained from this research should serve as a springboard for further study of this essential role.

Humans↗
PubMed1989

Chronic low frequency electrical activation for one week corrects nerve conduction velocity deficits in rats with diabetes of three months duration.

This study examined the effect of chronic electrical activation on conduction velocity deficits after three months of streptozotocin-induced diabetes. There were 30% and 20% reductions in conduction velocity in diabetic animals for tibialis anterior and saphenous nerves, respectively (p less than 0.01). Unilateral electrical stimulation of the common peroneal nerve, which contains axons supplying tibialis anterior but not saphenous nerve, was carried out in a group of diabetic and a group of normal control rats. Stimulation was given over seven days, at 10 Hz for 8 h/day. Final experiments were carried out at least 17 h after the last stimulation session. In normal rats stimulation had no effect on conduction velocity in either nerve. In diabetic animals, however, tibialis anterior conduction was within the normal control range for the stimulated nerve. In contrast, the contralateral unstimulated nerve had reduced conduction velocity (p less than 0.001), which was within the unoperated diabetic control range. There were no effects on saphenous nerve conduction, comparing stimulated and unstimulated legs. We conclude that chronic increases in nerve electrical activation promote mechanisms that reverse conduction deficits in diabetic rats.

Animals↗
PubMed1989

Contractile properties of cardiac papillary muscle in streptozotocin-diabetic rats and the effects of aldose reductase inhibition.

This study examined the preventative effect of an aldose reductase inhibitor, ponalrestat, on contractile properties of heart left ventricular papillary muscles in rats having streptozotocin induced diabetes for 13 weeks. Both contraction and relaxation were slowed by diabetes. The time to reach peak twitch tension was increased by 21%, and the time to relax to half peak tension was increased by 29% (p less than 0.01, respectively compared to normal control animals). With ponalrestat treatment, the increase in contraction time was only 11%, and relaxation was only slowed by 4% (p less than 0.05 and p less than 0.01, respectively compared to diabetic controls). Diabetes also reduced maximum rates of contraction (13%) and relaxation (19%) and prolonged the time taken to reach peak relaxation rate (36%, p less than 0.01). Ponalrestat had no effect on maximum contraction rates but was particularly effective in normalising relaxation rates (p less than 0.01). Deficiencies with diabetes were noted over a range of stimulation frequencies (0.1-4.0 Hz), and ponalrestat treatment was beneficial except at the highest rates. Diabetes and ponalrestat effects were observed over a temperature range of 25-37 degrees C. Ventricular sorbitol levels showed a 17-fold increase with diabetes (p less than 0.01) and this was reduced by 67% with ponalrestat (p less than 0.01). There were no changes in ventricular myo-inositol. It is possible that ponalrestat treatment prevented a defect in sarcoplasmic reticulum calcium handling which could be responsible in part for the deficits in contraction ability and mainly for the deficits in relaxation ability in diabetic cardiomyopathy, although this remains to be tested directly.

Aldehyde Reductase↗
PubMed1989

Autism diagnostic interview: a standardized investigator-based instrument.

The development of a new standardized investigator-based interview for use in the differential diagnosis of pervasive developmental disorders is described, together with a diagnostic algorithm (using ICD-10 criteria) based on its use. Good interrater reliability for algorithm items was shown between four raters, two in Canada and two in the UK, who rated 32 videotaped interviews. The items also significantly discriminated between 16 autistic and 16 nonautistic mentally handicapped subjects. The algorithm based on ICD-10 identified all 16 autistic individuals and none of the 16 nonautistic subjects.

Adolescent↗
PubMed1989

Juvenile and adult laryngeal papillomata: classification by in-situ hybridization for human papillomavirus.

We report the application of an in-situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin-streptavidin-polyalkaline phosphatase complex to paraffin processed tissue from a series of patients with laryngeal papillomata. All cases of juvenile papillomata, whether solitary or multiple, proved positive for HPV types 6 and/or type 11. However, only two cases of adult solitary papillomata and five cases of adult multiple papillomata were positive for HPV type 6 and/or type 11. All papillomata were negative for HPV types 16 and 18. Five specimens of normal vocal cord epithelium were uniformly negative for all four HPV types.

Adolescent↗
PubMed1989

Effects of long-term streptozotocin diabetes on the contractile and histochemical properties of rat muscles.

Contractile and histochemical properties of soleus (a slow-twitch muscle) and extensor digitorum longus (EDL, a fast-twitch muscle) were studied in mature rats after 3 months of streptozotocin-induced diabetes. Results were compared with age- and weight-matched controls. Diabetes produced profound wasting of fast muscles and particularly of the fast glycolytic (FG) fibres. Slow muscle fibres, both within the mixed EDL and in soleus, were less atrophied. Strength performance of EDL was reduced by diabetes, but maintained in soleus. Diabetes was without effect on the time to peak tension (TTP) and half-relaxation time (HRT) of EDL. However it produced profound slowing of soleus muscles, particularly of the relaxation phase. Part of the slowing effect of diabetes may be related to a histochemically demonstrable loss of fast oxidative glycolytic (FOG) fibres in soleus. Histochemical staining for the oxidative marker succinic dehydrogenase (SDH) revealed marked disruption of reaction product distribution in soleus, indicating an impairment of oxidative capacity.

