The relationship between pre-operative hypertension and intra-operative haemodynamic changes known to be associated with postoperative morbidity.

Hypertension is not consistently associated with postoperative cardiovascular morbidity and is therefore not considered a major peri-operative risk factor. However, hypertension may predispose to peri-operative haemodynamic changes known to be associated with peri-operative morbidity and mortality, such as intra-operative hypotension and tachycardia. The objective of this study was to determine whether pre-operative hypertension was independently associated with haemodynamic changes known to be associated with adverse peri-operative outcomes. We performed a five-day multicentre, prospective, observational cohort study which included all adult inpatients undergoing elective, non-cardiac, non-obstetric surgery. We recruited 343 patients of whom 164 (47.8%) were hypertensive. An intra-operative mean arterial pressure of < 55 mmHg occurred in 59 (18.2%) patients, of which 25 (42.4%) were hypertensive. Intra-operative tachycardia (heart rate> 100 beats.min-1 ) occurred in 126 (38.9%) patients, of whom 61 (48.4%) were hypertensive. Multivariable logistic regression did not show an independent association between the stage of hypertension and either clinically significant hypotension or tachycardia, when controlled for ASA physical status, functional status, major surgery, duration of surgery or blood transfusion. There was no association between pre-operative hypertension and peri-operative haemodynamic changes known to be associated with major morbidity and mortality. These data, therefore, support the recommendation of the Joint Guidelines of the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and the British Hypertension Society to proceed with elective surgery if a patient's blood pressure is < 180/110 mmHg.

Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study.

BACKGROUND: A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. METHODS: Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. RESULTS: Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. CONCLUSION: The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

Auricular prosthesis positioning using virtual planning in combination with additive manufacturing.

INTRODUCTION: This study focused on deformed or missing auricles and their replacement with silicone prostheses which are retained by craniofacial implants. Surgeons find it difficult to accurately place the implants in relation to the missing auricle in theatre. The aim of this study was to develop patient-specific devices using additive manufacturing technologies and associated software to indicate the positions of implants and to correctly orientate the prostheses relative to the positions of the implants. MATERIAL AND METHODS: The morphology of the patient was determined using Computed-Tomography (CT) scanning and the opposite auricle was mirrored in the virtual environment through specialized software from Materialise. A positioning guide for placing the implants was developed, together with an orientation guide that orientates the prosthesis accurately in relation to the implants. The orientation guide is a new development in the field of maxillofacial prosthetics and has not been attempted before. The guides are produced in nylon through laser sintering additive manufacturing. RESULTS: The accuracy of implant placements was determined and the results showed relatively accurate positioning using the guides. DISCUSSION: Implant placement showed some deviation which can largely be attributed to improper use of the guide by the surgeon during the marking of implant positions. The orientation guide can however somewhat compensate for this to still achieve aesthetically pleasing results. Using the guides significantly reduces risk, time and cost in placing the implants and producing auricular silicone prostheses.

A European perspective on costs and cost effectiveness of ophthalmic combinations in the treatment of open-angle glaucoma.

PURPOSE: Efficacy, safety, and cost implications are important considerations when choosing an ophthalmic treatment. Fixed-combination glaucoma medications containing brimonidine 0.2% and timolol 0.5%, or dorzolamide 2% and timolol 0.5%, were compared with brimonidine 0.2% and dorzolamide 2% that were used as adjunctive therapy to timolol 0.5%. METHODS: A literature review was conducted to determine the outcome parameters of intraocular pressure reduction and tolerability after 3 months of use of brimonidine or dorzolamide, each together with timolol as a fixed-combination or in concomitant therapy. Modelled cost-minimization and cost-effectiveness analyses were performed to investigate the economic consequences of ophthalmic therapy with brimonidine, dorzolamide, and timolol from a societal perspective. RESULTS: The literature review found that brimonidine and dorzolamide used as fixed combinations with timolol as well as in adjunctive therapy to timolol were equally effective and safe. Furthermore, in the European countries studied, the fixed combination of brimonidine/timolol represented a less costly option when compared to the fixed combination of dorzolamide/timolol evaluated over both a 3-month and a 12-month horizon. CONCLUSIONS: Brimonidine used as a fixed-combination therapy with timolol provided better cost value than dorzolamide/timolol in all the countries studied. For most countries, the fixed combination of brimonidine and timolol also provided better cost value than adjunctive therapy with brimonidine, which was more cost effective than adjunctive therapy with dorzolamide.

Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe.

BACKGROUND: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. METHODS: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. RESULTS: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated 86 for each incremental step ranging from 455 euro per person year for stage 0 to 969 euro per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. CONCLUSIONS: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.

Brimonidine in the prevention of intraocular pressure elevation following argon laser trabeculoplasty.

OBJECTIVE: To evaluate the efficacy of 0.5% brimonidine tartrate, an alpha 2-adrenergic agonist, in preventing intraocular pressure (IOP) elevation following argon laser trabeculoplasty. DESIGN: In a multicenter, double-masked, randomized study, 248 patients (248 eyes) who underwent argon laser trabeculoplasty were allocated to four treatment groups: (1) brimonidine administered before and after the procedure; (2) brimonidine administered before the procedure; (3) brimonidine administered after the procedure; and (4) a vehicle administered before and after the procedure. RESULTS: In the first 3 hours after argon laser trabeculoplasty, only one (0.54%) of the 183 brimonidine-treated patients had a postlaser IOP increase of 10 mm Hg or more, while increases of this magnitude occurred in 13 (23%) of the 56 patients who received only the vehicle (P < .001). The three brimonidine-treatment groups demonstrated significant mean reductions in IOP from the pretrabeculoplasty level (-4 to -8 mm Hg), whereas the vehicle-treated group showed an increase in mean IOP (4 mm Hg). Side effects associated with brimonidine treatment included conjunctival blanching (40.9%), lid retraction (7.6%), and a slight lowering of the systolic blood pressure. CONCLUSIONS: One drop of 0.5% brimonidine administered either before or after surgery was found to be efficacious and safe in preventing posttrabeculoplasty elevations in IOP.

Water homeostasis in desert-dwelling horses.

This study set out to investigate tolerance of the body water pool to short-term water deprivation in horses and, in particular, to assess whether feral horses from the Namib Desert showed tolerance to dehydration superior to Transvaal. Hydration status was compared in six feral horses from the Namib Desert and in six Boerperd farm horses under conditions of normal hydration and after 72 h of dehydration. Under normal hydration, the two groups did not differ significantly in water intake, plasma sodium and potassium concentrations, plasma osmolality, hematocrit, total plasma protein, body water content, or water turnover (ml.kg-0.82.day-1). The Namib horses were significantly smaller (P less than 0.0001) and turned over 5 liters less water per day than the Boerperd during normal hydration and 4 liters less during dehydration. Increases in plasma sodium concentration after 72 h of dehydration were greater (P less than 0.05) in the Namib horses. It was concluded that horses can easily tolerate water deprivation that results in a 12% reductions in body mass. The feral horses of the Namib desert were not significantly different per unit mass from domestic horses with regard to indexes of total body water content under conditions of normal hydration and after 72 h of dehydration. Their smaller size and, hence, lower water turnover might be mechanisms they use for survival in the Namib Desert.

Flurbiprofen 0.03% for the control of inflammation following cataract extraction by phacoemulsification.

We conducted a double-masked, vehicle-controlled study to evaluate the anti-inflammatory effect of topical flurbiprofen in cataract surgery by phacoemulsification and implantation of a posterior chamber intraocular lens. The 233 patients were randomized to receive either flurbiprofen or vehicle immediately prior to and for two weeks following surgery. No concomitant corticosteroid use was allowed. The flurbiprofen group had significantly less anterior chamber cells and flare at day 7 and significantly less conjunctival erythema, corneal edema, and lid edema at day 14. The investigator's global effectiveness rating was higher in the flurbiprofen group at day 14. Blood-aqueous barrier disruption, as measured by aqueous fluorophotometry, was statistically significantly diminished in the flurbiprofen group. Burning and stinging were rated significantly greater in the flurbiprofen group than in the vehicle group. Foreign-body sensation and photophobia were significantly more severe in the vehicle group than in the flurbiprofen group. Flurbiprofen provided postsurgical anti-inflammatory efficacy in clinical signs of inflammation and in blood-aqueous barrier disruption, and also showed improved subjective signs.

