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Biomedical subjects

J Knox

Publications and source records attributed to J Knox.

At least 73 records · Page 4Linked to original sources
PubMed1991

Relationship between the lung and systemic response to endotoxin: comparison of physiologic change and the degree of lipid peroxidation.

The lung and systemic response to Escherichia coli endotoxin either 2 or 5 micrograms/kg was measured in 16 sheep with chronic lung and soft tissue lymph fistulae. Oxidant-induced lung and liver lipid peroxidation was measured as tissue malondialdehyde (MDA). Conjugated dienes were also monitored. Both doses produced a comparable pulmonary hypertension and hypoxia as well as a comparable increase in protein-rich lymph flow, QL. However, lung MDA was significantly greater with the 5 micrograms/kg than with the 2 micrograms/kg dose, both being more than twofold greater than controls. The systemic physiologic responses between the two doses were quite different. The 5 microgram/kg dose resulted in a significant increase in oxygen delivery (DO2), oxygen consumption (VO2), and decrease in arterial O2 extraction in the 3-5 hr postendotoxin period compared with the 2 microgram/kg dose. A twofold increase in protein-rich soft tissue QL was also seen after the 5 micrograms/kg dose, whereas QL was not changed after 2 micrograms/kg. Liver MDA was only increased by 30% over controls with both doses. We conclude that the relationship between oxidant change and physiologic response varies considerably between lung and systemic tissues after endotoxemia with the degree of lung lipid peroxidation corresponding with the degree of impairment in systemic tissue O2 extraction and the onset of delivery-dependent O2 consumption.

Animals↗
PubMed1991

Topical flurbiprofen decreases burn wound-induced hypermetabolism and systemic lipid peroxidation.

We studied the effect of the topical application of the nonsteroidal anti-inflammatory agent, flurbiprofen, on postburn hypermetabolism and systemic lipid peroxidation. Twelve sheep with a 15% total body surface third-degree burn were monitored over a 4-day postburn period. In six sheep, a single application of a 5% flurbiprofen cream was placed on the burn wound on day 3. Data were compared to both burned and nonburned controls (n = 6). All animals were killed on day 4. Oxygen consumption was increased at day 3 by 28% +/- 10% over the preburn value in all animals. Flurbiprofen significantly attenuated the increase in oxygen consumption, returning the value essentially to baseline by 12 hours after application. Lung and liver peroxidation, as measured by malondialdehyde, was significantly increased in the burned, nontreated sheep at day 4 from a control value of 45 +/- 9 and 110 +/- 12 to 60 +/- 6 and 310 +/- 71 nmol/gm tissue, respectively. In flurbiprofen-treated animals, values were 42 +/- 8 and 160 +/- 18 nmol/gm at day 4, significantly attenuated from burn alone. Protein-rich burn lymph flow remained fourfold increased in both groups, indicating a persistent increase in burn tissue vascular permeability, not modified by flurbiprofen. Burn wound biopsies revealed bacterial contents of less than 10(4) organisms/gram tissue in all animals. We conclude that topical flurbiprofen significantly decreases burn wound-induced systemic hypermetabolism and oxidant-induced lipid peroxidation seen at 3 days after burn injury, but does not attenuate the remaining local burn-wound vascular permeability.

Administration, Cutaneous↗
PubMed1990

Benign oesophageal stricture: the place of surgery in the management of elderly patients.

The results of surgery for benign oesophageal stricture in 53 consecutive cases referred to a sub-regional Cardiothoracic Unit are presented. The operations included retrograde dilatation and either total fundoplication or Allison repair, or an oesophageal resection with gastro-oesophageal anastomosis through a trans-thoracic approach. Postoperative fatality was 9%. Most subsequent deaths were due to unrelated acute events with a 5-year survival rate of 62%. Sixty per cent were free from dysphagia and 82% led active and independent lives without support. Surgery offers an alternative to dilatation in elderly patients with oesophageal stricture.

Aged↗
PubMed1990

Effect of endotoxin and a burn injury on lung and liver lipid peroxidation and catalase activity.

Both endotoxin and a burn alone produce oxidant-induced tissue lipid peroxidation. The endotoxin response is due in large part to hydrogen peroxide. The combination of endotoxin after a burn results in an increased liver, but not lung, oxidant injury. Our purpose was to determine whether the burn oxidant injury inactivated endogenous liver tissue catalase, thereby amplifying a subsequent H2O2 insult. Twenty-six adult sheep were studied. Twelve sheep had a 15% TBS burn. Tissue catalase activity, measured in lung and liver 3 days postburn, was significantly decreased from a control of 3.58 +/- 1.8 and 193 +/- 63, respectively, to 1.72 +/- 0.63 and 148 +/- 33 k(sec-1)/0.5 gram tissue. The addition of endotoxin 3 days postburn resulted in an increase in liver malondialdehyde, MDA, a measure of lipid peroxidation, from a control of 110 +/- 80 to 450 +/- 54 nmol/gram tissue. This value was significantly greater than the 210 +/- 80 nmol/gram tissue seen after endotoxin alone. Lung tissue MDA with burn and endotoxin was 65 +/- 8 compared to 42 +/- 7 for control and 80 +/- 6 nmol/gram for endotoxin alone. We conclude that a decrease in liver catalase activity occurs after a burn. The decrease corresponds to an accentuated oxidant-induced lipid peroxidation after an added endotoxin insult where H2O2 is known to be an etiologic agent. The catalase activity also decreases in postburn lung, but accentuated lung damage was not seen, indicating a variable tissue response from the burn-induced decrease in antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Analysis of multiple forms of nuclear factor I in human and murine cell lines.

