Biomedical subjects

J R Griffiths

Publications and source records attributed to J R Griffiths.

At least 73 records · Page 4Linked to original sources

PubMed1998

Pattern recognition analysis of 1H NMR spectra from perchloric acid extracts of human brain tumor biopsies.

Pattern recognition techniques (factor analysis and neural networks) were used to investigate and classify human brain tumors based on the 1H NMR spectra of chemically extracted biopsies (n = 118). After removing information from lactate (because of variable ischemia times), unsupervised learning suggested that the spectra separated naturally into two groups: meningiomas and other tumors. Principal component analysis reduced the dimensionality of the data. A back-propagation neural network using the first 30 principal components gave 85% correct classification of meningiomas and nonmeningiomas. Simplification by vector rotation gave vectors that could be assigned to various metabolites, making it possible to use or to reject their information for neural network classification. Using scores calculated from the four rotated vectors due to creatine and glutamine gave the best classification into meningiomas and nonmeningiomas (89% correct). Classification of gliomas (n = 47) gave 62% correct within one grade. Only inositol showed a significant correlation with glioma grade.

Biomarkers, Tumor↗

PubMed1998

Pre-treatment energy status of primary rat tumours as the best predictor of response to 5-fluorouracil chemotherapy: a magnetic resonance spectroscopy study in vivo.

PURPOSE: Fluorine-19 magnetic resonance spectroscopy (19F-M RS) studies of the pharmacokinetics of the anticancer drug 5-fluorouracil (FU) in patients at several clinical centres have shown that increased tumour retention of FU is associated with patient response. The mechanism of this increased tumour retention (FU trapping) is unknown. We used a pre-clinical model to investigate whether other MRS-measurable parameters would correlate with the response to FU treatment and, thus, help elucidate the mechanism(s) involved in FU trapping. METHODS: MRS spectra were obtained using a double-tuned (31P/19F) surface coil from 29 N-methyl-N-nitrosourea-induced primary rat tumours. 31P-MRS spectra were acquired immediately prior to and at 2.5 h post-treatment with a bolus i.p. injection of FU (100 mg/ kg); 19F-MRS spectra were acquired during the intervening 2.5-h period for measurement of the tumour uptake and retention of FU and of its metabolism to the cytotoxic fluoronucleotides (FNuct). From these data, four parameters were measured: tumour pH and energy status (NTP/Pi) before treatment, total FU retention, and FU anabolism to FNuct (expressed as micromoles per gram per 2.5 h). In addition, tumour response was determined at 7 days post-treatment by measurement of the percentage of change in tumour weight and was classified according to standard oncological criteria as follows: progressive (P) for a > or =25% increase, remissive (R) for a > or =50% decrease or stable (S) for values lying between these two. RESULTS: Analysis of variance (ANOVA) for statistical assessment revealed that groups P, S and R were not distinguishable using the MRS parameters; although when S and R were combined as one group of non-progressive disease (NPD; n = 24), both the NTP/Pi ratio and the total FNuct formed were significantly greater (P = 0.04) than those observed in the P group (n = 5). Considering all 29 tumours, linear regression showed that there were positive significant correlations between the NTP/Pi ratio and (a) the percentage of response (P = 0.04), (b) the pre-treatment pH (P = 0.002) and (c) FU retention (P = 0.02), but not FNuct formation (P = 0.66). Unlike results reported in the clinic, the percentage of response and FU retention were neither significantly correlated (P = 0.22) nor associated when groups P and NPD were compared (P = 0.27, Fischer's exact test). FNuct, however, was significantly associated with response, as was the NTP/Pi ratio (P < or = 0.02). Combination of FNuct with the NTP/Pi ratio increased the significance of the association with response (P = 0.003, Fischer's exact test). CONCLUSIONS: Our results indicate that in this particular model the pre-treatment tumour NTP/Pi ratio was the best predictor of response to a bolus injection of FU, rather than FNuct formation or FU retention. An elevated NTP/Pi ratio could reflect a well-vascularised tumour with an improved capacity for energy-dependent FU uptake and metabolism to FNuct, suggesting that further investigation of this parameter could be an important line of research, which may aid the identification of tumours likely to be sensitive to FU chemotherapy in the clinic.

Analysis of Variance↗

PubMed1998

Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow.

