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Biomedical subjects

G S Robertson

Publications and source records attributed to G S Robertson.

At least 19 recordsLinked to original sources
PubMed1995

Optimization of the magnetic field used for immunomagnetic islet purification.

Purification of islets based on the physical differences in density between exocrine and islet tissue reduces islet yields and remains one of the factors limiting islet transplantation. Immunomagnetic cell separation methods provide an attractive, highly specific alternative capable of rapid, gentle, high volume cell separation, but they require modification to be applied effectively to separation of the much larger tissue fragments involved in islet purification. In this study, mAb to rat exocrine tissue were coupled to 4.5-microns magnetic beads (M450 Dynabeads), before incubation with standard aliquots of rat pancreatic digest. The effect on immunomagnetic islet purification of modifications in the magnetic field and the method of digest release into the field were investigated. The results showed that using vibration to maintain the immunomagnetically labeled digest in suspension in tissue culture medium whose density had been increased by the addition of BSA, significantly improved the purification process. When the digest suspension was slowly released and allowed to drift under gravity through a magnetic field applied across a narrow tube, the use of a quadripole of permanent magnets improved results compared with bipolar or unipolar magnetic fields. By modifying immunomagnetic cell separation techniques in this way, a median islet yield of 77% could be reliably achieved while removing 88% of the contaminating exocrine tissue. The use of such methods in human islet purification would significantly increase the yield of islets from each donor pancreas and increase the success rate of transplantation from single donors.

Amylases↗
PubMed1995

Making an advance directive.

The introduction in Britain of advance directives--which allow a person to state in advance of becoming incompetent that they wish to take part in treatment decisions when no longer mentally competent--has now been advocated by the medical and legal establishments. The practical application of directives relating to health care would be simplified by the adoption of a standard model document together with guidelines summarising the background clinical conditions and any subsequent acute events that may make it appropriate to trigger the use of a directive. As no specific legislation exists, good communication is needed at the various stages between the drafting and implementation of directives if the system of directives is to be successful.

Advance Directives↗
PubMed1995

Radical orchidectomy and benign testicular conditions.

The records of 149 patients who underwent testicular exploration for suspected malignancy were reviewed retrospectively. Malignancy was confirmed in 102 patients but benign pathology was noted in 47. Patients with benign disease were older, more likely to be Asian, gave a longer history and on examination were less likely to have a testicular mass. Increased levels of tumour markers, and ultrasonographic and operative appearance of the testis were highly predictive; with ultrasonography having a sensitivity of 100 per cent but a specificity of only 36 per cent for malignancy. Preoperative ultrasonography and an awareness of the potentially benign nature of many lesions with the use of frozen-section biopsy, where appropriate, may allow a decrease in the currently high rate of unnecessary orchidectomy without missing testicular malignancy.

Adult↗
PubMed1995

Laparoscopic Heller's cardiomyotomy without an antireflux procedure.

The treatment of achalasia by laparoscopic Heller's cardiomyotomy may combine the minimally invasive advantages of pneumatic dilatation with the success rate and low risk of perforation of conventional surgery. The requirement for an antireflux procedure remains a contentious issue, as in conventional surgery. Nine patients underwent laparoscopic cardiomyotomy; excellent symptomatic relief was obtained in eight at follow-up between 12 and 21 months after operation. Four of these patients agreed to 24-h pH monitoring and showed no evidence of acid reflux. One patient, however, developed recurrent symptoms associated with significant acidity on monitoring. Laparoscopic Heller's cardiomyotomy without an antireflux procedure produced effective symptomatic relief in this small group of patients.

Adult↗
PubMed1995

Laparoscopic Nissen fundoplication in children.

Laparoscopic surgery for the definitive treatment of gastroesophageal reflux (GOR) has become an accepted alternative to conventional techniques in adults. Although relatively rare, GOR in children represents an important clinical entity with symptoms including failure to thrive, nocturnal dyspnea, and vomiting. This paper details our experience in eight children who have undergone a laparoscopic Nissen fundoplication for failed medical treatment of severe GOR. Particular attention is paid to technical aspects of the procedure and the differences between adult and pediatric techniques are emphasized. The preliminary results suggest that a laparoscopic Nissen fundoplication is a safe procedure which significantly improves reflux symptoms in children and that these results are comparable to those obtained with conventional surgery.

