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Biomedical subjects

M Tyler

Publications and source records attributed to M Tyler.

At least 37 records · Page 2Linked to original sources

Liver regeneration after hepatic ischemia and reduced liver autotransplantation in the rat.

Current knowledge of liver regeneration after reduced liver transplantation is limited. Warm ischemia is one component of the reduced liver transplantation procedure that could have an impact on the regenerative response. To study this effect, we performed partial hepatectomy on male Long-Evans rats, with animals divided into four groups: group 1 underwent partial hepatectomy only; group 2 underwent partial hepatectomy and 40 min of ischemia; group 3 underwent partial hepatectomy, 40 min of ischemia and portocaval shunt surgery; and group 4 underwent partial hepatectomy and orthotopic autograft surgery. Group 5 consisted of sham-operated animals. Animals were killed 4, 24, 48, 72 and 96 hr after surgery. Thymidine kinase activity, mitotic index, a liver mass index and ornithine decarboxylase levels were used as parameters of liver regeneration. Aspartate transaminase was recorded. Maximal thymidine kinase and mitotic index were observed in group 1 animals at 24 hr. In groups 2, 3 and 4 maximal thymidine kinase activity and mitotic activity were observed 24 hr later at 48 hr. The magnitude of the peak response in these groups appeared to correlate with the duration of portal venous occlusion, with greatest increases occurring in those groups where portal stasis was most prolonged. The increase in liver mass for these groups was also delayed with respect to group 1 animals. The anticipated peak in ornithine decarboxylase levels was seen at 4 hr in group 1. The ornithine decarboxylase response in the other groups was disorganized, with delay of the recorded peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Identification of the loci of the collagen-associated Ehrlich chromogen in type I collagen confirms its role as a trivalent cross-link.

Collagenous peptides containing the Ehrlich chromogen (EC) were selectively isolated from a tryptic digest of bovine tendon by coupling to a diazotized polyacrylamide support. The isolated p-phenol-azo-EC peptides were purified and characterized by amino acid and sequence analyses. EC occurred in stoichiometric amounts in trimeric cross-linked chains originating from the known cross-link regions of type-I collagen. The major locus of the EC was alpha 2(I)Hyl-933 x alpha 1(I)Lys(Hyl)-9N x alpha 2(I)Lys(Hyl)-5N but it was also shown to occur at the loci alpha 1(I)Hyl-87 x alpha 1(I)Lys(Hyl)-16C x alpha 1(I)Lys(Hyl)-16C and alpha 1(I)Hyl-930 x alpha 1(I)Lys(Hyl)-9N x alpha 2(I)Lys(Hyl)-5N. After sequence analyses of the C-terminal helical cross-link region alpha 2(I)928-963, corrections are presented for residues 927, 930, 932 and 933 of the bovine alpha 2(I) chain. The collagen-associated EC is postulated to be a trisubstituted pyrrole formed by the reaction of the aldehyde form of a telopeptidyl lysine residue with a bifunctional keto amino cross-link. It is also proposed that when the telopeptidyl lysine residue is hydroxylated the above reaction will result in pyridinoline formation.

Amino Acid Sequence↗

Effect of total hepatectomy on coagulation and glucose homeostasis in the pig.

It has been suggested recently that patients with fulminant liver failure should be prepared for transplantation by early hepatectomy, yet the acute effects of removal of the liver upon the coagulation profile and certain hormones are not known. This study was conducted on totally hepatectomized pigs that survived up to 27 hr. Measurements were made of serum insulin, plasma glucagon (IRG and GLI), glucose, catecholamines, and the coagulation profile. The increase in serum insulin was directly related to levels of plasma glucose--there was a 100-fold increase in animals with plasma glucose levels greater than 400 mg/100 ml and none when blood glucose was less than 100 mg/100 ml. Plasma glucagon showed a sharp transient increase within 1 hr of hepatectomy and a slow rise thereafter with levels apparently unrelated to serum insulin or plasma glucose. There was a transient increase in plasma adrenaline but a sharp continuous increase in plasma norepinephrine. No changes of note occurred in the coagulation profile--even levels of fibrinogen only declined by 20% in 27 hr. The study has shown that early total hepatectomy is safe as far as changes in coagulation are concerned but changes in serum insulin and especially plasma norepinephrine may be of more significance.

Animals↗

How rapidly do hyperinsulinaemia and hyperglucagonaemia develop after portacaval shunting?

