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Biomedical subjects

P Rutherford

Publications and source records attributed to P Rutherford.

15 recordsLinked to original sources
PubMed2005

Protein substitute for children and adults with phenylketonuria.

BACKGROUND: Phenylketonuria is an inherited disease characterised by an absence or deficiency of the enzyme phenylalanine hydroxylase. The aim of treatment is to lower blood phenylalanine concentrations to prevent developmental delay. Current treatment is based on a low phenylalanine diet in combination with a protein substitute (mixtures of amino acids free from or low in phenylalanine). Guidance regarding the dosage and distribution of this protein substitute, over a 24-hour period, is unclear and there is variation in recommendation between treatment centres. OBJECTIVES: To assess in children and adults with phenylketonuria, who are adhering to a low phenylalanine diet, the benefits and adverse effects of protein substitute, its dosage and distribution of dose. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted manufacturers of the phenylalanine-free and low phenylalanine protein substitutes for any data from published and unpublished randomised controlled trials. Date of the most recent search of the Group's Trials Register: August 2005. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing: any dose of protein substitute with no protein substitute; an alternative dosage; or the same dose, but given as frequent small doses throughout the day compared with the same total daily dose given as larger boluses less frequently. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed trial quality. MAIN RESULTS: The searches identified 20 trials, of which one, including a total of 28 participants, was eligible for inclusion in the review. This was a two-phase trial, with only phase one being a randomised controlled trial. As data from both phases were combined in the analysis presented in the published paper, we are currently unable to include any data from the randomised controlled trial in the analysis of this review. AUTHORS' CONCLUSIONS: No conclusions could be made about the short- or long-term use of protein substitute in phenylketonuria due to the lack of adequate trial data. A randomised controlled trial is needed to investigate the use of protein substitute in phenylketonuria. Until further evidence is available current practice in the use of protein substitute should continue to be observed and monitored with care.

Adult↗
PubMed2003

Effect of introducing the Modified Early Warning score on clinical outcomes, cardio-pulmonary arrests and intensive care utilisation in acute medical admissions.

The effects of introducing Modified Early Warning scores to identify medical patients at risk of catastrophic deterioration have not been examined. We prospectively studied 1695 acute medical admissions. All patients were scored in the admissions unit. Patients with a Modified Early Warning score > 4 were referred for urgent medical and critical care outreach team review. Data was compared with an observational study performed in the same unit during the proceeding year. There was no change in mortality of patients with low, intermediate or high Modified Early Warning scores. Rates of cardio-pulmonary arrest, intensive care unit or high dependency unit admission were similar. Data analysis confirmed respiratory rate as the best discriminator in identifying high-risk patient groups. The therapeutic interventions performed in response to abnormal scores were not assessed. We are convinced that the Modified Early Warning score is a suitable scoring tool to identify patients at risk. However, outcomes in medical emergency admissions are influenced by a multitude of factors and so it may be difficult to demonstrate the score's benefit without further standardizing the response to abnormal values.

Aged↗
PubMed2001

Dietary treatment for familial hypercholesterolaemia.

