Biomedical subjects

D A Ross

Publications and source records attributed to D A Ross.

At least 37 records · Page 2Linked to original sources

PubMed2001

Adenoid cystic carcinoma: a retrospective clinical review.

Adenoid cystic carcinoma (ACC) are uncommon tumors, representing about 10% to 15% of head and neck tumors. We compare the survival and control rates at our institution with those reported in the literature, and examine putative predictors of outcome. All patients registered with the tumor registry as having had ACC were identified. Demographic and survival variables were retrieved from the database. Additionally, a chart review of all patients was done to obtain specific information. Minor gland tumors were staged using the American Joint Committee on Cancer's criteria for squamous cell carcinomas in identical sites. Histopathologic variables retrieved included grade of the tumor, margins, and perineural invasion. Treatment modalities, field sizes, and radiation doses were recorded in applicable cases. An effort to retrieve archival tumor specimens for immunohistochemical analysis was undertaken. A total of 69 patients were treated for ACC from 1955 to 1999. One patient, who presented with fatal brain metastasis, was excluded from further analysis. Of the remaining 68 patients, 30 were men and 38 were women. The average age at diagnosis was 52 years, and mean follow-up was 13.2 years. Mean survival was 7.7 years. Overall survival (OS) rates at 5, 10, and 15 years were 72%, 44%, and 34%, and cause-specific survival was 83%, 71%, and 55%, respectively. Recurrence-free survival rates were 65%, 52%, and 30% at 5, 10, and 15 years, with a total of 29 of 68 (43%) eventually suffering a recurrence. Overall survival was adversely affected by advancing T and AJCC stage. Higher tumor grades were also associated with decreased OS, although the numbers compared were small. Primaries of the nasosinal region fared poorly when compared with other locations. Total recurrence-free survival, local and distant recurrence rates were distinctly better in primaries of the oral cavity/oropharynx when compared with those in other locations. Reduced distant recurrence-free survival was significantly associated with increasing stage. No other variables were predictive for recurrence. Additionally, we found that nasosinal tumors were more likely to display higher stage at presentation, and were more often associated with perineural invasion. Also of interest was the association of perineural invasion with margin status, with 15 of 20 patients with positive margins displaying perineural invasion, while only 5 of 17 with negative margins showed nerve invasion (P = 0.02). On immunohistochemistry, 2 cases of the 29 (7%) tumor specimens found displayed HER-2/neu positivity. No correlation between clinical behavior and positive staining could be demonstrated. Our data concur with previous reports on ACC in terms of survival and recurrence statistics. Stage and site of primary were important determinants of outcome. Grade may still serve a role in decision making. We could not demonstrate any differences attributable to primary modality of therapy, perhaps due to the nonrandomization of patients into the various treatment tracks and the inclusion of palliative cases. Similarly, perineural invasion, radiation dose and field size, and HER-2/neu positivity did not prove to be important factors in our experience.

Carcinoma, Adenoid Cystic↗

PubMed2001

Genome-tagged mice (GTM): two sets of genome-wide congenic strains.

An important approach for understanding complex disease risk using the mouse is to map and ultimately identify the genes conferring risk. Genes contributing to complex traits can be mapped to chromosomal regions using genome scans of large mouse crosses. Congenic strains can then be developed to fine-map a trait and to ascertain the magnitude of the genotype effect in a chromosomal region. Congenic strains are constructed by repeated backcrossing to the background strain with selection at each generation for the presence of a donor chromosomal region, a time-consuming process. One approach to accelerate this process is to construct a library of congenic strains encompassing the entire genome of one strain on the background of the other. We have employed marker-assisted breeding to construct two sets of overlapping congenic strains, called genome-tagged mice (GTMs), that span the entire mouse genome. Both congenic GTM sets contain more than 60 mouse strains, each with on average a 23-cM introgressed segment (range 8 to 58 cM). C57BL/6J was utilized as a background strain for both GTM sets with either DBA/2J or CAST/Ei as the donor strain. The background and donor strains are genetically and phenotypically divergent. The genetic basis for the phenotypic strain differences can be rapidly mapped by simply screening the GTM strains. Furthermore, the phenotype differences can be fine-mapped by crossing appropriate congenic mice to the background strain, and complex gene interactions can be investigated using combinations of these congenics.

Animals↗

PubMed2001

The gene for the axonal cell adhesion molecule TAX-1 is amplified and aberrantly expressed in malignant gliomas.

