Showing papers by "Newcastle University published in 1987"
TL;DR: EGFR status divides the ER- population into good and poor prognosis subgroups, and the presence of EGFR was the most important variable in the primary tumours for predicting relapse-free and overall survival.
898 citations
TL;DR: A GAM offers an imaginative new approach to the analysis of point pattern data based on a fully automated process whereby a point data set is explored for evidence of pattern without being unduly affected by predefined areal units or data error.
Abstract: This paper presents the first of a new generation of spatial analytical technology based on a fusion of statistical, GIS and computational thinking. It describes how to build what is termed a Geographical Analysis Machine (GAM), with high descriptive power. A GAM offers an imaginative new approach to the analysis of point pattern data based on a fully automated process whereby a point data set is explored for evidence of pattern without being unduly affected by predefined areal units or data error. No prior information or specification of particular location-specific hypotheses is required. If geographical data contain strong evidence of pattern in geographical space, then the GAM will find it. This technology is demonstrated by an analysis of data on cancer for northern England.
507 citations
TL;DR: The aggregate data show health care to be, if anything, a necessity rather than a luxury good, and this paper argues that these implications rely upon the application of microeconomic analysis to macroeconomic data, and that this is not appropriate.
370 citations
TL;DR: M‐mode derived indices of myocardial contractility were all significantly reduced by 2 weeks and thereafter showed no further change, and no haemodynamic differences were found between lactating and non‐lactating mothers.
248 citations
TL;DR: In this paper, problems associated with activated diffusion, molecular sieve effects, cooperative adsorption effects, the use of polar adsorbates, and the understanding of limitations and value of theoretical adsorsion equations are assessed.
236 citations
TL;DR: Serial measurements of cardiac output and mean arterial pressure were performed in 15 women during the first stage of labour and at one and 24 hours after delivery to find haemodynamic changes of considerable clinical relevance in managing mothers with complicated cardiovascular function.
Abstract: Serial measurements of cardiac output and mean arterial pressure were performed in 15 women during the first stage of labour and at one and 24 hours after delivery. Cardiac output was measured by Doppler and cross sectional echocardiography at the pulmonary valve. Basal cardiac output (between uterine contractions) increased from a prelabour mean of 6.99 l/min to 7.88 l/min at greater than or equal to 8 cm of cervical dilatation as a result of an increase in stroke volume. Over the same period basal mean arterial pressure also increased. During uterine contractions there was a further increase in cardiac output as a result of increases in both stroke volume and heart rate. The increment in cardiac output during contractions became progressively greater as labour advanced. At greater than or equal to 8 cm of dilatation cardiac output increased from a basal mean of 7.88 l/min to 10.57 l/min during contractions. There were also further increases in mean blood pressure during contractions. One hour after delivery heart rate and cardiac output had returned to prelabour values, though mean arterial pressure and stroke volume remained raised. By 24 hours after delivery all haemodynamic variables had returned to prelabour values. Haemodynamic changes of the magnitude found in this series are of considerable clinical relevance in managing mothers with complicated cardiovascular function.
213 citations
TL;DR: The theoretical errors of the approach are restated, its limitations for policy are indicated and economics can offer something more useful than a method for estimating the ‘benefits of the unattainable’.
197 citations
TL;DR: Using a complementary DNA subclone of the DMD gene, screened 66 DMD and BMD patients who had not previously shown deletions with the probes, and is able to detect deletions directly in 40% of families requiring antenatal diagnosis or carrier detection.
Abstract: Duchenne and Becker muscular dystrophy (DMD and BMD) genes are located in Xp21 on the short arm of the X chromosome. DMD patients display a much more severe clinical course than BMD patients, and yet about 10% of cases of each have been reported to have deletions for parts of the gene. Using a complementary DNA subclone of the DMD gene we have screened 66 DMD and BMD patients who had not previously shown deletions with the probes then available. Fifteen patients have a deletion of this part of the gene, indicating a higher deletion frequency in this region (22%). Exons were deleted in five severely affected DMD patients and in ten BMD patients. Significantly, most of these deletions begin in the same region of the cDNA, which implies that there is a common mechanism for the generation of many of these mutations. An apparently identical deletion in one family gave classical BMD in two brothers (presenting in their teens) and only very mild muscle weakness in their 86-year-old great-great-uncle. Taking these data together with data using the probes previously published, we are able to detect deletions directly in 40% of our families requiring antenatal diagnosis or carrier detection.