BACKGROUND: Familial hypercholesterolaemia is an inherited disorder characterised by a raised blood cholesterol, the presence of xanthomatosis and premature ischaemic heart disease. The aim of treatment is the reduction of blood LDL cholesterol concentrations in order to reduce the risk of ischaemic heart disease. Current treatment is based on a cholesterol lowering diet alone or in combination with drug therapy. Many of the drugs found to be effective in treating adults with this disease are not licensed for use in children, therefore diet is the main treatment of children with familial hypercholesterolaemia. In addition to the cholesterol-lowering diet, several other dietary interventions have been suggested and consensus has yet to be reached on the most appropriate dietary treatment for children and adults with familial hypercholesterolaemia. OBJECTIVES: To examine the evidence that in children and adults with familial hypercholesterolaemia, a cholesterol lowering diet is more effective at lowering cholesterol and reducing incidence of ischaemic heart disease than no intervention or than other dietary interventions. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Trials Register, a specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Additional studies were identified from handsearching the Journal of Inherited Metabolic Disease (from inception, 1978 to 2000) and from the reference lists of identified studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), both published and unpublished, where a cholesterol lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention. Trials which include patients with familial hypercholesterolaemia alongside patients with non-familial hypercholesterolaemia were only included if the group of familial patients was well defined and the results for these patients were available. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trial eligibility and methodological quality and one reviewer extracted the data, with independent verification of data extraction by a colleague. MAIN RESULTS: Only short term outcomes could be assessed in this review due to the length of the five eligible studies. Compliance to treatment, quality of life, mortality and evidence of ischaemic or atheromatous disease were not assessed in the studies identified. No differences were found between the cholesterol-lowering diet and all other diets for all of the short term outcomes assessed. REVIEWER'S CONCLUSIONS: No conclusions can be made about the effectiveness of the cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, due to the lack of adequate data. A large, parallel, randomised controlled trial is needed to investigate the effectiveness of the cholesterol-lowering diet and other dietary interventions for FH. It is also possible that data from trials including subjects with both familial and non-familial hypercholesterolaemia could alter the results of future updates of this review and until further evidence is available current dietary treatment of FH should continue to be observed and monitored with care.

Adult↗
PubMed2001

Validation of a modified Early Warning Score in medical admissions.

The Early Warning Score (EWS) is a simple physiological scoring system suitable for bedside application. The ability of a modified Early Warning Score (MEWS) to identify medical patients at risk of catastrophic deterioration in a busy clinical area was investigated. In a prospective cohort study, we applied MEWS to patients admitted to the 56-bed acute Medical Admissions Unit (MAU) of a District General Hospital (DGH). Data on 709 medical emergency admissions were collected during March 2000. Main outcome measures were death, intensive care unit (ICU) admission, high dependency unit (HDU) admission, cardiac arrest, survival and hospital discharge at 60 days. Scores of 5 or more were associated with increased risk of death (OR 5.4, 95%CI 2.8-10.7), ICU admission (OR 10.9, 95%CI 2.2-55.6) and HDU admission (OR 3.3, 95%CI 1.2-9.2). MEWS can be applied easily in a DGH medical admission unit, and identifies patients at risk of deterioration who require increased levels of care in the HDU or ICU. A clinical pathway could be created, using nurse practitioners and/or critical care physicians, to respond to high scores and intervene with appropriate changes in clinical management.

Adolescent↗
PubMed2001

Adequacy targets can be met in anuric patients by automated peritoneal dialysis: baseline data from EAPOS.

OBJECTIVE: Conventional continuous ambulatory peritoneal dialysis (CAPD) in patients without residual renal function and with high solute transport is associated with worse clinical outcomes. Automated peritoneal dialysis (APD) has the potential to improve both solute clearance and ultrafiltration in these circumstances, but its efficacy as a treatment modality is unknown. The European Automated Peritoneal Dialysis Outcomes Study (EAPOS) is a 2-year, prospective, European multicenter study designed to determine APD feasibility and clinical outcomes in anuric patients. The present article describes the baseline data for patients recruited into the study. DESIGN: All PD patients treated in the participating centers were screened for inclusion criteria [urinary output < 100 mL/24 h, or residual renal function (RRF) < 1 mL/min, or both]. After enrollment, changes were made to the dialysis prescription to achieve a weekly creatinine clearance above 60 L per 1.73 m2 and an ultrafiltration rate above 750 mL in 24 hours. SETTING: The study is being conducted in 26 dialysis centers in 13 European countries. BASELINE DATA COLLECTION: The information collected includes patient demographics, dialysis prescription, achieved weekly creatinine clearance, and 24-hour ultrafiltration (UF). RESULTS: The study enrolled 177 anuric patients. Median dialysis duration before enrollment was 22.5 months (range: 0-285 months). Mean solute transport measured as the dialysate-to-plasma ratio of creatinine (D/P(Cr)) was 0.74 +/- 0.12. Patients received APD for a median of 9.0 hours overnight (range: 7-12 hours) using a median of 11.0 L of fluid (range: 6-28.75 L). Median daytime volume was 4.0 L (range: 0.0-9.0 L). Tidal dialysis was used in 26 patients, and icodextrin in 86 patients. At baseline, before treatment optimization, the weekly mean total creatinine clearance was 65.2 +/- 14.4 L/1.73 m2, with 105 patients (60%) achieving the target of more than 60 L/1.73 m2. At baseline, 81% of patients with high transport, 69% with high-average transport, and 40% with low-average transport met the target. At baseline, 70% of patients with a body surface area (BSA) below 1.7 m2, 60% with a BSA of 1.7-2.0 m2, and 56% with a BSA above 2.0 m2 achieved 60 L/1.73 m2 weekly. Median UF was 1090 mL/24 h, and 75% of patients achieved the UF target of more than 750 mL/24 h. CONCLUSION: This baseline analysis of anuric patients recruited into the EAPOS study demonstrates that a high proportion of anuric patients on APD can achieve dialysis and ultrafiltration targets using a variety of regimes. This 2-year follow-up study aims to optimize APD prescription to reach predefined clearance and ultrafiltration targets, and to observe the resulting clinical outcomes.

