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D L Francis

Publications and source records attributed to D L Francis.

At least 19 recordsLinked to original sources
PubMed2004

FDG-PET for the pre-operative evaluation of colorectal liver metastases.

INTRODUCTION: This study assesses the accuracy of routine whole body fluorodeoxyglucose-positron emission tomography (FDG-PET) in the pre-operative staging of patients with colorectal liver metastases (CLM). METHODS: A prospective study of patients referred for hepatic resection was undertaken. Patients were staged by spiral CT and FDG-PET. The results of these investigations were considered independently. RESULTS: Twenty-eight patients had confirmed CLM. Eleven patients had solitary CLM; 10 of whom were correctly identified by both modalities. In the remaining 17 patients, 10 had multiple CLM and seven had extrahepatic disease. FDG-PET detected all lesions (sensitivity 100%, specificity 91%). CT incorrectly diagnosed solitary CLM in five patients and failed to detect extrahepatic disease in four patients (sensitivity 47%, specificity 91%). FDG-PET resulted in altered management for 12 patients of whom seven avoided inappropriate surgery. CONCLUSION: FDG-PET is more sensitive and specific for pre-operative staging of CLM. FDG-PET confers clinical benefit through altered patient management.

Adult↗
PubMed2004

One year follow up of a randomized trial comparing Ligasure with open haemorrhoidectomy.

BACKGROUND: Ligasure haemorrhoidectomy is an effective treatment for prolapsing haemorrhoids, however, concerns exist regarding potential damage to the anal sphincters. METHODS: Patients previously included into a randomized trial comparing open and Ligasure haemorrhoidectomy were contacted by postal questionnaire to evaluate their overall satisfaction and continence at 12 months post operatively. RESULTS: Thirteen patients who underwent open and 17 who underwent Ligasure haemorrhoidectomy were evaluated. Three patients from the open group and 2 from the Ligasure group were unhappy with the result (P = 0.37) and minor incontinence was reported in 5 Ligasure and 2 open patients (P = 0.42). CONCLUSION: Patient satisfaction and post operative continence scores at 1 year post operatively are comparable for open and Ligasure haemorrhoidectomy.

Adult↗
PubMed2003

Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer.

Fluorine-18 labelled fluoro-2-deoxy- d-glucose ((18)FDG) positron emission tomography (PET) imaging demonstrates the increased glucose consumption of malignant cells, but problems with specificity have led to the development of new PET tracers. [(18)F]3'-deoxy-3'-fluorothymidine ((18)FLT) is a new tracer which images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study we compared the cellular uptake of (18)FLT and (18)FDG in patients with colorectal cancer (CRC). Seventeen patients with 50 primary or metastatic CRC lesions were prospectively recruited. Lesions were initially identified using computed tomography. Patients underwent both (18)FDG and (18)FLT scanning. Semi-quantitative analysis of tracer uptake was carried out using standardised uptake values. All the primary tumours ( n=6) were visualised by both tracers, with (18)FDG showing on average twice the uptake of (18)FLT. Similar uptake of both tracers was seen in lung and peritoneal lesions, with (18)FLT imaging five of the six lung lesions and all of the peritoneal lesions. Of the 32 colorectal liver metastases, 11 (34%) were seen as avid for (18)FLT, compared with 31 (97%) for (18)FDG. No correlation was seen between the uptake of the two tracers ( R(2)=0.03). (18)FLT shows a high sensitivity in the detection of extrahepatic disease but poor sensitivity for the imaging of colorectal liver metastases, making it unlikely to have a role as a diagnostic tracer in CRC. We have demonstrated that (18)FDG and (18)FLT image two distinct processes. The prognostic implications of the uptake of (18)FLT need to be assessed in terms of response to chemoradiotherapy and survival.

Aged↗
PubMed2003

In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography.

BACKGROUND: and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). RESULTS: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4). CONCLUSIONS: (18)FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.

Adenocarcinoma↗
PubMed2002

Randomized clinical trial of Ligasure versus open haemorrhoidectomy.