The human TAX-1 gene encodes a Mr 135,000 glycoprotein that is transiently expressed on the surface of a subset of neurons during development and is involved in neurite outgrowth. The TAX-1 gene has been mapped to a region on chromosome 1 that has been implicated in microcephaly and the Van der Woude syndrome. Using restriction landmark genome scanning to search for amplified genes in gliomas, we found TAX-1 to be amplified in 2 high-grade gliomas among a group of 26 gliomas investigated. Real-time reverse transcription-quantitative PCR analysis detected high levels of TAX-1 mRNA in glial tumors, even in the absence of TAX-1 gene amplification. Immunohistochemical analysis revealed abundant levels of TAX-1 in neoplastic glial cells of glioblastoma multiforme tumors. Because glial tumors are highly invasive and in view of the role of TAX-1 in neurite outgrowth, we investigated the potential role of TAX-1 in glioma cell migration. Using an in vitro assay, we found that the migration of glioma tumor cells is profoundly reduced in the presence of either an anti-TAX-1 antibody or a TAX-1 antisense oligonucleotide. Our findings suggest that TAX-1 plays a role in glial tumorigenesis and may provide a potential target for therapeutic intervention.

Blotting, Northern↗

PubMed2001

Magnetic resonance imaging of ethyl-nitrosourea-induced rat gliomas: a model for experimental therapeutics of low-grade gliomas.

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 +/- 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.

Angiogenesis Inhibitors↗

PubMed2001

Prevalence of HIV and Chlamydia trachomatis infection in 15--19-year olds in rural Tanzania.

OBJECTIVE: To estimate the prevalence of HIV and Chlamydia trachomatis (CT) infections amongst adolescents in rural Mwanza Region, Tanzania and their association with demographic variables. DESIGN: Population-based cross-sectional survey. METHODS: All 15--19-year olds living in households selected by random cluster sampling were invited to participate. After interview, urine was tested for HIV and CT. RESULTS: 9445 15--19-year olds were enrolled. HIV prevalence was 0.6% (95% CI: 0.4--0.8%) in males and 2.4% (95% CI: 2.0--2.8%) in females, and increased steeply with age (trend: P < 0.006 and P < 0.001, respectively). After adjustment for age, risk of HIV infection was significantly associated with female sex (OR=4.3), never having been to primary school in males (OR=2.7), and current symptoms of genital discharge (OR=2.3) or genital ulcer (OR=5.3) in females. The prevalence of CT was 1.0% (95% CI: 0.8--1.4%) in males and 2.4% (95% CI: 2.0-2.9%) in females. After adjustment for age, CT infection was associated with female sex (OR=2.4), reported current symptoms of STD (males OR=2.5, females OR=1.9) and positive leucocyte esterase (LE) test (males OR=3.1, females OR=2.6). Eighty-two percent of males and 79% of females with CT were asymptomatic. There was no association between CT and HIV infection in either sex. CONCLUSIONS: There is a high prevalence of HIV and CT amongst adolescents, especially young women, in this rural population, highlighting the need for effective interventions to improve adolescent reproductive health. The high rates of asymptomatic infection imply that innovative strategies are needed to reach and treat young people with STD.

Adolescent↗

PubMed2001

Positional cloning of the mouse saccharin preference (Sac) locus.

Differences in sweetener intake among inbred strains of mice are partially determined by allelic variation of the saccharin preference (Sac) locus. Genetic and physical mapping limited a critical genomic interval containing Sac to a 194 kb DNA fragment. Sequencing and annotation of this region identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial backcrossing of the 194 kb chromosomal fragment containing the Tas1r3 allele from the high-sweetener-preferring C57BL/6ByJ strain onto the genetic background of the low-sweetener-preferring 129P3/J strain rescued its low-sweetener-preference phenotype. Polymorphisms of Tas1r3 that are likely to have functional significance were identified using analysis of genomic sequences and sweetener-preference phenotypes of genealogically distant mouse strains. Tas1r3 has two common haplotypes, consisting of six single nucleotide polymorphisms: one haplotype was found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor responds to sweeteners.

Alleles↗

PubMed2001

A national agenda for public health informatics.

The American Medical Informatics Association 2001 Spring Congress brought together the public health and informatics communities to develop a national agenda for public health informatics. Discussions on funding and governance; architecture and infrastructure; standards and vocabulary; research, evaluation, and best practices; privacy, confidentiality, and security; and training and workforce resulted in 74 recommendations with two key themes: (1) all stakeholders need to be engaged in coordinated activities related to public health information architecture, standards, confidentiality, best practices, and research and (2) informatics training is needed throughout the public health workforce. Implementation of this consensus agenda will help promote progress in the application of information technology to improve public health.

Congresses as Topic↗

PubMed2001

The notch intracellular domain can function as a coactivator for LEF-1.