192 citations
TL;DR: In this paper, the authors identify the zones in which the cupriferous pyrite deposits of Cyprus were precipitated from hydrothermal solutions derived by interaction of contemporaneous seawater with hot mafic rock at the ancient Troodos spreading centre.
182 citations
TL;DR: Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.
Abstract: The functional characteristics of osmoregulated vasopressin secretion can be defined in terms of an osmotic threshold for its release and a sensitivity of the osmoreceptor and vasopressin-secreting unit. Osmotically stimulated thirst has features similar to osmoregulated vasopressin. There are wide individual variations in the functional characteristics of both thirst and vasopressin release in healthy humans, probably genetic in origin. The influence of aging appears to enhance the sensitivity of vasopressin secretion but blunt thirst appreciation. Yet in many physiological situations changes in osmoregulated vasopressin release and thirst occur in parallel. The fall in plasma osmolality associated with human pregnancy is accounted for entirely by a lowering of the osmotic thresholds for thirst and vasopressin release. Similar but less marked alterations accompany the ovulatory luteal phase of the menstrual cycle. A major nonosmotic stimulus to vasopressin secretion is hypotension and/or hypovolemia, mediated by high- (carotid sinus) and low- (left atrial) pressure receptors. Circulating catecholamines influence the release of vasopressin by alpha- and beta-adrenergic pathways. Drinking by hypertonic humans provides immediate reduction in thirst and vasopressin secretion probably mediated by pathways from the oropharynx. The modest but variable rise in plasma vasopressin in response to hypoglycemia appears to be due to cellular neuroglycopenia and is independent of parasympathetic pathways. Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.
166 citations
TL;DR: The complete nucleotide sequence of a cloned streptolysin O (SLO) gene and the amino acid sequence of SLO, predicted from the DNA sequence, are reported.
Abstract: The complete nucleotide sequence of a cloned streptolysin O (SLO) gene and the amino acid sequence of SLO, predicted from the DNA sequence, are reported. SLO contains a single cysteine residue located close to the C terminus of the molecule and shares extensive structural homologies with other thiol-activated toxins, which allow us to predict functionally important features.
TL;DR: The natural history of intellectual dysfunction soon after coronary bypass surgery and the incidence and functional impact of late neuropsychological impairment are described and the possible predisposing factors for long-term intellectual dysfunction are searched for.
Abstract: As part of a prospective study of neurological and neuropsychological complications of coronary bypass surgery, 259 patients underwent psychometric assessment before operation and at seven days and six months after operation using a battery of 10 standard tests of intellectual function. This report describes the natural history of intellectual dysfunction soon after surgery and the incidence and functional impact of late neuropsychological impairment. The mean neuropsychological scores for the whole group remained unchanged or improved compared with levels before operation for the majority of the 10 tests. Analysis of the test scores for individuals showed that 147 of 259 (57 per cent) patients showed deterioration on at least one test score at six months. The degree of impairment was usually mild. One hundred and thirty of the 147 patients showed mild cognitive dysfunction (score deterioration on one or two tests) and only 17 patients had moderate or severe impairment (score deterioration on three or more tests). Detectable neuropsychological deterioration at six months often did not matter to the patient in functional terms. Seventy-one per cent of these patients had no significant symptoms; 27 per cent had minor symptoms and only 2 per cent were seriously disabled. Of the patients unemployed at six months, in only one case was intellectual impairment the factor preventing return to work. A search for possible predisposing factors for long-term intellectual dysfunction was made using a multivariate analysis of 91 variables for each patient. Cardiac failure before surgery and global impairment of left ventricular function were the only factors showing significant correlation.
TL;DR: In this paper, the authors examined three oils, with presumed Late-Precambrian (Vendian) source rocks, from this region for C 15 + saturated hydrocarbon biomarkers using gas chromatography (GC) and GC-MS, and found these oils to have many characteristics in common with other oils of similar age from Eastern Siberia and Oman.
TL;DR: It is suggested that azathioprine has no unwanted effects on the periodontal health of post-renal transplant patients and cyclosporin therapy caused an increase in gingival hyperplasia, which may be related to plasma concentrations of the drug.