BACKGROUND: Postoperative pain associated with open haemorrhoidectomy remains problematic. Haemorrhoidectomy performed using bloodless bipolar diathermy--Ligasure--may have advantages over conventional open haemorrhoidectomy in terms of operating time and postoperative pain. METHODS: Thirty-four patients were randomized to undergo Ligasure (18 patients) or diathermy (16) haemorrhoidectomy. The operating time, amount of pain and postoperative analgesic requirement, postoperative complications and overall patient satisfaction were documented. RESULTS: The median duration of operation was shorter in the Ligasure haemorrhoidectomy group (5.1 versus 9.2 min; P < 0.001). There was no statistically significant difference in the postoperative pain score, but the median analgesic requirement was lower in the Ligasure group (850 versus 1600 mg tramadol; P = 0.013). Patient satisfaction was similar in both groups. CONCLUSION: Ligasure haemorrhoidectomy is quick and bloodless and, although as painful as diathermy haemorrhoidectomy, is associated with a reduced analgesic requirement.

Adult↗
PubMed1981

Model of opiate dependence in the guinea-pig isolated ileum.

1 Segments of ileum, incubated for 2-24 h at 22 degrees C with normorphine (0.01 - 1.0 muM), in the presence of hexamethonium, contracted when challenged with naloxone (0.03 muM). No response to this dose of naloxone was induced either by incubation in control solution without opiate for 2-24 h or by exposure of the preparation to opiate for 30 min at 37 degrees C.2 When segments were incubated for 24 h, the size of the response to naloxone was directly related both to the normorphine concentration in the incubation fluid (0.01 to 0.1 muM), and to the concentration of naloxone applied (0.03 to 0.1 muM).3 A spontaneous withdrawal contracture was elicited in ilea that had been incubated with normorphine (1.0 muM), when the normorphine-containing bathing fluid was exchanged for one without opiate.4 Normorphine restored to resting level the tension of the withdrawal contracture, whether it had been elicited spontaneously or by naloxone challenge.5 Addition of naloxone (1.0 muM) to normorphine (1.0 muM) in the incubation fluid abolished the withdrawal contracture to subsequent challenge with naloxone.6 Naloxone elicited a contracture from segments incubated for 24 h at 22 degrees C with levorphanol (0.1 muM) but not from those incubated with dextrorphan.7 Application of (+)-naloxone (0.03 muM) to segments previously incubated with normorphine (0.1 muM) did not elicit a contracture.8 The contracture elicited by naloxone in preparations incubated with morphine (10 muM) was associated with a reduction in sensitivity to the acute inhibitory effect of morphine on the electrically-evoked response.9 Addition of hyoscine (0.5 muM) immediately after challenge with naloxone restored the tension of the withdrawal contracture to resting level.10 Tetrodotoxin (3.0 muM) given before challenge, prevented naloxone from eliciting a withdrawal contracture.11 The inclusion of 5-hydroxytryptamine (10 muM) with morphine (10 muM) inhibited the induction of tolerance to morphine.12 These experiments, together with those described earlier, indicate that incubation with opiate induces a dependence in the final cholinergic motor neurones of the myenteric plexus, manifested as a contracture of the longitudinal muscle on removal of opiate or administration of an antagonist. This dependence is associated with tolerance, expressed as a decrease in sensitivity to inhibition by morphine of the electrically-evoked contracture. Tolerance and dependence are induced and withdrawal precipitated through specific and stereospecific opiate receptors.

Animals↗
PubMed1981

Clonidine dependence in the guinea-pig isolated ileum.

1 Compared with the response of preparations incubated in solutions without clonidine, a three to four fold increase in the magnitude of the contracture of the longitudinal muscle to challenge with phentolamine (1.0 mum) was induced by incubating the guinea-pig isolated ileum at 22 degrees C for 24 h with clonidine (1.0 mum) in Krebs solution containing hexamethonium (70 mum). Incubation of the ileum with clondine (1.0 mum) for 0.5 h at 37 degrees C did not increase responsiveness to phentolamine.2 The increase in responsiveness to phentolamine was directly related to the clonidine concentration in the incubation fluid over the range 0.01 to 1.0 mum.3 The magnitude of the contracture to phentolamine of ilea incubated with clonidine (1.0 mum) (withdrawal contracture) was directly related to the challenge dose of phentolamine over the range 0.3 to 1.0 mum.4 Yohimbine (1.0 mum) or piperoxane (1.0 mum) elicited a response comparable to that elicited by phentolamine but propranolol (1.0 mum) was inactive.5 Addition of phentolamine (1.0 mum) to clonidine (1.0 mum) in the incubation fluid abolished the increased response of the preparation to subsequent challenge with phentolamine.6 Addition of hyoscine (0.5 mum) immediately after challenge with phentolamine restored the tension of the withdrawal contracture to its resting level.7 Tetrodotoxin (3.0 mum) given before challenge, prevented phentolamine from eliciting a withdrawal contracture.8 Ileal segments incubated with clonidine (1.0 mum) were unresponsive to challenge with naloxone (100 nm); and segments incubated with normorphine (1.0 mum) were unresponsive to phentolamine (1.0 mum), although responsive to naloxone.9 Normorphine (1.0 mum) restored to resting level the tension of the clonidine withdrawal contracture; and clonidine (0.1 mum) restored to resting level the tension of the contracture to naloxone in ileal segments incubated with normorphine.10 These experiments indicate that incubation with clonidine induces, in the final cholinergic motor neurones of the myenteric plexus of the isolated ileum, a dependence the withdrawal from which is expressed as a contracture in response to alpha-adrenoceptor antagonists.11 Although opiate receptors are not involved in clonidine dependence nor alpha-adrenoceptors in opiate dependence, the findings that normorphine suppresses the clonidine withdrawal-contracture and that clonidine suppresses the contracture of opiate-dependent ileum to naloxone, suggest that the withdrawal effect studied in both clonidine and normorphine dependence in this preparation is mediated by release of acetylcholine from the final motor neurone.

