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K Baxter

Publications and source records attributed to K Baxter.

At least 37 records · Page 2Linked to original sources
PubMed1998

Protein model determination from crystallographic data.

Crystallographic studies play a major role in current efforts towards protein structure determination. However, despite recent advances in computational tools for molecular modeling and graphics, the task of constructing a model of the tertiary structure of a protein from experimental data remains complex and time-consuming, requiring extensive expert intervention. This paper describes an approach to protein model determination that incorporates crystallographic data, along with sequence data. A model is represented as an annotated graph that traces the backbone and side chains for a protein. The proposed approach incorporates numerical techniques that are applied to construct and analyze an electron density map for a unit cell of a crystal. The purpose of this work is to advance the ability to discern meaningful features of protein structure through the use of topological analysis of the relative density. Experimental results, which demonstrate the viability of the approach, are reported.

Computer Graphics↗
PubMed1998

Modified technique of abdominal heart transplantation in the rat.

BACKGROUND: A rapid, reproducible screening model is essential for evaluation of novel preservation regimens. This study describes a modification of the abdominal rat heart transplantation model reducing anastomosis time and allowing quantitative assessment for 7 days. METHODS: Hearts, obtained from inbred Dark Agouti rats, were arrested and stored in cold colloid-free University of Wisconsin solution until transplantation. The Dark Agouti recipient underwent a left nephrectomy. The donor left common carotid artery was anastomosed to the recipient left renal artery with a "sleeve" anastomosis. The "cuffed" donor left pulmonary artery was inserted into the left renal vein. Study 1 examined continuing viability by daily palpation and morphologic study by examination of hematoxylin and eosin-stained sections on days 4 or 90. Study 2 examined quantitative assessment of cardiac function in the anesthetized recipient. The model was further modified by introducing an externalized, fluid-filled, balloon-tipped catheter into the left ventricle. RESULTS: The new technique allowed vascular anastomoses to be completed in 5 to 12 minutes, minimizing rewarming of the graft. Most (25 of 28) grafts beat for 90 days, and 80% of these showed normal structure. There was evidence of myocyte damage or arteriosclerosis in 5 of 25 at 90 days and in 4 of 17 at 4 days. Cardiac function parameters were similar in consecutive runs and did not change between days 1 and 7. CONCLUSION: This abdominal rat heart transplant model is quick and easy to perform, minimizes warm ischemia, and is suitable for both short- and long-term studies. Quantitative parameters, assessed by use of an in situ intraventricular balloon-tipped catheter, are reproducible and maintained for 7 days.

Animals↗
PubMed1997

Long-term follow-up in outpatient clinics. 1: The view from general practice.

BACKGROUND: Nearly three-quarters of patients seen in specialist outpatient clinics in England are in follow-up. It has been suggested that the care of many of these patients could be transferred to general practice. OBJECTIVES: We aimed to estimate the proportion of patients in general practice who are in long-term outpatient follow-up, and to identify GPs' perspectives on the appropriateness and implications of the discharge of their patients to primary care. METHOD: Prevalence data were collected by identifying correspondence from outpatient clinics to GPs in four Manchester practices (population 29,000). GPs were asked to assess the suitability for discharge of their patients who were seen in medical outpatient clinics. Semi-structured interviews were carried out with 15 of these GPs, and with 11 GPs who had patients recently discharged from medical clinics. RESULTS: At least 4.5% of the practice populations were in long-term outpatient follow-up (median duration 25 months). These patients had consulted their GP a median of seven times during the previous year. GPs were willing to take over the care of 48% of patients in medical clinics, and in many cases did not expect that this would lead to an increase in their workload. Some resource needs were identified in general practice, and improvements to the process of discharge were suggested. CONCLUSION: The need for continued follow-up in outpatient clinics should be reviewed. Many patients could be discharged without increasing GPs' workload. For more complex cases, additional resources may be needed to provide co-ordinated care within general practice. When patients are discharged, GPs need information quickly and need access to specialist advice for their patients when necessary without long delays.

