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Biomedical subjects

S J Graham

Publications and source records attributed to S J Graham.

At least 19 recordsLinked to original sources

Prevalence of Huntington disease in New South Wales in 1996.

OBJECTIVE: To estimate the prevalence of Huntington disease (HD) in New South Wales on Australian Census Day (6 August) 1996. DESIGN: Survey of records of the Huntington Disease Service and major hospitals, and of neurologists, psychiatrists, clinical geneticists and genetic counsellors. SUBJECTS AND SETTING: All patients in NSW who, on Census Day 1996, either had a definite diagnosis of HD (motor signs of chorea or ataxia and family history of HD or positive DNA test result) or would have had signs and later received a definite diagnosis (assessed 1 April 1997 to 1 July 1999). MAIN OUTCOME MEASURES: Prevalence (HD patients per 100,000 population); patient characteristics; year and basis of diagnosis. RESULTS: 380 patients with definite HD were identified, giving a prevalence of HD in NSW in 1996 of 6.29 per 100,000 population (95% CI, 5.68-6.96). A third of HD patients were aged 60 years or older. Diagnosis was confirmed by DNA testing for 171 patients (45%), including 30 (8%) with no recorded family history. Average numbers of new diagnoses per year were 11.8 (1984-1988), 21.8 (1989-1993) and 28.6 (1994-1998). Estimated number of people with a 50% risk of inheriting the HD mutation was 25.2 per 100,000 population. Estimated incidence of HD in 1996 was 0.65 per 100,000 population. CONCLUSIONS: Prevalence of HD in NSW is similar to estimated prevalence in other Australian and Western populations. Increasing numbers of cases are being diagnosed, and the 18 chronic care beds currently designated for HD patients in NSW are unlikely to be sufficient.

Adult↗

Quantifying tissue damage due to focused ultrasound heating observed by MRI.

Focused ultrasound heating of ex vivo bovine kidney and liver was monitored using magnetic resonance imaging (MRI) to investigate the quantitative relationship between time-dependent temperature elevations and altered contrast in MR images due to thermal coagulation. Proton resonance frequency shift MR thermometry was performed during heating at 10 sec intervals (single-slice fast spoiled GRASS [FSPGR], theta/TE/TR 30 degrees/11/39 msec, field of view 8 cm, 256 x 256, 3 mm slice thickness, 1 NEX); post-heating MR images were T1-weighted (3D-FSPGR, theta/TE/TR 60 degrees/25/200 msec, 1 mm slice thickness, 3 NEX). Analysis of the resulting temperature versus time data using the Arrhenius relationship and a simple binary discrimination model showed that thermal coagulation occurred with heating at approximately 54 degrees C for 10 sec in both tissues and could be predicted with approximately 625 microm spatial resolution. These results suggest that quantitative MR guidance of thermal coagulation therapy is feasible, and they provide information useful for designing future investigations in vivo.

Animals↗

Analysis of changes in MR properties of tissues after heat treatment.

To characterize changes in the MR parameters of tissues due to thermal coagulation, a series of T(1), T(2), diffusion, and magnetization transfer measurements were performed on a variety of ex vivo tissues: murine slow twitch skeletal muscle, murine cardiac muscle, murine cerebral hemisphere, bovine white matter, murine liver tissue, bovine retroperitoneal adipose tissue, hen egg white, human prostate and human blood. Standardized heat treatments were performed for each tissue type, over the temperature range from 37 degrees C to 90 degrees C. For all tissues, changes in each MR measurement resulting from thermal coagulation were observed above a threshold temperature of approximately 60 degrees C. These changes are explained based on biophysical knowledge of thermal damage mechanisms and the MR properties of normal tissues, and are particularly relevant for interpreting the changes in image contrast that are observed when MRI is used to guide and monitor thermal coagulation therapy procedures. Magn Reson Med 42:1061-1071, 1999.

Adipose Tissue↗

Pulsed magnetization transfer imaging: evaluation of technique.

With use of an established physical model, numeric simulations were performed to evaluate current imaging protocols for the two primary applications of magnetization transfer: cerebral magnetic resonance angiography and neuroimaging of white matter disease. The authors found that the current technique is appropriate in the former but suboptimal in the latter. Further clinical investigations could potentially improve magnetization protocols for neuroimaging.

Animals↗

Time and temperature dependence of MR parameters during thermal coagulation of ex vivo rabbit muscle.

Detailed measurements of the T1-weighted, T2-weighted, and MT-weighted signal were performed for ex vivo muscle samples heated to various temperatures for different times. Consistent, monotonic increases in signal intensity were observed with progressive thermal coagulation, corresponding to an increase in T2 relaxation time and an increase in MT-weighted signal for temperatures above 60 degrees C. The relationship for T1 relaxation was more complex, showing a decrease in T1 relaxation from 40 to 60 degrees C and an increase above 60 degrees C. These techniques provide a more direct measure of tissue thermal coagulation than that provided by MR thermometry and suggest MR imaging strategies for the optimization and monitoring of thermal coagulation therapy protocols that create thermal damage in target tissues.

