Search PubMed⌕ Search

Biomedical subjects

M Baker

Publications and source records attributed to M Baker.

At least 109 records · Page 6Linked to original sources
PubMed1998

Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.

Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10. The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.

Alternative Splicing↗
PubMed1998

Exclusion of genetic linkage to 4q21-23 and 17q21 in a family with Lewy body parkinsonism.

Genetic analysis of markers from chromosomes 4q21-23 and 17q21 in a family with apparently autosomal dominant Lewy body parkinsonism is presented. This analysis shows that the locus leading to this disease is not allelic with that previously shown to lead to Lewy body parkinsonism on chromosome 4 or to the locus on chromosome 17 leading to frontotemporal dementia with parkinsonism. A brief clinical comparison of this family with families showing linkage to these loci is presented. The data suggest that at least one other major genetic determinant for Lewy body parkinsonism remains to be identified.

Adult↗
PubMed1998

Injecting behaviours and prevalence of hepatitis B, C and D markers in New Zealand injecting drug user populations.

AIM: To determine the seroprevalence of hepatitis C virus (HCV), hepatitis B virus (HBV) & hepatitis D virus (HDV) markers of infection among injecting drug user populations in New Zealand and to examine the relationship between demographic features, risk behaviours and infection. METHODS: A total of 323 current injecting drug users completed a questionnaire that explored their needle and syringe using behaviours. Information was collected on injection pattern, sharing behaviours and methods of cleaning needles and syringes. Two hundred and forty-one respondents gave blood samples which were tested for hepatitis B, C and D markers. RESULTS: Over half the respondents (59%) were male and 41% were female. Most (89%) identified as European. Sixty-four percent were anti-HCV positive. The likelihood of infection increased with age and duration of injecting. Forty-one percent (33/81) of those aged 25 or under, sixty-four percent (45/70) of those aged 26-30 and eighty-seven percent (78/90) over 30 were anti-HCV positive. Those who tested anti-HCV positive had been injecting for an average of 12.0 years compared to 6.0 years for those were anti-HCV negative. The results for hepatitis B are to be reported fully at a later date. Sharing behaviour was also a factor although this was less important as an independent factor. Comparisons with earlier surveys suggested that there has not been a significant decline in the rate of sharing needles and syringes since the initial period following introduction of the needle exchange programme. CONCLUSION: The prevalence of hepatitis C infection is common among injecting drug users of all ages. Without a significant reduction in sharing behaviour, particularly among younger injecting drug users, it is unlikely that the prevalence of hepatitis C among injecting drug users will decline in the future. Evidence suggests that the carriage of hepatitis C is higher than that of hepatitis B which would help explain the differing rates of prevalence. However, the risk of future transmission of other parenterally transmitted diseases remains high without a further significant decline in sharing behaviour.

Adolescent↗
PubMed1998

ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families.

The apolipoprotein E (ApoE) genotype is a significant risk factor and modulator of age of onset of Alzheimer's disease (AD). We analyzed the effect of the ApoE genotype in two distinct early-onset familial AD groups: families with a mutation in the presenilin-1 gene (PS-1) on chromosome 14, and families without a mutation detectable in the PS-1, presenilin-2 (PS-2), and the amyloid precursor protein (APP) gene (non-PS early-onset familial AD). The ApoE genotype is clearly shown not to modulate age of onset in families with a mutation in the PS-1 gene and families with no lesion detectable in either the presenilin or APP gene. The effects of a double dose of ApoE4 on age of onset were not assessed in the PS-1 AD families due to the lack of any affected ApoE4 homozygotes in the sample set; this insufficiency will need to be assessed in further studies. There was no association between the ApoE4 allele and AD in the PS-1 families. Non-PS early-onset AD families were shown to have a significantly higher frequency of ApoE4 compared to controls and the PS-1 AD group. These observations are important and suggest that 1) other genetic and environmental factors modify the AD phenotype in PS-1 and non-PS early-onset families; and 2) the ApoE4 allele is a significant risk factor in the etiology of non-PS early-onset AD and will be a useful adjunct in the diagnosis of unaffected family members.

Alleles↗
PubMed1998

Cloning and characterization of the presenilin-2 gene promoter.

Mutations in the presenilin-2 (PS-2) have been shown to cause early onset Alzheimer's disease (AD) in a series of families known as the Volga Germans and in an unrelated Italian kindred. Expression of the PS-2 gene is regulated during AD, aging, development and brain injury. Although expressed primarily in neurons, enhanced levels of PS-2 have been reported in astrocytes activated by neuronal damage. Understanding the regulation of the PS-2 gene may thus provide an insight into its role in AD. We have isolated a 3635 bp DNA fragment that contains 2934 bp of DNA sequence upstream from the PS-2 gene. Primer extension analysis was used to map three major transcriptional start sites within the PS-2 gene. The promoter sequence, upstream of each transcriptional start site, does not contain TATA or CAAT boxes but does contain several GC rich sites (Sp-1 and AP-2). A reporter gene construct containing the PS-2 promoter (PS2P, -2934 to +702) transfected into M17 cells drives basal transcription to 20% of the levels of the SV-40 viral promoter. Addition of NGF to PC-12 cells was found to upregulate the PS2P promoter and an NGF-responsive element was localized by deletional analysis between -403 and +13 within the promoter. Since the PS-2 gene has multiple start sites and the upstream sequence is GC rich with no TATA box, the PS-2 promoter is consistent with the GC class of 'housekeeping' genes.