Abstract: The periodontal health of 24 adult renal transplant patients was investigated in a longitudinal study. Post-transplant patients were receiving either azathioprine or cyclosporin to prevent graft rejection. No significant difference (P greater than 0.05) was observed for plaque scores on gingival inflammation, either between treatment groups or throughout the investigation period. However, patients on cyclosporin therapy had significantly more gingival hyperplasia and probing sites greater than 3 mm than those on azathioprine (P less than 0.05). In the cyclosporin group, a significant increase in hyperplasia and probing sites greater than 3 mm was observed at 3 and 6 months post-transplant. A significant correlation (rs = 0.55, P less than 0.05) was observed between mean plasma concentrations of cyclosporin throughout the 6-month investigation period and the increase in gingival hyperplasia. The finding from this study would suggest that azathioprine has no unwanted effects on the periodontal health of post-renal transplant patients. Cyclosporin therapy caused an increase in gingival hyperplasia, which may be related to plasma concentrations of the drug.
TL;DR: In this paper, the authors investigated the change in event-horizon area in cosmological models that depart slightly from de Sitter space and proved that the area is non-decreasing.
Abstract: The author investigates the change in event-horizon area in cosmological models that depart slightly from de Sitter space. If the gravitational source is a perfect inviscid fluid satisfying the dominant energy condition, the area is proved to be non-decreasing. If the fluid is viscous, the area can decrease, but the attendant generation of entropy ensures that the generalised second law of thermodynamics remains unviolated.
TL;DR: A recent review by Rosen et al. (1981) claims that Dipnoi (lungfish) are the sister‐group of the Tetrapoda, that Osteolepiformes is a non‐taxon and that Eusthenopteron is more distant from tetrapods than are Dip noi, coelacanths and probably the fossil Porole piformes, are refuted by use of the same cladistic technique.
Abstract: SUMMARY
I. The traditional view of the origin of tetrapod vertebrates is that they are descendants of fossil osteolepiform fish, of which Eusthenopteron is best known. In recent years both that conclusion and the methodology by which it has been reached have been challenged by practitioners of cladistic analysis. Particularly a recent review by Rosen et al. (1981) claims that Dipnoi (lungfish) are the sister-group of the Tetrapoda, that Osteolepiformes is a non-taxon and that Eusthenopteron is more distant from tetrapods than are Dipnoi, coelacanths and probably the fossil Porolepiformes. We attempt to refute all these concludions by use of the same cladistic technique.
2. We accept that all the above-mentioned groups, together with some less well-known taxa, can be united as Sarcopterygii by means of shared derived (apomorph) characters. We also agree that Porolepiformes and Actinistia (coelacanths) can be characterized as valid taxa. The primitive and enigmatic fossil fish Powichthys is accepted as representing the plesiomorph sister-group of true porolepiforms.
3. Only two apomorph features, the course of the jaw adductor muscles and the position of incurrent and excurrent nostrils, appear to unite all the fish, living and fossil, currently regarded as Dipnoi. The characteristic tooth plates and the presence of petrodentine both exclude important primitive fossil forms.
4. Contrary to the opinion of Rosen et al., Osteolepiformes can be characterized — by the arrangement of bones forming the cheek plate, the presence of basal scutes to the fins and by the unjointed radials of the median fins. However, if these are true autapomorphies they exclude any osteolepiform from direct tetrapod ancestry.
5. Tetrapoda is a monophyletic group characterized by ten or more autapomorphies, including the bones of the cheek plate, a stapes and fenestra ovalis, and a series of characters of the appendicular skeleton.
6. Tetrapods have a true choana (internal nostril). We accept that the posterior (excurrent) nostril of Dipnoi is the homologue of the tetrapod choana. However, we assert that the posterior nostril of all bony fish is the homologue of the choana. This assertion would be refuted if any fish showed separate posterior nostril and choana. We reject the claim that this ‘three nostril condition’ occurred in porolepiforms and osteolepiforms. The evidence for a choana in porolepiforms is inadequate. Osteolepiforms had a true choana, characterized as in tetrapods by its relationship to the bones of the palate, but no third nostril. Dipnoans are not choanate.
7. Following cladistic practice, the relationship of the extant taxa is established first. Dipnoi are thus shown to be the living sister-group of tetrapods, but only on ‘soft anatomy’ characters unavailable in fossils. Coelacanths are the living sister-group of the taxon so formed.