Notch signaling commences with two ligand-mediated proteolysis events that release the Notch intracellular domain, NICD, from the plasma membrane. NICD then translocates into the nucleus and interacts with the DNA binding protein CSL to activate transcription. We found that NICD expression also potentiates activity of the transcription factor LEF-1. NICD stimulation of LEF-1 activity was context dependent and occurred on a subset of promoters distinct from those activated by beta-catenin. Importantly, the effect of NICD does not appear to be mediated through canonical components of the Wnt signaling pathway or downstream components of the Notch pathway. In vitro assays show a weak association between the C-terminal transactivation domain of NICD and the high-mobility group domain of LEF-1, suggesting that the two proteins interact in vivo. Our data therefore describe a new nuclear target of Notch signaling and a new coactivator for LEF-1.

Animals↗

PubMed2001

Effect of varying carbohydrate and fat content of milk replacer on body composition of Holstein bull calves.

The objective of this study was to determine the effect of varying concentrations of dietary fat and carbohydrate on changes in body composition of Holstein bull calves fed under isocaloric and isonitrogenous intake conditions. Thirty-two calves were assigned to a randomized block design with three dietary treatments, eight calves per treatment, and one baseline group of eight calves. Animals were reared from birth to 85 kg live BW (SEM = 0.57). All calves began treatments between 2 and 6 d of age. Three different milk replacer treatment diets were designed to deliver 14.8 (low fat, LF), 21.6 (medium fat, MF), or 30.6% of DM (high fat, HF) fat; 55.3, 46.7, or 35.4% of DM lactose; and 23.5, 24.8, or 27.0% of DM CP, respectively. Gross energy values were 4.62, 5.09, and 5.77 Mcal/kg for the LF, MF, and HF milk replacers, respectively. From d 1 to 14, calves were offered 0.24 Mcal intake energy/kg BW(0.75), adjusted weekly based on increases in BW, and 0.28 Mcal intake energy/kg BW(0.75) from d 15 to slaughter. Dry feed was not offered. Dry matter, energy, CP, and fat intakes were 55.2 kg, 257.6 Mcal, 13.0 kg, and 8.2 kg; 52.8 kg, 268.8 Mcal, 13.1 kg, and 11.4 kg; and 46.8 kg, 270.3 Mcal, 12.6 kg, and 14.3 kg for the LF, MF and HF treatments, respectively. Energy and CP intakes did not differ among treatments (P = 0.63 and 0.79, respectively). Fat and DMI were different among treatments (P = 0.001 and 0.02, respectively). Empty BW gains were 0.61, 0.61, and 0.65 kg/d for LF, MF, and HF, respectively, and were not different among treatments (P = 0.27). Empty body CP, water, and ash gain were not different among treatments (P = 0.65, 0.99, and 0.57, respectively). Empty body retained energy and fat gain were 27.2 and 57.7% greater for calves fed the HF than for those fed the LF diet (P = 0.06 and 0.006, respectively). Fat as a percentage of the whole empty body on a water-free basis was lower for calves consuming the LF diet (28.6%) than for those fed the HF diet (34.6%), whereas percentage of CP on an empty body, water-free basis was greater for calves consuming the LF diet (59.2%) than for those fed the HF diet (54.9%) (P = 0.006). The results of this study demonstrated that, under isocaloric and isonitrogenous intake conditions, equivalent dietary energy from fat compared to carbohydrate, above 15% fat, has no beneficial purpose unless additional fat deposition is required in the animal. Further, the data demonstrate significant changes in body composition independent of growth rate.

Animal Feed↗

PubMed2001

The Soho nail bomb: the UCH experience. University College Hospital.

This paper documents the clinical course of the casualties treated at University College Hospital, following the detonation of a terrorist nail bomb in a public house in Soho, London. The need for adequate primary debridement is paramount, including consideration of definitive primary limb amputation.

Adult↗

PubMed2000

Increased secondary generalization of partial seizures after temporal lobectomy.