Child↗
PubMed1995

D1 and D2 dopamine receptors differentially increase Fos-like immunoreactivity in accumbal projections to the ventral pallidum and midbrain.

Alterations in dopaminergic neurotransmission have profound effects on neuronal expression of the putative activity marker, Fos, in both the dorsal and ventral striatum. Stimulants such as D-amphetamine and cocaine increase Fos-like immunoreactivity by enhancing the activation of D1 dopamine receptors. In contrast, neuroleptics such as haloperidol and raclopride increase Fos-like immunoreactivity by blocking striatal D2 dopamine receptors. In the dorsal striatum, D1 receptor stimulation elevates Fos-like immunoreactivity predominantly in neurons projecting to the midbrain (substantia nigra), whereas D2 receptor antagonism enhances Fos-like immunoreactivity principally in neurons projecting to the pallidum (globus pallidus). These findings are consistent with the proposal that D1 receptors are located chiefly on striatonigral neurons, whereas D2 receptors reside mainly on striatopallidal neurons. Since the nucleus accumbens (largest component of the ventral striatum) also sends projections to the midbrain (ventral tegmental area and substantia nigra) and pallidum (ventral pallidum), the present study utilized retrograde tract-tracing techniques to determine if there was a similar segregation of D1 agonist- and D2 antagonist-induced Fos-like immunoreactivity in these accumbal projections. In addition, we examined whether these relationships were the same in the core and shell regions of the nucleus accumbens. Like the dorsal striatum, D1 agonists (D-amphetamine and CY 208-243), but not D2 antagonists (haloperidol and clozapine), increased Fos-like immunoreactivity in accumbal neurons projecting to the midbrain (ventral tegmental area and substantia nigra). Also like the dorsal striatum, D2 antagonist-induced Fos-like immunoreactivity was located preferentially in accumbal neurons projecting to the pallidum (ventral pallidum). However, unlike the dorsal striatum, where the vast majority of neurons which display D1 agonist-induced Fos-like immunoreactivity project to the midbrain, nearly 50% of those neurons in the nucleus accumbens which were Fos-immunoreactive after D-amphetamine or CY 208-243 projected to the ventral pallidum. Thus, a similar number of accumbal neurons which expressed D1 agonist-induced Fos-like immunoreactivity were retrogradely labelled from the midbrain and ventral pallidum. Accumbal projections to the midbrain and ventral pallidum were retrogradely labelled with different retrograde tracers in order to determine the degree of collateralization between these pathways. Approximately 20% of retrogradely labelled neurons displayed both tracers, indicating that collateralization and damage to fibres of passage could not account for all of those cases in which D1 agonist-induced Fos-like immunoreactivity was detected in accumbal neurons projecting to the ventral pallidum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

C-fos mediates antipsychotic-induced neurotensin gene expression in the rodent striatum.

The ubiquitous inducibility of the immediate-early gene c-fos in the central nervous system has led to the search for downstream genes which are regulated by its product, Fos. Recent evidence suggests that c-fos induction by a single injection of the classical antipsychotic haloperidol may contribute to the subsequent increase in neurotensin gene expression in the rodent striatum. Consistent with this proposal, in the present study haloperidol-induced Fos-like immunoreactivity and neurotensin/neuromedin N messenger RNA were found to be expressed by the same population of striatal neurons. Moreover, inhibition of haloperidol-induced c-fos expression by intrastriatal injection of antisense phosphorothioate oligodeoxynucleotides complimentary either to bases 109-126 or 127-144 of c-fos attenuated the subsequent increase in neurotensin/neuromedin N messenger RNA. However, injection of a sense phosphorothioate oligodeoxynucleotide corresponding to bases 127-144 of c-fos did not reduce haloperidol-induced c-fos or neurotensin/neuromedin N expression. Furthermore, constitutive expression of Jun-like immunoreactivity in the striatum was not reduced by either the sense or antisense phosphorothioate oligodeoxynucleotides. Similarly, the sense and antisense phosphorothioate oligodeoxynucleotide failed to reduce proenkephalin messenger RNA, which is located in the same striatal neurons that express haloperidol-induced neurotensin/neuromedin N messenger RNA, which is located in the same striatal neurons that express haloperidol-induced neurotensin/neuromedin N messenger RNA. Lastly, haloperidol-induced increases in nerve growth factor I-A-, JunB- and FosB-like immunoreactivity and fosB messenger RNA were not decreased by intrastriatal injection of either the sense or antisense phosphorothioate oligodeoxynucleotides. These results indicate that the antisense phosphorothioate oligodeoxynucleotides attenuated haloperidol-induced neurotensin/neuromedin N expression by selectively reducing c-fos expression and emphasize the potential importance of immediate-early gene induction in the mechanism of action of this antipsychotic drug.