The application of functional magnetic resonance (MR) imaging techniques to the measurement of oxygenation and blood flow in tumors is described. Gradient recalled echo MR imaging (GRE-MRI) offers a real-time noninvasive method for monitoring tumor response to vasomodulators such as carbogen (95% O2/5% CO2) breathing in attempts to overcome tumor hypoxia and improve treatment efficacy. Although the response is tumor-type dependent, increases in signal intensity of up to 100% have been observed in several animal tumor types. Responses are also seen in human tumors. The observed increases in GRE-MRI signal intensity are due to a combination of a reduction of deoxyhemoglobin in the blood causing changes in the MR imaging relaxation time T2* and changes in blood flow and may also reflect the capillary density. Thus, the magnitude of the GRE image intensity change gives an indication of the potential response of an individual tumor to treatments that aim to improve tissue oxygenation and therefore how the tumor may respond to therapy. In addition, carbogen breathing by the host has been shown to increase the uptake and efficacy of chemotherapeutic agents in animal tumors.

Administration, Inhalation↗

PubMed1998

The relationship between tumour oxygenation determined by oxygen electrode measurements and magnetic resonance spectroscopy of the fluorinated 2-nitroimidazole SR-4554.

The relationship between two methods of assessing tumour oxygenation in vivo, namely oxygen electrode measurement and magnetic resonance spectroscopy (MRS) of the fluorinated 2-nitroimidazole SR-4554, was investigated. Using three tumour models (two sites), no linear correlation was observed between 19F retention index and pO2 parameters (r < or = 0.3). Substantial retention of SR-4554 (19F retention index > 0.5) was, however, associated with low tumour pO2 (% pO2 < or = 5 mmHg = 60%). Depending on the pO2 parameters used, SR-4554 administration was shown to produce either a significant or a non-significant increase in tumour oxygenation. We conclude that measurement of SR-4554-related compound(s) by 19F-MRS has the potential to detect clinically relevant levels of tumour hypoxia.

Animals↗

PubMed1998

Influence of pH on the uptake of 5-fluorouracil into isolated tumour cells.

To investigate the possible dependence of 5-fluorouracil (5FU) uptake in tumours on the intra- (pHi) and extracellular (pHe) pH, a pH gradient (deltapH) was imposed across the plasma membrane of ascites tumour cells in vitro, similar to that known to occur in some solid tumours in vivo, by incubation in media of PHe 5-8. A > or = 2:1 (intracellular/extracellular) accumulation of radiolabelled 5FU occurred after 5 min incubation of the cells with 0.5 mM 5FU at pHe of 5.0, 5.5 or 6.0. 5FU metabolism is slow under these conditions, and 5FU uptake was not affected by longer incubations up to 20 min, nor by the absence of a sodium gradient. pHi was estimated from the distribution of the weak acid, 5.5-dimethyl-2,4-oxazolidione ([14C]DMO) across the cell membrane. There was significant correlation between the intracellular/extracellular 5FU ratio and pHe (from pHe 6-8), deltapH and pHi (P < 0.02). Similar results were obtained with HT29 cells. Incubation with a drug that made plasma membranes permeable to H+ significantly decreased 5FU uptake in Lettre cells. The co-transport of 5FU may occur on a proton symport using the proton motive force of the deltapH.

Adenocarcinoma↗

PubMed1998

31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models.

The objective of this study was first to determine whether three slowly growing early-generation murine transplantable tumours, the T40 fibrosarcoma, T115 mammary carcinoma and T237 lung carcinoma, exhibit patterns of energetics and blood flow during growth that are different from those of the faster growing RIF-1 fibrosarcoma. Serial measurements were made with 31P-magnetic resonance spectroscopy (MRS), relating to nutritive blood flow and 2H-magnetic resonance imaging (MRI), which is sensitive to both nutritive and large-vessel (non-nutritive) flow. All four tumour lines showed a decrease in betaNTP/Pi and pH with growth; however, each line showed a different pattern of blood flow that did not correlate with the decrease in energetics. Qualitative histological analysis strongly correlated with the 2H-MRI. Second, their response to 5 mg kg(-1) hydralazine i.v. was monitored by 31P-MRS. A marked decrease in betaNTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge. In contrast, the fourth generation T40 fibrosarcoma and T237 lung carcinoma showed no change in 31P-MRS parameters. However, a fifth-generation T237 cohort, which grew approximately three times faster than fourth-generation T237 cohorts, exhibited a significant deterioration in betaNTP/Pi and pH in response to hydralazine. These data are consistent with a decoupling between large-vessel and nutritive blood flow and indicate that early-generation transplants that have a slow growth rate and vascular tone are more appropriate models of human tumour vasculature than more rapidly growing, repeatedly transplanted tumours.

Animals↗

PubMed1998

The effects of host carbogen (95% oxygen/5% carbon dioxide) breathing on metabolic characteristics of Morris hepatoma 9618a.

Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% carbon dioxide) breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.

