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F Anderson

Publications and source records attributed to F Anderson.

At least 19 recordsLinked to original sources
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2006

Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy.

BACKGROUND: The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. AIMS: We evaluated the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. PATIENTS: Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. METHODS: Patients were retreated with peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (<50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. RESULTS: A total of 312 patients (212 non-responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non-responders and relapsers were similar although more non-responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non-responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. CONCLUSIONS: These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non-responders and relapsers by retreating with peginterferon alfa-2a (40KD) plus ribavirin.

Adult↗
PubMed2005

Using a 360 degrees diagnostic screening tool to provide an evidence trail of junior doctor performance throughout their first postgraduate year.

New medical graduates in the UK are known as Preregistration House Officers (PRHOs). At the end of this first postgraduate year, the Postgraduate Dean is responsible for allowing the PRHO to be fully registered with the General Medical Council. During the period 1999-2002 Professor Miriam Friedman Ben-David designed a more robust approach to appraisal and assessment of PRHOs, which provided educational feedback to all trainees, allowed any poor performers to be detected at an early stage, and provided 'hard' observable evidence for certification decisions. This paper describes the more recent development of her work resulting from further piloting of her system. The key tool, a 360 degrees diagnostic questionnaire, is designed to identify strengths and weaknesses in individual performance. It is presently being used as a screening tool to identify any trainees needing additional support and further assessment. The tool also forms part of an evidence trail for all PRHOs and helps inform formative assessment as well as contributing, along with other evidence, to full registration decisions. The evaluation of this tool, also described in this paper, shows the feasibility of implementing such a system on a wider scale and illustrates the successful balance made between robustness and feasibility.

Attitude of Health Personnel↗
PubMed2005

Clinical utility of viral load measurements in individuals with chronic hepatitis C infection on antiviral therapy.

SUMMARY: Both absolute viral load and log decline in viral load from baseline were found clinically useful in predicting sustained virological response and lack of sustained virological response (non-sustained virological response, NSVR) to treatment. We assessed the clinical utility of hepatitis C virus (HCV) RNA quantitation and changes in viral load using the VERSANT HCV RNA 3.0 Assay (bDNA) in 351 HCV-infected individuals treated with interferon plus ribavirin. We show that viral load decision thresholds provided negative predictive values (NPVs) of >95% at week 4 using a 100 000 IU/mL cut-off and at weeks 8 and 12 using 10 000 IU/mL cut-offs. A 2-log decline from baseline provided NPVs >95% at weeks 8 and 12. Combinations of absolute viral loads and changes in viral load from baseline did not enhance the performance of the decision rules for predicting NSVR. The positive predictive values (PPVs) at weeks 8 and 12 were 59.1 and 67.3%. This study highlights the critical importance of viral quantitation in gauging therapeutic response in patients with chronic HCV infection on antiviral therapy. Early changes in viral load, measured as absolute viral loads or change in viral load from baseline, are highly predictive of NSVR at 8 and 12 weeks. PPVs are modest but these data may provide encouragement to patients who are in the early phases of treatment when side effects are frequent. Additionally, we demonstrated the need for cautious interpretation of stopping rules when the values are at or near the decision thresholds.

Adult↗
PubMed2004

Preoperative biliary stenting--a prequel to pancreatic resection in selected patients.

