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Biomedical subjects

G McKinnon

Publications and source records attributed to G McKinnon.

At least 19 recordsLinked to original sources

Prevalence of hypogonadism in male patients with renal failure.

BACKGROUND: Hypogonadism in men may be secondary to renal failure and is well recognised in patients with end-stage renal disease. It is thought to contribute to the sexual dysfunction and osteoporosis experienced by these patients. However, the association between hypogonadism and lesser degrees of renal dysfunction is not well characterised. METHODS: The gonadal status of 214 male patients (mean age 56 (SD 18) years) attending a renal centre was studied; 62 of them were receiving haemodialysis and 22 continuous ambulatory peritoneal dialysis for end-stage renal disease, whereas 34 patients had functioning renal transplants and 96 patients were in the low-clearance phase. Non-fasting plasma was analysed for testosterone, follicle-stimulating hormone, luteinising hormone, sex hormone-binding globulin, parathyroid hormone and haemoglobin. Creatinine clearance was estimated in patients not on dialysis, and Kt/V and urea reduction ratio were assessed in patients on dialysis. Testosterone concentrations were classified as normal (>14 nmol/l), low-normal (10-14 nmol/l) or low (<10 nmol/l). RESULTS: 56 (26.2%) patients had significantly low testosterone levels and another 65 (30.3%) had low-normal levels. No significant changes were seen in sex hormone-binding globulin or gonadotrophin levels. Gonadal status was not correlated with haemoglobin level, parathyroid hormone level, creatinine clearance, or dialysis duration or adequacy. CONCLUSION: Over half of patients with renal failure, even in the pre-dialysis phase, have low or low-normal levels of testosterone, which may be a potentially reversible risk factor for osteoporosis and sexual dysfunction. These patients may be candidates for testosterone-replacement therapy, which has been shown to improve bone mineral-density and libido in men with low and low-normal testosterone levels.

Adolescent↗

Cystadenomas of the liver: a spectrum of disease.

OBJECTIVES: To describe the wide variation in presentation of cystadenomas of the liver and to delineate useful tests for diagnosis and effective surgical treatment. DESIGN: A case series. SETTING: A university-affiliated hospital. PATIENTS: Four patients (3 women, 1 man) having cystadenoma of the liver, 2 of whom had associated mesenchymal stroma. MAIN OUTCOME MEASURES: Serum and cyst fluid carcinoembryonic antigen (CEA) and CA19-9 levels, type of surgery, morbidity and recurrence rates. RESULTS: Cyst fluid CEA and CA19-9 levels were elevated. One patient had resection, 2 had complete enucleation and 1 had partial enucleation. There were no deaths. Morbidity included 1 wound infection; there were no biliary fistulas. The patient with partial enucleation had a radiologically confirmed recurrence. CONCLUSIONS: Analysis of cyst fluid CEA and CA19-9 is useful for diagnosis; besides hepatic resection, complete enucleation should be considered as a reasonable treatment for patients with this disease.

Adult↗

A multireflection cell for enhanced absorbance detection in microchip-based capillary electrophoresis devices.

The design, fabrication and testing of a photolithographically fabricated, glass-based multireflection absorbance cell for microfluidic devices, in particular microchip-based capillary electrophoresis (CE) systems is described. A multireflection cell was fabricated lithographically using a three-mask process to pattern aluminum mirrors above and below a flow channel in a chip, with 30 microm diameter optical entrance or exit apertures (one in each mirror) positioned 200 microm apart. Source and detector were positioned on opposite sides, and the metal mirrors were made 1 cm square, to reduce stray light effects. Calibration curves using bromothymol blue (BTB) with a 633 nm source (He:Ne laser) were linear to at least 0.5 absorbance units, with typical r2 values of 0.9997, relative standard deviations in the slopes of +/- 1.3%, and intercepts of zero within experimental error. Effective optical pathlengths of 50-272 microm were achieved, compared to single-pass pathlengths of 10-30 microm, corresponding to sensitivity enhancements (i.e., optical path length increase) of 5 to 10-fold over single-pass devices. Baseline absorbance noise varied within a factor of two in almost all devices, depending only weakly on path length. This device can give much higher absorbance sensitivity, and should be much easier to manufacture than planar, glass-based devices previously reported.