Animals↗
PubMed1995

Does subclinical pancreatic inflammation occur after parathyroidectomy?

Pancreatitis is accepted as an uncommon complication of parathyroid surgery, but it has been suggested that up to 35% of patients may experience hyperamylasaemia after parathyroidectomy indicating subclinical inflammation of the pancreas. A series of 26 patients undergoing parathyroidectomy were studied by preoperative biochemical analyses repeated 24 and 48 h postoperatively allowing changes in calcium metabolism and serum and urinary amylase levels to be documented. Of the patients, 21 also underwent a CT scan of the pancreas between 24 and 48 h after operation. Despite highly significant changes in serum parathormone, calcium and phosphate levels postoperatively, there was no evidence in any patient of acute pancreatic inflammation or hyperamylasaemia. Twenty-one patients underwent unilateral neck exploration, and we suggest that the absence of any detectable amylase elevation supports the suggestion that such elevation may reflect an increase in salivary isoamylase as a result of extensive neck dissection, rather than reflecting a subclinical pancreatitis. The development of postparathyroidectomy pancreatitis appears to be an all or nothing phenomenon of unknown aetiology.

Acute Disease↗
PubMed1995

Use of laparoscopic instruments in conventional mobilisation of the rectum.

The use of conventional instruments for dissection within confined operating fields such as the pelvis may obscure the surgeon's view, and limit his reach. The long, narrow instruments used during laparoscopic surgery, particularly the diathermy scissors can facilitate bloodless dissection under direct vision during conventional surgery, improving the accuracy of procedures such as mobilisation of the rectum.

Dissection↗
PubMed1995

Serum gastrin levels in the pre-operative localization and surgical treatment of gastrinomas.

The introduction of sensitive radioimmunoassays for gastrin has led to the earlier and more accurate diagnosis of gastrinomas and, as methods for tumour localization both pre- and intraoperatively have improved, the emphasis of surgery has changed from control of gastric acid secretion to tumour removal. We present three cases of sporadic gastrinoma who underwent exploratory laparotomy. In two cases, gastrinomas were discovered and excised resulting in cure for one patient. The third case underwent a negative laparotomy. The changes in serum gastrin levels taken during and immediately after surgery were related to the success or otherwise of tumour removal in each of the three cases. As in parathyroid surgery, with the development of rapid radioimmunoassays, the intraoperative measurement of declining serum gastrin levels will help in the early definition of surgical success supplementing frozen section and clinical judgement and improving patient management.

Adult↗
PubMed1994

Storage of pancreatic digest before islet purification. The influence of colloids and the sodium to potassium ratio in University of Wisconsin-based preservation solutions.