INTRODUCTION: Biliary drainage is necessary to improve immediate survival in patients with profound co-morbidities associated with jaundice. We report on our experience with this category of patients in whom subsequent pancreaticoduodenectomy was performed. PATIENTS AND METHODS: In the period January 2001-June 2002, 6 patients underwent biliary drainage to reverse potentially fatal complications or to optimise nutritional status. There were 2 female and 4 male patients (age range 50-70 years). The reasons for biliary drainage were suboptimal albumin levels in all patients, cholangitis in 4 patients and renal impairment in 2 male patients and profound acute jaundice in 1. RESULTS: There was failure of stent placement at endoscopic retrograde cholangiopancreatography (ERCP) in 3 patients. Two had an ERCP performed before referral and had a metal stent deployed at percutaneous transhepatic cholangiography (PTC). In the other a plastic stent was placed at a combined PTC/ERCP session. The 3 others had stents placed by ERCP. None of the patients had complications related to the stenting procedure. All the lesions were deemed resectable following imaging by ultrasound and computed tomography (CT) scan. Laparotomy with intent to resect was planned once the complications had resolved. The average duration of stenting before surgery was 46 days (range 12-100 days). All patients underwent pancreatoduodenectomy. One patient developed postoperative superficial wound sepsis, which resolved with topical management. There were no perioperative deaths. The postoperative hospital stay ranged from 10 to 21 days. Histological examination revealed pancreatic adenocarcinomas in 4 patients, an ampullary tumour in 1 patient and a non-functioning islet cell tumour in the other. CONCLUSION: Biliary drainage for complications should not be regarded as definitive treatment. It optimises co-morbidity factors and allows staging so that resection can be carried out successfully in selected patients.

Aged↗
PubMed2004

Changes in the management of ALS since the publication of the AAN ALS practice parameter 1999.

OBJECTIVE: To determine if the publication in 1999 of the AAN Practice Parameter on ALS was associated with an improvement in the standard of management of the disease. METHODS: Data on 646 patients enrolled in the ALS CARE database and on 465 patients who died in the period May 2001 to November 2002 were compared with similar data obtained from the database from 1996 to May 1999. RESULTS: The specialty ALS clinics were the most important source of information about ALS. The internet was a source for 39%. The treatment of sialorrhea, pseudobulbar emotional lability, and failure of swallowing and breathing had all improved significantly in the period after the publication of the Practice Parameter. However many patients still did not receive a gastrostomy tube or non-invasive positive pressure ventilation when indicated by the Practice Parameter, mainly because of lack of patient compliance. Cost was the main reason why 41% of patients did not receive riluzole, though they spent a third of the cost of this medication on alternative medicines. CONCLUSIONS: The publication of the AAN Practice Parameter was associated with improvement in the standard of care. Most cases in the database come from specialized ALS centers, and further information on the community care of ALS patients is needed.

Academies and Institutes↗
PubMed2001

Current management of ALS: comparison of the ALS CARE Database and the AAN Practice Parameter. The American Academy of Neurology.

BACKGROUND: The American Academy of Neurology (AAN) ALS Practice Parameter was published in April 1999. The ALS CARE Database has been collecting data on the management of patients with ALS in North America since 1996. OBJECTIVE: To compare the management of patients with ALS in North America as recorded in the ALS CARE Database with the recommendations of the AAN ALS Practice Parameter. METHODS: Data were analyzed from 2018 patients at enrollment and from 373 of these patients who died between enrollment and May 1999. RESULTS: Eighty-two percent of the enrolled patients reported that they had been given enough information about ALS. Only 54% of patients with drooling were receiving medication for this problem. Only 41% of those who reported being depressed most of the time were receiving antidepressant medications. Only 28% of those with dyspnea and only 9.2% of those with a forced vital capacity <40% predicted were receiving noninvasive positive pressure ventilator support. Only 30% of those with moderate to severe dysphagia had a gastrostomy tube. Half of the patients who died did so at home, but only 47% of them received residential hospice services. Although 89% of patients who died were recorded as having done so peacefully, 17% were reported to have had breathing difficulties (i.e., respiratory distress), 8% anxiety, 3.3% pain, and 2.5% choking. Advance directives were in place for 90% of the patients who died, and in 97% of cases these directives were followed. CONCLUSIONS: These findings indicate that in the 3-year period prior to the publication of the AAN Practice Parameter, many but not all patients received the care that is recommended in that parameter; there were deficiencies, particularly in the key areas of gastrostomy and noninvasive positive pressure ventilation.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis.