Elevation of serum insulin and plasma glucagon have been reported during and immediately after clinical and experimental liver transplantation and in patients with cirrhosis and surgically created or spontaneous portacaval shunts. There is controversy about the relative roles of portal diversion and impaired liver function in the genesis of these elevated levels of pancreatic hormones. End-to-side portacaval shunt was made in normal pigs which were fitted with catheters which allowed transhepatic sampling during and for 4 hr after the operation. Within 5 min of opening the shunt, there was a sixfold increase in portal venous insulin concentrations but hepatic clearance of insulin and the arterial concentration were unaltered. The increase in insulin was sustained for 2 hr. A twofold increase occurred within 1 hr in portal venous glucagon concentration which appeared to be predominantly of pancreatic origin and which continued for the 4 hr of the study. Hepatic glucose uptake did not occur after portacaval shunting despite levels of glucose elevated two-fold by iv infusion. There were no changes in aspartate aminotransferase, hepatic tissue energy charge, or total adenine nucleotides, suggesting that hepatic function was intact. It is concluded that portal diversion results in an increase in insulin and glucagon secretion and in the absence of hepatic uptake of glucose. This is a novel observation with relevance especially in liver transplantation when portal diversion for at least 1 hr forms part of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Energy charge as an indication of liver viability. A comparison of changes in livers that remained intact with those subjected to autografting.

As efforts to assess the viability of liver grafts continue, the recent description of noninvasive measurement by fluorimetry or magnetic resonance spectrometry of adenine nucleotides has brought energy charge into focus again as an index of viability. Many previous studies have been conducted in human donor livers that have clinical relevance but which cannot be standardized, or in rats in which the hepatic artery is not anastomosed. In the present study, pig livers were definitively rendered ischemic for 1 or 2 hr. In one group the livers were then revascularized (intact) while in the other, the livers were removed during the final 20-30 min of the ischemic period and were subjected to autograft. There was a marked difference in survival between the intact and the autograft groups. One hour of ischemia in the intact group was associated with survival comparable to that of autograft controls (8-100 days); 2 hr of ischemia caused shortened survival, ranging from 2 to 18 days. In the recipients of autografts, survival after 1 hr of ischemia ranged from 3 to 16 days; after 2 hr of ischemia no autograft recipient survived overnight. The energy charge returned to the preoperative level after 2 hr of ischemia in both intact and autograft groups. The concentrations remained depressed after 2 hr of ischemia in autografted animals, thus being associated with survival. However, the patterns of total adenine nucleotide and adenosine triphosphate were not always similar to those of energy charge. The concentrations of aspartate aminotransferase were similarly elevated in all ischemic groups irrespective of duration or subsequent survival. There was, however, a close association between euglobulin lysis times (ELT) and survival. In the autograft recipients of livers subjected to 2 hr of ischemia that did not survive overnight the ELT remained significantly shortened. It is concluded that adenine nucleotide metabolism is important as an index of viability, but that concentrations of total and individual adenine nucleotides and the energy change all need to be computed. There does, however, appear to be an absolute relationship between survival and euglobulin lysis time that would be clinically useful in patients undergoing liver transplantation or hepatic vascular exclusion.

Adenine Nucleotides↗

Transesophageal echocardiographic evaluation for mural thrombus following radiofrequency catheter ablation of accessory pathways.

BACKGROUND: Catheter ablation of accessory pathways (APs) provides a definitive therapy for patients with Wolff-Parkinson-White Syndrome. The reported incidence of thrombus formation on ablation-induced injuries with direct current shock varies from 0%-20% in animal studies. The purpose of this study was to determine the prevalence of mural thrombus following catheter ablation with radiofrequency current of accessory pathways in humans. METHODS AND RESULTS: Radiofrequency current (30-35 watts) was applied through a catheter electrode placed against the mitral or tricuspid annulus guided by catheter recordings of AP potentials. Transthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 95 of 111 patients, at 18 +/- 6 hours following catheter ablation. After ablation, no thrombus was identified at or near the ablation site in any patient. Two out of 95 patients had a mural thrombus at a remote site that was detected by TEE but not by TTE. No new wall motion abnormality was detected in any patient. No significant regurgitant valvular lesion was found in any patient. CONCLUSION: Intracardiac thrombus was not identified at the site of catheter ablation, possibly owing to the small lesions produced by radiofrequency energy and high blood flow normally present in those areas. However, patients may be at small risk for mural thrombus at a remote site from prolonged placement of catheters.

Adult↗

Transhepatic sampling during experimental porcine liver autotransplantation--its application to measurements of insulin, glucagon, and glucose.