5' Untranslated Regions↗
PubMed1998

Accuracy of CT biopsy: laser guidance versus conventional freehand techniques.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether laser-guided computed tomographic (CT) biopsy is more accurate than CT-guided biopsy with conventional freehand techniques. MATERIALS AND METHODS: Two independent operators performed an equal number of freehand and laser-guided needle passes at varying single and double angles (0 degree, 30 degrees, 60 degrees, 25 degrees/30 degrees, and 25 degrees/60 degrees) on targets within six pork and beef phantoms. A total of 180 biopsy passes were performed, and error distances of needle tip to target were tabulated. Data were analyzed by means of repeated measures analysis of variance (ANOVA) to compare the accuracy of laser guidance with freehand passes. ANOVA and correlation analysis were also used to confirm the relative equivalency of phantom targets and biopsy parameters. RESULTS: Overall, laser-guided passes were statistically significantly more accurate than freehand passes. Mean error with laser guidance was 5.01 mm (standard error [SE] = 0.41 mm), whereas mean error with freehand techniques was 10.58 mm (SE = 0.82 mm) (F = 52.0, df = 1.17, P = .0001). Ninety-three percent of laser-guided passes and 56% of freehand passes were within 1 cm of the intended target. Error increased for both laser-guided and freehand techniques with larger angles or double-angle biopsies, but the increases were greater with freehand technique. No statistically significant differences existed between the targets themselves or biopsy parameters for the two operators. CONCLUSION: Laser-guided CT biopsies were more accurate than freehand CT biopsies. Practical advantages of laser guidance over freehand CT biopsy methods may include decreased procedure times and reduced patient morbidity.

Animals↗
PubMed1998

A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1.

We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree with 17 affected individuals of both sexes in three generations. The disease is characterized by progressive dementia which is, in most cases, preceded by spastic paraparesis. Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for Abeta but lacked a congophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (delta9) of the presenilin 1 (PS1) gene from the mRNA: unlike previous examples of the delta9 variant, the deletion was not caused by a splice acceptor site mutation.

Age of Onset↗
PubMed1998

Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations.

Adapalene 0.1% gel (Differin gel) is a recently introduced topical treatment for mild to moderate acne which has been demonstrated to be much better tolerated and at least as effective as tretinoin 0.025% gel. We compared the tolerance of adapalene 0.1% gel with six different formulations and concentrations of tretinoin. A total of 55 healthy human subjects were enrolled in two controlled, randomized, observer blinded, intraindividual comparison studies. In the first study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.01% and 0.025% gel, and petrolatum (control). In the second study, adapalene 0.1% gel was evaluated for its 21-day cumulative irritation potential compared with tretinoin 0.025%, 0.05% and 0.1% cream, tretinoin 0.1% gel microsphere, and petrolatum (control). In both studies, cumulative irritation scores helped to define three groups of common irritancy potential, with significant differences between each group. In study A, the three groups were in descending order of irritancy: tretinoin 0.1% cream and tretinoin 0.05% cream; tretinoin 0.025% gel, tretinoin 0.01% gel and tretinoin 0.025% cream; adapalene 0.1% gel and petrolatum (control). In study B, the three groups were in descending order of irritancy: tretinoin 0.1% cream; tretinoin 0.05% cream, tretinoin 0.025% cream and tretinoin 0.1% gel microsphere; adapalene 0.1% gel and petrolatum (control). The experimental results show that adapalene 0.1% gel is significantly better tolerated than any of six formulations of tretinoin, including two gels, three creams and a microsphere formulation, ranging in potency from 0.01% to 0.1%.

Acne Vulgaris↗
PubMed1998

Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris.

A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.

Acne Vulgaris↗
PubMed1997

Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation.

We describe a new mutation causing Alzheimer's disease (AD) in presenilin-1 (N135D) that is at the homologous site to the presenilin 2 mutation (N141I) in Volga German kindreds. The phenotype of PS1 N135D is an early-onset (34-38 years) disease. The mutation forms part of, and extends, the alpha-helical array of mutations in transmembrane 2 of the presenilins and leads to the suggestion that disruption of this helical face is the molecular insult that leads to disease.

Adult↗
PubMed1997

Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22.

An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We mapped the disease locus to an approximately 26-cM region of chromosome 17q21-22 with a maximum two-point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP-17 candidate region, were also sequenced. This analysis included the microtubule-associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed.

Adult↗
PubMed1997

Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients.

BACKGROUND: Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris. METHODS: A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products. RESULTS: A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p < 0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported. CONCLUSION: The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.