The receptor activator of NF-kappaB (RANKL) is the essential signal required for full osteoclast (OC) development, activation, and survival. RANKL is highly expressed in areas of trabecular bone remodeling and inflammatory bone loss, is increased on marrow stromal cells or osteoblasts by osteotropic hormones or cytokines, and is neutralized by osteoprotegerin (OPG), a soluble decoy receptor also crucial for preventing arterial calcification. Vascular endothelial cells (VEC) are critically involved in bone development and remodeling and influence OC recruitment, formation, and activity. Although OCs develop and function in close association with bone VEC and sinusoids, signals mediating their interactions are not well known. Here, we show for the first time that human microvascular endothelial cells (HMVEC) express transcripts for both RANKL and OPG; inflammatory cytokines tumor necrosis factor-alpha and interleukin-1alpha elevate RANKL and OPG expression 5-40-fold in HMVEC (with an early OPG peak that declines as RANKL rises), and RANKL protein increases on the surface of tumor necrosis factor-alpha-activated HMVEC. Cytokine-activated HMVEC promoted the formation, fusion, and bone resorption of OCs formed in co-cultures with circulating human monocytic precursors via a RANKL-mediated mechanism fully antagonized by exogenous OPG. Furthermore, paraffin sections of human osteoporotic fractured bone exhibited increased RANKL immunostaining in vivo on VEC located near resorbing OCs in regions undergoing active bone turnover. Therefore, cytokine-activated VEC may contribute to inflammatory-mediated bone loss via regulated production of RANKL and OPG. VEC-derived OPG may also serve as an autocrine signal to inhibit blood vessel calcification.

Base Sequence↗
PubMed2001

Assessing health status quality of life in ALS: comparison of the SIP/ALS-19 with the ALS Functional Rating Scale and the Short Form-12 Health Survey. ALS C.A.R.E. Study Group. Clinical Assessement, Research, and Education.

BACKGROUND: The progressive loss of function affects the quality of life of the ALS patient. Quality of life depends on a spectrum of factors. Available instruments for assessment include questionnaires developed for generic illness-related disabilities and ALS-specific questionnaires that focus on function. METHODS: Comparisons were made between two ALS-specific questionnaires (ALS Functional Rating Scale and SIP/ALS-19) and a generic instrument (Short Form-12) given to 1,513 patients from the (North American) ALS Patient Care Database. RESULTS: The SIP/ALS-19 correlates well with the ALS Functional Rating Scale and less well with the Short Form-12. CONCLUSIONS: The SIP/ALS-19 can be used as an effective surrogate for the ALS Functional Rating Scale, with the advantage that the SIP/ALS-19 also includes questions that encompass the psychological and social domains of quality of life.

Activities of Daily Living↗
PubMed2001

Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment.

OBJECTIVE: In patients chronically infected with hepatitis C virus (HCV) undergoing antiviral therapy, sustained virologic response is suggested by viral clearance by end of treatment (EOT). Viral clearance is defined by nondetection of serum HCV RNA, usually by qualitative PCR-based assays with limits of detection ranging from 100 to 1000 copies/ml. However, some individuals relapse after achieving apparent viral clearance by EOT. These individuals may have low levels of viremia not detected by current PCR methods. The aim of this retrospective study was to determine whether the Bayer HCV RNA Qualitative Assay, which employs Transcription Mediated Amplification (TMA) and detects 50 HCV RNA copies/ml, could detect residual serum HCV RNA in patients who achieved apparent viral clearance by EOT and subsequently relapsed. METHODS: Samples were obtained at EOT (wk 24 or 48) and follow-up (wk 24-26 posttreatment) from 97 patients treated for HCV (78 relapsing patients, 19 sustained responders). All samples in which HCV RNA was not detected by PCR were tested in a blinded manner for HCV RNA by the TMA-based assay. RESULTS: HCV RNA was detected by the TMA-based assay in 27 (34.6%) EOT and 76 (97.4%) follow-up samples from relapsing patients, but not in any of the EOT or follow-up samples from sustained responders. CONCLUSION: Residual serum HCV RNA was detected by the TMA-based assay in EOT samples from 34.6% of patients that had achieved apparent viral clearance by PCR. The detection of HCV RNA by the TMA-based assay could help redefine EOT response and assist in the antiviral management of HCV infection.