Adult↗
PubMed2000

Dietary interventions for phenylketonuria.

BACKGROUND: Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap however the diet is very restrictive and unpalatable and can be difficult to follow. Whether the diet can be relaxed or discontinued during adolescence or should be continued for life remains a contraversial issue which we aim to address in this review. OBJECTIVES: To assess the effects of a phenylalanine restricted diet commenced early in life for patients with phenylketonuria. To assess the possible adverse effects of relaxation or termination of the diet on intelligence, neuropsychological outcomes and mortality, and to assess the effect on growth, nutritional status and eating behaviour and quality of life. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Trials Register which is a specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Additional studies were identified from handsearching the Journal of Inherited Metabolic Disease (from inception, 1978 to 1998). The manufacturers of dietary products for phenylketonuria were also contacted. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised controlled trials comparing a phenylalanine restricted diet to either relaxation or termination of dietary restrictions in patients with phenylketonuria. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trial eligibility, methodological quality and extracted the data. MAIN RESULTS: Four studies were included in this review including a total of 251 patients. Few statistically significant differences were found between treatment and comparison groups for any of the outcomes apart from for blood phenylalanine level and intelligence quotient. Blood phenylalanine levels were significantly lower in those subjects with phenylketonuria following a phenylalanine restricted diet compared to those on a less restricted or relaxed diet (weighted mean difference at three months -672.203, 95% Confidence interval (CI) -813.799 to - 530.608). Intelligence quotient was significantly higher in subjects who continued on the phenylalanine restricted diet compared to those who terminated the diet (weighted mean difference after 12 months -5.00, 95% CI -9.595 to -0.405). However this is based on the results of only one study. REVIEWER'S CONCLUSIONS: The results of non-randomised studies have concluded that a phenylalanine restricted diet is effective in reducing blood phenylalanine levels and improving intelligence quotient and neuropsychological outcome. No randomised controlled trials have assessed the effect of a phenylalanine restricted diet versus no dietary restrictions from diagnosis. In view of evidence from non-randomised studies, such a trial would now be unethical and it is recommended that phenylalanine restricted diet should be commenced at the time of diagnosis. There is uncertainty about the precise level of phenylalanine restriction and when, if ever, the diet should be relaxed. These questions should be addressed by randomised controlled trials with careful consideration given to which patients to include.

Humans↗
PubMed2000

Tyrosine supplementation for phenylketonuria.