Acne Vulgaris↗
PubMed1997

An experimental study of intra aortic balloon pumping within the intact human aorta.

OBJECTIVE: Intra-aortic balloon pumping is a therapeutic technique which carries a significant morbidity related to the interaction between the balloon catheter and the aorta. The aim of this study was to visualise directly the dynamic action of the balloon catheter within the cadaveric human aorta in an artificial circulation. METHODS: An artificial circulation was constructed using of PVC tubing, a filter and a roller pump. A series of five intact cadaveric human aortas were then individually studied by placing each in series within the circuit. A balloon catheter was advanced via the left common iliac artery into the descending aorta under direct angioscopic vision. Balloon pumping was then commenced. The circuit was perfused with normal saline at a flow rate of 3 l/min. Pump actions of 1:1 and 1:2 were simulated. Each aorta at the end of the experiment was subjected to histological examination. RESULTS: The balloon only appeared to make direct contact with the wall of the aorta during deflation when it was swept to one side by the circulating fluid. During maximal inflation the only points of contact were the tip of the catheter and the entry site. Side branches of the aorta were not occluded by the balloon. There was considerable atheromatous debris visualised within the lumen of the aorta. Atheromatous plaques were seen to fissure and disrupt by a pressure wave action and not by direct contact with the balloon. CONCLUSION: The balloon catheter moves relative to the wall of the aorta during inflation and deflation. Contact between the balloon and the aorta only occurs during deflation. Side branches of the aorta are not occluded by the catheter. Plaque disruption and embolus formation appear to result from pressure wave action rather than direct contact with the balloon. This may have implications for future balloon design. Further investigation of this poorly understood interaction between the balloon and the aortic wall is required.

Adult↗
PubMed1997

'Ending up a GP': a qualitative study of junior doctors' perceptions of general practice as a career.

OBJECTIVE: This study aimed to investigate junior doctors' perception of general practice as a career. METHOD: In-depth interviews with a purposive sample of 54 junior doctors were carried out. RESULTS: Three main criteria were identified: clinical content of practice, lifestyle, and organizational context of practice. Clinical content was most highly valued, but was recognized to conflict with lifestyle. Compared with hospital medicine, general practice was associated with inferior clinical content but superior lifestyle. Views on organizational context were more equivocal. Choice of general practice as a career was often based on negative judgements. CONCLUSIONS: Junior doctors' perceptions of general practice are expressions of a hospital-centric culture. Criteria for career choice are diffuse and complex. There was no evidence that the 1990 GP Contract deterred recruitment. The compromise between intrinsic satisfaction and lifestyle may be significant for GP morale.

Adult↗
PubMed1997

An assessment of residents' competence in the delivery of bad news to patients.

PURPOSE: To assess the level of residents' competence in delivering bad news to patients. METHOD: In June 1995, 25 residents (of 116) in the Wayne State University general internal medicine residency program volunteered to participate in the study, which consisted of videotaped interviews of a simulated patient whose profile had been developed to highlight the delivery of a diagnosis of lung cancer. The residents were evaluated using an instrument based on a review of the current literature regarding the skills considered necessary for giving bad news in a caring and informative manner. The instrument contained 16 items, seven in the informative category and nine in the affective category. Each item was rated on a five-point Likert scale (from 1 = "doesn't do this" to 5 = "does this very well"). A rating of > or = 4 on any item indicated competence in the skill area measured by that item. All interviews included in the study were rated by all six of the authors. Interrater reliability was calculated to be .91. RESULTS: In all, 22 interviews (three by women, 19 by men) were included in the study. The residents' ages ranged from 26 to 35 years; the numbers of years since graduation from medical school ranged from two to six. Twenty were third- or fourth-year residents ready to graduate; the other two were completing their first year. Mean ratings in the informative category ranged from 1.51 to 4.51; for three items, mean ratings were > or = 4. The total mean rating for all the items in this category was 3.42. Mean ratings in the affective category ranged from 1.15 to 4.75; for three items, mean ratings were > or = 4. The total mean rating for all the items in this category was 3.45. CONCLUSION: The residents showed a general lack of competence in delivering bad news. The skill items with the lowest ratings were primarily related to eliciting the patient's perspective, which may represent a weakness on the part of the residency program in teaching the residents to use a "patient-centered" interviewing style. The results of this study will form the basis of a curriculum to improve residents' comfort with and skills for delivering bad news to patients.

Adult↗
PubMed1997

Cefsulodin chocolate blood agar: a selective medium for the recovery of Haemophilus influenzae from the respiratory secretions of patients with cystic fibrosis.

A modified chocolate blood agar medium incorporating cefsulodin, a semi-synthetic cephalosporin, was developed and compared with non-selective chocolate blood agar and selective haemin-bacitracin blood agar for the routine isolation of Haemophilus influenzae from the respiratory secretions of patients with cystic fibrosis. The results showed that cefsulodin chocolate blood agar improved the recovery rate of H. influenzae in this group of patients. The medium was stable on storage for 10 days at 4 degrees C.

Agar↗