Animals↗

A flexible magnetization transfer line shape derived from tissue experimental data.

To summarize and compare magnetization transfer data from biological tissues, a method was developed to extract the average absorption lineshape of the semi-solid pool directly from magnetization transfer experimental data along with the four other parameters that characterize the two-pool model of exchange. Magnetization transfer data for several biological tissues were analyzed using this method and the resulting "flexible" lineshapes were compared with super-Lorentzian and "Kubo-Tomita" lineshapes. The use of flexible lineshapes noticeably improves the fit of the two-pool model to the data. The derived flexible lineshapes of all the tissues analyzed are physically realistic and show remarkably consistent behavior.

Animals↗

Magnetic resonance properties of ex vivo breast tissue at 1.5 T.

The magnetic resonance absorption spectrum, T1 and T2 relaxation time distributions, and magnetization transfer properties of ex vivo breast tissue have been characterized at 1.5 T and 37 degrees C. The fraction of fibroglandular tissue within individual tissue samples (n = 31) was inferred from the tissue volumetric water content obtained by integration of resolvable broad-line fat and water resonances. The spectroscopically estimated water content was strongly correlated with that extracted enzymatically (Pearson correlation coefficient 0.98, P < < 0.01), which enabled the assignment of principal relaxation components for fibroglandular tissue (T2=0.04+/-0.01, T1=1.33+/-0.24 s), and for adipose tissue (T2=0.13+/-0.01, T1=0.23+/-0.01 s, and T2=0.38+/-0.03, T1=0.62+/-0.16 s). Th e relaxation components for fibroglandular tissue exhibited strong magnetization transfer, whereas those for adipose tissue showed little magnetization transfer effect. These results ultimately have applicability to the optimization of clinical magnetic resonance imaging and research investigations of the breast.

Breast↗

Metered dose inhalers III: Metaproterenol sulphate; particle size distribution and dose uniformity.

Three American products and one Canadian product were examined for content uniformity and particle size distribution. The results showed that not all products performed equally well. Some of the products exhibited high sprays early in the canister lifetime and all products demonstrated loss of prime. The particle size distributions were determined using the Andersen cascade impactor (USP Induction Port) and the fine particle fraction was determined using the twin impinger. The results showed that three of the four products had similar particle size distribution profiles. Both the Andersen cascade impactor and the twin impinger yielded the same trends in the amount of drug substance delivered to the fine particle fraction.

Bronchodilator Agents↗

Criteria for analysis of multicomponent tissue T2 relaxation data.

Monte Carlo simulations were performed to determine whether the multicomponent T2 distribution of tissue can be estimated accurately from T2 decay data acquired in vivo. Simulated data were generated for white matter, fast twitch muscle, and breast tissue. The signal-to-noise ratio, number of data samples, and minimum echo time were varied from the experimental conditions currently achievable with MRI to those achievable for in vitro experiments. Data were fitted by a distribution of T2 values using the T2NNLS algorithm, and statistics characterizing the estimated T2 components were determined. Current MRI techniques were found to provide conditions insufficient for accurate multicomponent T2 analysis on a pixel-by-pixel basis. However, volume localization methods that measure T2 decay from a large volume of interest have potential for this analysis. These results illustrate a general framework for development of new techniques to measure T2 decay accurately in vivo.

Brain Chemistry↗

MR measurement of relative water content and multicomponent T2 relaxation in human breast.

MR techniques providing accurate measurement of relative volumetric water content and multicomponent T2 relaxation times from a large volume of interest, have been implemented for characterization of breast tissue in vivo. In a sequence of 20-s breath-holds, data are obtained from much of the breast volume while suppressing signal from the chest wall and torso. Relative water content of each breast is calculated from one-dimensional fat and water profiles obtained using a hybrid two-point Dixon method (TE/TR = 17/5000 ms). Multicomponent T2 relaxation measurements are calculated from T2 decay curves obtained using a CPMG train of rectangular pulses (TE/TR = 8/5000 ms, 140 echoes) preceded by saturation pulses to localize longitudinal magnetization spatially. These techniques, validated in phantoms and human volunteers, are suitable for quantitative study of breast tissue in vivo, and in particular to investigate the potential role of MR for assessment of breast cancer risk.

Body Water↗

Metered-dose inhalers, I: Drug content and particle size distribution of beclomethasone dipropionate.

Four commercially available beclomethasone metered dose inhalers were analyzed for both spray content uniformity and particle size. The drug contents of primed and unprimed sprays collected at the beginning of the lifetime of the canister were not significantly different from those collected throughout the experiment. Particle size analysis of the four products using the Andersen Cascade Impactor Mark II showed that the distribution profiles were not identical. An existing HPLC method was modified to quantitate single sprays for content uniformity and to measure the amount on an impactor stage for particle sizing.