8. The relationship of the fossil taxa to the extant sarcopterygians is then considered. The synapomorphy scheme proposed by Rosen et al. is discussed at length. Virtually all the characters they use to exclude close relationship of Eusthenopteron (and hence all osteolepiforms) to tetrapods, in favour of coelacanths and dipnoans, are invalid.
9. A series of synapomorphies uniting osteolepiforms and tetrapods is proposed, including a true choana (hence the taxon Choanata), the histology of the teeth, and a number of characters of the humerus. The recently discovered fossil Youngolepis, which lacks a choana, represents the sister-group of the Choanata, and is not uniquely close to Powichthys. The latter, as a porolepiform (s.l.) is a member of the sister-group to Choanata plus Youngolepis.
10. Our cladistic analysis suggests that all the extinct taxa considered are more closely related to tetrapods than are the Dipnoi. Moreover fossil evidence suggests that Dipnoi, considered as an extant taxon, may not even be the living sister-group of Tetrapoda. Early fossil dipnoans appear to have been marine fish without specific adaptations for air breathing. If so the apparent synapomorphies of Dipnoi and Tetrapoda may be homoplastic — the insistence on grouping extant taxa first would then have yielded an invalid inference.
TL;DR: In an incomplete 5 X 5 Latin square experiment, four cattle were given grass silage in two meals per d to satisfy 1.15 maintenance energy requirements and intraruminal infusions had no significant effects on rumen pH, concentrations of volatile fatty acids or their molar proportions.
Abstract: In an incomplete 5 X 5 Latin square experiment, four cattle were given grass silage in two meals per d to satisfy 1.15 maintenance energy requirements. In addition, water or casein (21 g nitrogen and 0.17 kg organic matter (OM)/d) or urea (U; 28 g N/d) or a glucose syrup (G; 0.87 kg OM/d) or casein and glucose syrup (CG; 17 g N and 0.93 kg OM/d) were infused intraruminally at a constant rate. A 24 h collection of duodenal digesta was made using chromic oxide for flow estimation and 35S as a marker of microbial N entering the small intestine. Samples of rumen fluid were also taken for estimation of rumen pH, and concentrations of ammonia-N and volatile fatty acids. The intraruminal infusions had no significant effects on rumen pH, concentrations of volatile fatty acids or their molar proportions. Infusion of either C or U significantly (P less than 0.05) increased rumen NH3-N concentrations whereas infusions of either G or CG lowered rumen NH3-N concentrations. Infusions of C or U had no significant effect on the quantities of OM, acid-detergent fibre (ADF) or N constituents which entered the small intestine. Infusions of G or CG increased the quantities of OM (G P less than 0.05, CG P less than 0.01), ADF (CG P less than 0.05), non-NH3-N (G P less than 0.05, CG P less than 0.01), amino acid N (G P less than 0.05, CG P less than 0.01) and microbial N (G P less than 0.05, CG P less than 0.01) which entered the small intestine. The efficiency of rumen microbial N synthesis was unchanged by the infusion of C, U or G (P greater than 0.05) but increased significantly (P less than 0.05) when CG were infused.
TL;DR: It is concluded that in these early hominids, crown formation times in posterior teeth, particularly in the large thick enamelled molar teeth of the east African 'robust' australopithecines, were shorter than those of modern humans.
Abstract: A recent study1 of the surface manifestation of incremental lines associated with enamel formation suggested that the crowns of early hominid incisor teeth were formed more rapidly than those of modern humans. In the absence of comparative data, the authors were forced to assume that enamel increments in fossil teeth were similar to those in modern humans. We have used evidence from the fractured surfaces of molar teeth to deduce estimates for both long- and short-period incremental growth markers within enamel in east African 'robust' australopithecine and early Homo teeth. We conclude that in these early hominids, crown formation times in posterior teeth, particularly in the large thick enamelled2 molar teeth of the east African 'robust' australopithecines, were shorter than those of modern humans. This evidence, considered together with data on crown and root formation times in modern apes3, suggests that the posterior teeth in these hominids both formed and erupted more rapidly than those of modern man. These results have implications for attempts to assess dental and skeletal maturity in hominids.
TL;DR: A non‐invasive technique for the measurement of cardiac output in pregnancy by combined cross‐sectional and Doppler echocardiography at three intracardiac sites is described, with close agreement for all three measurement sites.