BACKGROUND: Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap however the diet is very restrictive and unpalatable and can be difficult to follow. A deficiency of the amino acid tyrosine has been suggested as a cause of some of the neuropsychological problems exhibited in PKU. Therefore, this review aims to assess the efficasy of tyrosine supplementation for phenylketonuria. OBJECTIVES: To assess the effects of tyrosine supplementation alongside or instead of phenylalanine restricted diet for patients with phenylketonuria who commenced on diet at diagnosis and either continued on the diet or relaxed the diet later in life. To assess the evidence that tyrosine supplementation alongside, or instead of phenylalanine restricted diet improves intelligence, neuropsychological performance, growth and nutritional status, mortality rate and quality of life. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Trials Register which is a specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Additional studies were identified from handsearching the Journal of Inherited Metabolic Disease (from inception, 1978, to 1998). The manufacturers of prescribable dietary products used in the treatment of phenylketonuria were also contacted for further references. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudo-randomised trials investigating the use of tyrosine supplementation versus placebo in patients with phenylketonuria in addition to, or instead of, a phenylalanine restricted diet. Patients treated for maternal phenylketonuria were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trial eligibility, methodological quality and extracted the data. MAIN RESULTS: Two trials were included with a total of 47 patients. The blood tyrosine concentrations were significantly higher in the patients receiving tyrosine supplements than those in the placebo group (weighted mean difference 22.526, 95% Confidence interval (CI) 12.182 - 32.870). No significant differences were found between any of the other outcomes measured. REVIEWER'S CONCLUSIONS: From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice. Further randomised controlled studies are required to provide further evidence.

Dietary Supplements↗
PubMed1999

Conditional transformation of rat embryo fibroblast cells by a cyclin D1-cdk4 fusion gene.

Cyclin D1 gene overexpression is a frequent event in a number of human cancers. These observations have led to the suggestion that cyclin D1 alterations might play a role in the etiology of cancer. This possibility is supported by the finding that transfection of mammalian cells with cyclin D1 can accelerate progression through the G1 phase of the cell cycle. Moreover, cyclin D1 can function as an oncogene by cooperating with activated Ha-ras to transform primary rat embryo fibroblasts (REFs). In addition, cyclin D1 transgenics develop hyperplasia and neoplasia of the thymus and mammary gland. We have constructed a novel fusion gene consisting of full-length human cyclin D1 and cdk4 genes. This fusion gene was expressed in insect cells and the fusion protein was shown to be enzymatically active. The fusion gene was expressed in mammalian cells under the control of tet-repressor. This fusion gene immortalized primary REFs, and cooperated with activated Ha-ras to transform primary REFs, in terms of anchorage-independent growth in vitro and formation of tumors in vivo. Utilizing a tet-regulated gene expression system, we have shown that proliferation of stably transfected primary REFs in vitro and in vivo is dependent on the continued expression of the cyclin D1-cdk4 fusion gene. These cell lines could be useful in the discovery of novel cancer therapeutics to modulate cyclin D1.cdk4 activity.

Animals↗
PubMed1997

Sodium-hydrogen exchange isoform expression in blood cells: implications for studies in diabetes mellitus.

There have been many reports of increased Na-H exchange (NHE) activity in the peripheral blood cells (erythrocytes, lymphocytes and platelets) of patients with diabetes mellitus compared to nondiabetic controls. This raised NHE activity has been hypothesized to reflect increased NHE activity in kidney and vascular smooth muscle. Raised NHE activity in these tissues could play a pathophysiological role in mediating hypertension, vascular smooth muscle cell proliferation and progressive renal impairment. It is now known that there are at least five NHE isoforms, but a specific study examining expression of NHE isoforms in peripheral blood cells has not been reported. This study used specific antisera to NHE isoforms 1, 3 and 4 to examine NHE expression by immunoblot analysis. Erythrocyte, lymphocyte and platelet membranes from both rabbit and rat were separated by standard methods. A monoclonal antibody to NHE-1 reacted with a 100-110 kDa band in rabbit and rat platelets and lymphocytes (identical to that observed in basolateral-enriched renal cortical vesicles) and a 100 kDa band in rabbit and rat erythrocytes. In both species, the intensity of the staining was greatest in platelet membranes. A polyclonal antibody to NHE-3, the isoform present on the apical membranes of renal proximal tubule, showed no evidence of staining in any of the peripheral blood cell preparations. Similarly there was no evidence of expression of NHE-4 in the peripheral blood cell preparations. Peripheral blood cells express NHE-1, which likely accounts for amiloride-sensitive Na-H exchange in these cells, playing a role in cell volume and pH regulation. However, there is no evidence that there is expression of NHE-3 or NHE-4 in peripheral blood cells. These data have implications for studies in hypertension and diabetes mellitus which measure peripheral blood cell Na-H exchange and hypothesize regarding a direct pathophysiological role for this increased activity.