Antiviral Agents↗
PubMed2000

Decreased nitric oxide levels stimulate osteoclastogenesis and bone resorption both in vitro and in vivo on the chick chorioallantoic membrane in association with neoangiogenesis.

High nitric oxide (NO) levels inhibit osteoclast (OC)-mediated bone resorption in vivo and in vitro, and nitrate donors protect against estrogen-deficient bone loss in postmenopausal women. Conversely, decreased NO production potentiates OC bone resorption in vitro and is associated with in vivo bone loss in rats and humans. Previously, we reported that bone sections from rats administered aminoguanidine (AG), a selective inhibitor of NO production via inducible NO synthase, exhibited both increased OC resorptive activity as well as greater numbers of OC. Here, we investigated further whether AG promoted osteoclastogenesis, in addition to stimulating mature OC function, using a modified in vivo chick chorioallantoic membrane (CAM) system and an in vitro chick bone marrow OC-like cell developmental model. AG, focally administered in small agarose plugs placed directly adjacent to a bone chip implanted on the CAM, dose-dependently elicited neoangiogenesis while stimulating the number, size, and bone pit resorptive activity of individual OC ectopically formed in vivo. In addition to enhancing OC precursor recruitment via neoangiogenesis, AG also exerted other vascular-independent effects on osteoclastogenesis. Thus, AG promoted the in vitro fusion and formation from bone marrow precursor cells of larger OC-like cells that contained more nuclei per cell and exhibited multiple OC differentiation markers. AG stimulated development was inversely correlated with declining medium nitrite levels. In contrast, three different NO donors each dose-dependently inhibited in vitro OC-like cell development while raising medium nitrite levels. Therefore, NO sensitively regulates OC-mediated bone resorption through affecting OC recruitment (angiogenesis), formation (fusion and differentiation), and bone resorptive activity in vitro and in vivo. Possibly, the stimulation of neoangiogenesis and OC-mediated bone remodeling via AG or other pro-angiogenic agents may find clinical applications in reconstructive surgery, fracture repair, or the treatment of avascular necrosis.

Acid Phosphatase↗
PubMed1998

Inhibition of avian osteoclast bone resorption by monoclonal antibody 121F: a mechanism involving the osteoclast free radical system.

Osteoclasts generate high levels of superoxide anions during bone resorption that contribute to the degradative process, although excessive levels of this free radical may be damaging. One mechanism for their removal is via superoxide dismutase (SOD), a protective superoxide scavenging enzyme. We have previously described a novel developmentally regulated 150 kDa plasma membrane glycoprotein of avian osteoclasts which is reactive with the osteoclast-specific monoclonal antibody (Mab) 121F and is related immunologically, biochemically, and in protein sequence to mitochondrial Mn2+/Fe2+ SOD. We hypothesized that this unusual osteoclast surface component may be involved in protection against superoxides generated during active bone resorption. Increasing concentrations of monovalent Fab fragments prepared from Mab 121F, but not those from another antiosteoclast Mab designated 29C, markedly inhibited both bone particle and bone pit resorption by avian osteoclasts, while reducing tartrate-resistant acid phosphatase activity and causing the morphological contraction of osteoclasts on bone. Thus, the SOD-related membrane antigen may be essential for osteoclast bone resorption. Osteoclast superoxide production, monitored kinetically by cytochrome c reduction and histochemically by nitroblue tetrazolium reduction staining, was significantly greater in the presence of 121F, but not 29C, Fab treatment. Furthermore, the release of another free radical known as nitric oxide, which is produced by osteoclasts, can scavenge superoxides, and acts to potently inhibit osteoclast bone resorption, was dose-dependently increased by 121F Fab in resorbing osteoclast cultures. Therefore, Mab 121F binding may block the potential protective function of the osteoclast plasma membrane SOD-related glycoprotein, leading to a rapid elevation of superoxide levels and a subsequent rise in osteoclast nitric oxide release, feedback messages which may be sensed by the osteoclast as signals to cease active bone resorption.

Acid Phosphatase↗
PubMed1997

Illicit use of clonidine in opiate-abusing pregnant women.