Ambulatory Care Facilities↗
PubMed1997

Double-blind, randomized study of the effect of cisapride on gastric emptying in critically ill patients.

OBJECTIVES: To investigate the absorption of the gastrokinetic drug, cisapride, and effect of cisapride on gastric emptying in critically ill patients; and to assess the usefulness of clinical signs of gastric emptying. DESIGN: Prospective, randomized, controlled study. SETTING: Medical/surgical/trauma intensive care unit (ICU) in a university hospital. PATIENTS: Twenty-seven consecutively enrolled patients, aged 18 to 65 yrs, with normal hepatic and renal biochemistry who were not receiving enteral nutrition and who had no contraindications to enteral nutrition. These patients were expected to stay in the ICU for at least 4 days. INTERVENTIONS: Patients were randomized to receive either placebo or rectal cisapride, 60 mg initially followed by two doses of 30 mg at 8-hr intervals. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was estimated, using acetaminophen absorption on day 1 of the study. Placebo or cisapride was administered and a second acetaminophen absorption test for gastric emptying was carried out on day 2,24 hrs after the first test. Four patients were excluded because of incomplete data. Statistical analysis was performed, using the area under the acetaminophen absorption curve from 0 to 60 mins as the primary measure of gastric emptying. There was no significant change in the area under the acetaminophen absorption curve from 0 to 60 mins from day 1 to day 2 in patients who received placebo or cisapride. Using the combination of the time to maximum acetaminophen concentration (< or = 30 mins) with a maximum concentration (> 12 mg/L) to define "normal" emptying, on day 1, four of the 11 placebo patients had the "normal" gastric emptying, and by day 2, five patients fulfilled this criterion. Before administration of cisapride, four of the 12 patients fulfilled this criterion, whereas nine fulfilled the criterion after receiving cisapride. There was a large variation in gastric emptying from day 1 to day 2; a power calculation suggests that approximately 150 patients would have to be studied to determine the effect of cisapride. There was no correlation between gastric emptying and the volume of gastric aspirate or the presence of bowel sounds. Plasma cisapride concentrations 4 hrs after the third dose, during the second acetaminophen absorption test, averaged 53 ng/mL (range 20 to 111). CONCLUSIONS: Rectal cisapride in the dose given achieved average plasma concentrations similar to those concentrations achieved in healthy subjects after 30 mg of cisapride rectally. There is a large variation in gastric emptying from one day to the next and large numbers of patients are required to determine if cisapride administration improves early gastric emptying in critically ill patients. The volume of gastric aspirate and the presence of bowel sounds do not correlate with gastric emptying.

Administration, Rectal↗
PubMed1996

From electron density and sequence to structure: integrating protein image analysis and threading for structure determination.

This paper presents a computational methodology for integrating techniques from protein image interpretation and protein sequence threading, applied to the problem of structure determination from experimental X-ray crystallographic electron density maps. In the proposed architecture, image interpretation of an electron density map produces candidate structural segments; threading is applied to evaluate these hypothesized segments and thus to constrain the set of possible image interpretations. We present the results of experiments designed to test ability of the threading module to discriminate between correct and incorrect alignments of protein sequences onto structural models derived from protein image interpretation. The long-term goal of this research is to improve our ability to determine protein structures from crystallographic data, and to further our understanding of the underlying relationship between sequence and structure.

Algorithms↗
PubMed1995

The effect of ureteric stenting on the function and morphology of long-term rat renal allografts.

In the development of a reliable model for chronic rejection in rat renal allografts, the effect of modifying the ureteric anastomosis was tested. Rats, tolerized by pretreatment with two donor blood transfusions under Cyclosporin A, received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long-term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long-term allografts.

Animals↗
PubMed1995

A reproducible model of chronic rejection in rat renal allografts.

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 66% after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.

