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Biomedical subjects

N Richards

Publications and source records attributed to N Richards.

At least 19 recordsLinked to original sources
PubMed2002

Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.

The disease-free survival of patients with myeloma and severe renal failure after high-dose melphalan and autologous stem cell rescue is similar to those with normal renal function at the time of the autograft. However, recovery of renal function after intensive treatment is uncommon and patients with end-stage renal failure continue to be dialysis-dependent. We report two patients with myeloma who required regular haemodialysis from diagnosis, but became dialysis-independent after a high-dose melphalan autograft. Thus, in some patients, renal function may be partially salvageable despite the requirement for dialysis at the time of autografting.

Disease-Free Survival↗
PubMed2001

Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis.

Patients with familial Mediterranean fever suffer sporadic inflammatory attacks characterized by fever and intense pain (in joints, abdomen, or chest). Pyrin, the product of the MEFV locus, is a cytosolic protein whose function is unknown. Using pyrin as a "bait" to probe a yeast two-hybrid library made from neutrophil cDNA, we isolated apoptotic speck protein containing a caspase recruitment domain (CARD) (ASC), a proapoptotic protein that induces the formation of large cytosolic "specks" in transfected cells. We found that when HeLa cells are transfected with ASC, specks are formed. After co-transfection of cells with ASC plus wild type pyrin, an increase in speck-positive cells is found, and speck-positive cells show increased survival. Immunofluorescence studies show that pyrin co-localizes with ASC in specks. Speck localization requires exon 1 of pyrin, but exon 1 alone of pyrin does not result in an increase in the number of specks. Exon 1 of pyrin and exon 1 of ASC show 42% sequence similarity and resemble death domain-related structures in modeling studies. These findings link pyrin to apoptosis pathways and suggest that the modulation of cell survival may be a component of the pathophysiology of familial Mediterranean fever.

Actins↗
PubMed2001

Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states.

Familial Mediterranean fever (FMF; MIM 249100) is an autosomal recessive disease characterized by recurrent attacks of fever with synovial, pleural or peritoneal inflammation. The disease is caused by mutations in the gene encoding the pyrin protein. Human population studies have revealed extremely high allele frequencies for several different pyrin mutations, leading to the conclusion that the mutant alleles confer a selective advantage. Here we examine the ret finger protein (rfp) domain (which contains most of the disease-causing mutations) of pyrin during primate evolution. Amino acids that cause human disease are often present as wild type in other species. This is true at positions 653 (a novel mutation), 680, 681, 726, 744 and 761. For several of these human mutations, the mutant represents the reappearance of an ancestral amino acid state. Examination of lineage-specific dN/dS ratios revealed a pattern consistent with the signature of episodic positive selection. Our data, together with previous human population studies, indicate that selective pressures may have caused functional evolution of pyrin in humans and other primates.

Amino Acid Sequence↗
PubMed2001

Do children who become autistic consult more often after MMR vaccination?

A close temporal association has been reported between the measles, mumps, and rubella (MMR) vaccination and dramatic behavioural decline in children subsequently diagnosed as autistic. We hypothesised that such a decline would be reflected in increased consultations with the child's general practitioner. The Doctor's Independent Network database was used to examine whether children subsequently diagnosed as autistic consulted more frequently than controls after MMR vaccination. No difference in consulting behaviour was seen in the six months post MMR. Any dramatic effect of MMR on behaviour seems unlikely.

Autistic Disorder↗
PubMed2000

Torsional properties of stainless-steel and nickel-titanium files after multiple autoclave sterilizations.

This study tested the hypothesis that multiple sterilizations of endodontic stainless-steel and nickel-titanium files will lead to a continuous decrease in the resistance of files to separation by torsion. One hundred stainless-steel and 100 nickel-titanium #30 K-type files were divided into 20 groups of 10 and sterilized in increments of 10 cycles, using a full cycle and a fast cycle autoclave. These files were tested by twisting each of them in a clockwise direction until fracture (torque g-cm). Samples of the fractured files were embedded in an epoxy resin and polished for Knoop hardness tests. In addition, the samples were chemically etched to reveal changes in microstructure. The findings of this study indicate that neither the number of sterilization cycles nor the type of autoclave sterilization used affects the torsional properties, hardness, and microstructure of stainless-steel and nickel-titanium files.