OBJECTIVE: This study tests the primary hypothesis that secondary generalization of partial seizures is more likely after anterior temporal lobectomy (ATL) than before ATL, and the secondary hypothesis that antiepileptic drug withdrawal accounts for increased generalization of seizures postoperatively. BACKGROUND: The authors observed that some patients had generalized tonic-clonic (GTC) seizures after but not before ATL, by using a new classification of outcome that compares preoperative and postoperative seizure frequencies by seizure type. METHODS: Twenty patients with refractory temporal lobe epilepsy had postoperative GTC seizures or nongeneralizing complex partial (CP) seizures in a consecutive ATL series. All had reduced seizure frequency postoperatively and more than 2 years of follow-up on antiepileptic drugs. The authors calculated a generalization fraction, as (number of GTC seizures)/(number of CP and GTC seizures), for 2 years before and 2 years after surgery. RESULTS: Postoperative generalization fractions were greater than preoperative generalization fractions (Wilcoxon signed-rank test, p < 0.01). Most postoperative GTC seizures were not associated with antiepileptic drug withdrawal, and postoperative GTC seizures were not more associated with drug withdrawal than were postoperative CP seizures. Patients with more than two GTC seizures per year preoperatively were more likely than other patients to have postoperative GTC seizures. CONCLUSIONS: Patients with reduced seizure frequency after ATL have a greater tendency for partial seizures to secondarily generalize postoperatively. This phenomenon is not explained by antiepileptic drug withdrawal.

Anticonvulsants↗

PubMed2000

Young people's health in developing countries: a neglected problem and opportunity.

Although the number of young people in developing countries is increasing, their health has not been considered a priority. This is partly because of their lower mortality relative to other age groups, but also because of a lack of appropriate data collection and analysis. However, the burden of disease in young people is not trivial, and most importantly, it is during adolescence that long-term health-related behaviours are formed. Most research investigating health problems in young people has tended to concentrate on a narrow conception of problem areas, such as those relating to reproduction and substance abuse. However, in many developing countries diseases such as schistosomiasis and intestinal parasites may also have a disproportionate impact on young people's health. Young people often have radically different perceptions and priorities in terms of health and disease to those of health planners. Successful programmes will need to incorporate the views of young people themselves. Interventions targeted at young people have enormous potential for primary and secondary prevention of a huge range of health problems and present an opportunity that should not be ignored.

Adolescent↗

PubMed2000

Investigation of the causal relationship between tracheotomy and aspiration in the acute care setting.

OBJECTIVE: To investigate the causal relationship, if any, between tracheotomy and incidence of aspiration in the acute care setting. STUDY DESIGN: Prospective, consecutive. PATIENTS AND METHODS: Twenty adult patients evaluated between February 1997 and October 1999 participated. Criteria for inclusion were a dysphagia evaluation before tracheotomy, subsequent tracheotomy and placement of a tracheotomy tube, and then a repeat dysphagia evaluation after tracheotomy prior to decannulation. This permitted the causal relationship between tracheotomy and incidence of aspiration to be investigated. Differences between duration of tracheotomy placement and age were analyzed with the Student t test and for non-parametric nominal data the chi2 test was applied. RESULTS: No causal relationship between tracheotomy and aspiration was exhibited, as 19 of 20 (95%) subjects exhibited the same aspiration status before and after tracheotomy. All 12 (100%) subjects who aspirated before tracheotomy also aspirated after tracheotomy and 7 of 8 (88%) subjects who did not aspirate before tracheotomy also did not aspirate after tracheotomy (P > .05). In addition, no significant differences were observed between aspiration status and days since tracheotomy or age (P > .05). CONCLUSION: In the acute care setting, no causal relationship between tracheotomy and aspiration status was exhibited.

Adult↗

PubMed2000

Stereotactic radiosurgery of cerebral arteriovenous malformations with a multileaf collimator and a single isocenter.

OBJECTIVE: To prospectively demonstrate the safety and efficacy of stereotactic radiosurgery for arteriovenous malformations (AVMs) of the brain with a linear accelerator fitted with a multileaf collimator. METHODS: A novel radiosurgery system was developed at the University of Michigan Medical Center with a standard multileaf collimator and a computer-controlled radiotherapy system. Data were accumulated prospectively on all patients undergoing treatment with this system since treatment began in 1995. RESULTS: Thirty-six patients with 37 AVMs have undergone treatment to date. At more than 3 years since treatment, 15 of 16 AVMs with a volume of less than 10 cc were proven to be obliterated by angiography or magnetic resonance imaging, and one was considered a treatment failure. At more than 24 months since therapy, all four AVMs with a volume of 10 to 25 cc were obliterated. Four patients with AVMs with a volume of more than 25 cc have undergone staged therapy, treating the entire volume to 10 Gy twice, but none has been followed long enough to demonstrate a final outcome. There were four transient and no permanent complications. CONCLUSION: Our early data indicate that stereotactic radiosurgery of cerebral AVMs with a linear accelerator and a multileaf collimator is safe and effective. Large AVMs may be especially suitable for this mode of therapy. Staged treatment of very large AVMs seems to be a promising addition to standard treatment, but longer follow-up is necessary to confirm that complete obliteration can be achieved.

Adolescent↗

PubMed2000

Persistent headache after supratentorial craniotomy.