TL;DR: There was no difference between siblings and patients for dental caries, gingivitis, and oral hygiene, mouth opening, overjet, and overbite, but enamel opacites and hypoplasia were more common in patients than siblings and in the leukemia than in the solid tumor group.
Abstract: Fifty-two long-term survivors of childhood leukemia or solid tumors had a clinical dental examination along with 49 of their sibling. The 52, with an additional 30 examined in a previous study, were studied radiologically with a panoramic tomogram. All children with leukemia had received chemotherapy for 2 or 3 years and irradiation on standard protocols and the solid tumor group had received chemotherapy for 6 to 24 months. There was no difference between siblings and patients for dental caries, gingivitis, and oral hygiene, mouth opening, overjet, and overbite. More solid-tumor patients had abnormal occlusion (P less than 0.02) and those with abnormalities tended to have been treated at an earlier age. Enamel opacities and hypoplasia were more common in patients than siblings and in the leukemia than in the solid tumor group. Sixty-five percent of the children had abnormalities on radiologic examination including failure of the tooth to develop, small crown, hypoplasia of the crown, and abnormal root development. In most cases the radiologic abnormality could be correlated in time with the patient's treatment and a knowledge of the normal time of tooth development. Three teeth extracted during the course of the study were examined histologically and these showed prominent incremental lines which could be correlated in time with vincristine treatment.
TL;DR: In this paper, carbon fibres were anodically surface treated by passing them continuously through an electrochemical bath, thus simulating a possible industrial surface treatment process, and composites were made from these fibres with an epoxy resin and their interlaminar shear strength (ILSS) tested.
Abstract: Carbon fibres were anodically surface treated by passing them continuously through an electrochemical bath, thus simulating a possible industrial surface-treatment process. Composites were made from these fibres with an epoxy resin and their interlaminar shear strength (ILSS) tested. The surfaces of the fibres were examined by X-ray photoelectron spectroscopy after treatment. Both golvanostatic and potentiostatic cell control led to treated fibres that produced composites with high interlaminar shear strengths (80 to 90 MPa). The effect of potential, reaction time, electrolyte and subsequent heating of the fibres in a vacuum on the ILSS of the composites is reported. The rise in ILSS with surface treatment is not dependent upon the O-1 s: C-1 s ratios or the amount of carboxyl functionality present on the surface. This suppors the view that mechanical keying of the resin to the fibre surface plays an important role in forming the fibre-resin bond.
TL;DR: In this article, the authors argue that a major local factor influencing the rate of new-firm formation is the rate at which jobs are shed in a locality, and that there appears to be no association between changes in, or absolute national levels of, profitability in the ith industry and new firm formation rates in that industry.
Abstract: This paper argues that a major local factor influencing the rate of new-firm formation is the rate at which jobs are shed in that locality. The evidence presented shows that in Northern England there appears to be no association between changes in, or absolute national levels of, profitability in the ith industry and new firm formation rates in that industry. On the other hand, formation rates in the ith industry in the region are positively correlated with job shedding. Copyright 1987 by Scottish Economic Society.
Journal Article•
TL;DR: These results, taken together with the earlier observation that the rate of drug accumulation is identical in these two lines, suggest that enhanced cytoplasmic drug detoxification is the underlying resistance mechanism in CHO-Chlr cells.
Abstract: We have reported previously (C. N. Robson et al., Cancer Res., 46: 6290–6294, 1986) the isolation of a Chinese hamster ovary cell line, designated CHO-Chlr, that exhibits resistance to bifunctional nitrogen mustards while maintaining the normal parental level of sensitivity to several other alkylating agents. We have compared the rate of formation and repair of DNA cross-links induced by mechlorethamine in CHO-Chlr and parental CHO-K1 cells, both in intact cells and in isolated nuclei. Equimolar doses of mechlorethamine induce significantly fewer DNA interstrand cross-links in CHO-Chlr cells than in CHO-K1 cells, but levels of DNA-protein adducts are approximately equivalent in the two lines. There is a correlation between the relative resistance of CHO-Chlr cells to mechlorethamine (34-fold) and the amount of drug required to induce approximately equal numbers of DNA interstrand cross-links in the two cell lines. This strongly implicates DNA-DNA adducts in the cytotoxic action of mechalorethamine. DNA cross-linking studies on isolated nuclei reveal only minor differences between the two lines even with identical drug treatments. The rate of cross-link repair is comparable in the two cell lines. These results, taken together with our earlier observation that the rate of drug accumulation is identical in these two lines, suggest that enhanced cytoplasmic drug detoxification is the underlying resistance mechanism in CHO-Chlr cells. We have measured cellular glutathione S-transferase activity, using both the general substrate 1-chloro-2,4-dinitrobenzene, and substrates with some specificity for the different classes of transferase isoenzymes. Total enzyme activity (as measured with 1-chloro-2,4-dinitrobenzene) is elevated 3-fold in the resistant cells. A 2- and 5-fold increase, respectively, in activity against ethacrynic acid and cumene hydroperoxide is detectable in CHO-Chlr cells. This elevation in catalytic activity in the resistant cells is reflected in higher levels of both the Yf- and Ya-type transferase subunits.