Acid Etching, Dental↗
PubMed1999

Analysis of linked human epsilon and gamma transgenes: effect of locus control region hypersensitive sites 2 and 3 or a distal YY1 mutation on stage-specific expression patterns.

Stage-specific expression of the human beta-like globin genes is controlled by interactions between regulatory elements near the individual genes and additional elements located upstream in the Locus Control Region (LCR). Elucidation of the mechanisms that govern these interactions could suggest strategies to reactivate fetal (gamma) or embryonic (epsilon) genes in individuals with severe hemoglobinopathies. This study extends an earlier analysis of a transgenic construct, HS3epsilon gamma, testing: (A) the effect of substitution of HS2 for HS3 on stage-specific expression of the epsilon and gamma genes and, (B) the role of an evolutionarily conserved YY1 binding site in transcriptional regulation of the gamma gene. The data show that both HS3epsilon gamma and HS2epsilon gamma can individually support embryonic expression of epsilon and fetal expression of Agamma. Thus, the cis regulators of distinct expression patterns for epsilon and gamma are likely to reside near the genes, rather than in specific hypersensitive sites of the LCR. Alterations in Agamma expression patterns observed in transgenic lines carrying a construct with a mutation in a conserved YY1 binding site at -1086 indicate that this site might function to facilitate active transcription of the gamma gene in fetal life.

Animals↗
PubMed1999

The duration of antibiotic administration in penetrating abdominal trauma.

BACKGROUND: The epidemiology of penetrating abdominal trauma is changing to reflect an increasing incidence of multiple injuries. Not only do multiple injuries increase the risk of infection, a very high risk of serious infection is conferred by immunosuppression from hemorrhage and transfusion and the high likelihood of intestinal injury, especially to the colon. Optimal timing and choice of presumptive antibiotic therapy has been established for penetrating trauma, but duration has not been studied extensively in such seriously injured patients. The purpose of this study was to test the hypothesis that 24 hours of antibiotic therapy remains sufficient to reduce the incidence of infection in penetrating abdominal trauma. METHODS: Three hundred fourteen consecutive patients with penetrating abdominal trauma were prospectively randomized into two groups: Group I received 24 hours of intravenous cefoxitin (1 g q6h) and group II received 5 days of intravenous cefoxitin. The development of a deep surgical site (intra-abdominal) infection as well as any type of nosocomial infection, as defined by the Centers for Disease Control and Prevention, (ie, surgical site infections, catheter-related infections, urinary tract, pneumonia), was recorded. Hospital length of stay was a secondary endpoint. Statistical analysis included chi-square tests for coordinate variables and two-tailed unpaired t tests for continuous variables. The independence of risk factors for the development of infection was assessed by multivariate analysis of variance. Significance was determined when P <0.05. RESULTS: Three hundred patients were evaluable. There was no postoperative mortality, and no differences in overall length of hospitalization between groups. The duration of antibiotic treatment had no influence on the development of any infection (P = 0.136) or an intraabdominal infection (P = 0.336). Only colon injury was an independent predictor of the development of an intraabdominal infection (P = 0.0031). However, the overall infection incidence was affected by preoperative shock (P = 0.003), colon (P = 0.0004), central nervous system (CNS) injuries (P = 0.031), and the number of injured organs (P = 0.026). Several factors, including intraoperative shock (P = 0.021) and injuries to the colon (P = 0.0008), CNS (P = 0.0001), and chest (P = 0.0006), were independent contributors to prolongation of the hospital stay. CONCLUSIONS: Twenty-four hours of presumptive intravenous cefoxitin versus 5 days of therapy made no difference in the prevention of postoperative infection or length of hospitalization. Infection was associated with shock on admission to the emergency department, the number of intra-abdominal organs injured, colon injury specifically, and injury to the central nervous system. Intra-abdominal infection was predicted only by colon injury. Prolonged hospitalization was associated with intraoperative shock and injuries to the chest, colon, or central nervous system.

Abdominal Injuries↗
PubMed1999

A cost analysis on the pattern of asthma prescribing in the UK.