Electrophoresis, Capillary↗

A fast 3D look-locker method for volumetric T1 mapping.

We introduce a fast technique, based on the principles of the 2D Look-Locker T1 measurement scheme, to rapidly acquire the data for accurate maps of T1 in three dimensions. The acquisition time has been shortened considerably by segmenting the acquisition of the k(y) phase encode lines. Using this technique, the data for a 256 x 128 x 32 volumetric T1 measurement can be acquired in 7.6 min. T1 measurements made in phantoms with T1s between 200 and 1200 ms had an accuracy of 4% and a reproducibility of 3.5%. Measurements of T1 made in normal brain using the fast 3D sequence corresponded well with inversion-recovery fast spin-echo measurements.

Brain↗

An integrated microfluidics-tandem mass spectrometry system for automated protein analysis.

We describe an integrated analytical system consisting of a microfluidics device micromachined using photolithography/etching technology, a panel of computer-controlled high-voltage relays, and an electrospray ionization tandem mass spectrometer. Movement of solvents and samples on the device and off the device to the mass spectrometer was achieved by directed electroosmotic pumping induced by the activation of a suitable constellation of high-voltage relays. The system was used for the sequential automated analysis of protein digests. We demonstrate low femtomole per microliter sensitivity of detection and compatibility of the system with the automated analysis of proteins separated by two-dimensional gel electrophoresis.

Amino Acid Sequence↗

Micromachined analytical devices: microchips for semen testing.

Micromachined devices (microchips) have been designed and tested for a range of clinically important assays. In this study we compare sperm motility determined using disposable glass microchips and a conventional Makler chamber. The 17 x 14 mm glass microchips contained three etched test structures each comprising either duplicate or quadruplicate analytical microchannels. Semen samples with sperm counts ranging from 21 to 78 million sperm per ml and forward progression scores of from 1+ to 3+ were evaluated and swimming times ranging from 360 s (3.3+ progression) to 770 s (1+,2 forward progression) observed in the microchips. Motility determined by the time taken for sperm to swim to the end of a microchannel (100 microns wide x 40 microns deep x 10 mm long) in the microchip correlated with forward progression of the sperm determined by the conventional Makler chamber method. This study demonstrates the feasibility of microchips for sperm motility testing and suggests that this technique would be applicable to the study of other types of motile cells.

Biotechnology↗

Fast spin-echo inversion-recovery imaging versus fast T2-weighted spin-echo imaging in bone marrow abnormalities.

RATIONALE AND OBJECTIVES: The purpose of this investigation is to compare a fat-suppressed T2-weighted fast spin-echo (FSE) sequence in bone marrow abnormalities with an FSE STIR sequence that recently has become commercially available. METHODS: Fast spin-echo images (repetition time [TR], 3500-5000 mseconds; echo time [TE], 96-114 mseconds) and FSE STIR images (TR, 3000-5000 mseconds; TE, 32-40 mseconds; inversion time [TI], 140-150 mseconds) were compared quantitatively and qualitatively calculating signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and lesion conspicuity and using a qualitative scoring system. RESULTS: Signal-to-noise ratio (mean +/- standard deviation) was 36.4 +/- 19.3 for the FSE and 29.0 +/- 15.9 for the FSE STIR images (P = .002). Contrast-to-noise ratio (mean +/- standard deviation) was 18.7 +/- 14.3 for the FSE and 20.3 +/- 16.0 for the FSE STIR images (P = .45). Lesion conspicuity (mean +/- standard deviation) was 1.7 +/- 1.5 for the FSE and 3.5 +/- 4.0 for the FSE STIR images (P = .025). The most important difference in the qualitative evaluation related to the better signal homogeneity on the FSE STIR images. CONCLUSIONS: Fast spin-echo STIR images may be preferable to FSE images with fat suppression due to better image homogeneity and lesion conspicuity.

Adolescent↗

CT of the liver after cryotherapy of hepatic metastases: imaging findings.