Administration, Inhalation↗

PubMed1997

The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging.

PURPOSE: Gradient-Recalled Echo (GRE) Magnetic Resonance Imaging (MRI), which detects changes in blood vessel deoxyhaemoglobin content, has been investigated as a noninvasive monitor of changes in human tumor oxygenation and blood flow, in response to carbogen (95% O2, 5% CO2) breathing. METHODS AND MATERIALS: GRE images (TE = 60 ms, TR = 200 ms, alpha = 40 degrees, 256[2] matrix) were acquired from 31 patients with primary and metastatic disease, prior to and during carbogen breathing. Three patients underwent a follow-up examination after radiotherapy. RESULTS: Seventeen out of 34 tumors showed enhanced image intensity, consistent with an improvement in tumor oxygenation and blood flow, while 11 showed no response; 6 studies were technical failures. In one patient a metastatic node that had eluded orthodox investigation was visualized. A reduction in response was observed in the three patients studied postradiotherapy. CONCLUSION: This method, which can be performed on a standard clinical MRI instrument, provides a noninvasive measurement of tumor response to oxygenation/blood flow modification. In principle, this should enable the clinician to optimize treatment protocols, such as carbogen breathing, for individual radiotherapy patients.

Administration, Inhalation↗

PubMed1997

Preclinical evaluation of the fluorinated 2-nitroimidazole N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554) as a probe for the measurement of tumor hypoxia.

A novel probe, N-(2-hydroxy-3,3,3,-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554), has been used to detect tumor hypoxia noninvasively by 19F magnetic resonance spectroscopy (19F MRS). The compound was designed to undergo a hypoxia-dependent, one-electron reduction to metabolites that are selectively retained in tumors and has attractive pharmacokinetic, toxicological, and detection sensitivity properties. As a prelude to clinical studies, we report here for the first time on the ability to detect a MR signal following SR-4554 administration in various transplantable tumors and describe validation studies, consisting of a correlation between signal retention and radiobiological hypoxic fraction, and the effects of modulating the degree of hypoxia by hydralazine and carbogen breathing. SR-4554 was absorbed and then eliminated from EMT6 tumors with a half-life of 51 min following an injection of 180 mg/kg i.p. of SR-4554. Using a quantitative 19F MRS technique, the 19F retention index (19FRI; 19F signal level at 6 h/45 min) was determined for four commonly used murine tumors (EMT6, SCCVII, KHT, and RIF-1). The retention of high tumor concentrations of fluorinated probe at 6 h, despite the much lower (20-fold) concentration of parent SR-4554 detected by high-performance liquid chromatography, was consistent with the involvement of one or more nitroreduced metabolites and suggested that 19F MRS might give a quantitative measure of tumor hypoxia. In these murine tumors, 19FRI correlated with the reported radiobiological hypoxic fraction of the tumors (r = 0.988; P = 0.01). In addition, changes in tumor microenvironment were detected by 19F MRS. An increase in hypoxia induced by hydralazine treatment of RIF-1 tumor-bearing mice was associated with a 2.4-fold increase in 19FRI compared to untreated controls. In contrast, carbogen breathing by C3H mammary tumor-bearing mice produced a 6-fold decrease in the 19FRI compared to air-breathing mice. The data presented support the preclinical and clinical development of SR-4554 as a noninvasive probe for tumor hypoxia.

Animals↗

PubMed1997

A pharmacokinetic and pharmacodynamic study in vivo of human HT29 tumours using 19F and 31P magnetic resonance spectroscopy.

19F-MRS (magnetic resonance spectroscopy) was used to study the pharmacokinetics of 5-fluorouracil (5-FU) in human (HT29) tumour xenografts, with and without pretreatment of the mice using either thymidine (40 min) or interferon-alpha (2 and 24 h). A 200 mg/kg i.p. bolus dose of 5-FU was eliminated from control tumours with a t1/2 of 25.4 +/- 2 min (mean +/- SEM, n = 11), while both thymidine (500 mg/kg) and interferon (50,000 IU/mouse) significantly increased t1/2 to 36.5 +/- 6.1 (n = 5) and 48.1 +/- 13.6 min (n = 4), respectively (P = 0.04, Gabriel's ANOVA). Thymidine increased 5-FU anabolism to cytotoxic 5-fluoronucleotides, and decreased the amount of tumour catabolites; the latter probably recirculated from liver since isolated HT29 cells did not catabolize 5-FU. These in vivo observations were confirmed by 19F-MRS quantification of tumour extracts. Interferon did not significantly affect 5-FU metabolism in the tumour or liver, nor the 5-FU t1/2 in liver. Treatment of tumours with 5-FU or interferon had no effect on tumour growth, whereas the combination strongly inhibited growth. 31P-MRS of HT29 tumours showed that 2 and 24 h after i.p. injections of interferon there was a significant increase in the pHint of 0.3 +/- 0.04 units (P = 0.002), while pHext and the tumour NTP/Pi ratio were unchanged. The large increase in the negative pH gradient (-delta pH) across the tumour plasma membrane caused by interferon suggest the delta pH may be a factor in tumour retention of 5-FU, as recently shown in isolated tumour cells.

