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Biomedical subjects

L Potter

Publications and source records attributed to L Potter.

At least 19 recordsLinked to original sources
PubMed2004

A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma.

The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as predicted by tumour (Breslow) thickness, has been reported previously. We now report a novel adenine-guanine substitution -1012 bp relative to the exon 1a transcription start site (A-1012G), found following screening by single-stranded conformational polymorphism of this promoter region. There was a total of 191 MM cases, which were stratified according to conventional Breslow thickness groups, cases being randomly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area, and this population (n=176) was compared to 80 controls. The A allele was over-represented in MM patients and, with GG as reference, odds ratio (OR) for AG was 2.5, 95% confidence interval (CI) 1.1-5.7, (P=0.03) and AA 3.3, CI 1.4-8.1, (P=0.007). The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis, the Kaplan-Meier estimates of the probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4-16%; AA 21%, CI 12-36%; (P=0.008), and to thicker Breslow thickness groups (P=0.04). The effect on metastasis was independent of tumour thickness and A-1012G may have predictive potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants (f and t) were significantly related to the development of metastasis, although there was a strong relationship of fftt with the thickest Breslow thickness group (P=0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms (P=0.025) and the Fok 1 variant enhanced the effect of the A allele of the A-1012G polymorphism on metastasis, the probability of metastasis for AAff at 5 years follow-up being 57%, CI 24-92%.

DNA Mutational Analysis↗
PubMed2004

Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation.

BACKGROUND: Virtually all BCCs have deregulation of the Hedgehog (Hh) signalling pathway and a proportion show nuclear beta-catenin accumulation. The latter is thought to be due to Hh pathway-directed Wnt expression but this has not been tested. An alternative cause of nuclear beta-catenin accumulation is gene mutation, which stabilizes the protein. Theoretically, reduced E-cadherin expression could also be important because it can sequester beta-catenin at the cell membrane. In turn, nuclear beta-catenin can increase expression of MYC and cyclin D1, thus potentially altering proliferation. OBJECTIVES: To assess whether nuclear beta-catenin occurs in BCC, and to look at potential causes and consequences. METHODS: Nuclear beta-catenin was assessed by immunohistochemistry, and its causes by analysis of E-cadherin expression, beta-catenin exon 3 mutation and WNT5A expression. Its consequences were assessed by analysing proliferation. RESULTS: We found nuclear beta-catenin in 20 of 86 paraffin-embedded sections of BCCs using immunohistochemistry. BCCs showed increased WNT5A relative to the surrounding skin. No mutations in exon 3 of the beta-catenin gene were found in 10 cases. There was no association between beta-catenin localization and E-cadherin expression. Tumours with nuclear beta-catenin had significantly higher proliferation (P < 0.01). CONCLUSIONS: The absence of beta-catenin gene mutations indicate that the Hh pathway-directed Wnt signalling remains the most likely cause of nuclear beta-catenin accumulation in BCC. Additionally, the correlation with increased proliferation is the first evidence that nuclear beta-catenin may have a biological effect. However, a causal link between Hh pathway deregulation, Wnt ligand overexpression, nuclear beta-catenin accumulation and increased proliferation remains to be confirmed.

Aged↗
PubMed2001

School-associated violent deaths in the United States, 1994-1999.

