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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 37 records · Page 2Linked to original sources
PubMed2003

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.

Adolescent↗
PubMed2003

Contribution of clinical breast examination to mammography screening in the early detection of breast cancer.

OBJECTIVES: As the benefit of clinical breast examination (CBE) over that of screening mammography alone in reducing breast cancer mortality is uncertain, it is informative to monitor its contribution to interim measures of effectiveness of a screening programme. Here, the contribution of CBE to screening mammography in the early detection of breast cancer was evaluated. SETTING: Four Canadian organised breast cancer screening programmes. METHODS: Women aged 50-69 receiving dual screening (CBE and mammography) (n = 300,303) between 1996 and 1998 were followed up between screen and diagnosis. Outcomes assessed by mode of detection (CBE alone, mammography alone, or both CBE and mammography) included referral rate, positive predictive value, pathological features of tumours (size, nodal status, morphology), and cancer detection rates overall and for small cancers (< or = 10 mm or node-negative). Heterogeneity in findings across programmes was also assessed. RESULTS: On first versus subsequent screen, CBE alone resulted in 28.5-36.7% of referrals, and 4.6-5.9% of cancers compared with 52.6-60.1% of referrals and 60.0-64.3% of cancers for mammography alone. Among cancers detected by CBE, 83.6-88.6% were also detected by mammography, whereas for mammographically detected cancers only 31.7-37.2% were also detected by CBE. On average, CBE increased the rate of detection of small invasive cancers by 2-6% over rates if mammography was the sole detection method. Without CBE, programmes would be missing three cancers for every 10,000 screens and 3-10 small invasive cancers in every 100,000 screens. CONCLUSIONS: Inclusion of CBE in an organised programme contributes minimally to early detection.

Breast Neoplasms↗
PubMed2002

Evaluation of a selective medium for Brucella isolation using natamycin.

AIMS: To select an anti-fungal agent to replace cycloheximide in the media used for isolation of Brucella. METHODS AND RESULTS: One potential agent, natamycin, was evaluated using 28 Brucella isolates, 18 yeasts and 14 fungi. The material for the evaluation included 37 bovine milk samples, six bovine vaginal swabs and 45 milk samples artificially infected with Brucella. The recovery of Brucella only from the artificially-inoculated milk samples increased with the use of the medium containing natamycin instead of cycloheximide, at the same time significantly inhibiting the growth of yeasts, fungi and other bacteria. The inclusion of either anti-fungal agent allowed growth of the 28 Brucella isolates and totally prevented the growth of all 18 yeasts and 13 of the 14 fungi. CONCLUSIONS: Based on the results it was concluded that natamycin would be a suitable alternative to cycloheximide. SIGNIFICANCE AND IMPACT OF THE STUDY: Cycloheximide has become unavailable worldwide and is currently an anti-fungal constituent of the medium often used for isolation of Brucella organisms. The use of natamycin as a replacement in the formulation did not inhibit growth of Brucella and was effective at eliminating most contaminants.

Animals↗
PubMed2002

Evaluation of selective media for Campylobacter isolation when cycloheximide is replaced with amphotericin B.

AIMS: Laboratory media for the isolation of Campylobacter usually contain various selective agents, designed to allow these bacteria to grow whilst suppressing that of other organisms. For example, cycloheximide has often been incorporated into Campylobacter media to inhibit the growth of fungi. The production and availability of cycloheximide, however, has recently decreased due to concerns relating to its potential toxicity for mammalian cells and the compound has also become more expensive as a result. An alternative antifungal agent is necessary, and to address this, the effect of using amphotericin B in place of cycloheximide in Campylobacter selective broths and agars was examined. METHODS AND RESULTS: The growth of Campylobacter strains and the suppression of potential competitor organisms in selective broths or on selective agars containing either amphotericin B or cycloheximide was quantified, using pure microbial cultures. The results were then confirmed by testing food and water samples that contained high levels of micro-organisms, including Campylobacter. CONCLUSIONS: The results of this study indicate that amphotericin B is a suitable replacement for cycloheximide in Campylobacter selective media.

Amphotericin B↗
PubMed2002

Experience with laparoscopic adrenalectomy in pediatric patients.