Animals↗
PubMed1989

The effect of aldose reductase inhibition on the pattern of nerve conduction deficits in diabetic rats.

Conduction deficits caused by 2-4 months diabetes were examined in one sensory and six motor nerve branches of mature rats. The effect of aldose reductase inhibitor (ponalrestat) treatment was assessed in preventative and reversal studies. The efficacy of 1% dietary myoinositol supplementation was also examined in a 2 month preventative group. Diabetes suppressed a maturation-related increase in conduction velocity in the interosseus nerve supplying foot muscles. This was unaffected by any treatment. Large conduction velocity reductions (22-29%) seen for fast nerves supplying four calf muscles and sensory saphenous nerves were prevented by ponalrestat treatment. In a reversal group, which had 2 months of diabetes followed by 2 months of treatment, restoration of conduction varied between nerves, ranging from 100% in sensory saphenous to 25% in soleus motor branches. Myo-inositol supplementation had little effect. Sciatic nerves accumulated the sugar alcohol sorbitol with diabetes. This was markedly reduced by treatment, and correlated with the conduction velocity improvement. There was a 40% reduction in nerve free myo-inositol levels after 2 months diabetes. Ponalrestat normalized myo-inositol in the short term but failed to do so in 4 month preventative and reversal groups. Myo-inositol treatment did not affect nerve levels. The data implicate the polyol pathway in the diabetic conduction velocity deficits seen in normally fast conducting motor and sensory nerves and suggest that aldose reductase inhibitor action does not depend on restoration of nerve myo-inositol levels.

Aldehyde Reductase↗
PubMed1989

PEEP increases non-pulmonary microvascular fluid flux in healthy and septic sheep.

The potential for significant interaction between PEEP and the peripheral microcirculations is not as well appreciated as are its central circulatory effects. Therefore, we studied the effects of PEEP, 15 mm Hg, on microvascular fluid flux in the hindlimb of ten mature sheep. Changes in prefemoral lymph flow (QL) and in lymph to plasma [L/P] total protein (TP) ratios were measured following the application of PEEP for 2 h, before and during hyperdynamic sepsis. Sepsis was induced by cecal ligation and perforation (CLP). Although the onset of sepsis was not associated with an increase in prefemoral QL, the [L/P] ratio of iodinated 125I human serum albumin (125I-HSA) was significantly greater 72 h after CLP than during the nonseptic baseline study. Histologic examination of gastrocnemius muscle also demonstrated an increase in protein-rich interstitial edema during the septic studies. During the 2 h of PEEP, prefemoral QL increased equally (p less than 0.05) in three study periods: (1) baseline nonseptic, delta QL = +1.2 +/- 1.4 ml/h; (2) septic period 1, 24 to 48 h after CLP, delta QL = +1.3 +/- 1.2 ml/h; and, (3) septic period 2, 72 h after CLP, delta QL = 1.0 +/- 0.6 ml/h. Calculated microvascular hydrostatic pressures also rose significantly during PEEP therapy in all three study periods. We conclude that PEEP, 15 mm Hg, increased hindlimb microvascular fluid flux and may thereby increase interstitial fluid content in tissues drained by the prefemoral lymph node. These effects of PEEP were not aggravated by hyperdynamic sepsis, despite a presumed increase in systemic microvascular permeability at this time.

Animals↗
PubMed1989

Drugs that keep AIDS patients alive.

A battery of once-obscure drugs is buying time for AIDS patients. Expect toxicity when you administer them, and know the interventions that can keep the patient's discomfort at a minimum.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Truncated variants of apolipoprotein B cause hypobetalipoproteinaemia.

Familial hypobetalipoproteinaemia is a rare autosomal dominant disorder in which levels of apo-B-containing plasma lipoproteins are approximately half-normal in heterozygotes and virtually absent in homozygotes. Here we describe mutations of the apo-B gene that cause two different truncated variants of apo-B in unrelated individuals with hypobetalipoproteinaemia. One variant, apo-B(His1795----Met-Trp-Leu-Val-Thr-Term) is predicted to be 1799 amino acids long and arises from deletion of a single nucleotide (G) from leucine codon 1794. This protein was found at low levels in very low density and low density lipoprotein fractions in the blood. The second, shorter variant, apo-B(Arg1306----Term), is caused by mutation of a CpG dinucleotide in arginine codon 1306 converting it to a stop codon and predicting a protein of 1305 residues. The product of this allele could not be detected in the circulation. The differences in size and behaviour of these two variants compared to apo-B100 or apo-B48 point to domains that may be important for the assembly, secretion or stability of apo-B-containing lipoproteins.

Amino Acid Sequence↗
PubMed1988

Determination of morphine in human plasma by radioimmunoassay utilising a preliminary liquid-solid extraction.

Numerous assays are available for the pharmacokinetic study of morphine. Two of these methods are compared with a new assay procedure, which involves a solid-phase extraction to clean up human plasma before radioimmunoassay allowing the determination of morphine levels to a sensitivity of 1 mugl(-1). Data are presented to show the importance of correct method choice if clinical studies are to be used in pharmacokinetic interpretations.

Journal Article↗