Search PubMed⌕ Search

Biomedical subjects

J E Martin

Publications and source records attributed to J E Martin.

At least 55 records · Page 3Linked to original sources
PubMed1999

Transchromosomal mouse embryonic stem cell lines and chimeric mice that contain freely segregating segments of human chromosome 21.

At least 8% of all human conceptions have major chromosome abnormalities and the frequency of chromosomal syndromes in newborns is >0.5%. Despite these disorders making a large contribution to human morbidity and mortality, we have little understanding of their aetiology and little molecular data on the importance of gene dosage to mammalian cells. Trisomy 21, which results in Down syndrome (DS), is the most frequent aneuploidy in humans (1 in 600 live births, up to 1 in 150 pregnancies world-wide) and is the most common known genetic cause of mental retardation. To investigate the molecular genetics of DS, we report here the creation of mice that carry different human chromosome 21 (Hsa21) fragments as a freely segregating extra chromosome. To produce these 'transchromosomal' animals, we placed a selectable marker into Hsa21 and transferred the chromosome from a human somatic cell line into mouse embryonic stem (ES) cells using irradiation microcell-mediated chromosome transfer (XMMCT). 'Transchromosomal' ES cells containing different Hsa21 regions ranging in size from approximately 50 to approximately 0.2 Mb have been used to create chimeric mice. These mice maintain Hsa21 sequences and express Hsa21 genes in multiple tissues. This novel use of the XMMCT protocol is applicable to investigations requiring the transfer of large chromosomal regions into ES or other cells and, in particular, the modelling of DS and other human aneuploidy syndromes.

Abnormalities, Multiple↗
PubMed1999

Magnetic-field-induced optical transmittance in colloidal suspensions.

Through simulation and experiment we demonstrate that when a magnetic field is applied to a suspension of magnetic particles, the optical attenuation length along the direction of the field increases dramatically, due to the formation of chainlike structures that allow the transmission of light between the strongly absorbing particles. This phenomenon is interesting for two reasons; first, there might be practical applications for this effect, such as optical-fiber-based magnetic field sensors, and second, measuring the time evolution of the optical attenuation length enables us to determine the kinetics of structure formation, which can be compared to the predictions of simulation and theory. In agreement with both simulation and theory, the optical attenuation length increases as a power of time, but much less light is actually transmitted than expected, especially at higher particle concentrations. We conclude that particle roughness, which is not included in either theory or simulation, plays a significant role in structural development, by pinning structures into local minima.

Journal Article↗
PubMed1999

The clinical and economic potential of cyclosporin drug interactions.

The introduction of cyclosporin significantly improved solid organ transplantation outcomes. However, the costs associated with immunosuppressive therapy increased from approximately $US1000 to $US2000 per patient per year with azathioprine (AZA) and prednisone to $US5000 to $US8000 per patient per year with the addition of cyclosporin (1997 values). Because of the financial demands placed on medical care in the current era, research has been directed towards developing drug combinations which potentiate the therapeutic effect of cyclosporin whereby reducing the amount of drug administered and consequently the costs of long term immunosuppressive therapy. To date, many drugs that interact with cyclosporin have been recognised. Included in this list are the azole antifungal drugs, ketoconazole, fluconazole and itraconazole; the calcium channel blockers, diltiazem, verapamil and nicardipine; and the macrolide antibacterials, erythromycin and related compounds. Although all of these drugs increase cyclosporin drug concentrations when used concomitantly, ketoconazole and diltiazem appear to be the best candidates on the basis of reducing financial pressures of chronic immunosuppressive therapy without sacrificing patients' well-being. Studies of various regimens involving the combined use of ketoconazole and cyclosporin have shown that cyclosporin dosages can be reduced by approximately 70 to 85% while maintaining therapeutic blood concentrations in renal, cardiac and liver transplant recipients. The calcium channel blocker, diltiazem, allows a decrease in cyclosporin dosage by approximately 30 to 50% in this same group of organ transplant patients. These reductions in cyclosporin dosage have been achieved with no reported severe adverse effects that would discourage the use of these agents concurrently in practice. The combined use of cyclosporin and ketoconazole or diltiazem could reduce medication costs by approximately $US915 to $US3000 per year per patient. If all patients treated with cyclosporin are considered, these combinations could reduce medication costs by hundreds of millions of dollars per year in the US alone. While these are promising approaches, further characterisation of these drug interactions is necessary before this practice is adopted as standard protocol worldwide. The objective of this paper is to review the clinical and economic potential of cyclosporin-sparing agents such as the azole antifungal drugs and calcium channel blockers in an attempt to decrease the costs associated with this expensive immunosuppressive agent.

Cyclosporine↗
PubMed1998

RET-like immunostaining of spinal motoneurons in amyotrophic lateral sclerosis.