Cryotherapy is the in situ destruction of abnormal tissue using subzero temperatures (Fig. 1). Recent studies have demonstrated the technical feasibility, safety, and effectiveness of hepatic cryotherapy in the treatment of liver tumors [1, 2]. Such treatment can be precisely focused on the tumor, thereby preserving surrounding normal tissue. In addition, because major vessels with flowing blood are protected from cryoablation, tumors adjacent to these vessels can be treated without sacrificing vasculature. Hepatic cryoablation is therefore particularly suitable for patients who do not qualify for surgical resection because of multiple metastases involving both lobes of the liver, or because of lesions close to major blood vessels. After the procedure, CT during arterioportography is of little value in distinguishing cryolesion from malignant tumor (Fig. 2), and CT with IV contrast enhancement is recommended for follow-up. It is important to distinguish CT findings of successful and unsuccessful treatment, treatment complications such as abscess and cholestasis, and recurrent tumor. The purpose of this essay is to illustrate the findings on CT with IV contrast enhancement in various situations, emphasizing features that are useful in making accurate differential diagnosis.

Aged↗

The impact of the ISIS experiment order on spatial contamination.

When performing volume-localized spectroscopy measurements, the amount of spatial contamination is an important quality criterion. With the ISIS localization technique contamination cannot only arise from the transition regions around the volume of interest, but also from remote regions of the sample. The latter contamination component is a consequence of inhomogeneous excitation pulses, if short repetition times TR are used. Its severity depends both on the order of the eight phase cycling experiments needed for an ISIS measurement, and on the ratio TR/T1. Here it is theoretically discussed from which regions of the sample contamination can arise for a specific phase cycling order. For the worst orders the contaminating regions are almost three times as large as for the optimal orders. The ratio for the effectively measured contamination, however, can be moderated in real experiments, because cancellation effects occur due to the phase distribution of the contaminating signals. 31P phantom experiments clearly demonstrate that contamination is present even if adiabatic excitation pulses are applied and that spatial contamination can be reduced to about a third by an optimal choice of the phase cycling order.

Brain↗

Glycogen detection by in vivo 13C NMR: a comparison of proton decoupling and polarization transfer.

The performance of gated proton decoupling and polarization transfer with respect to glycogen detection by 13C NMR was investigated. Experiments were performed on a 1.5-T whole-body scanner using a 13C surface coil in combination with a proton head coil. Spectra were acquired from a glycogen phantom and from the lower leg of a healthy volunteer using proton decoupling and the polarization transfer method SINEPT. The signal strength of the C1 resonance of glycogen was determined and compared to a reference spectrum acquired without any form of sensitivity enhancement. In the phantom experiment both decoupling and SINEPT produced a signal gain of 3.5. Under in vivo conditions, the signal gain was approximately 2.5 for both techniques. We conclude that decoupling and polarization transfer are equivalently useful techniques for glycogen detection.

Glycogen↗

A cytotoxic T-lymphocyte clone derived from mice with progressively growing tumors.

Tumor-specific T-cell clones were derived from spleen cells of mice bearing a syngeneic PHS-5 tumor (a P815 mastocytoma mutant). Cells were expanded in vitro and characterized and assayed for activity against the relevant tumor in vivo. Clone cells were CD4-, CD8+ T lymphocytes, as determined by fluorescence activated cell sorting analysis and were specifically cytotoxic against P815 tumor cells in vitro, as shown in chromium 51 release assays. These cells require both antigen and interleukin 2 to proliferate; neither alone is sufficient, even with the addition of interleukin 1. In an experimental P815 liver metastasis model, the adoptive transfer of GD11 or GD11.17 clone cells and injection of recombinant interleukin 2 (7500 U intraperitoneally) 3 days after infusion of tumor cells reduced the number of tumor nodules, while the adoptive transfer of lymphokine-activated killer cells was ineffective.

Animals↗

Toward fully automatic estimation of in vivo 31P spectra.

Fitting a model to an experimental spectrum is a difficult nonlinear estimation problem. The solution presented here is to start an iterative search procedure sufficiently close to the optimal model parameter set. This is achieved by providing tissue-dependent a priori peak information and by a novel correlation method to get good primary estimates of the resonance and phase offset parameters. The resulting estimation procedure is fully automatic and has proven to be robust for 31P data.

