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Biomedical subjects

G Wilson

Publications and source records attributed to G Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Identification of inguinal lymph node metastases from vulval carcinoma by magnetic resonance imaging: an initial report.

AIM: Magnetic Resonance Imaging (MRI) has the potential to assess inguinal lymph nodes more accurately than palpation and less invasively than surgical exploration. The objective of this study was to measure the accuracy of MRI in identifying inguinal metastases by demonstrating abnormal lymph node morphology. MATERIALS AND METHODS: 10 women with vulval malignancy underwent T1- and fat-suppressed T2-weighted surface coil MRI of both groins before surgery. Each groin was prospectively categorised as normal or as having metastatic lymphadenopathy using criteria established in normal volunteers. Histopathological findings in patients undergoing groin dissection for invasive vulval carcinoma were used as validation. RESULTS: MRI had a positive predictive value of 89%, negative predictive value of 91%, sensitivity of 89%, specificity of 91% and accuracy of 90%. The most useful observations on MRI to identify metastatic lymphadenopathy were those of lymph node contour irregularity, cystic change in a lymph node, short axis diameter exceeding 10mm and abnormal long: short axis diameter ratio. CONCLUSION: High resolution MRI of the inguinal regions has potential to screen for lymph node metastases in patients with vulval cancer, with the aim of reducing the number of women who have to undergo groin dissection.

Adult↗
PubMed2002

Phenobarbitone, neonatal seizures, and video-EEG.

AIMS: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates. METHODS: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20-40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score. RESULTS: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor. CONCLUSION: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal.

Anticonvulsants↗
PubMed2001

Acetylcholine receptor channel structure in the resting, open, and desensitized states probed with the substituted-cysteine-accessibility method.

The nicotinic acetylcholine (ACh) receptors cycle among classes of nonconducting resting states, conducting open states, and nonconducting desensitized states. We previously probed the structure of the mouse-muscle ACh receptor channel in the resting state obtained in the absence of agonist and in the open states obtained after brief exposure to ACh. We now have probed the structure in the stable desensitized state obtained after many minutes of exposure to ACh. Muscle-type receptor has the subunit composition alpha(2)betagammadelta. Each subunit has four membrane-spanning segments, M1-M4. The channel lumen in the membrane domain is lined largely by M2 and to a lesser extent by M1 from each of the subunits. We determined the rates of reaction of a small, sulfhydryl-specific, charged reagent, 2-aminoethyl methanethiosulfonate with cysteines substituted for residues in alphaM2 and the alphaM1-M2 loop in the desensitized state and compared these rates to rates previously obtained in the resting and open states. The reaction rates of the substituted cysteines are different in the three functional states of the receptor, indicating significant structural differences. By comparing the rates of reaction of extracellularly and intracellularly added 2-aminoethyl methanethiosulfonate, we previously located the closed gate in the resting state between alphaG240 and alphaT244, in the predicted M1-M2 loop at the intracellular end of M2. Now, we have located the closed gate in the stable desensitized state between alphaG240 and alphaL251. The gate in the desensitized state includes the resting state gate and an extension further into M2.

Acetylcholine↗
PubMed2001

Sonographic appearance of primary liver liposarcoma.

Primary malignant mesenchymal tumors of the liver are extremely rare. We report a case of a primary liposarcoma in the right hepatic lobe of a 50-year-old man. Sonography showed a poorly defined, lobulated, infiltrating echogenic tumor with shadowing. Within the tumor were hyperechoic and hypoechoic foci thought to represent areas of hemorrhage and necrosis. Color Doppler sonography showed the mass to be avascular. A low-attenuation mass of fat density was confirmed on CT. The resected tumor was reasonably well circumscribed, with demonstrable infiltration of the liver parenchyma. Histologic analysis showed liposarcoma with high-grade sarcomatous features.

Humans↗
PubMed2001

Temporal lobe-oriented CT scanning and dementia in Down's syndrome.

BACKGROUND: Although individuals with Down's syndrome (DS) are uniquely at risk of developing Alzheimer's disease, the diagnosis of dementia in DS is problematic because of the difficulty in detecting cognitive decline in individuals with pre-existing learning disability. AIM: To determine if dementia in DS is associated with Medial Temporal Lobe (MTL) atrophy as measured by temporal lobe-oriented CT scanning. METHOD: Ten individuals with DS who were experiencing functional decline had CT scans with temporal lobe-oriented views. All individuals were assessed for the presence of dementia according to modified DSM-IIIR criteria. The minimal thickness of the MTL, corrected for age-related atrophy was measured using a computer calipers at the level of the mid-brainstem by a radiologist blind to the dementia diagnosis. RESULTS: All six individuals who met modified DSM-IIIR criteria for dementia showed significant MTL atrophy. CONCLUSIONS: The utility of temporal lobe-oriented CT scanning as an adjunct to the diagnosis of dementia in DS appears promising and warrants further study.