The receptor tyrosine kinase RET is part of a functional receptor for glial cell derived neurotrophic factor (GDNF) and neurturin (NTN) which are potent neurotrophic factors for motoneurons. Here, we have studied RET-like immunoreactivity of motoneurons in post-mortem spinal cords of patients with amyotrophic lateral sclerosis (ALS) and in controls. We report that the intensity of RET-like immunostaining of motoneurons in ALS is decreased significantly to 81% of control values. Despite this change, the proportion of all large (>40 micron diameter) motoneurons showing RET-like immunoreactivity in ALS remains high (82-85%) and is not significantly different to controls. The persistence of RET-like immunoreactivity in the majority of large motoneurons in ALS could be important in the design of clinical trials of GDNF and NTN.

Aged↗
PubMed1998

Olfactory disorder in motor neuron disease.

In Parkinson's disease and Alzheimer's disease there is profound disorder of olfaction. The extent to which this modality is involved in motor neuron disease (MND) has been studied little. To address this further we assessed olfaction by three methods-a smell identification test ("UPSIT") in 58 patients and 135 controls; olfactory-evoked response (OEP) to H2S in 15 patients, and pathological examination of olfactory bulbs obtained from 8 cadavers. It was found that smell identification compared with the controls was slightly worse overall in the MND group as a whole, but only the bulbar patients scored significantly less on the UPSIT. Patients displayed a subtle defect in cheese odor recognition. OEPs were normal in 9 subjects and delayed in 1 subject. The remaining 5 OEPs were unsuccessful. Histopathological studies of olfactory bulbs showed excess lipofuscin deposition in all 8 cases examined, indicating subclinical neuronal damage. Olfactory neurons with a degree of antioxidant defect may be more susceptible to cellular damage than other neuronal groups because of their direct relationship to environmental agents. Overall we found the degree of olfactory dysfunction in MND to be mild and in contrast with the marked changes described by others.

Adolescent↗
PubMed1998

Treatment of type I spinal muscular atrophy with noninvasive ventilation and gastrostomy feeding.

Type I spinal muscular atrophy (SMA) is a rapidly progressive, degenerative neuromuscular disease of infancy. In severe SMA, weakness, hypotonia, and bulbar involvement lead to progressive respiratory insufficiency and swallowing dysfunction, which are frequently complicated by aspirations. There are few studies reported in the literature that address the respiratory management of type I SMA. This article reports the results of treating four patients with infantile SMA with noninvasive positive pressure ventilation and gastrostomy feeding. All patients had gastroesophageal reflux disease, which was managed medically. Despite these therapies, survival was only 1 to 3.5 months after presenting with severe aspirations. The treatment strategy, which can be effective in less rapidly progressive neuromuscular diseases, did not alter the very poor prognosis of type I SMA. The treatment options are reviewed, and a strategy designed to optimize quality of life for infants with this fatal disease is presented.

Deglutition Disorders↗
PubMed1998

Fat necrosis in free and pedicled TRAM flaps.

One purported advantage of the free transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction is that, compared with the conventional TRAM flap, it has a better blood supply and therefore a lower incidence of fat necrosis. We tested this claim by reviewing the incidence of fat necrosis, both clinically and mammographically, in a group of 110 patients with 116 TRAM flap breast reconstructions who had undergone mammography of their reconstructed breasts. Of the 49 breasts reconstructed with free TRAM flaps, 4 (8.2 percent) had clinically evident fat necrosis, and 1 (2.0 percent) had fat necrosis that was detectable by mammography. Of the 67 breasts reconstructed with conventional TRAM flaps, 18 (26.9 percent) had clinically detectable fat necrosis, and 9 (13.4 percent) had fat necrosis that was detectable mammographically. Both of these differences were statistically significant (p = 0.0113 for clinical fat necrosis; p = 0.031 for mammographic fat necrosis). Fat necrosis was more common in patients who were obese or had a history of smoking, but neither association was statistically significant. We conclude that the use of the free TRAM flap reduces the incidence of fat necrosis in the reconstructed breast.

Abdominal Muscles↗
PubMed1998

Effectiveness of cognitive-behavioral therapy for smokers with histories of alcohol dependence and depression.