CONTEXT: Despite the public alarm following a series of high-profile school shootings that occurred in the United States during the late 1990s, little is known about the actual incidence and characteristics of school-associated violent deaths. OBJECTIVE: To describe recent trends and features of school-associated violent deaths in the United States. DESIGN, SETTING, AND SUBJECTS: Population-based surveillance study of data collected from media databases, state and local agencies, and police and school officials for July 1, 1994, through June 30, 1999. A case was defined as a homicide, suicide, legal intervention, or unintentional firearm-related death of a student or nonstudent in which the fatal injury occurred (1) on the campus of a public or private elementary or secondary school, (2) while the victim was on the way to or from such a school, or (3) while the victim was attending or traveling to or from an official school-sponsored event. MAIN OUTCOME MEASURES: National estimates of risk of school-associated violent death; national trends in school-associated violent deaths; common features of these events; and potential risk factors for perpetration and victimization. RESULTS: Between 1994 and 1999, 220 events resulting in 253 deaths were identified; 202 events involved 1 death and 18 involved multiple deaths (median, 2 deaths per multiple-victim event). Of the 220 events, 172 were homicides, 30 were suicides, 11 were homicide-suicides, 5 were legal intervention deaths, and 2 were unintentional firearm-related deaths. Students accounted for 172 (68.0%) of these deaths, resulting in an estimated average annual incidence of 0.068 per 100 000 students. Between 1992 and 1999, the rate of single-victim student homicides decreased significantly (P =.03); however, homicide rates for students killed in multiple-victim events increased (P =.047). Most events occurred around the start of the school day, the lunch period, or the end of the school day. For 120 (54.5%) of the incidents, respondents reported that a note, threat, or other action potentially indicating risk for violence occurred prior to the event. Homicide offenders were more likely than homicide victims to have expressed some form of suicidal behavior prior to the event (odds ratio [OR], 6.96; 95% confidence interval [CI], 1.96-24.65) and been bullied by their peers (OR, 2.57; 95% CI, 1.12-5.92). CONCLUSIONS: Although school-associated violent deaths remain rare events, they have occurred often enough to allow for the detection of patterns and the identification of potential risk factors. This information may help schools respond to this problem.

Adolescent↗
PubMed2001

Nitrate reduction in the periplasm of gram-negative bacteria.

In contrast to the bacterial assimilatory and membrane-associated, respiratory nitrate reductases that have been studied for many years, it is only recently that periplasmic nitrate reductases have attracted growing interest. Recent research has shown that these soluble proteins are widely distributed, but vary greatly between species. All of those so far studied include four essential components: the periplasmic molybdoprotein, NapA, which is associated with a small, di-haem cytochrome, NapB; a putative quinol oxidase, NapC; and a possible pathway-specific chaperone, NapD. At least five other components have been found in different species. Other variations between species include the location of the nap genes on chromosomal or extrachromosomal DNA, and the environmental factors that regulate their expression. Despite the relatively small number of bacteria so far screened, striking correlations are beginning to emerge between the organization of the nap genes, the physiology of the host, the conditions under which the nap genes are expressed, and even the fate of nitrite, the product of Nap activity. Evidence is emerging that Nap fulfills a novel role in nitrate scavenging by some pathogenic bacteria.

Amino Acid Sequence↗
PubMed2000

Survival of bacteria during oxygen limitation.

Regulatory mechanisms that enable bacteria associated with food, drinks and the human body to adapt to changes in the availability of oxygen are reviewed. Excess oxygen induces two adaptive responses to oxidative stress. Five or more control circuits enable enteric bacteria to generate energy and grow well in anaerobic environments. Two sets of enzymes catalyse both nitrate and nitrite reduction, and dual two-component regulatory systems sense and respond to the available nitrate and nitrite in the environment. The periplasmic nitrate reductase enables bacteria to scavenge low concentrations of nitrate: similar systems are found in food-borne and other pathogens.

Anaerobiosis↗
PubMed2000

Three years' experience of collaborative care pathways on a maxillofacial ward.

Collaborative care pathways (CCPs) provide a framework for multidisciplinary patient care. They provide guidelines and a mechanism for audit, and were first introduced at the Regional Unit, Walton Hospital, Liverpool, in November 1994. They have been designed for many surgical groups. Between August 1996 and 31 July 1997, 955 patients were admitted on to the nine established pathways: fractured mandible (n=213), fractured zygoma (n=117), minor oral surgery (n=244), abscess (n=18), examination under anaesthesia (n=73), nasal surgery (n=73), osteotomy (n=80), salivary (n=63), and temporomandibular joint (n=74). The purpose of this article is to report the introduction of CCP in a maxillofacial ward and give results from a one-year audit. CCP have proved to be an extremely useful tool and have several advantages over traditional documentation. They are more accurate, easily computerized, and facilitate audit. They promote the development of guidelines and standardized perioperative care, and this in turn facilitates training and raises standards of care.