Animals↗
PubMed1981

Character and meaning of quasi-morphine withdrawal phenomena elicited by methylxanthines.

A quasi-morphine withdrawal syndrome (QMWS) is a pattern of behavior closely resembling the true withdrawal syndrome in the opiate-dependent animal, which can be elicited acutely by a nonopiate drug in an opiate-naive animal. The main criteria proposed for the QMWS, in addition to its resembling the true withdrawal syndrome, are that the effects of opiates and of opiate antagonists on the QMWS should parallel those on true opiate withdrawal. Drugs that wholly or largely fulfill these criteria are 3-isobutyl-1-methylxanthine (IBMX), theophylline, caffeine, ICI 63197, and RO 201724. From the evidence given, it is concluded that these drugs act by inhibiting brain cyclic AMP phosphodiesterase, thus raising the level of cyclic AMP in appropriate neurons. These findings are consistent with the view that the molecular mechanisms of opiate dependence is the hypertrophy of a neuronal cyclic AMP system in compensation for the inhibition by opiate of an adenylate cyclase. Our studies and those of others suggest that: a) very rapid tests for opiate activity and for addictive liability can be devised by use of IBMX; b) opiates may be used clinically to counter poisoning by caffeine or theophylline; and c) a relationship may exist between caffeine consumption and opiate addiction.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Mechanism of quasi-morphine withdrawal behaviour induced by methylxanthines.

Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome (QMWS) in opiate-naive rats, five were effective in a dose-related way. These, in descending order of potency, were IBMX, ICI-63197, RO-201724, theophylline and caffeine. Their potencies in inducing a QMWS correlated significantly (P less than 0.05) with those in inhibiting low Km cyclic AMP phosphodiesterase of rat brain homogenate. There was no correlation with potencies in inhibiting cyclic GMP phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Opiates, cyclic nucleotides, and xanthines.

In rat brain homogenate, opiates exert a dose-related inhibition of PGE-stimulated cyclic (AMP) formation. This effect is stereospecific and is correlated with agonist potency. Naloxone antagonizes heroid in a dose-related way, without, at effective concentrations, itself inhibiting PGE-stimulated cyclic AMP formation. In morphine-dependent rats, intracerebroventricular injection of cyclic AMP intensifies and of dibutyryl cyclic GMP diminishes precipitated abstinence effects. In naive rats, the xanthines, theophylline and 3-isobutyl-1-methylxanthine, produce a quasimorphine-abstinence syndrome that is readily suppressed by heroin and intensified by nalosone. In rat brain homogenate, these xanthines inhibit cyclic AMP phosphodiesterase. These findings are concistent with these views: (a) The opiates specifically inhibit an adenylate cyclase of morphine-sensitive neurons that is sensitive to stimulation by PGEs. (b) Opiate agonist action is associated with the lowering of a neuronal cyclic AMP. (c) Both the morphine-abstinence syndrome in dependent rats and the quasi-abstinence syndrome in naive rats are associated with a rise in this neuronal cyclic AMP. (d) There are two types of endogenous humoral mediator acting on morphine-sensitive neurons, one of which is morphine-like and the other antimorphine-like in action.

3',5'-Cyclic-AMP Phosphodiesterases↗