Adult↗
PubMed2001

Influence of ambient temperature on plasma ammonia and lactate accumulation during prolonged submaximal and self-paced running.

This study examined the effects of heat stress on the accumulation of plasma ammonia, lactate, and urate during prolonged running. Nine highly trained endurance runners completed two running trials in a counterbalanced fashion in cool (15 degrees C) and in hot (35 degrees C) humid (60% relative humidity) conditions. Subjects ran on a motorised treadmill at 70% of peak treadmill running speed for 30 min (submaximal) followed by a self-paced 8-km performance run. Blood was drawn at pre-exercise, end-submaximal and end-performance run and analysed for plasma ammonia, lactate, and urate. Four subjects failed to complete the performance run in the heat and the performance times for the rest of the subjects was increased from 27.3 (0.6) min in cool conditions to 31.3 (1.2) min in hot conditions (P < 0.05). The end-performance rectal temperature was 38.6 (0.1) and 39.2 (0.1) degrees C (P<0.05) in cool and hot conditions, respectively. Differences in plasma lactate at the end of submaximal running were not significant. However, at the end of performance runs lactate was 6.0 (0.9) m mol x l(-1) in cool and 3.1 (0.5) mmol x l(-1) in hot conditions, values that were significantly different (P<0.05). Plasma ammonia increased from pre-exercise to approximately equal to 59 micromol x l(-1) at the end-submaximal runs for both coditions and further at the end of performance runs to 108.5 (11) micromol x l(-1) (P<0.05) in hot but not in cool conditions. Plasma urate increased from pre-exercise to 311.2 (25.9) micromol x l(-1) at end-submaximal runs and to approximately equal to 320.4 micromol x l(-1) at end-performance runs in hot and cool environments. The findings that plasma urate accumulation was similar at the completion of running in both conditions, while ammonia was significantly augmented in hot conditions compared with cool, suggest that ammonia accumulation during heat stress exercise might be derived from sources other than purine catabolism.

Adult↗
PubMed2001

Quantification of polynuclear aromatic hydrocarbons in transformer oils by enzyme immunoassay.

Many polynuclear aromatic hydrocarbons (PAHs) are either known or suspected carcinogens and are a common constituent of mineral oils. Due to the large number of possible PAH structures, standard quantification methods fail since they either lack specificity or are too complex, requiring individual fractionation, identification, and quantification. A rapid, low-cost, novel analytical screening method, incorporating a silica-based solid-phase extraction (SPE) method linked to co-solvent dilution and quantification of total and carcinogenic PAH levels by immunoassay, is reported here. The method yielded high extraction efficiencies and minimal matrix effects. This novel approach yielded total and carcinogenic PAH levels x 5.7 and x 126, respectively, lower than that recorded by the industry-recognised BS2000 Pt. 346 (IP346) method which estimates the polyaromatic carbon (PAC) content of oils by gravimetry. The method is expected to be of benefit where an indication of PAH levels in oils is important for purchasing, management or disposal purposes and also for risk assessment and for appropriate labelling of oils in line with current legislation.

Carcinogenicity Tests↗
PubMed2001

Sustained in vivo activity of recombinant bovine granulocyte colony stimulating factor (rbG-CSF) using HEPES buffer.