BACKGROUND: Laparoscopic adrenalectomy (LA) is now being recognized as the standard in the management of benign adrenal pathology in adult patients. Few reports have described the use of this technique in pediatric patients. This study combines experience from 2 institutions with lateral transperitoneal LA in children to analyze our results and the clinical and biochemical response to laparoscopic adrenalectomy in patients with hormonally active adrenal tumors. METHODS: A bi-institutional retrospective review of all patients undergoing LA between January 1997 and January 2001 was performed. Clinical and biochemical data were obtained during routine follow-up. RESULTS: Seventeen laparoscopic adrenalectomies were performed during this period. The average operating time was 120 minutes, mean estimated blood loss was 25 mL, the mean size of the adrenal lesion was 4.8 cm, and the mean length of hospitalization was 35 hours. Resolution of clinical and biochemical parameters of adrenal hyperfunction was accomplished in all patients with adrenocortical hyperplasia and pheochromocytoma in postoperative follow-up. CONCLUSIONS: Laparoscopic adrenalectomy can be performed safely and effectively with a short hospital stay, minimal blood loss, and excellent functional outcome in this age group. The authors believe laparoscopic adrenalectomy is an excellent approach for the management of benign pediatric adrenal pathology.

Adenoma↗
PubMed2001

Short tandem repeat profiling provides an international reference standard for human cell lines.

Cross-contamination between cell lines is a longstanding and frequent cause of scientific misrepresentation. Estimates from national testing services indicate that up to 36% of cell lines are of a different origin or species to that claimed. To test a standard method of cell line authentication, 253 human cell lines from banks and research institutes worldwide were analyzed by short tandem repeat profiling. The short tandem repeat profile is a simple numerical code that is reproducible between laboratories, is inexpensive, and can provide an international reference standard for every cell line. If DNA profiling of cell lines is accepted and demanded internationally, scientific misrepresentation because of cross-contamination can be largely eliminated.

Cell Line↗
PubMed2001

Vitamin B12 and hepatitis C: molecular biology and human pathology.

Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.

Antiviral Agents↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2001

A high-resolution genetic, physical, and comparative gene map of the doublefoot (Dbf) region of mouse chromosome 1 and the region of conserved synteny on human chromosome 2q35.

The mouse doublefoot (Dbf) mutant exhibits preaxial polydactyly in association with craniofacial defects. This mutation has previously been mapped to mouse chromosome 1. We have used a positional cloning strategy, coupled with a comparative sequencing approach using available human draft sequence, to identify putative candidates for the Dbf gene in the mouse and in homologous human region. We have constructed a high-resolution genetic map of the region, localizing the mutation to a 0.4-cM (+/-0.0061) interval on mouse chromosome 1. Furthermore, we have constructed contiguous BAC/PAC clone maps across the mouse and human Dbf region. Using existing markers and additional sequence tagged sites, which we have generated, we have anchored the physical map to the genetic map. Through the comparative sequencing of these clones we have identified 35 genes within this interval, indicating that the region is gene-rich. From this we have identified several genes that are known to be differentially expressed in the developing mid-gestation mouse embryo, some in the developing embryonic limb buds. These genes include those encoding known developmental signaling molecules such as WNT proteins and IHH, and we provide evidence that these genes are candidates for the Dbf mutation.

Animals↗
PubMed2001

Research and teaching access to a large clinical picture archiving and communication system.

PURPOSE: To identify practical issues surrounding delivering digital images from picture archiving and communication systems (PACS) for research and teaching purposes. The complexity of Digital Imaging and Communications in Medicine (DICOM) access methods, security, patient confidentiality, PACS database integrity, portability, and scalability are discussed. A software prototype designed to resolve these issues is described. SYSTEM ARCHITECTURE: A six-component, three-tier, client server software application program supporting DICOM query/retrieve services was developed in the JAWA language. This software was interfaced to a large GE (Mt Prospect, IL) Medical Systems clinical PACS at Northwestern Memorial Hospital (NMH). CONCLUSION: Images can be delivered from a clinical PACS for research and teaching purposes. Concerns for security, patient confidentiality, integrity of the PACS database, and management of the transactions can be addressed. The described software is one such solution for achieving this goal.

Computer-Assisted Instruction↗
PubMed2001

Implementing managed competition in Israel.