Administration, Inhalation↗

Quantitative correlation of breast tissue parameters using magnetic resonance and X-ray mammography.

Previous investigators have shown that there is a strong association between the fraction of fibroglandular tissue within the breast as determined by X-ray mammography (per cent density) and breast cancer risk. In this study, the quantitative correlation between per cent density and two objective magnetic resonance (MR) parameters of breast tissue, relative water content and mean T2 relaxation time, as investigated for 42 asymptomatic subjects. Using newly developed, rapid techniques MR measurements were performed on a volume-of-interest incorporating equal, representative portions of both breasts. X-ray mammograms of each subject were digitised and analysed semiautomatically to determine per cent density. Relative water content showed a strong positive correlation with per cent density (Pearson correlation coefficient rp = 0.79, P < 0.0001) and mean T2 value showed a strong negative correlation with per cent density (rp = -0.61, P < 0.0001). The MR and X-ray parameters were also associated with sociodemographic and anthropometric risk factors for breast cancer (P < 0.05). The potential use of MR parameters to assess risk of breast cancer and to provide a frequent, non-hazardous monitor of breast parenchyma is discussed.

Adipose Tissue↗

Prognostic implications of a bone marrow histopathologic classification system in mycosis fungoides and the Sézary syndrome.

BACKGROUND: The authors devised a histopathologic classification system for interpreting bone marrow biopsy materials in patients with mycosis fungoides and the Sézary syndrome and correlated histopathologic findings with clinical stage and outcome. METHODS: Bone marrow specimens from 90 consecutively staged patients were examined for lymphoid infiltrates, benign or cytologically atypical lymphoid aggregates, and large or cytologically transformed cells. RESULTS: Thirty-seven (41%) marrows were involved, two with diffuse lymphomatous infiltrates and 35 with lymphoid aggregates. Twelve of the 35 had lymphoid aggregates consisting of cytologically normal-appearing lymphocytes, and 23 had aggregates composed of cytologically atypical lymphocytes. Eleven patients had greater than 5% large cytologically transformed cells. Patients with infiltrative disease or cytologically atypical aggregates had an inferior survival compared with those with cytologically normal lymphocytes (P2 = 0.0042), and patients with aggregates consisting of cytologically normal lymphocytes had a survival comparable with that of patients with uninvolved marrows (P2 = 0.33). Whereas most patients with cytologically atypical marrows had advanced skin and lymph node involvement, 28% had early skin stage. Bone marrow eosinophilia was noticed in 38% of patients and was not consistently associated with peripheral blood eosinophilia or clinical stage. CONCLUSIONS: These results suggest that patients with cytologically atypical lymphoid aggregates or diffuse lymphomatous infiltration of the marrow have an inferior survival regardless of clinical stage, whereas those with lymphoid aggregates consisting of cytologically normal-appearing lymphocytes have a survival indistinguishable from that of patients without lymphoid aggregates.

Adult↗

Whole-body pathologic analysis of a patient with Thorotrast-induced myelodysplasia.

An autopsy was performed on a 72-y-old Caucasian female who had received a carotid artery injection of thorium dioxide in 1953. The body was dissected in such a manner as to provide for radiobiological evaluation as well as to determine histologically the distribution of Thorotrast in the tissues and its complications. Thorotrast was identified within the liver, spleen, lymph nodes, bone marrow, and surrounding the right carotid artery (the injection site). The cause of death was gastric hemorrhage complicating pancytopenia secondary to refractory anemia with excess of blasts (myelodysplastic syndrome).

Aged↗

Inferior punctal occlusion with removable silicone punctal plugs in the treatment of dry-eye related contact lens discomfort.

Thirty subjects complaining of a decrease in soft contact lens wearing time secondary to dry eye discomfort were selected for our study. All subjects were between the ages of 25 and 40 and selected on the basis of subjective dry eye complaints alone. Five of these subjects had punctum that were too small to facilitate plug placement and were therefore eliminated from further study. Removable silicone punctal plugs were monocularly placed in the lower puncta of the remaining 25 subjects. In an attempt to minimize the placebo effect, both puncta were manipulated equally prior to plug insertion and the patient was not told which eye had been treated. Three weeks following plug placement, blind data assessment showed that 18 of the 25 subjects reported, on average, a 34.6 percent increase in comfortable contact lens wearing time in the treated eye. Three subjects reported no subjective increase in comfortable wearing time and four subjects were unable to tolerate the punctal plugs for more than a week due to plug-related discomfort. Problematic epiphora was not reported in any of the treated eyes. Reversible inferior punctal occlusion, when tolerated, can significantly increase comfortable contact lens wearing time while still allowing enough drainage from the upper puncta to prevent epiphora.

Adult↗