The separation of some volatile fatty acids on a "Sephadex" partition chromatogram.

The suitability of Sephadex LH-20 as a solid support for the partition chromatography of acetic, propionic and butyric acids was investigated by using standard mixtures of 14C-labelled acids. The clear separation that was obtained between the acids was confirmed by the negligible cross contamination found between the acid peaks. Furthermore, the Sephadex LH-20 column gave a convenient elution volume and time similar to those found for a Celite Analytical Filter Aid column, without the progressive deterioration in separation normally associated with Celite.

Some observations on the use of D-glucose-2-3H as a tracer in turnover studies in merino sheep.

Bolus injection of a mixture of D-glucose-2-3H and -(U)-14C into each sheep enabled a turnover rate to be calculated for each isotope and to be compared in the same animal. No statistically significant differences were found in pool size, or glucose space. The total entry rates calculated from the D-glucose-2-3H results were found to be significantly higher (P is greater than 0,95 paired t test) than those calculated from the D-glucose -(U)-14C results, the average difference being 18%. This difference indicated that the extent of glucose recycling was somewhat less than that reported for monogastric mammals (30%--Katz & Dunn, 1967) and similar to that found by Judson & Leng (1972) in sheep. Glycogen was isolated from skeletal, cardiac and smooth muscle as well as from the liver and the 3H:14C ratios determined. These ratios were found to be significantly higher than those reported for monogastric mammals such as the rat or dog.

Volatile fatty acid metabolism in sheep. 1. Average daily volatile fatty acid production in the rumen of sheep fed lucerne hay.

Changes in the total concentration of the volatile fatty acid (VFA) pool in the rumen were followed over a 24 hour period in 2 groups of sheep, 1 fed at 08h00 and the other twice daily at 08h00 and 20h00. Although similar maximum (143 and 147 meq/1) and average (100, 3 and 102, 1 meq/1) levels were found in the 12 and 24 h groups respectively, the twice daily feeding regimen resulted in a lower variation (S.D.=17, 0 meq/1 and 28, 9 meq/1 respectively). It was concluded from changes in the percentage molar composition of the VFA pool over the same period that the other of VFA absorption from the rumen was propionate greater than acetate greater than butyrate for both groups, but that the differences were less marked for the twice daily fed sheep. Long term infusions of 14C labelled acetic, propionic and butyric acids into the rumen of sheep fed a total of 1 600 g lucerne hay twice daily (08h00 and 20h00), gave an average net total VFA production rate of 4,52+/-1,01 moles/800 g/12 hours irrespective of the acid infused. The net individual turnover rates for acetic (2,81 moles/12 h), propionic acid (0,82 moles/12 h) and butyric acid (0,55 moles/12 h), derived by the subtraction of the inter-conversion factors from the gross production rates of the acids, and expressed as the percentage contribution of each acid to the total net VFA turnover (acetic=62%, propionic=18% and butyric=12%) closely resembled the percentage molar composition of the VFA pool in the rumen (acetic=60%, propionic=23% and butyric=12%). The total net VFA production was found to be directly proportional to the total VFA concentration in the rumen (correlation coefficient=0,83), and the relationships can be described by the equation y=0,034 x + 0,16 where y=VFA production in moles/12 hour and x=VFA concentration in meq/1. A specific VFA production rate of 0,85 moles per 100 g digestible organic matter was calculated from the average daily VFA production rate and the composition of the lucerne hay.

Glucose turnover, tolerance and insulin response in wethers, ewes and pregnant ewes in the fed and fasted state.