As of January 1, 1995, Israel's National Health Insurance (NHI) Law laid the foundations for regulating competition among the country's four private, not-for-profit sick funds. Prior to NHI the sick funds (SFs) had competed without governmental control. Extensive research on NHI implementation and the behavior of the sick funds (SFs) after passage of NHI reveals a paradoxical development: The NHI bill drew on the rhetoric of managed competition and did indeed establish a legal and structural framework for regulating competition among the SFs. Nevertheless, in practice, SF autonomy was constrained and competition over provision of statutory care was limited. Rather than fostering competition, the main thrust of the NHI reforms was to enhance central government's control over SF expenses in order to constrain government expenditures. The NHI reforms did encourage the SFs to cut costs and make visible service improvements. However, the reforms did not lead the SFs to reorganize, expand the scope of their services, or improve clinical quality, as the reformers had hoped. Nor did the reforms help eliminate the SF's operating deficits or insure financial stability for the whole health system. Furthermore, the reforms had unanticipated and undesired outcomes, including aggressive and illegal marketing by SFs and collaboration among SFs to restrict the extent of care provided under compulsory insurance. The Israeli case suggests that the theory of managed competition contains unrealistic assumptions about the types of competitive behavior that result from exposure to managed competition and the capacity of government and health providers to monitor quality. In addition to stemming from universal limitations to the managed competition model, the implementation pattern in Israel reflects local, historical forces and the interplay of Israel's powerful health system actors.

Facility Regulation and Control↗
PubMed2001

Parents' reactions and recommendations after diagnosis and hearing aid fitting.

This study was designed to explore parent reactions to the early stages of audiologic assessment and intervention. A total of 213 parents whose children were under the age of 6 years returned a mail survey. Respondents from 45 states participated. Parents were asked to (1) report the approximate age of diagnosis and hearing aid fitting; (2) comment on reasons for any delays encountered from diagnosis to fitting; and (3) respond to questions concerning their reactions to the initial fitting of amplification. The median age of identification was earlier than some previous investigations; however, substantial delays occurred between diagnosis and hearing aid fitting. Reasons for delay included the need for further audiologic evaluation, problems obtaining return appointments, illness of the child, and difficulties obtaining adequate earmolds. Parent reactions to hearing aids, once fitted, included concerns about appearance and questions about maintenance and use, but attitudes regarding hearing aids and their perceived benefits improved over time.

Adult↗
PubMed2001

Comparison of quality and cost-effectiveness in the evaluation of symptomatic cholelithiasis with different approaches to ultrasound availability in the ED.

Ultrasound is the imaging study of choice for the detection of gallstones, but ultrasound through medical imaging departments (MI Sono) is not readily available on an immediate basis in many emergency departments (EDs). Several studies have shown that emergency physicians can perform ultrasound themselves (ED Sono) to rule out gallstones with acceptable accuracy after relatively brief training periods, but there have been no studies to date specifically addressing the effect of ED Sono of the gallbladder on quality and cost-effectiveness in the ED. In this study, we investigated measures of quality and cost-effectiveness in evaluating patients with suspected symptomatic cholelithiasis during three different years with distinctly different approaches to ultrasound availability. The study retrospectively identified a total of 418 patients who were admitted for cholecystectomy or for a complication of cholelithiasis within 6 months of an ED visit for possible biliary colic. The percentage of patients who had gallstones documented at the first ED visit improved from 28% in 1993, when there was limited availability of ultrasound through the Medical Imaging Department (MI Sono), to 56% in 1995, when MI Sono was readily available, to 70% in 1997, when both MI Sono and ED Sono were readily available (P <.001). There were also significant differences over the 3 years in the mean number of days from the first ED visit to documentation of gallstones (19.7 in 1993, 10.7 in 1995, 7.4 in 1997, P <.001); the mean number of return visits for possible biliary colic before documentation of gallstones (1.67 in 1993, 1.24 in 1995, and 1.25 in 1997, P <.001); and the incidence of complications of cholelithiasis in the interval between the first ED visit for possible biliary colic and the date of documentation of cholelithiasis (6.8% in 1993, 5.9% in 1995, 1.5% in 1997, P =.049). The number of MI Sonos ordered by emergency physicians per case of symptomatic cholelithiasis identified increased from 1.7 in 1993 to 2.5 in 1995 and dropped back to 1.7 in 1997, when 4.2 ED Sonos per study case were also done. The cost of ED Sonos was more than offset by savings in avoiding calling in ultrasound technicians after regular Medical Imaging Department hours. The indeterminate rate for ED Sonos was 18%. Excluding indeterminates, the sensitivity of ED Sono for detection of gallstones was 88.6% (95% CI 83.1-92.8%), the specificity 98.2% (95% CI 96.0-99.3%), and the accuracy 94.8% (95% CI 92.5-96.5%). We conclude that greater availability of MI Sono in the ED was associated with improved quality in the evaluation of patients with suspected symptomatic cholelithiasis but also with increased ultrasound costs. The availability of ED Sono in addition to readily available MI Sono was associated with further improved quality and decreased costs. The indeterminate rate for ED Sono was relatively high, but excluding indeterminates, the accuracy of ED Sono was comparable with published reports of MI Sono.

Adolescent↗