TL;DR: Biosynthetic human C-peptide was used to determine its kinetic parameters in 10 normal subjects and measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate, which accounted for 50±8% of total insulin secretion.
Abstract: An understanding of the metabolic abnormalities rising from inappropriate insulin delivery in diabetic patients demands a knowledge of 24-h and basal insulin secretion rates in normal man. We have used biosynthetic human C-peptide to determine its kinetic parameters in 10 normal subjects and applied these to measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate. Metabolic clearance rate measured by stepped primed infusion of biosynthetic human C-peptide at rates of 10, 19 and 26 nmol/h was 4.7 +/- 0.7 (+/- SD) ml X kg-1 X min-1, and was independent of infusion rate. Fractional clearance (T1/2, 26 +/- 3 min) and distribution volume (0.178 +/- 0.039 l/kg) were calculated from the decline in concentration after cessation of the highest rate infusion. Basal insulin secretion calculated from the C-peptide metabolic clearance rate and plasma concentrations for the period 02.00 to 07.00 hours was 1.3 +/- 0.4 U/h. Over 24 h total insulin secretion on a standard high carbohydrate diet was 63 +/- 15 U, calculated from the area under the C-peptide concentration curve. Basal insulin secretion, therefore, accounted for 50 +/- 8% of total insulin secretion. Although only 5.6 +/- 1.1% of C-peptide was detected in 24-h urine collections, urinary C-peptide excretion was significantly related to 24-h C-peptide secretion (r = 0.74, p less than 0.02).
TL;DR: In this article, it was shown that the crack velocity-strain rate relationship in the presence of multiple cracked specimens can be computed by considering the number of cracks, in which case it is possible to calculate (involving electrochemical data) the crack velocities.
Abstract: One of the problems in relation to predicting the rates of defect growth in structures displaying stress corrosion cracking (SCC) is that knowledge relating to realistic stress corrosion crack velocities is very limited. In monotonic slow strain rate tests (SSRTs) taken to total failure at usual strain rates and in tests on precracked specimens at stress intensity factors in excess of KISCC, stress corrosion crack velocities may be appreciably higher than are likely to occur in service, except in the very late stages of crack growth before a service failure. These differences probably develop partly because of differences in the effective crack tip strain rate, and consideration is given to various expressions for calculating the latter from the applied strain rate. For multiple cracked specimens, as in SSRTs, the importance of considering the number of cracks is demonstrated, in which case it is possible to calculate (involving electrochemical data) the crack velocity-strain rate relationships i...
TL;DR: Multivariate analysis revealed that extra‐coronary vascular disease, severe and prolonged duration of heart disease prior to operation, and large drop in haemoglobin level during surgery may predispose to neuro‐ophthalmological complications.
Abstract: In a prospective study of neurological complications of coronary bypass surgery, detailed pre- and post-operative bedside ophthalmological evaluation was undertaken in 312 patients. Post-operative neuro-ophthalmological complications developed in 80/312 (25.6%) patients and included: areas of retinal infarction (17.3%); retinal emboli (2.6%); visual field defects (2.6%); reduction of visual acuity (4.5%) and Horner's syndrome (1.3%). Neuro-ophthalmological complications were not observed in a control group of 50 patients undergoing major peripheral vascular surgery. Ten of 75 patients reviewed at 6 months still had detectable neuro-ophthalmological abnormalities, but functional disability occurred only in those with persistent visual field defects. Multivariate analysis revealed that extra-coronary vascular disease, severe and prolonged duration of heart disease prior to operation, and large drop in haemoglobin level during surgery may predispose to neuro-ophthalmological complications.