Nuclear factor I (NFI) is a group of related site-specific DNA-binding proteins that function in adenovirus DNA replication and cellular RNA metabolism. We have measured both the levels and forms of NFI that interact with a well-characterized 26-base-pair NFI-binding site. Five different NFI-DNA complexes were seen in HeLa nuclear extracts by using a gel mobility shift (GMS) assay. In addition, at least six forms of NFI were shown to cross-link directly to DNA by using a UV cross-linking assay. The distinct GMS complexes detected were composed of different subspecies of NFI polypeptides as assayed by UV cross-linking. Different murine cell lines possessed varying levels and forms of NFI binding activity, as judged by nitrocellulose filter binding and GMS assays. The growth state of NIH 3T3 cells affected both the types of NFI-DNA complexes seen in a GMS assay and the forms of the protein detected by UV cross-linking.

Animals↗
PubMed1988

Stimulation of transcription in vitro by binding sites for nuclear factor I.

Nuclear factor I (NFI) is a site-specific DNA binding protein required for the replication of adenovirus DNA in vitro and in vivo. We have examined the effect of natural and synthetic binding sites for NFI (FIB sites) on RNA synthesis in HeLa whole cell extracts. The natural binding site used is the 26bp FIB-2 site previously isolated from the human genome. When present upstream of the TATA box of the adenovirus major late promoter, the FIB-2 site stimulates RNA synthesis 3 to 5-fold. This stimulation occurs with either orientation of the FIB-2 site. A point mutation in FIB-2 that decreases NFI binding at least 100-fold reduces, but does not completely abolish, the stimulation of transcription. A number of synthetic binding sites for NFI were tested for the ability to increase RNA synthesis. The strongest binding sites stimulated transcription the most, while the weakest sites had the least effect. These studies strongly suggest a role for NFI and cellular FIB sites in the control of RNA synthesis.

Binding Sites↗
PubMed1987

Sympathoadrenal and other responses to hypoglycaemia in the young foal.

The effects of insulin-induced hypoglycaemia on plasma catecholamines, cortisol and metabolites have been examined in newborn and 7-14-day-old foals. The fall in plasma glucose elicited by the highest dose of insulin (1.0 i.u./kg) given to the neonates was slower in onset and less severe in effect than 0.5 i.u./kg in the older foals. There was a significant inverse correlation between the concentrations of glucose and adrenaline (but not noradrenaline) in plasma once the glucose level had fallen below 2 mmol/l; the adrenergic response to hypoglycaemia was greater in the 7-14-day-old foals than in the neonates. No significant changes in glucose or catecholamines were seen after fasting alone. The adrenocortical response to hypoglycaemia was poor after birth, but significant changes occurred in the older foals with a 3-fold increase in plasma cortisol at 60 min after 0.5 i.u. insulin/kg. There were significant increases in plasma FFA after hypoglycaemia in both groups of animals, but the rise was less pronounced in the neonates. A significant positive correlation was found between plasma adrenaline and FFA values. Hypoglycaemia also resulted in a significant rise in plasma lactate and a slow fall in alpha-amino nitrogen. These findings show that hypoglycaemia in the foal is followed by stimulation of the adrenal medullary component of the sympathetic system and by activation of the adrenal cortex with a number of consequent metabolic changes. The hypoglycaemic effects of insulin were more intense and the response more rapid in the older foals than in the neonates, which exhibited some degree of insulin resistance.

Animals↗
PubMed1986

An open study of sub-lingual buprenorphine in the treatment of chronic pain in the elderly.

Fifty-one patients aged over 65 years with chronic pain entered an open study to assess the efficacy and tolerance of low-dose (0.1 mg) sub-lingual buprenorphine administered 3 to 4-times a day over a 14-day period. There was significant improvement in symptoms during the treatment period and the drug was well tolerated, with good compliance. Patients aged over 80 years responded comparatively better than those aged between 65 and 80 years. The incidence of unwanted effects was low and constipation was only reported by 1 patient.

Administration, Cutaneous↗
PubMed1984

General practitioners, court reports, and alcohol related offences.

General practitioners may have to submit medical reports to the courts on patients who have a suspected alcohol problem, 98% of such requests coming from magistrates courts. When, however, a defendant decides to plead "not guilty" to an offence on the grounds of intoxication general practitioners are often asked to prepare a report to support the plea. We present guidelines on preparing such reports and discuss the implications of the contents.

Alcoholism↗
PubMed1984

Studies on equine prematurity 2: Post natal adrenocortical activity in relation to plasma adrenocorticotrophic hormone and catecholamine levels in term and premature foals.

Adrenocortical and medullary function was investigated during the immediate post natal period in premature and full term foals. High plasma cortisol concentrations were characteristic of the term foals in the first 2 h after birth and these were accompanied by significant arteriovenous differences in plasma cortisol across the umbilical circulation at birth, indicating enhanced adrenal activity before delivery. No such arteriovenous differences were detected in the premature group and post natal changes in plasma cortisol were minimal. The apparent inability of the premature foal adrenal to secrete cortisol was not due to the lack of endogenous adrenocorticotrophic hormone (ACTH) because high levels of this hormone were found immediately after birth in both groups of foals. Tests on the sensitivity of the foal adrenal to exogenous ACTH1-24 (0.125 mg intramuscularly [im]) showed that a maximum response to this hormone could be elicited in term foals on the day of birth. Subsequently basal cortisol levels and the response of the adrenal to ACTH1-24 declined. By contrast, only a slight response was observed following the same dose of ACTH1-24 in the premature group. Exposure to Depot ACTH1-24 over 24 h enhanced the basal secretion of cortisol in both premature and term foals but no consistent response to the same ACTH test dose could be elicited in the former. A wide range of total plasma catecholamine concentrations was observed in both groups of newborn foals. The highest values were seen in acidotic animals and there was a significant inverse relationship between blood pH and total plasma catecholamine level at delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