OBJECTIVE: To examine prevalence rates and psychosocial correlates of clonidine use in a sample of opiate-dependent pregnant women. METHODS: Clonidine use was assessed in 90 treatment-seeking, pregnant, opiate-abusing women using both self-report and urinalysis toxicology. Clonidine-positive and -negative subjects were compared for selected demographic, substance use, and psychosocial measures. RESULTS: One-third of the sample was clonidine-positive. Urinalysis identified 26 clonidine-positive subjects, whereas self-report detected only six cases. Logistic regression identified four predictors of clonidine use at treatment admission: recent clinical anxiety, greater severity of family or social problems, recent cocaine use, and recent drug treatment. CONCLUSION: Clonidine use is prevalent in treatment-seeking opiate abusers, particularly those with concurrent cocaine use. The abuse potential of the drug warrants further study in this high-risk population.

Adult↗
PubMed1997

Ca2+ or phorbol ester but not inflammatory stimuli elevate inducible nitric oxide synthase messenger ribonucleic acid and nitric oxide (NO) release in avian osteoclasts: autocrine NO mediates Ca2+-inhibited bone resorption.

Osteoclast bone resorption is essential for normal calcium homeostasis and is therefore tightly controlled by calciotropic hormones and local modulatory cytokines and factors. Among these is nitric oxide (NO), a multifunctional free radical that potently inhibits osteoclast bone resorption in vitro and in vivo. Previous findings led us to propose that NO might serve as an autocrine, as well as paracrine, regulator of osteoclast function. This premise was investigated using isolated bone-resorptive avian osteoclasts and focusing on the inducible isoform of NO synthase (iNOS) responsible for inflammatory stimulated high-level NO synthesis in other cells. Avian osteoclasts expressed both iNOS messenger RNA (mRNA) and protein. However, inflammatory cytokines that induce iNOS mRNA, protein, and NO in other cells did not do so in avian osteoclasts, consistent with the known role of inflammatory stimuli in promoting osteoclast resorption and localized bone loss. In searching for potential modulators of osteoclast iNOS, protein kinase C activation [by phorbol 12-myristate 13-acetate (PMA)] and intracellular Ca2+ rises (A23187) were each found to elevate osteoclast iNOS mRNA and protein levels, while increasing NO release and reducing osteoclast bone resorption. The iNOS selective inhibitor aminoguanidine suppressed stimulated osteoclast NO production elicited by either signal, but reversed only the resorption inhibition due to raised Ca2+. Thus, whereas additional inhibitory signals are presumably coproduced in osteoclasts treated with PMA, osteoclast iNOS-derived NO may act as an autocrine signal to mediate Ca2+-inhibited bone resorption. These findings document for the first time an iNOS whose mRNA levels are regulated by Ca2+ or PMA, but not inflammatory stimuli, and the autocrine production of NO as a Ca2+ sensing signal to suppress osteoclast bone resorption. The unusual regulation of osteoclast iNOS makes it a potentially attractive target for designing novel therapeutic agents to alleviate excessive bone loss.

Animals↗
PubMed1996

Palliative performance scale (PPS): a new tool.

The Palliative Performance Scale (PPS), a modification of the Karnofsky Performance Scale, is presented as a new tool for measurement of physical status in palliative care. Its initial uses in Victoria include communication, analysis of home nursing care workload, profiling admissions and discharges to the hospice unit, and, possibly, prognostication. We assessed 119 patients at home, of whom 87 (73%) had a PPS rating between 40% and 70%. Of 213 patients admitted to the hospice unit, 175 (83%) were PPS 20%-50% on admission. The average period until death for 129 patients who died on the unit was 1.88 days at 10% PPS upon admission, 2.62 days at 20%, 6.70 days at 30%, 10.30 days at 40%, 13.87 days at 50%. Only two patients at 60% or higher died in the unit. The PPS may become a basis for comparing drug costs at home and for studying the effects of treatments (e.g. hypodermoclysis) at various levels of physical performance. Validity and reliability testing are currently being undertaken.

British Columbia↗