Abscess↗
PubMed2000

Liver transplantation in a patient at psychosocial risk.

Psychosocial assessment of transplant candidates is a challenging task. Securing adequate information is made more difficult when patients present with fulminant hepatic failure. When the patient cannot be interviewed and the family is reluctant to provide vital information, a comprehensive pretransplant psychosocial evaluation is virtually impossible. However, even the most difficult cases have the potential for a positive result when a good psychosocial profile of the patient is obtained after transplantation, a team treatment plan is developed and carried out which addresses current and anticipated problems, and the patient obtains mental health treatment.

Adult↗
PubMed2000

An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia.

OBJECTIVE: To examine treatment costs of community-acquired pneumonia (CAP) in adult outpatients given oral (p.o.) levofloxacin or cefuroxime axetil as initial therapy. STUDY DESIGN: Patients with a primary diagnosis of CAP were enrolled in a multicenter, prospective, randomized, open-label, active-controlled Phase III clinical trial. Both inpatients and outpatients were assigned to 1 of 2 treatment groups: (1) intravenous (i.v.) or p.o. levofloxacin; or (2) i.v. ceftriaxone and/or p.o. cefuroxime axetil. METHODS: To make legitimate and meaningful cost comparisons between similar types of patients receiving drugs via the same route of administration (i.e., orally), this outpatient economic study examined the resource utilization of the 211 patients enrolled as outpatients who received oral formulations as initial treatment (levofloxacin, 103 patients; cefuroxime axetil, 108 patients). Resource utilization data and clinical trial data were collected concurrently. To generate cost estimates, Medicare cost estimates for resources were multiplied by the resource units used by patients in each treatment arm. RESULTS: Cost estimates indicated a total cost difference that favored the levofloxacin group (base case: $169; sensitivity analysis: $223 [P = .008]). The results for the base case were not significant (P = .094). In addition, within the cost categories, there was a statistically significant study drug cost differential favoring levofloxacin ($86; P = .0001 for both the base case and sensitivity analysis). CONCLUSION: Oral levofloxacin is less costly than oral cefuroxime axetil in the outpatient treatment of adults with CAP.

Adult↗
PubMed1999

The periplasmic nitrate reductase from Escherichia coli: a heterodimeric molybdoprotein with a double-arginine signal sequence and an unusual leader peptide cleavage site.

The periplasmic nitrate reductase, NapA, from Escherichia coli was identified as a 90 kDa molybdoprotein which comigrated during polyacrylamide gel electrophoresis with the di-haem c-type cytochrome, NapB. The DNA sequence of the 5' end of the napA gene and the N-terminal amino acid sequences of both NapA and NapB were determined. The 36 residue leader peptide for NapA includes the double-arginine motif typical of proteins to which complex redox cofactors are attached in the cytoplasm prior to targeting to the periplasm. The pre-NapA leader sequence is both unexpectedly long and, unless two successive proteolysis steps are involved, is cleaved at the unprecedented sequence G-Q-Q-. Nap activity was suppressed during growth in the presence of tungstate and was absent from a mutant unable to synthesise the molybdopterin cofactor.

Amino Acid Sequence↗
PubMed1999

The managed care contract: survival or closure?

The managed health care contract can be considered the most powerful tool in the health care environment today. Providers of care as well as insurers need to fully comprehend the legal and financial impact of these contracts. Too many organizations (providers and insurers) are getting caught in financial failure, resulting in bottom line-driven health care. It seems that the days of providing the most ethically appropriate health care are gone. Too much emphasis has been put on providers and administrators to provide the care that will result in positive income. The only way to "protect" oneself is in the creation, negotiation, and administration of the managed health care contract.

Colorado↗
PubMed1998

The expression of Huntingtin-associated protein (HAP1) mRNA in developing, adult and ageing rat CNS: implications for Huntington's disease neuropathology.