There is a need to establish the proportion of adult asthmatics at each step of the recommended asthma management guidelines, the cost of their prescribed treatment, and a revised cost of treatment assuming patients who were suboptimally controlled were moved up a step. Actual prescription and cost figures and a theoretical projection of an ideal scenario was calculated from a sample of general practices in Great Britain from the Doctors Independent Network. They comprised 102 nationally distributed practices and 17,206 adult patients with a diagnosis of, and prescription related to, asthma recorded between October 1993 and March 1994. Ninety-one per cent of patients received treatment within a recognized step of the guidelines. Of these, 80% were at steps 1 and 2. Employing excess inhaled beta-agonist use as a proxy for control of asthma, between 55% and 69% of patients at Steps 1-3 should receive treatment at a higher step. This could lead to an increased expenditure of up to Pound Sterling 4.66 per adult patient per month. This would imply a rise in the annual UK cost of antiasthma prescriptions for adults from Pound Sterling 388m to a possible Pound Sterling 533m. The United Kingdom Government audit commission has suggested that current expenditure on asthma treatment appears to be insufficient. Using an entirely different approach this study has confirmed that a significant increase in asthma prescribing costs is likely to be needed if optimal control of asthma is to be achieved.

Adolescent↗
PubMed1998

Immunochemical detection of hepatic cocaine-protein adducts in mice.

Cocaine is capable of producing hepatic necrosis in laboratory animals and humans. Studies in mice indicate that N-oxidative metabolism of cocaine is required for hepatotoxicity and have suggested that toxicity may result from the adduction of proteins by cocaine-reactive metabolites. To aid in identifying protein targets for cocaine-reactive metabolites, an antibody was raised in rabbits immunized with cocaine linked via the tropane nitrogen to a carrier protein (bovine serum albumin). Hepatic proteins from cocaine-treated mice (ICR males, 50 mg of cocaine/kg of body weight, ip) and saline-treated controls were prepared from whole liver homogenate or following subcellular fractionation, and Western blot analyses of hepatic proteins using this antibody were conducted following one- and two-dimensional SDS-PAGE. Analysis of liver homogenate from cocaine-treated mice revealed major protein targets with approximate molecular masses of 20 kDa (pI = 6.0), 44 kDa (two proteins with pI's of 5.0 and 7.0), 52-54 kDa (pI = 4.5), and 64 kDa (pI = 5.5). These specific protein targets were shown to be localized in the mitochondria and microsomes. Several minor bands of immunoreactivity were also seen in mice treated with cocaine, but not in saline-treated controls. Pretreatment of mice with the P450 inhibitor SKF 525A diminished or eliminated the formation of these cocaine-protein adducts. Liver sections from cocaine-treated mice immunostained using the antibody indicated the presence of cocaine-adducted proteins in the centrilobular and midzonal regions of the lobule, corresponding to areas of hepatocyte swelling and necrosis. This study indicates that reactive metabolites from cocaine bind to discrete proteins in specific regions of the liver, consistent with a role for protein adduction in cocaine hepatotoxicity.

Animals↗
PubMed1998

Construction of an approximately 700-kb transcript map around the familial Mediterranean fever locus on human chromosome 16p13.3.

We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the approximately 700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron-exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16.

Amino Acid Sequence↗
PubMed1997

A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the approximately 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (approximately 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

Alleles↗
PubMed1997

Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate region for the familial Mediterranean fever locus (MEFV) on chromosome 16p 13.3.

In this paper we describe the assembly and restriction map of a 1.05-Mb cosmid contig spanning the candidate region for familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation localized to 16p13.3. Using a combination of cosmid walking and screening for P1, PAC, BAC, and YAC clones, we have generated a contig of genomic clones spanning approximately 1050 kb that contains the FMF critical region. The map consists of 179 cosmid, 15 P1, 10 PAC, 3 BAC, and 17 YAC clones, anchored by 27 STS markers. Eight additional STSs have been developed from the approximately 700 kb immediately centromeric to this genomic region. Five of the 35 STSs are microsatellites that have not been previously reported. NotI and EcoRI mapping of the overlapping cosmids, hybridization of restriction fragments from cosmids to one another, and STS analyses have been used to validate the assembly of the contig. Our contig totally subsumes the 250-kb interval recently reported, by founder haplotype analysis, to contain the FMF gene. Thus, our high-resolution clone map provides an ideal resource for transcriptional mapping toward the eventual identification of this disease gene.

Base Sequence↗
PubMed1996

An audit of peripheral catheter care in a teaching hospital.