Glucose turnover parameters were obtained in fed and fasted wethers, ewes and pregnant ewes in their 2nd and 3rd trimesters, using a jugular bolus injection of D-glucose-2-3H. Fasting significantly (P less than 0,05) reduced glucose turnover (c. 40%) in both the wether and the non-pregnant ewe. A somewhat larger difference (c. 54%) between the fed and fasted ewes was found in their 3rd trimester of pregnancy due to an increase when fed (c. 29% higher turnover than in the non-pregnant ewe) rather than a decrease when fasted, since there was no statistical difference (P less than 0,1) between glucose turnover values of pregnant or non-pregnant fasted ewes. Glucose tolerance was estimated from an intrajugular glucose load (1 g/kg0,75 body mass) in these 3 groups of sheep under both fed and fasted conditions, and the resulting insulin response was followed for 4 hr after the injection. Fasting reduced the plasma clearance rate of glucose by c. 63% in both the wether and the non-pregnant ewe while the reduction was somewhat smaller (c. 51%) during the 2nd trimester of pregnancy. Only the pregnant ewe group showed a corresponding reduction in the resulting insulin response of 46% which was similar in magnitude to the diminished clearance, indicating that factors other than insulin are responsible for the reduced glucose clearance associated with fasting in the wether and non-pregnant ewe. Despite similar baseline plasma glucose values the glucose load appeared to distribute in a space that was significantly less than that found in all 3 groups of fed sheep when trace amounts were injected.

An accurate, sensitive and reproducible method for the colorimetric estimation of free fatty acids in plasma.

A sensitive and reproducible method permitting the estimation of 0,030-3,000 mM free fatty acids (FFA) in plasma with a standard error of 0,006 5 was developed. The method is based on the extraction of phosphate-buffered plasma with a chloroform-heptane-methanol mixture, formation of the cobalt complex and on the subsequent determination of the metal with 1-nitroso-2-naphthol. The method was used to obtain normal values (mean 0,547 mM range 0,147-1,197 mM) for Merino wethers fed lucerne hay.

A rapid quantitative colorimetric determination of blood acetone applied to the assessment of ketosis in fasted pregnant ewes.

A simple, accurate, colorimetric method for determining blood acetone as an adjunct to the enzymic method of estimating the other ketones was developed and tested on a group of fasted pregnant ewes. Acetone reacted with 2-hydroxybenzaldehyde to form a stable coloured complex that followed Beer's Law up to an acetone concentration of at least 4 mg/100 ml of the test solution at 490 nm. While the optimum incubation time of the reaction mixture was found to be 3 h at 40 degrees C, it could also be left to incubate overnight at room temperature. When tested in a blood matrix, the method gave a mean within-batch coefficient of variation of 0,7%, and a day to day variation of 0,3-1,2%, while an overall recovery of 100, 6+/-1,4% was achieved over 5 concentration ranges (2,86-10,53 mg/100 ml). The values obtained from this method corresponded closely to those from the diffusion technique previously employed and it considerably simplified the procedure. A direct linear relationship, y = 2,594x + 2,917 with a coefficient of determination r2 = 0,958 for 49 pairs of data, was found between the acetone (= x mg/100 ml) and total ketone (= y mg/100 ml) concentrations in blood samples drawn from fasted pregnant sheep. This relationship can therefore be used to estimate accurately the degree of ketosis from the blood acetone concentration alone.

Eicosanoids: a short review.

The biochemical reactions leading to the formation of eicosanoid compounds are reviewed. Arachidonic acid and similar homologous polyunsaturated acids are shown to be important precursors of these compounds. The partitioning of precursors between the cyclo-oxygenase and lipoxygenase enzyme systems leads to the prostanoid/thromboxane/prostacyclin and leukotriene families groups are reviewed. The mechanism of action of the prostacyclin group is briefly discussed.

A review of energy metabolism in producing ruminants. Part 1: Metabolism of energy substrates.

The efficiency of metabolisable energy utilisation, for growth and fattening, is dependent upon the relative VFA proportions produced in the rumen. Sufficient propionate is required to meet glucose demand for producing NADPH, glycerol and nucleic acid synthesis. Since diet has the greatest effect on the pattern of VFA fermentation, it will play a major role in controlling the supply of VFA to the animal. Magnitude of the acetate supply determines the proportion of acetate supplied to oxidation or to fatty acid synthesis, which is also dependent upon the extracellular supply of glucose, NADPH and ATP. Since the optimal levels of acetate and glucose for lipogenesis appear to vary with glucose concentration, a diet that decreases the supply of glucogenic precursors, but increases the acetate supply, may suppress fatty acid synthesis. An increased supply of propionate may suppress glucose synthesis from other sources. The isoenergetic replacement of roughage by concentrate, appears to increase the glucose entry rate, due to both an increase in propionate, and glucose absorbed from the small intestine. Dietary nitrogen source also affects the rate of gluconeogenesis. An optimum dietary energy-protein ratio exists for maximum efficiency of utilisation of both dietary energy and protein. In dairy cows, for example, the energy is most effectively metabolised when protein content of the diet is 15-25% of net energy.