Animals↗

PubMed1997

In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas.

The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% carbon dioxide) breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

Animals↗

PubMed1997

The response to carbogen breathing in experimental tumour models monitored by gradient-recalled echo magnetic resonance imaging.

Gradient-recalled echo magnetic resonance imaging (GRE MRI), which gives information on blood flow and oxygenation changes (Robinson SP, Howe FA, Griffiths JR 1995, Int J Radiat Oncol Biol Phys 33: 855), was used to observe the responses of six rodent tumour models to carbogen breathing. In one transplanted rat tumour, the Morris hepatoma 9618a, and a chemically induced rat tumour, the MNU-induced mammary adenocarcinoma, there were marked image intensity increases, similar to those previously observed in the rat GH3 prolactinoma. In contrast, the rat Walker carcinosarcoma showed no response. In two mouse tumours, the RIF-1 fibrosarcoma and the human xenograft HT29, carbogen breathing induced a transient fall in signal intensity that reversed spontaneously within a few minutes. The rat GH3 prolactinoma was xenografted into nude mice, and an increase in image intensity was found in response to carbogen, suggesting that any effects that carbogen may have had on the host were not significant determinants of the tumour response. The increases in GRE image intensity of the MNU, H9618a and GH3 tumours during carbogen breathing are consistent with increases in tumour oxygenation and blood flow, whereas the responses of the RIF-1 and HT29 tumours may be the result of a transient steal effect followed by homeostatic correction.

Administration, Inhalation↗

PubMed1997

Nuclear magnetic resonance spectroscopy of cancer.

Nuclear magnetic resonance spectroscopy (MRS) offers a non-invasive approach for studying tumour biochemistry and physiology. This review highlights NMR nuclei (31P, 1H, 19F, 13C, 2H) that have been observed in both pre-clinical and clinical spectroscopic studies of cancer.

Carbon Isotopes↗

PubMed1996

31P-magnetic resonance spectroscopy studies of nucleated and non-nucleated erythrocytes; time domain data analysis (VARPRO) incorporating prior knowledge can give information on the binding of ADP.

Human erythrocytes have no nucleus, mitochondria or endoplasmic reticulum, whereas chicken erythrocytes have a nucleus and mitochondria and are closer in internal morphology, to cells such as the hepatocyte. Erythrocytes were used to test the hypothesis that 31P-MRS invisibility of ADP is associated with the presence of intracellular organelles. Simple frequency domain spectral analysis methods showed that all the acid extractable ADP (and ATP) was MR-visible in human erythrocytes. However, such methods gave variable estimates for 31P-NMR spectra of fresh chicken erythrocytes from which no conclusions could be drawn about the MR-visibility of ADP. Only when the data were fitted by a method incorporating prior knowledge of the ATP and ADP peak structure, using the time domain VARPRO method, was it possible to conclude that in fresh chicken erythrocytes, similar to other nucleated cells (liver, muscle), all the acid extractable ADP appeared to be MRS invisible, indicating binding or sequestration by intracellular organelles.

Adenosine Diphosphate↗

PubMed1996

Modification of tumour perfusion and oxygenation monitored by gradient recalled echo MRI and 31P MRS.

Gradient recalled echo (GRE) 1H images can be used to monitor changes in blood oxygenation via the dephasing effects of paramagnetic deoxyhaemoglobin (Hb). We have modulated the blood flow/oxygenation of GH3 rat tumours by i.v. calcitonin gene-related peptide (CGRP) or carbogen (95% O2, 5% CO2) inhalation, and obtained GRE 1H images interleaved with 31P spectra before, during and after the insult. With CGRP the GRE image intensity decreased (6/10) by > 10% with a concomitant 40% decrease (4/4) in beta NTP/P1 and a small decrease in pH. Both the image intensity and 31P spectra returned to near their pre-CGRP levels after 50 min, consistent with a transient episode of hypoxia. Carbogen breathing (5/5) caused > 40% increases in average GRE image intensity, with no significant changes in the 31P spectra (4/4). Three-dimensional GRE images were obtained to confirm that a T2* increase, rather than just an 'in-flow' effect due to increased blood flow, was responsible for the GRE enhancement. Increases in average image intensity > 40% were observed for the three-dimensional GRE images (2/2), indicating a T2* increase. Using Hb as an endogenous contrast agent, the high sensitivity of the GRE technique may provide a method of monitoring heterogeneous tumour perfusion and oxygenation, both in the laboratory and the clinic.