Animals↗
PubMed1994

Blockade by ifenprodil of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N-methyl-D-aspartate receptor antagonist actions.

1. The block by ifenprodil of voltage-activated Ca2+ channels was investigated in intracellular free calcium concentration ([Ca2+]i) evoked by 50 mM K+ (high-[K+]o) in Fura-2-loaded rat hippocampal pyramidal neurones in culture and on currents carried by Ba2+ ions (IBa) through Ca2+ channels in mouse cultured hippocampal neurones under whole-cell voltage-clamp. The effects of ifenprodil on voltage-activated Ca2+ channels were compared with its antagonist actions on N-methyl-D-aspartate- (NMDA) evoked responses in the same neuronal preparations. 2. Rises in [Ca2+]i evoked by transient exposure to high-[K+]o in our preparation of rat cultured hippocampal pyramidal neurones are mediated predominantly by Ca2+ flux through nifedipine-sensitive Ca2+ channels, with smaller contributions from nifedipine-resistant, omega-conotoxin GVIA-sensitive Ca2+ channels and Ca2+ channels sensitive to crude funnel-web spider venom (Church et al., 1994). Ifenprodil (0.1-200 microM) reversibly attenuated high-[K+]o-evoked rises in [Ca2+]i with an IC50 value of 17 +/- 3 microM, compared with an IC50 value of 0.7 +/- 0.1 microM for the reduction of rises in [Ca2+]i evoked by 20 microM NMDA. Tested in the presence of nifedipine 10 microM, ifenprodil (1-50 microM) produced a concentration-dependent reduction of the dihydropyridine-resistant high-[K+]o-evoked rise in [Ca2+]i with an IC50 value of 13 +/- 4 microM. The results suggest that ifenprodil blocks Ca2+ flux through multiple subtypes of high voltage-activated Ca2+ channels. 3. Application of the polyamine, spermine (0.25-5 mM), produced a concentration-dependent reduction of rises in [Ca2+]i evoked by high-[K+]o. The antagonist effects of ifenprodil 20 micro M on high-[K+]0-evoked rises in [Ca2+]. were attenuated by spermine 0.25 mM but not by putrescine 1 or 5 mM. In contrast,spermine 0.1 mM increased rises in [Ca2+]i evoked by NMDA and enhanced the ifenprodil (5 micro M) block of NMDA-evoked rises in [Ca2+]i.4. Similar results were obtained in mouse cultured hippocampal pyramidal neurones under whole-cell voltage-clamp. Ifenprodil attenuated both the peak and delayed whole-cell IB. with an IC% value of 18 +/- 2 micro M, whilst it attenuated steady-state NMDA-evoked currents with an IC50 of 0.8 +/- 0.2 micro M. Block of IBa by ifenprodil 10 JaM was rapid in onset, fully reversible and occurred without change in thecurrent-voltage characteristics of Ba. The ifenprodil block of IBa was enhanced on membrane depolarization and was weakly dependent on the frequency of current activation. Spermine 0.1 mM potentiated control NMDA-evoked currents but attenuated IB,. In agreement with the microspectrofluorimetric studies, co-application of spermine produced a small enhancement of the inhibitory effect of ifenprodil 10 micro M on NMDA-evoked responses whereas the reduction of I4 by ifenprodil 10 micro M in the presence of spermine was less than expected if the inhibitory effects of ifenprodil and spermine on IBa were simply additive.5. The results indicate that ifenprodil blocks high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones. Although the Ca2+ channel blocking actions of ifenprodil are observed at higher concentrations than those associated with NMDA antagonist activity, Ca2+ channel blockade may contribute, at least in part, to the established neuroprotective and anticonvulsant properties of the compound.

Animals↗
PubMed1994

Segmentation and interpretation of 3D protein images.