Animals↗
PubMed1987

Characterization of monoclonal antibodies against human sperm antigens by immunoassays including sperm function assays and epitope evaluation.

Fifteen monoclonal antibodies (MAbs) raised against human sperm cells were evaluated for reactions against human sperm by indirect immunofluorescence, immunocytochemistry, agglutination, complement-dependent immobilization, cervical mucus penetration, and hamster egg penetration assays. The MAbs were analyzed for specificity by immunofluorescent reactions with peripheral blood lymphocytes and sperm and classified into three main groups based on regional staining, ie, acrosome, plasma membrane, or tail. One MAb (218) bound to the sperm neck. Three MAbs, (80, 85, and HS-126) were found to react with lymphocytes. Three of five acrosome-reactive MAbs (11, 63, 106), two of five tail-staining MAbs (97, HS-30), and the neck reactor (218) showed significant to highly significant inhibition of sperm penetration of eggs but without significant effects on sperm agglutination, immobilization, or the mucus penetration assay. The three non-specific MAbs gave strong plasma membrane reactions in the agglutination and immobilization assays and also caused highly significant inhibition of sperm penetration of both cervical mucus and zona-free ova. Preliminary analysis of the complementary antigens suggested that epitopes reacting with MAbs 33 (acrosome) and 85 (plasma membrane) were carbohydrate chains on glycoproteins. Three of five MAbs recognizing tail antigen, the neck-staining MAb, and the non-specific MAb (HS-126) appeared to be reactive against glycolipid moieties. Seven of the 12 specific MAbs also reacted in indirect immunofluorescence with mouse and rabbit sperm in patterns similar to those observed with human sperm.

Animals↗
PubMed1984

Munchausen's syndrome by proxy (child abuse) presenting as apparent autoerythrocyte sensitization syndrome: an unusual presentation of Polle syndrome.

Munchausen's syndrome was initially described in 1951. It has become increasingly recognized since that time. Recently, Munchausen's syndrome by proxy or Polle syndrome has been described. In this disease entity, a parent causes a factitious disease in a child. The disease may require extensive medical testing and the result may even be death. A wide variety of presentations of Polle syndrome have been reported including cardiac arrest, recurrent sepsis, and factitious bleeding. Autoerythrocyte sensitization, a syndrome of spontaneous purpura, was initially described in 1955. The diagnostic test described is intradermal injection of autologous blood which produces an area of painful purpura. The syndrome is therefore postulated to be due to hypersensitivity in the patient's own RBCs. The majority of patients with autoerythrocyte sensitization have had psychiatric disorders and the symptoms have improved only with psychotherapy. An infant who had a clinical picture of autoerythrocyte sensitization and who was later found to be a victim of Polle syndrome is reported.

Autoimmune Diseases↗
PubMed1981

Clopenthixol decanoate in schizophrenia.

Clopenthixol decanoate was given to 20 chronic schizophrenic patients for 11 months in doses ranging from 100 mg initially up to 1000 mg 3-weekly subsequently, according to clinical response and the occurrence of adverse effects. A further 3 patients received the depot injections for periods of 6 to 9 months. Improvement in individual symptoms was rated on a 4-point scale. Unwanted effects were recorded on a checklist and routine biochemical and haematological tests were carried out at the beginning and end of the treatment period. There were highly significant improvements in the mean overall symptom score and in the 5 single symptom scores (hallucinations, delusions, depression, aggressive behaviour and non-aggressive behaviour disturbance). The 2 'negative' symptoms of apathy and social withdrawal showed improvement up to 16 weeks but not at 11 months. The incidence of depression was less at the end of the study than at the time fo entry. Three patients stopped the drug after the sixth month because of extrapyramidal symptoms (2) or drowsiness (1). Three others developed severe extra-pyramidal side-effects. Unwanted effects, though recorded in 70% of patients--drowsiness and extrapyramidal symptoms were the commonest--were for the most part trivial, and were fewer and less severe than they were on entry to the study. There was no evidence of toxicity. It was considered that on the basis of this experience the drug was an effective, safe antipsychotic agent, warranting more extensive clinical trial.

Adult↗