Controversy still exists in the published literature about the need for administration of intravenous glucose during liver transplantation. The ability of the grafted liver to metabolize insulin and glucagon and the appropriateness of secretion of these hormones are addressed in the present study. Two groups of pigs received unstored liver autografts, one with free infusion of 10% glucose and the other with limited infusion of 2.5% glucose solution, while attempting to maintain plasma glucose levels less than 200 mg/100 ml. In these animals, irrespective of moderate or major hyperglycemia, serum insulin levels were appropriate for blood glucose concentrations. However, in both groups, plasma glucagon levels rose three- to fourfold more than preoperative values and were inappropriate. Although facilities for measurement of blood flow were not available, application of the technique of transhepatic sampling has revealed that hepatic handling of insulin seems to be unimpaired after autograft with limited ischemia. Pancreatic secretion of glucagon, however, appeared to increase during the period immediately after revascularization. It is suggested that transhepatic sampling methods may be used in experimental transplantation to elucidate the effects of storage for prolonged periods.

Animals↗

The effect of portal diversion upon function of the reticuloendothelial system and upon plasma fibronectin levels.

A previous publication suggested that for 9 weeks after portal diversion in dogs, there were no changes in reticuloendothelial function assessed by measurement of t1/2 or phagocytic index of reticuloendothelial test lipid emulsion. The present study was conducted in rats over 18 weeks. It was observed that the phagocytic index decreased and the t1/2 lengthened at 18 weeks after either portacaval shunt or portacaval transposition and that plasma levels of fibronectin were elevated four- or five-fold after either form of diversion, whilst only being elevated two-fold after sham operation. There was an increase in portacaval shunt rats in liver tissue distribution of administered lipid emulsion when tested between 6 and 12 weeks post-operatively which then returned towards normal. The activity in portacaval transposition and sham-operated rats was unaltered. These studies suggest that the delay in clearance of administered particles in portacaval shunt and portacaval transposition rats is related to the portal diversion rather than to altered blood flow and thus the finding is of relevance in patients with cirrhosis who also have significant portacaval shunting.

Animals↗

The group approach to living with stress: four years on.

In 1984, working as health visitors in the East Dorset Health Authority, we began to run courses to assist people with stress related conditions. The courses were based on counselling and group activity methods to encourage a positive health approach to solving the patients' problems. The initial results were very encouraging, and after completing three groups, we assessed our results which were reported in the Journal in January 1986 in a paper entitled 'the group approach to living with stress'. Requests for places in the stress groups have continued to be high, and courses are now a regular feature of the services offered at the health centre. This paper discusses the development of our stress management programmes, after a further three years experience, summarising our current methods, together with an assessment of the benefits achieved for patients. The study to determine the degree of improvement achieved, and whether this is maintained in the long term has been carried out with advice from Gerald Bennett, a clinical psychologist who also works for East Dorset Health Authority. Dr Bennett analysed the results of the study, and we are grateful to him for his considerable assistance in helping to present an objective view of our work, and in particular for the clear way in which he has written up the analysis, which has been embodied in this paper.

Counseling↗

Severe contact dermatitis due to nitroglycerin patches.

As shown by the two cases described, contact dermatitis due to nitroglycerin patches can be severe. Patients should be counseled to rotate application sites daily and report to the physician any signs of skin irritation.

Administration, Topical↗

Tubulo-interstitial disease in lupus nephritis. A morphometric study.

To test the hypothesis that immune complex deposition can mediate tubulo-interstitial damage in lupus nephritis, a correlative immunofluorescent (IF) and morphometric study of 43 renal biopsies from 39 patients with diffuse proliferative lupus glomerulonephritis was done. The point-counting method was used to determine the percentage of the cortical tubulo-interstitial system occupied by the mononuclear cell infiltrates (infiltrate index) and by the interstititum (interstitial index). The estimated amount of deposits containing immunoglobulin along tubular basement membranes and within the interstitium was expressed as a percentage of tubulo-interstitial volume. Interstitial cell infiltrates were present in 40 of the 43 biopsies and tubulo-interstitial immune deposits were noted in 29 biopsies. Linear regression analysis showed a statistically significant correlation between interstitial and infiltrate indices (r = 0.553, P less than 0.001). Correlations between (a) the extent of immune deposits and interstitial index (r = 0.239) and (b) immune deposits and infiltrate index (r = 0.280) were not significant. The results do not support the hypothesis that immune deposits mediate tubulo-interstitial injury and suggest that the damage is effected by the inflammatory cell infiltrates.

Adolescent↗

Comparative study of pancreatic polypeptide (PP) secretion, endocrine and exocrine function, and structural damage in chronic alcohol induced pancreatitis (CAIP).