Brain↗

[In vivo 31P-cardiac magnetic resonance spectroscopy: methods and the first clinical results].

31P-magnetic resonance (MR) spectra of the heart can be obtained from well-defined myocardial regions by combined MR imaging and variable selected volumes for spectroscopy. 31P-spectra of 33 volunteers and of 43 patients with dilated and hypertrophic cardiomyopathy and with coronary artery disease were quantified using a curve-fitting routine. To optimize our technique, we recorded unsaturated and partially saturated spectra in several volunteers. Relative peak areas and signal-to-noise ratios showed significant changes with varying pulse repetition times. Saturation factors were applied to correct spectra from volunteers and patients for the effects of partial saturation. Under resting conditions, peak areas of volunteers and patients from the various groups were statistically indistinct.

Adult↗

Capillary and venous blood glucose measurements using a direct glucose-sensing meter.

The aim of the study was to evaluate the precision and accuracy of the ExacTech home blood glucose meter when used with either capillary or venous blood and to compare this with a reference whole blood glucose assay. Non-fasting glucose measurements were used since a validation study showed no capillary-venous differences between fasting and post-prandial states. In a cross-sectional study, blood was taken from 182 patients and measured in duplicate on three batches of strips. Altogether we analysed 1089 readings. The regression of the data from capillary blood samples (meter vs reference method) had a correlation coefficient, of 0.93, and a mean bias of 0.2 mmol l-1. The corrected 90% confidence interval was +/- 1.5 mmol l-1 overall, and +/- 0.9 mmol l-1 for readings under 7.0 mmol l-1. Regression of the data from venous blood samples (meter vs reference method) had a correlation coefficient of 0.93 and a slope of x 1.1. The corrected 90% confidence interval was +/- 1.7 mmol l-1. Thus venous blood may be used even though the meter is calibrated for capillary samples but the value must be corrected by dividing by 1.1. Error-grid analysis showed that day-to-day clinical decisions could be made on the basis of ExacTech readings, although a diagnosis of borderline diabetes may not be possible.

Blood Glucose↗

The reaction of acetaldehyde with brain microtubular proteins: formation of stable adducts and inhibition of polymerization.

Stable adducts were formed by treatment of bovine brain microtubular proteins (MTP) with acetaldehyde, followed by gel filtration to remove excess acetaldehyde. The extent of stable adduct formation was determined using [14C]acetaldehyde and was correlated with acetaldehyde concentration and reaction time. Significant inhibition of MTP polymerization was observed at adduct concentrations of 0.6 mol acetaldehyde/mol tubulin dimer. The data suggest that repeated exposure of MTP to low concentrations of acetaldehyde, as would occur in the brain and other tissues of alcoholics, may inhibit MTP polymerization with neurological consequences.

Acetaldehyde↗

Effects of acetaldehyde on polymerization of microtubule proteins.

The in vitro effects of ethanol and acetaldehyde on polymerization of calf brain microtubular proteins (MTP) were examined. While ethanol up to 100 mM had no effect on the polymerization of MTP, acetaldehyde above 0.5 mM had an inhibitory effect. This effect was not dependent on the presence of microtubule-associated proteins (MAPs), since acetaldehyde had a similar effect on the polymerization of highly purified tubulin. Electron microscopy revealed that the number and the length of microtubules at equilibrium was reduced by the presence of acetaldehyde. Acetaldehyde raised the critical concentration for tubulin assembly and caused greater inhibition at lower tubulin concentrations. Acetaldehyde augmented the depolymerizing effects of Ca2+ on preassembled microtubules. In addition, acetaldehyde itself caused depolymerization of microtubules but only in the absence of MAPs. Long-term (19.5 h) incubation of MTP with acetaldehyde led to significant loss of polymerization ability which could not be reversed by removal of acetaldehyde. This loss of activity was apparently independent of the observed formation of reducible adducts between acetaldehyde and MTP.

Acetaldehyde↗