OBJECTIVE: Although the incidence, possible causes, and treatment of persistent headache after suboccipital craniotomy have been discussed extensively, few data have been published regarding persistent headache after supratentorial craniotomy. METHODS: We retrospectively analyzed the senior author's patient series of 145 consecutive anterior temporal lobectomies for intractable epilepsy performed during a 9-year period. To eliminate confounding causes of headache, all patients studied were seizure-free, none had progressive mass lesions or persisting vascular anomalies, and none had major complications of surgery. With the permission of the institutional review board, information on headache was obtained from patient records, the patients' neurologists, and the patients themselves. RESULTS: Of the 145 consecutive patients who underwent operations, 126 patients had adequate follow-up for analysis. Of the 126 patients, 104 did not have headaches and were not using regular analgesics 2 months postoperatively. Twenty-two patients had headaches persisting beyond 2 months. Seven (5.6%) of the 126 patients had headaches that lasted more than 2 months but less than 1 year, and they were free of recurrent headaches 1 year postoperatively. Fifteen (11.9%) of the 126 patients had ongoing headaches 1 year after surgery. Regarding headache severity, 4.0% of patients had medically uncontrolled headaches, and 3.2% continued to require prescription drugs for headaches 1 year postoperatively. CONCLUSION: Although the incidence of persistent head pain after supratentorial craniotomy is lower than that reported for posterior fossa procedures, the incidence is not trivial. The cause of persistent pain deserves further investigation.

Craniotomy↗

PubMed2000

A direct brain interface based on event-related potentials.

Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERP's. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.

Adult↗

PubMed2000

Ictal spiking patterns recorded from temporal depth electrodes predict good outcome after anterior temporal lobectomy.

PURPOSE: Investigators have shown that the presence of ictal spiking (IS) recorded from temporal depth electrodes is associated with mesial temporal sclerosis (MTS). We investigated the relation of IS to seizure control and pathology after anterior temporal lobectomy (ATL). METHODS: All patients undergoing intracranial ictal monitoring from a single institution since 1989 were identified. Those who did not undergo ATL or had postoperative follow-up of <1 year were excluded. All received at a minimum bilateral temporal depth electrodes. Ictal recordings were reviewed for the presence of IS, and the proportion of seizures with IS was determined for each patient. Outcome was determined by using Engel's classification. Surgical specimens were reviewed for pathology. Statistics used were chi2, Fisher exact test, and Wilcoxon rank sum. RESULTS: Forty patients with 571 seizures were reviewed. In 292 seizures from 32 patients, IS was seen. Outcomes were 24 class I (22 with IS), five class II (four with IS), three class III (one with IS), seven class IV (four with IS), and one lost to follow-up (with IS). Pathologic review revealed 25 with MTS, 22 of whom had IS. The presence of IS was associated with class I outcomes (p = 0.04), but not MTS (p = 0.06). Patients with class I outcomes had a significantly greater proportion of seizures with IS (mean, 0.58 +/- 0.3) compared with other outcomes (mean, 0.30 +/- 0.3, p = 0.02). CONCLUSIONS: The presence of IS and higher proportion of seizures with IS correlated with good seizure outcome after ATL. This information may be used in preoperative counseling.

Electrodes, Implanted↗

PubMed2000

Prevalence of eye diseases in primary school children in a rural area of Tanzania.

AIMS: The study measured the prevalence of eye diseases in primary school children between 7 and 19 years of age in a rural area of Tanzania, and investigated whether teachers could successfully provide the first component of a school eye screening service. METHODS: Teachers from each of three primary schools in Mwanza Region tested visual acuity using a Snellen's E chart in 1438 pupils. 1386 of these pupils were then interviewed and underwent a full eye examination by an eye team. RESULTS: 10 pupils (0.7%) had bilateral poor eyesight (visual acuity worse than 6/12), and an additional 14 pupils (1.0%) had unilateral poor eyesight. Significant refractive errors causing visual acuity less than 6/12 (1.0%), strabismus (0. 5%), and amblyopia (0.2%) were uncommon. Overall, 76 pupils (5.5%) had active trachoma, though the prevalence was 15.5% in the poorest school. 73 pupils (5.3%) reported night blindness, eight (0.6%) had Bitot's spots, and 11 (0.8%) had corneal scars. Simple screening by teachers correctly identified 80% of the pupils who were found to have bilateral poor eyesight by the eye team, with 91% specificity. CONCLUSION: The prevalence of significant refractive errors was not high enough to justify a school eye screening programme solely for this purpose. However, a programme may be justified in areas where trachoma is common. Further research is needed to validate the frequent reports of night blindness and to establish the public health importance of vitamin A deficiency in this age group.

Adolescent↗