The density-dependent purification of islets from several species of mammalian pancreata is improved by prior storage of the dispersed, collagenase-digested pancreas in suitable storage solutions, such as University of Wisconsin (UW) solution. The optimal composition of such solutions, however, is not fully established, although previous investigations have suggested separately that cellular impermeants and colloids are important components. To investigate this issue further, dispersed tissues from 7 porcine and 7 human pancreata were stored in UW or in solutions containing the impermeants lactobionate and raffinose, with either no added colloid or in the presence of the colloids hydroxyethyl starch, dextran 40, dextran 250, or Ficoll 400; hydroxyethyl starch-containing solutions in which the principal cation was sodium, rather than potassium, were also studied. Subsequent purification of islets on continuous linear density gradients of BSA was then assessed by insulin/amylase assay of gradient fractions. Islet purity was slightly reduced using solutions containing impermeants but lacking a colloid, compared with using UW. In the combined presence of impermeants and a colloid, however, islet purity was similar to that obtained with UW, and for porcine pancreata, solutions containing Ficoll 400 or dextran 40 were slightly superior to UW. Purity was not, however, influenced by the sodium to potassium ratio of storage media. In conclusion, impermeants and colloids are both essential components of solutions used to preserve pancreatic tissue before islet purification, findings which may be relevant when designing media for use during other phases of islet isolation, e.g., during collagenase digestion/density gradient purification.

Adenosine↗
PubMed1994

D1 dopamine receptor agonist-induced Fos-like immunoreactivity occurs in basal forebrain and mesopontine tegmentum cholinergic neurons and striatal neurons immunoreactive for neuropeptide Y.

The present study sought to determine whether the D1 dopamine receptor agonist CY 208-243 increases Fos-like immunoreactivity in neurochemically distinct populations of interneurons in the 6-hydroxydopamine-denervated striatum. In vivo microdialysis studies indicate that cholinergic interneurons in the striatum are excited by the administration of CY 208-243 and that this effect is potentiated by dopaminergic deafferentation. Since Fos is considered to be a marker of neuronal activity, we examined the overlap between CY-208-243-induced Fos-like immunoreactivity and striatal cholinergic interneurons labelled with the cholinergic marker enzyme choline acetyltransferase. Unexpectedly, cholinergic interneurons in the striatum were not found to express Fos-like immunoreactivity. However, D1 agonist-induced Fos-like immunoreactivity was found in neurons immunoreactive for neuropeptide Y. Consequently, the failure of cholinergic neurons in the striatum to express D1 agonist-induced Fos-like immunoreactivity does not appear to be a general property of striatal interneurons. Indeed, CY 208-243 increased Fos-like immunoreactivity in choline-acetyltransferase-positive neurons in the basal forebrain and lateral dorsal tegmental nucleus. In the case of cholinergic basal forebrain neurons, administration of CY 208-243 has been shown to enhance the release of acetylcholine from their terminals located in the frontal cortex. Thus, unlike cholinergic interneurons in the striatum, the expression of Fos-like immunoreactivity in cholinergic basal forebrain neurons is correlated with an increase in transmitter release. Choline acetyltransferase immunoreactivity was markedly reduced in cholinergic basal forebrain neurons ipsilateral to the 6-hydroxydopamine lesion. This decrease in choline acetyltransferase immunoreactivity was confined to a pocket of cortically projecting neurons located in the posterior part of the horizontal limb of the diagonal band which included the medial preoptic nucleus. Interestingly, D1 agonist-induced Fos-like immunoreactivity was located predominantly in those cholinergic neurons which displayed depressed choline acetyltransferase immunoreactivity. Since Fos is often induced as a consequence of increased activity, it is tempting to speculate that those neurons which stained weakly for choline acetyltransferase had been excited by the D1 agonist administration. Accordingly, the destruction of mesencephalic dopaminergic neurons with 6-hydroxydopamine may have deprived these cholinergic neurons of an excitatory D1 receptor-mediated drive, resulting in a reduction of choline acetyltransferase immunoreactivity. These results suggest that the degeneration of nigrostriatal dopamine neurons may contribute to the loss of cholinergic basal forebrain function in Parkinson's disease.

Acetylcholine↗
PubMed1994

Thoracoscopic oesophago-gastrectomy--a new technique for intra-thoracic stapling.