Using radioactive in situ hybridization, we have mapped the expression of Huntingtin-associated protein (HAP1) mRNA in rat brain at developmental stages (E12-E19, PO-P21), in adult rats (3 months) and in 'aged' (19-21 months) rats. Using two pairs of 45mer oligonucleotide probes specific for HAP1A and a probe which recognizes regions of both the HAP1A and HAP1B mRNA sequences (panHAP1), we find that the expression of HAP1 mRNA is specific to the CNS and restricted predominantly to anatomically connected limbic structures, particularly the amygdala (medial and corticomedial nuclei), the hypothalamus (arcuate, preoptic, paraventricular and lateral hypothalamic area), bed nucleus of the stria terminalis (BNST) and the lateral septal nuclei. HAP1 mRNA was detected in embryos at E12 and displayed a prevalent distribution in the developing limbic structures by E15. In aged, 19-21-months-old, rats there is a downregulation of HAP1 mRNA expression across all CNS loci where HAP1 was previously abundant. The lowest levels of HAP1 mRNA expression corresponded with the areas of greatest pathological cell loss in Huntington's disease (HD); the caudate putamen, globus pallidus and neocortex. These observations support the suggestion that HAP1 plays an important role in the neuropathology of HD.

Aging↗
PubMed1997

Workshop: the use of muscarinic toxins in the study of muscarinic receptors.

One of the most interesting recent developments in the pharmacology of muscarinic receptors has been the finding of small proteins in the venoms of mamba snakes that bind with high affinity and selectivity to different subtypes of muscarinic receptors. In the workshop on muscarinic toxins, the practicalities of isolating, characterising and using these toxins as tools in the study of muscarinic receptors were discussed.

Animals↗
PubMed1997

Revision of a parent-completed development screening tool: Ages and Stages Questionnaires.

Examined the Ages and Stages Questionnaires (ASQ), a series of 11 developmental questionnaires designed to be completed by parents and caregivers of young children from 4 to 48 months of age. The ASQ were recently revised and additional psychometric data were gathered. Analyses on over 7,000 questionnaires indicated high test-retest reliability, interobserver reliability, and internal consistency. Concurrent validity using standardized measures yielded on overall agreement of 85%, with a range of 76-91%. Specificity was high across questionnaire intervals while sensitivity was lower and varied across intervals. Use of parent-completed screening tools such as the ASQ is attractive in terms of cost-effectiveness, parental involvement, and flexibility in administration procedures.

Case-Control Studies↗
PubMed1997

The health status of elderly persons in the last year of life: a comparison of deaths by suicide, injury, and natural causes.

OBJECTIVES: This study identified health status variables related to suicide by elderly persons and compared the health status of suicide decedents with natural death and injury decedents. METHODS: Data were obtained from the 1986 National Mortality Followback Survey. RESULTS: When other variables were controlled for, suicide decedents were significantly more likely than injury decedents to have a history of cancer (odds ratio [OR] = 51.94), moderate (OR = 29.37) or heavy (OR = 22.87) alcohol use, and mental or emotional disorder (OR = 10.91) and to be White (OR = 18.54) and male (OR = 9.12). CONCLUSIONS: The findings indicate that a history of cancer should be considered as a risk for suicide in the elderly.

Activities of Daily Living↗
PubMed1995

A pseudoepidemic of Rhodotorula rubra: a marker for microbial contamination of the bronchoscope.

Rhodotorula rubra was isolated from bronchoscopy specimens from 11 patients. An investigation of the bronchoscopy equipment and the bronchoscopy suite revealed contamination of the suction channel with R rubra, as well as potentially pathogenic bacteria. Disinfection control methods included gas sterilization of the bronchoscope and the institution of an alcohol and air flush through the suction channel to allow complete drying of the scope between each patient use. We have had no further isolates of R rubra from bronchoscopy specimens since these measures were instituted, and repeat cultures from the suction channel have been negative.

Adult↗