OBJECTIVE: Alcohol dependence and major depression have been associated with heavy cigarette use and poor smoking-treatment outcomes. This preliminary study examined the efficacy of a mood management intervention for smoking cessation in abstinent alcoholics with a history of major depression. METHOD: Participants were 29 (15 female, 14 male) heavy smokers (mean cigs/day = 30.2), with an average of 6.8 years of continuous abstinence from alcohol and drugs, randomized to behavioral counseling (BC) (n = 16) or behavioral counseling + cognitive-behavioral mood management (CBT) (n = 13). A 2 x 5 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline, posttreatment and at 1-, 3- and 12-month-follow-up. Self-reported smoking status was verified with biochemical (COa) and informant report. RESULTS: Verified self-report indicated that significantly more smokers in CBT quit by posttreatment (69.2%; 9 of 13) than in BC (31.3%; 5 of 16) (chi2 = 4.14, 1 df, p = .04). These abstinence rates remained unchanged at 1-month follow-up. At 3-month follow-up, differences in smoking abstinence rates were nonsignificant between CBT (46.2%; 6 of 13) and BC (25.0%; 4 of 16) conditions. However, at 12-month follow-up, significantly more participants in CBT were abstinent from smoking (46.2%; 6 of 13) than in BC (12.5%; 2 of 16) (chi2 = 4.07, 1 df, p = .04). CONCLUSIONS: The results suggest that interventions focused on managing negative mood may benefit these high-risk, comorbid smokers.

Adult↗
PubMed1998

Conservative treatment of plantar fasciitis. A prospective study.

A randomized, prospective study was conducted to compare the individual effectiveness of three types of conservative therapy in the treatment of plantar fasciitis. One hundred three subjects were randomly assigned to one of three treatment categories: anti-inflammatory, accommodative, or mechanical. Subjects were treated for 3 months, with follow-up visits at 2, 4, 6, and 12 weeks. For the 85 patients who completed the study, a statistically significant difference was noted between groups, with mechanical treatment with taping and orthoses proving to be more effective than either anti-inflammatory or accommodative modalities.

Adult↗
PubMed1998

A home-based behavioral intervention to promote walking in sedentary ethnic minority women: project WALK.

A home-based telephone and mail intervention was evaluated for its effectiveness in promoting walking in a sample of sedentary, ethnic minority women. One hundred twenty-five women (ages 23-54) were randomly assigned to behavioral or brief educational interventions. Women in the 8-week behavioral condition received behavior change materials through the mail and 6 structured telephone counseling sessions. Educational condition participants received a single 5-min telephone call and educational information. Both groups reported significantly increased walking at a 2-month posttest (M change = 86 and 81 min per week for behavioral and educational groups, respectively) and 5-month follow-up (M change = 40 and 52 min per week). A 30-month follow-up of 50 participants indicated both groups continued to report more walking than at baseline. The behavioral intervention was not superior to the educational condition at any assessment point. The findings may be explained as (a) both interventions were equally effective, so extensive telephone counseling is unnecessary; (b) changes over time reflected secular trends; or (c) increases in self-reported walking may be due to socially desirable reporting. Other strategies need to be evaluated for promoting walking that are tailored to the needs of ethnic minority women.

Adult↗
PubMed1997

Noninvasive ventilation during percutaneous gastrostomy placement in Duchenne muscular dystrophy.

Noninvasive positive pressure ventilation (NPPV) is used for respiratory support in a number of diseases causing acute or chronic respiratory failure. We describe a novel use of NPPV to provide respiratory support during sedation for percutaneous placement of a gastrostomy tube in a patient with Duchenne muscular dystrophy (DMD). The patient had severe respiratory insufficiency, progressive dysphagia, and undernutrition. In addition to the case in this report, we have used NPPV to provide respiratory support to DMD patients during five other gastrointestinal endoscopies without complication. The technique is highly labor intensive and requires physicians and respiratory therapists familiar with NPPV. The primary risk associated with this technique is lack of definitive airway protection during the procedure, which must be balanced against the risks of intubation in an anesthetized patient with neuromuscular disease. The potential benefit to selected patients is substantial, such as initiation of gastrostomy tube feeding in our patient, with subsequent improvement in his quality of life and nutritional status.

Adolescent↗
PubMed1997

Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment.

For an understanding of the aberrant biology seen in mouse mutations and identification of more subtle phenotype variation, there is a need for a full clinical and pathological characterization of the animals. Although there has been some use of sophisticated techniques, the majority of behavioral and functional analyses in mice have been qualitative rather than quantitative in nature. There is, however, no comprehensive routine screening and testing protocol designed to identify and characterize phenotype variation or disorders associated with the mouse genome. We have developed the SHIRPA procedure to characterize the phenotype of mice in three stages. The primary screen utilizes standard methods to provide a behavioral and functional profile by observational assessment. The secondary screen involves a comprehensive behavioral assessment battery and pathological analysis. These protocols provide the framework for a general phenotype assessment that is suitable for a wide range of applications, including the characterization of spontaneous and induced mutants, the analysis of transgenic and gene-targeted phenotypes, and the definition of variation between strains. The tertiary screening stage described is tailored to the assessment of existing or potential models of neurological disease, as well as the assessment of phenotypic variability that may be the result of unknown genetic influences. SHIRPA utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse. These paradigms can be refined to test the function of specific neural pathways, which will, in turn, contribute to a greater understanding of neurological disorders.

Animals↗