A new technique for performing a standard Ivor Lewis oesophagectomy avoiding the need for a conventional right thoracotomy is described. The intrathoracic dissection and the intrathoracic anastomosis, using a conventional EEA circular staple-gun, is done thoracoscopically. Eight patients with carcinoma of the gastric cardia or distal oesophagus were prepared for a palliative Ivor Lewis two-stage oesophago-gastrectomy. The details of the technique for placing the anvil of a circular staple gun in the upper oesophagus and performing the intrathoracic stapled anastomosis are described. Intrathoracic stapling under thoracoscopic video control was successful in five of the eight patients. The three other patients received 10 cm mini-thoracotomies. All patients were transferred from the intensive care unit within 24 hours and were discharged from hospital within 14 days. There were no complications and no deaths. We believe that this procedure offers many patients better palliation with reduced morbidity because the standard right thoracotomy is avoided.

Adenocarcinoma↗
PubMed1994

Induction patterns of Fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity.

Clozapine and haloperidol produce different induction patterns of c-fos expression in the forebrain, with haloperidol increasing Fos-like immunoreactivity (FLI) in the striatum, nucleus accumbens, lateral septal nucleus and clozapine producing such effects in the nucleus accumbens, prefrontal cortex and lateral septal nucleus. Accordingly, it was deemed possible that this approach may be useful in characterizing compounds with known or suggested antipsychotic actions. We therefore examined the effects of 17 compounds considered to be either typical, or atypical, antipsychotics on FLI in the prefrontal cortex, medial and dorsolateral striatum, nucleus accumbens and the lateral septal nucleus. Consistent with the hypothesis that the prefrontal cortex may be a target for some antipsychotic actions, FLI was elevated in this structure by clozapine, ICI 204,636, fluperlapine, RMI-81,582, remoxipride, molindone, melperone and tiospirone. Likewise, the ability of all of the compounds, except for risperidone, to enhance FLI in the lateral septal nucleus suggests that this limbic region also may be an important locus of antipsychotic action. All of the compounds examined elevated FLI in the nucleus accumbens and medial striatum, indicating that potential antipsychotic activity is predicted most consistently on this basis. Neuroleptics with a clearly documented liability for producing extrapyramidal side effects (EPS) such as chlorpromazine, fluphenazine, haloperidol, loxapine, metoclopramide and molindone elevated FLI in the dorsolateral striatum. In contrast, compounds unlikely to produce EPS such as clozapine, thioridazine, risperidone, remoxipride, fluperlapine, sulpiride, melperone and RMI-81,582 either failed to increase or produced minor elevations in FLI in the dorsolateral striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Destruction of the nigrostriatal pathway increases Fos-like immunoreactivity predominantly in striatopallidal neurons.

Unilateral destruction of the nigrostriatal pathway by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) produces a long-lasting (> 3 months) increase in the expression of Fos-like immunoreactivity (FLI) in medium-sized neurons (12-18 microns) of the ipsilateral striatum. In order to determine the nature of neurons which contain FLI in the 6-OHDA-denervated striatum, striatonigral and striatopallidal neurons were retrogradely labelled with the fluorescent tracer Fluoro-Gold. Nuclei displaying FLI were frequently found in striatopallidal neurons (72% overlap) but seldom in striatonigral neurons (11% overlap). These results are consistent with studies suggesting that dopamine tonically inhibits striatopallidal neurons which become more active in its absence. Moreover, the preferential localization of FLI in striatopallidal neurons supports the proposal that the AP-1 transcriptional regulating factor may contribute to neuropeptide and/or D2 dopamine receptor increases which occur in these neurons after 6-OHDA lesions.

Animals↗
PubMed1993

Resuscitation and senility: a study of patients' opinions.

In the context of 'Do-not-resuscitate' (DNR) decisions, there is a lack of information in the UK on the opinions of patients and prospective patients. Written anonymous responses to questionnaires issued to 322 out-patient subjects showed that 97 per cent would opt for cardiopulmonary resuscitation (CPR) in their current state of health. In the hypothetical circumstance of having advanced senile dementia only 10 per cent would definitely want CPR, with 75 per cent preferring not to have CPR. There were no significant correlations between the responses and sex or age. Of 270 patients asked verbally if they found the questions disturbing, none said they did. These findings show that the great majority of patients would not wish CPR if severely senile, and that patients are not disturbed by questions relating to their choice for or against CPR. This should encourage further investigations of patients' opinions on CPR in a broader range of conditions, and greater use of DNR orders.

Advance Directives↗