The purpose of this study was to develop a long-acting injectable formulation of bG-CSF for veterinary use. However, in order to achieve sustained in vivo activity it was first necessary to stabilize the protein at the injection site. Preformulation studies, as well as literature, suggest that bG-CSF aggregates at neutral pH ranges (i.e., pH 6-8) and at temperatures of approximately 40 degrees C. Therefore, bG-CSF will not retain its activity for an extended period of time at the injection site. During this study we determined that HEPES buffer has a very significant impact on protein stability as well as on biological performance. Recombinant bovine granulocyte colony stimulating factor (rbG-CSF) was formulated in 1 M HEPES buffer for subcutaneous injection into cows. bG-CSF formulated in 1 M HEPES buffer resulted in sustained in vivo activity of bG-CSF compared to the "control" formulation (control formulation: 5% mannitol, 10 mM acetate buffer, 0.004% tween-80, pH 4). White blood cell (WBC) count was used as a marker to evaluate in vivo activity of the formulation. WBC numbers remained above a threshold value for only 24-30 h for the control formula. However, when bG-CSF was formulated in 1 M HEPES, the WBC remained above threshold for 3 days or 72 h. Formulating bG-CSF in 1 M HEPES at pH 7.5 also resulted in greater solution stability. This was surprising since bG-CSF is intrinsically not stable at neutral pH. The effect of 1 M HEPES on the T(M) (temperature at maximum heat flow on calorimetry scan) of bG-CSF was determined by microcalorimetry. In the absence of 1 M HEPES buffer the T(M) was 48 degrees C (onset approximately 40 degrees C), while bG-CSF formulated in 1 M HEPES buffer has a T(M) of 59 degrees C (onset approximately 50 degrees C). Similar organic buffers, such as MOPS, HEPPS, TES, and tricine, also resulted in improved solution stability as well as in sustained in vivo activity. The dramatic effect of these buffers on stability and biological performance of bG-CSF is not well understood. One hypothesis is that the electrostatic interaction between the zwitterionic form of these buffers and bG-CSF provides stabilization against denaturation.

Animals↗
PubMed2001

Irradiation selectively inhibits expression from the androgen-dependent Pem homeobox gene promoter in sertoli cells.

How radiation blocks spermatogenesis in certain strains of rats, such as LBNF(1), is not known. Because the block depends on androgen, we propose that androgen affects Sertoli cell function in irradiated LBNF(1) rats, resulting in the failure of spermatogonial differentiation. To begin to identify genes that may participate in this irradiation-induced blockade of spermatogenesis, we investigated the expression of several Sertoli genes in response to irradiation. The expression of the PEM: homeobox gene from its androgen-dependent Sertoli-specific proximal promoter (Pp) was dramatically reduced more than 100-fold in response to irradiation. In contrast, most other genes and gene products reported to be localized to the Sertoli cell, including FSH receptor (FSHR), androgen receptor (AR), SGP1, and the transcription factor CREB, did not exhibit significant changes in expression, whereas transferrin messenger RNA (mRNA) expression dramatically increased in response to irradiation. Irradiation also decreased Pp-driven PEM: mRNA levels in mouse testes (approximately 10-fold), although higher doses of irradiation than in rats were required to inhibit PEM: gene expression in testes of mice, consistent with their greater radioresistance. The decrease in Pem gene expression in mouse testis was also selective, as the expression of CREB, GATA-1, and SGP1 were little affected by irradiation. We conclude that the dramatic irradiation-triggered reduction of Pem expression in Sertoli cells is a conserved response that may be a marker for functional changes in response to irradiation.

Androgens↗
PubMed2001

Testosterone inhibits spermatogonial differentiation in juvenile spermatogonial depletion mice.

The juvenile spermatogonial depletion (jsd) mutation results in spermatogonial arrest after the first wave of spermatogenesis. In homozygous jsd mice in a hybrid background (C3HxB6) that were identified with microsatellite markers, the percentage of tubules showing differentiating germ cells [tubule differentiation index (TDI)] rapidly decreased after 7 weeks of age with a correlative increase in the intratesticular testosterone (ITT) levels. Treatment with a GnRH antagonist, Cetrorelix, suppressed ITT and stimulated spermatogonial differentiation at the end of treatment. When treated mice were killed 5-13.3 weeks after the end of treatment, the ITT progressively increased, and the TDI progressively declined, but there was a transient appearance of tubules with mature spermatids. To delineate the role of testosterone (T) in spermatogonial arrest, we gave 7.6-week-old jsd mice exogenous T and/or the androgen receptor antagonist flutamide with or without GnRH antagonist for 4 weeks. Flutamide alone moderately stimulated spermatogonial differentiation (TDI = 30%). GnRH antagonist increased the TDI to 73%, and the addition of flutamide to the GnRH antagonist treatment further increased it to 95%. When T was combined with GnRH antagonist treatment, ITT was increased, and the TDI was reduced to 7%. Addition of flutamide to this combination reversed the T inhibition of GnRH antagonist stimulation of spermatogonial differentiation to a TDI of 57%. ITT levels showed a good negative correlation to the TDI obtained with various treatments, but no such correlation was observed for FSH or LH levels. The results indicate that T inhibits the ability of spermatogonia to differentiate in jsd mice through an androgen receptor-mediated process.

Androgen Antagonists↗
PubMed2001

Peak rates of diuresis in healthy humans during oral fluid overload.