Post-insertion care of peripheral venous catheters (PVCs) in 100 patients on general medical and surgical wards of a teaching hospital was audited. A variety of methods were used to attach the PVC to the patients' skin including 'Vecafix' dressings, bandages and adhesive tape. Sixty-eight PVC were incorrectly attached, and of these 49 (71%) were associated with two or more symptoms or signs of inflammation at the insertion site. Of those PVC that were correctly attached only five out of 32 (16%) were associated with inflammation. There was a significant association between incorrect dressing application and inflammation (P < 0 center dot 01). Similarly, there was a direct relationship between inflammation and PVCs that had been in situ for greater than 48 h (P < 0 center dot 01). The results suggest that a significant reduction in the incidence of inflammation associated with PVC use may be achieved by correct application of dressings and replacing the catheters after 48 h in situ.

Bandages↗
PubMed1995

Organizing and implementing a hospital-wide first-responder automated external defibrillation program: strengthening the in-hospital chain of survival.

First-responder automated external defibrillation (AED) in the hospital is consistent with the American Heart Association's (AHA) early defibrillation standard or care. With trained personnel and automated external defibrillators immediately available, early defibrillation should have a greater impact on survival than early cardiopulmonary resuscitation (CPR). Therefore, in our hospitals we modified basic life support to include automated external defibrillation (BLS-AED) for all personnel who are expected to respond to a cardiac arrest, with rapid defibrillation taking priority over CPR. We describe how we organized and implemented this hospital-wide first-responder BLS-AED program. Planning the process includes gaining support from key leaders who are responsible for resuscitation practice, and identifying the target audience of the training program. Hospital unit needs for AED or conventional defibrillation and equipment must be identified, the training program developed, and existing policies and procedures modified. Several barriers to implementation may exist. Education about the efficacy and safety of AED and experience once the BLS-AED program is in place can overcome attitudes and bias. Concerns about the cost of equipment and training must be addressed. Program evaluation may include patient issues such as measuring the time to the first defibrillation and patient outcome; as well as training and retention issues.

Adult↗
PubMed1995

Strengthening the in-hospital chain of survival with rapid defibrillation by first responders using automated external defibrillators: training and retention issues.

STUDY OBJECTIVE: To determine whether staff outside critical care areas who were proficient in basic life support (BLS) could be easily trained to use automated external defibrillators (AEDs) and whether they would retain these skills. DESIGN: Prospective, longitudinal cohort series. SETTING: Two university teaching hospitals. PARTICIPANTS: One hundred forty nurses who had previously learned BLS and constituted the staff from three medical/surgical nursing units from each study hospital. INTERVENTIONS: The nurses were taught how to use the Heartstart 1000s, a lightweight portable shock-advisory AED, in a 2-hour class with an instructor and manikin-to-student ratio of 1:5. The course emphasized hands-on practice of the BLS-AED algorithm on a computerized manikin. RESULTS: Using a similar scenario, each nurse was evaluated on the computerized manikin immediately after training (posttest). At 1 to 3, 4 to 6, and 7 to 9 months after the initial training, convenience samples of the cohort in three different groups were evaluated for retention. Satisfactory performance was defined as delivery of the first AED shock within 2 minutes of recognition of the arrest. At the posttest after training, 139 of 140 nurses (99%) demonstrated satisfactory performance. Of 77 nurses evaluated, 31 of 32 at 1 to 3 months, 18 of 18 at 4 to 6 months, and 24 of 27 at 7 to 9 months after initial training (95% overall) performed satisfactorily. CONCLUSION: As has been demonstrated with prehospital emergency personnel, nurses outside critical care areas who are proficient in BLS can easily learn and retain the knowledge and skills to use AEDs. Automated external defibrillation, a BLS skill, should be incorporated into BLS programs (BLS-AED) for all hospital personnel expected to respond to a patient in cardiac arrest, with rapid defibrillation taking priority over CPR.

Algorithms↗
PubMed1995

Creating the role of the retention program coordinator.

During healthcare restructuring, nurse satisfaction can suffer. The following article describes how nurse executives and human resource professionals can implement a full- or part-time retention coordinator role for their healthcare facility. These authors describe how a retention coordinator can use formal and informal meetings to keep track of nurse satisfaction and develop strategies that identify and solve nurse satisfaction problems.

Humans↗