A review of energy metabolism in producing ruminants. 2. Control of nutrient partitioning.

Insulin is the primary short-term hormonal regulator of metabolism in the resting ruminant. The concentration of plasma insulin is positively correlated with energy intake. Diets producing hyperinsulinaemia, direct the balance towards body gain (anabolic). However, in lactating animals, the postprandial rise in insulin is reduced, thereby favouring movement of nutrients to the mammary gland and promoting gluconeogenesis. Similar mechanisms balance the demands of foetal and maternal growth. Glucagon, on the other hand, stimulates both glycogenolysis and gluconeogenesis in the liver from glucogenic amino acids, thereby indirectly diminishing protein synthesis in muscle. Homeorhetic hormones from both the pituitary and reproductive glands, play a major role in the long-term control of nutrient partitioning. Oestrogens appear to affect feed intake, promote RNA and protein synthesis and inhibit gluconeogenesis in the liver, thereby promoting the metabolic adaptations necessary for pregnancy. Progesterone, on the other hand, appears to block the action of the oestrogens at cellular level, and may actually increase feed intake. The pituitary hormones, prolactin and somatotropin, bring about significant improvements in production, especially in milk yield. The action of the somatomedins appears to be responsible for the paradoxical spectrum of effects attributed to somatotropin.

The effects of xylazine and fentanyl on various hormones and metabolites in karakul sheep and a blesbok.

Xylazine and fentanyl are commonly used in combinations for immobilisation of wild antelope. In order to ascertain the effects of the combination of these drugs on certain metabolites and hormones in ruminants, blood was sampled from 8 karakul sheep (4 experimental and 4 control) and one tame blesbok (Damaliscus dorcas phillipsii) for 30 min before and after immobilisation. The samples were assayed for glucose, free fatty acids, insulin, thyroxine, triidothyronine, progesterone and oestrogen. Significant changes, after the administration of xylazine and fentanyl, were recorded in circulating concentrations of glucose, which increased, and free fatty acids and insulin, which decreased. The other hormones tested were not affected within the sampling period. It is suggested that the combination of xylazine and fentanyl may act directly on pancreatic Beta cells to inhibit the secretion of insulin, which will consequently affect circulating concentrations of glucose and free fatty acids.

The effect of Babesia canis induced haemolysis on the canine haemoglobin oxygen dissociation curve.

Samples of blood from normal healthy (n = 7) and Babesia canis-infected dogs (n = 7) were subjected to varying oxygen tensions in a tonometer, after which the samples were subjected to blood gas analysis and haemoximetry. This data was used to plot haemoglobin oxygen dissociation curves (ODC) for both groups of dogs. States of acidosis and hypercapnia were then simulated by modelling, and the response of the 2 haemoglobin oxygen dissociation curves compared. The ODC of the B. canis-infected group showed a decreased ability to shift to the right when compared to that of the normal, healthy ODC. This decreased Bohr effect probably exacerbates the severe tissue hypoxia associated with this disease by impairing the ability of haemoglobin to off-load oxygen at the tissue level.

Effect of a 72 hour fast on physiological stress indicators in feedlot cattle.

Feedlot oxen (n = 15) were herded and subjected to venepuncture on a daily basis for 2 weeks. Plasma glucose, lactate, free fatty acids, total lipids, total protein, cortisol, catecholamines, osmolarity and haematocrit were compared between Days 1 and 14. Plasma glucose concentration and haematocrit decreased significantly while total plasma lipid and free fatty acid concentrations increased significantly over the 14 d. Thereafter, food was withdrawn for 72 h from the experimental group (n = 10) and the same blood variables were compared in the control and the experimental groups. Plasma free fatty acid concentrations rose, while glucose concentrations declined in the experimental group during the fasting period. It is concluded that food deprivation for 72 h in cattle cannot be regarded as a major stressor.