TL;DR: It is indicated that K+ homoeostasis is maintained in uraemic patients undergoing long-term dialysis by a combination of K+ losses during dialysis, and enhanced large intestinal K+ excretion.
Abstract: 1. The role of the large intestine in the maintenance of K+ balance in uraemic patients established on long-term dialysis was studied with a rectal dialysis technique in 14 normal subjects, ten normokalaemic patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and seven patients undergoing haemodialysis. Dietary K+ intakes in the normal subjects, CAPD patients and haemodialysis patients were 80-100 mmol/24 h, 70-80 mmol/24 h and 60-70 mmol/24 h, respectively. 2. At an initial intraluminal K+ concentration of 45 mmol/l, rectal K+ secretion in the CAPD patients (2.4 +/- 0.4 mumol h-1 cm-2) was greater than in normal subjects (1.2 +/- 0.2 mumol h-1 cm-2, P less than 0.02). Under similar conditions, rectal K+ secretion was also greater in the haemodialysis patients than in normal subjects, both predialysis (3.7 +/- 0.4 mumol h-1 cm-2, P less than 0.001) and postdialysis (2.4 +/- 0.5 mumol h-1 cm-2, P less than 0.05), even though haemodialysis decreased plasma K+ concentration from 5.3 +/- 0.1 mmol/l to 3.5 +/- 0.2 mmol/l (P less than 0.001). 3. There were no significant differences in rectal Na+ absorption, rectal potential difference, plasma aldosterone concentration, or total body K+ content (measured by whole-body counting of 40K), between the normal subjects and either the CAPD or the haemodialysis patients. 4. These results indicate that K+ homoeostasis is maintained in uraemic patients undergoing long-term dialysis by a combination of K+ losses during dialysis, and enhanced large intestinal K+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Integer programming is proposed and demonstrated as a method of selecting between mutually exclusive projects and published economic appraisals of health care techniques.
TL;DR: In human pregnancy, effective renal plasma flow and glomerular filtration rate increase to levels 50-80% above non-pregnant values, related in part to altered tubular function.
Abstract: Summary In human pregnancy, effective renal plasma flow and glomerular filtration rate increase to levels 50–80% above non-pregnant values. The increments occur shortly after conception, persist throughout the second trimester and reduce slightly in late pregnancy. The hyperfiltration of pregnancy does not seem to be a potentially damaging process, as intraglomerular pressure remains unchanged. The increased excretion of glucose and other nutrients, as well as uric acid and protein, is related in part to altered tubular function. Renal physiology is altered so much in pregnancy that non-pregnant norms cannot be used in antenatal care.
TL;DR: The available evidence favours the use of drugs with a short elimination half-life which are extensively metabolised and which have no active metabolites.
Abstract: Oral hypoglycaemic drugs have widely differing pharmacokinetic properties. Possible pharmacodynamic benefits include greater efficacy and fewer adverse effects. In general, it has not been possible to demonstrate unequivocal differences in clinical efficacy between the sulphonylureas during long term use, although there are clear differences in potency. These differences have been emphasised to the extent that the term ‘second-generation’ has been used for the most potent sulphonylureas, but there is little to suggest that potency is of any therapeutic significance. Trials to study differences in efficacy have rarely been of acceptable design. They have often used fixed doses of drugs, begging the question of whether true potency ratios have been established for chronic treatment. They have rarely involved substantial numbers of patients in double-blind crossover studies with a suitable washout period. Trials which show that there is a clear relationship between drug concentrations in blood and drug effects (whether therapeutic effects or adverse effects such as severe hypoglycaemia) are generally lacking. Qualitative and semiquantitative analysis of adverse effects supports the concept that drugs with a long half-life (e.g. chlorpropamide), renally excreted active metabolites (e.g. acetohexamide) or unusual properties (e.g. glibenclamide, which accumulates progressively in islet tissue) are more likely to cause prolonged hypoglycaemia, which may be fatal. The major adverse effect of treatment with biguanides is lactic acidosis, and this probably occurs more commonly in patients treated with phenformin than those treated with metformin because of pharmacogenetic variation in phenformin metabolism. The available evidence therefore favours the use of drugs with a short elimination half-life which are extensively metabolised and which have no active metabolites.