OBJECTIVE: To determine whether rates of intestinal fluid absorption and renal diuresis can match high rates of fluid ingestion in healthy humans exposed to oral fluid overload, thereby preventing the development of hyponatraemia either by reverse sodium movement across the intestine (the Priestley-Haldane effect) or by expansion of the extracellular fluid volume. METHODS: Changes in renal function and in plasma chemical measurements in response to an oral fluid overload (0.9-1.8 l/h x 3 h) were investigated in 6 healthy control subjects at rest, and in a subject with a history of exercise-induced symptomatic hyponatraemia, during both prolonged (160-minute) exercise and at rest. FINDINGS: All control subjects gained weight (2.7 +/- 0.2 kg, mean +/- standard error of mean (SEM)) because the rate of oral fluid intake exceeded the peak rate of urine production (778 +/- 39 ml/h). Blood volume rose by 7.1 (+/- 0.5)% and plasma sodium concentrations fell progressively from 144 +/- 2.6 to 136 +/- 1.1 mmol/l (P < 0.05) in the control subjects. Plasma potassium and angiotensin II concentrations were unchanged and creatinine clearance was normal (approximately 125 ml/min). Free water clearance reached a maximum of 11.2 +/- 0.9 ml/min after 2 hours. The increase in body mass could be accounted for by calculated or measured changes in extra- and intracellular fluid volumes. Similar changes were measured in the subject with a previous history of symptomatic hyponatraemia. CONCLUSION: The rate of intestinal fluid absorption appeared to match the rate of oral fluid ingestion and there was no evidence of fluid accumulation in the intestine with reverse sodium movement from the extracellular space into intestinal fluid. The results of this study are therefore at variance with the Priestley-Haldane hypothesis and suggest that reverse sodium movement did not contribute to the hyponatraemia induced by oral fluid overload in these subjects. Rather it appears that humans may have a limited capacity to excrete fluid at rates in excess of approximately 900 ml/h in response to higher rates of oral fluid intake. When the rate of intestinal fluid absorption matches the rate of fluid ingestion and exceeds the kidneys' maximum capacity for fluid excretion, the excess fluid accumulates in the extra- and intracellular fluid compartments, inducing the dilutional hyponatraemia of water intoxication. These findings may have relevance to other clinical conditions in which hyponatraemia develops in response to high rates of oral or intravenous fluid provision.

Adult↗
PubMed2000

Minisatellite mutation frequency in human sperm following radiotherapy.

Screening pedigrees for inherited minisatellite length changes provides an efficient means of monitoring repeat DNA instability but has given rise to apparently contradictory results regarding the effects of radiation on the human germline. To explore this further in individuals with known radiation doses and to potentially gain information on the timing of mutation induction, we have used an extremely sensitive single molecule approach to quantify the frequencies of mutation at the hypervariable minisatellites B6.7 and CEB1 in the sperm of three seminoma patients following hemipelvic radiotherapy. Scattered radiation doses to the testicles were monitored and pre-treatment sperm DNA was compared with sperm derived from irradiated pre-meiotic, meiotic and post-meiotic cells. We show no evidence for mutation induction in any of the patients and discuss this finding in the context of previous population studies using minisatellites as reporter systems, one of which provided evidence for radiation-induced germline mutation.

Adult↗
PubMed2000

Lipid-coated microgels for the triggered release of doxorubicin.

We have systematically engineered a polymeric, multi-component drug delivery system composed of a lipid-coated hydrogel microparticle (microgel). The design of this delivery system was motivated by the recent elucidation of the mechanism of regulated secretion from the secretory granule and the compositional and structural features that underlie its ability to store and release endogenous drug-like compounds. The present work describes the assembly and response of a prototype construct which displays several important features of the secretory granule, including its high drug loading capacity, and triggered microgel swelling, resulting in the burst release of drug. To achieve this, ionic microgels were synthesized, and loaded with doxorubicin via ion exchange. These microgels were then coated with a lipid bilayer, and the release of doxorubicin was triggered from the gels using either lipid-solubilizing surfactants or electroporation. The use of a microanalytical technique is featured utilizing micropipette manipulation that allows the study of the behavior of individual microparticles. The lipid-coated microgels were electroporated in saline solution; they swelled and disrupted their bilayer coating over a period of several seconds and exchanged doxorubicin with the external plasma saline over a period of several minutes. It is envisioned that this system will ultimately find utility in drug delivery systems that are designed to release chemotherapeutic agents and peptides by the application of a triggering signal.

Antineoplastic Agents↗