The segmentation and interpretation of three-dimensional images of proteins is considered. A topological approach is used to represent a protein structure as a spanning tree of critical points, where each critical point corresponds to a residue or the connectivity between residues. The critical points are subsequently analyzed to recognize secondary structure motifs within the protein. Results of applying the approach to ideal and experimental images of proteins at medium resolution are presented.

Computer Simulation↗
PubMed1993

Development of chronic injury and nature of interstitial infiltrate in a model of chronic renal allograft rejection.

A model of chronic renal rejection in the Dark-Agouti to Albino-Surgery rat combination is described. In a number of cases, the original allograft was replaced by a second Dark-Agouti allograft. Seventy-five percent of rats experienced early episodes of rejection that subsided spontaneously. Second allografts had better initial renal function. Variable degrees of tubular atrophy, interstitial fibrosis, vascular damage, glomerulosclerosis, deposition of humoral mediators, and mononuclear leukocyte infiltrate were observed in all long-term allografts. Chronic damage increased with time, and was less severe in second allografts. At 5 days, total interstitial infiltrate was similar to that seen in unmodified rejection, but there was a significant increase in CD4+ cells and a decrease in ED2 and IL-2R expression. Subsequently, the total interstitial infiltrate decreased with time, although it remained significantly higher than in isografts and residual kidneys from uninephrectomized rats. No significant decrease over time was seen in numbers of CD4+ and CD45RC+ cells. The latter had a marked focal distribution after 100 days. Total leukocyte infiltrate was similar in original and second allografts, but there were changes in the proportions of leukocyte subpopulations, including significantly lower numbers of CD45RC+ cells in the latter. The persistence of CD45RC+ cells throughout the course of chronic rejection and their lower numbers in the second allografts favors a role for these cells in the development of chronic injury. The model of chronic renal allograft rejection characterized in this study will be valuable in further studies of the mechanisms of injury in this pathology.

Animals↗
PubMed1993

Do diagnosis related groups separate the case-mix of a specialist children's hospital and a paediatric unit in a general hospital?

The ability of diagnosis related groups (DRG) and refinement diagnosis related groups (RDRG) to measure differences in case-mix was investigated using discharge data for patients < 18 years of age from three specialist children's hospitals and four district hospitals. While the three children's hospitals each had a greater percentage of RDRG for more complex patients, only one children's hospital had more complex patients based on DRG and RDRG cost weights and on the percentage of diagnoses per discharge. Cost weights based on USA practices may be inappropriate in Australia, and Australian weights will be necessary for firm conclusions. Refinement diagnosis related groups with appropriate cost weights may be acceptable measures of case-mix in specialist children's hospitals, but they have inherent limitations for paediatric patients in that many complex paediatric patients are ill very seriously with one disorder, whereas complex adult patients usually have secondary diagnoses and secondary procedures. Moreover, no DRG version developed in the US will be suitable for use in Australia unless it takes account of medical costs and transfer practice.

Adolescent↗
PubMed1993

Hospitalisation of children under 15 years in Victoria.

OBJECTIVE: To determine whether the separation rate from the hospital for children aged 0-15 years in Victoria was higher for those resident in the country area of the State in comparison with the metropolitan area and, if it was, to investigate possible explanations. DESIGN: Discharge data from all public hospitals in Victoria for children aged 0-15 years for the financial years 1988-89, 1989-90 and 1990-91 were analysed with detailed analysis being done on the 1990-91 data set. Discharge rates were determined according to the local authority area of residence. Patients were grouped according to Diagnosis Related Groups (DRGs) version 5. RESULTS: Children living in the country area showed a separation rate of 50 per cent greater than that for the metropolitan area. Separation rates for local authority areas were remarkably constant over the three years. Country local authority areas with the highest separation rates had separation rates for asthma and bronchitis (DRG 98), almost four times that of metropolitan residents, and for otitis media and upper respiratory infection (URI), a rate almost ten times that of metropolitan residents. CONCLUSION: It is suggested that variation in medical practice was the most likely explanation for the observed differences.

Adolescent↗