Animals↗

PubMed1996

The acute and chronic effects of alcohol upon cardiac nucleotide status.

The aim of the investigation was to ascertain the biochemical and morphological basis for the functional impairments in the heart due to alcohol. In chronic studies rats were fed a nutritionally complete liquid diet containing 35% of total calories as ethanol, controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. In acute studies rats were injected with ethanol at a dose of 75 mmol/kg body weight. Pre-treatment of acute ethanol-dosed rats with cyanamide (ALDH inhibitor) was designed to raise acetaldehyde levels. In chronic studies ventricular adenine nucleotides, ATP, ADP and AMP; NAD(+), ATP ratios and the energy charge showed no alteration after 6 weeks of alcohol feeding. Light and electron microscopy sections indicated very little structural damage to muscle fibres and organelles (especially the mitochondria) in both atria and ventricles. Ventricular fibre diameters, throughout the different ranges, showed no significant differences between chronically alcohol and control-fed rats. In acute studies an increase in ventricular AMP levels (micromoles/g wet weight) occurred following cyanamide and cyanamide + ethanol treatment (+57%, p < 0.025 and +76%, p<0.01, respectively), but not as a consequence of ethanol alone. Cyanamide+ethanol caused marked elevation in ADP levels (+28%, p < 0.05) and again ethanol was without effect. ATP and GTP levels were not altered by any of the acute treatments. The energy charge was slightly reduced in both cyanamide and cyanamide+ethanol groups (-8%, p < 0.01 and -7%, p < 0.05, respectively), but not by ethanol alone. In conclusion, chronic alcohol appears to have minimal effects upon cardiac nucleotides which suggest that possible adaptive mechanisms are induced during the 6-week period and that alternative pathways other than defects in adenine nucleotide concentrations are involved in the pathogenesis of AHMD. The acute study suggests that the heart is resilient to toxic levels of alcohol and acetaldehyde in terms of ATP and GTP levels, despite the elevated AMP, ADP and GDP levels.

Journal Article↗

PubMed1996

Application of magnetic resonance neurography in the evaluation of patients with peripheral nerve pathology.

Currently, diagnosis and management of disorders involving nerves are generally undertaken without images of the nerves themselves. The authors evaluated whether direct nerve images obtained using the new technique of magnetic resonance (MR) neurography could be used to make clinically important diagnostic distinctions that cannot be readily accomplished using existing methods. The authors obtained T2-weighted fast spin-echo fat-suppressed (chemical shift selection or inversion recovery) and T1-weighted images with planes parallel or transverse to the long axis of nerves using standard or phased-array coils in healthy volunteers and referred patients in 242 sessions. Longitudinal and cross-sectional fascicular images readily distinguished perineural from intraneural masses, thus predicting both resectability and requirement for intraoperative electrophysiological monitoring. Fascicle pattern and longitudinal anatomy firmly identified nerves and thus improved the safety of image-guided procedures. In severe trauma, MR neurography identified nerve discontinuity at the fascicular level preoperatively, thus verifying the need for surgical repair. Direct images readily demonstrated increased diameter in injured nerves and showed the linear extent and time course of image hyperintensity associated with nerve injury. These findings confirm and precisely localize focal nerve compressions, thus avoiding some exploratory surgery and allowing for smaller targeted exposures when surgery is indicated. Direct nerve imaging can demonstrate nerve continuity, distinguish intraneural from perineural masses, and localize nerve compressions prior to surgical exploration. Magnetic resonance neurography can add clinically useful diagnostic information in many situations in which physical examinations, electrodiagnostic tests, and existing image techniques are inconclusive.

Adolescent↗

PubMed1996

Consent--Scots law and the patient's right to know.

Four cases highlight interesting points in relation to the legal considerations, in Scotland, of consent to medical treatment. MOYES sets the broad parameters and deals with the situation or risk established but a reasonable warning given of that risk. INGRAM and COSGROVE are cases where the risk averred to exist was not proved to exist. GOORKANI brings together risk, a causal link between the risk and the injury, and negligent failure to warn of the risk. And it has the interesting twist of the nature of the loss which had to be compensated--not infertility but the loss of the opportunity to adjust to the prospect of infertility.

Adult↗