The serum pancreatic polypeptide response to intravenous Boots secretin (1.5 U/kg), glucose tolerance, and insulin responses have been studied in 25 patients with chronic alcohol induced pancreatitis of varying severity, and these results compared with a secretin-pancreozymin test, and the structural damage noted on pancreatography. For the pancreatic polypeptide response 16 healthy subjects acted as controls. There was a marked reduction in pancreatic polypeptide response in patients with advanced structural changes of chronic alcohol induced pancreatitis compared with patients with minimal/moderate changes (p less than 0.01) and with healthy controls (p less than 0.05) although there was no difference between the latter two groups. Similarly, while the ratio of peak to mean basal pancreatic polypeptide concentration was also significantly reduced in patients with advanced changes compared with healthy controls (p less than 0.05) there was a marked degree of overlap in patients with lesser degrees of structural damage and control subjects. For all patients with chronic alcohol induced pancreatitis, however, there was a significant correlation between the pancreatic polypeptide response and each parameter of the standard secretin-pancreozymin test and with glucose tolerance and the integrated insulin response. We conclude therefore that while the secretin stimulated pancreatic polypeptide response correlates significantly with accepted tests of pancreatic structure and function, there is a significant degree of overlap in the response obtained in patients who have minimal/moderate damage and healthy controls making the test insufficiently sensitive for routine diagnostic use.

Adult↗

Correlates of attendance and compliance in the hypertension detection and follow-up program.

The Hypertension Detection and Follow-Up Program (HDFP) screened 159,000 individuals aged 30-69 years in 14 communities. Using a two-stage process, 10,940 hypertensives were randomized into two treatment groups. The first group was referred to community sources for care (RC), and the second received free Stepped Care (SC) treatment with extensive efforts to reduce the barriers to care. One year after enrollment, attendance showed 85% of SC participants active (white males 88%, white females 84%, black males 83%, and black females 84%). One year attendance rates ranged from a low of 84% for those with baseline DBP 90-104 mm Hg to a high of 90% for those with baseline DBP greater than or equal to 115 mm Hg. There was no apparent association with age, however, attendance exhibited a positive relationship with education, ranging from 83% for those completing less than high school to 94% for those with degrees beyond college. Life tables analyses demonstrated that race, sex, and blood pressure level compliance differences manifest themselves at the early stages of enrollment with little variation among participants once in the program. Pill counts correlated with percent with controlled blood pressure as well as serum potassium and calcium levels. Educational level was also a major predictor of drug adherence ranging from 74.7% to 89.7% (from under 7th grade to above college) having taken greater than or equal to 80% of their pills.

Actuarial Analysis↗

Characterisation and subunit structures of the vicilin storage proteins of pea (Pisum sativum L.).

Investigations of the vicilin fraction of the storage proteins of pea (Pisum sativum L.) have shown that its major components are a number of protein species of Mr 170 000. Convicilin (Mr 280 000, composed of 71 000-Mr subunits) is a separable component of this fraction. The vicilin proteins are composed principally of approximately equal to 50 000-Mr polypeptides, but also contain a number of smaller polypeptides. The sub-unit polypeptide composition of vicilin changes during seed development quantitatively and qualitatively. Vicilin sub-units have been shown to be synthesised as polypeptides of Mr approximately equal to 50 000 by means of pulse-labelling experiments in vivo, and synthesis of vicilin in vitro directed by mRNA, polysomes and microsomes extracted from pea cotyledons in cell-free translation systems. Polypeptides then undergo two distinct types of proteolytic modification: (a) co-translational removal of a small polypeptide (Mr less than 1000); (b) 'nicking' of polypeptide chains in assembled vicilin molecules, which occurs more than 4 h after their initial synthesis. The basic structure of the vicilin molecule is thus a multimer, possibly a trimer, of approximately equal to 50 000-Mr subunits. The heterogeneity of the initially synthesised 50 000-Mr subunits accounts not only for the several different 50 000-Mr polypeptides found in vicilin, but also for the range of minor polypeptides, since the 'nicking' points will differ among subunits. It also accounts for the observed partial separation of vicilin into different molecular species, since different subunit combinations will give rise to molecules with different properties. Vicilin is also glycosylated and this is a source of further variation.

Chemical Phenomena↗

In vitro release of cholecystokinin octapeptide-like immunoreactivity from rat brain synaptosomes.

Enriched synaptosome fractions prepared by differential centrifugation and ultracentrifugation of homogenates of rat cortex, striatum, thalamus and hypothalamus contained over 65% of the total immunoreactive cholecystokinin octapeptide (CCK-8) in each area. A calcium-dependent release of immunoreactive CCK-8 from these fractions in vitro in response to 2 depolarizing stimuli (60 mM KCl and 75 microM veratrine) has been demonstrated. Released CCK-8 immunoreactivity showed parallelism when dilutions were compared with the CCK-8 dose-response curve and eluted similarly to synthetic CCK-8 on Sephadex G-50 superfine chromatography. These results provide further evidence for a neurotransmitter or neuromodulator role for CCK-8 in brain.

Animals↗