Michael Powell - Academia.edu (original) (raw)

Papers by Michael Powell

Research paper thumbnail of A memorable patient: Keep looking for a reason

Research paper thumbnail of The Association between Calcitonin Gene-Related Peptide (CGRP), Substance P and Headache in Pituitary Tumours

Pituitary, 2004

Objectives: To determine if the differential expression of calcitonin gene-related peptide (CGRP)... more Objectives: To determine if the differential expression of calcitonin gene-related peptide (CGRP) or substance P (SP) in a range of pituitary tumours was related to the presence or absence of headache. Methods: Using recognised immunohistochemical techniques we examined twenty-six consecutive pituitary adenoma specimens for the presence of CGRP and SP. We included one normal post mortem pituitary specimen for comparison. A separate observer divided the patients into two groups: headache and non-headache. The association between the presence of CGRP, SP and headache was observed. Results: We observed CGRP in seven specimens (27%) and SP in six tumour specimens (23%), with cytoplasmic staining being the predominant morphological picture. CGRP and SP were co-expressed in the same tumour specimen in five cases. There was no significant association between the presence of CGRP and headache (χ 2 0.86; P = 0.35). We did not observe CGRP or SP in the control specimen. There was no correlation between tumour subtype and the presence of CGRP or SP. Conclusions: The mechanism of pituitary tumour-associated headache remains undetermined. The significance of the presence of CGRP and SP in pituitary tumours is unknown but does not appear to be related to headache or endocrine activity of the tumour.

Research paper thumbnail of Relapsing intracranial Rosai-Dorfman disease

Journal of Neurology, Neurosurgery & Psychiatry, 2001

Two patients presenting with recurrent visual impairment due to relapsing intracranial Rosai-Dorf... more Two patients presenting with recurrent visual impairment due to relapsing intracranial Rosai-Dorfman disease are described. In both patients a preoperative diagnosis of meningioma was made. Histological examination disclosed the characteristic picture of S100 and CD68 positive histiocytosis with prominent lymphophagocytosis. In both patients complete tumour removal by surgery was impossible with residual tissue being the origin of relapsing disease. Low dose radiation led to partial recovery of vision and resolution of the intracranial mass. Review of the literature on intracranial Rosai-Dorfman disease leads to the suggestion that postoperative radiotherapy may be advisable in all cases.

Research paper thumbnail of Characterization of SNARE Proteins in Human Pituitary Adenomas: Targeted Secretion Inhibitors as a New Strategy for the Treatment of Acromegaly?

The Journal of Clinical Endocrinology & Metabolism, 2013

Context:Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins ... more Context:Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins engineered from botulinum toxin, represent a novel approach for treating diseases with excess secretion. They inhibit hormone secretion from targeted cell types through cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) proteins. qGHRH-LHN/D is a TSI targeting pituitary somatotroph through binding to the GHRH-receptor and cleavage of the vesicle-associated membrane protein (VAMP) family of SNARE proteins.Objective:Our objective was to study SNARE protein expression in pituitary adenomas and to inhibit GH secretion from somatotropinomas using qGHRH-LHN/D.Design:We analyzed human pituitary adenoma analysis for SNARE expression and response to qGHRH-LHN/D treatment.Setting:The study was conducted in University Hospitals.Patients:We used pituitary adenoma samples from 25 acromegaly and 47 nonfunctioning pituitary adenoma patients.Outcome:Vesicle-SNARE (...

Research paper thumbnail of Drug points: Intranasal chlorhexidine resulting in anaphylactic circulatory arrest

BMJ, 1997

was 12.6 weeks and at counselling 15.3 weeks. Three out of four further couples referred to the s... more was 12.6 weeks and at counselling 15.3 weeks. Three out of four further couples referred to the specialist centre had prenatal diagnosis (at 11, 11.3, and 17.3 weeks). No fetus was diagnosed as affected, but one pregnancy miscarried. One woman declined prenatal testing because of a poor obstetric history, and she later miscarried. Two out of 17 liveborn children had a sickle cell disorder. Overall, 1 in 10 affected pregnancies was detected prenatally and terminated.

Research paper thumbnail of Sir Victor Horsley—an inspiration

BMJ, 2006

see as particularly important. The company could be profit led (any drug would do, provided it ra... more see as particularly important. The company could be profit led (any drug would do, provided it raised money), disease led (focusing on drugs that target a particular disease, tuberculosis perhaps), or drug led (developing biotech products, or drugs from products now used as folk or herbal medicines, for example).

Research paper thumbnail of The lasting legacy of Sir Victor Horsley

Acta Neurochirurgica, 2013

Research paper thumbnail of Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

The Journal of Clinical Endocrinology & Metabolism, 2015

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same... more Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

Research paper thumbnail of Pituitary Volume and Headache

Archives of Neurology, 2004

Background: Pituitary tumors are commonly associated with disabling headache. The accepted mechan... more Background: Pituitary tumors are commonly associated with disabling headache. The accepted mechanisms for headache are dural stretch and cavernous sinus invasion. Objective: To determine if there is a relationship between pituitary tumor size and the report of headache. Design: We prospectively studied 63 patients who were initially seen with pituitary tumors. Clinical headache scores, pituitary tumor volume, and the extent of cavernous sinus invasion were obtained for each patient. Results: The prevalence of headache was 70%. There was no positive correlation the between clinical headache score and pituitary volume (r=−0.32, P=.01, Spearman rank correlation). There was also no association between cavernous sinus invasion and headache. There was a strong association between pituitary-associated headache and a family history of headache (2 =8.36, P=.004). Conclusions: These data suggest that a pituitary tumorassociated headache may not simply be a structural problem. Other factors such as family history of headache, and the endocrine activity of the tumor may be equally important determinants of headache. Elucidating these mechanisms will aid in the treatment of these patients and further our understanding of other headache syndromes.

Research paper thumbnail of The clinical characteristics of headache in patients with pituitary tumours

Brain, 2005

The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache we... more The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitaryassociated headache is given.

Research paper thumbnail of Correlation of target site with histology and cell culture in CT-directed stereotactic biopsy

Biology of Brain Tumour, 1986

38 suspected brain tumours were biopsied using the Brown Roberts Wells stereotactic CT guided sys... more 38 suspected brain tumours were biopsied using the Brown Roberts Wells stereotactic CT guided system. Multiple target sites were biopsied in each lesion including the tumour centre and edge as defined by CT. Histology and cell culture were studied at each site. 34 tumours were identified. In 16 there was histological variation between the centre and the periphery as defined by CT. In 11 of these the enhancing edge was histologically free of tumour. 8 of these 11 were from the glioma series including 7 malignant gliomas. Cell culture studies were less conclusive but confirm that culture is feasible from small samples. Two types of short term culture were seen, those with malignant features and those without.

Research paper thumbnail of A Prospective Observational Study of the Yield of Olfactory Ensheathing Cells Cultured from Biopsies of Septal Nasal Mucosa

Neurosurgery, 2008

We sought to study the yield of olfactory ensheathing cells from biopsies of the mucosa of the na... more We sought to study the yield of olfactory ensheathing cells from biopsies of the mucosa of the nasal septum. These specialized cells encourage regeneration of nerves of the central nervous system and may be of value for spinal cord and nerve injuries. METHODS: We undertook a prospective observational study of biopsies of nasal mucosa by endonasal dissection of the mucosa of the nasal septum during the approach for routine transsphenoidal surgeries. Samples were cultured in the laboratory, and the yield of olfactory ensheathing cells was compared as to the location, size, and weight of the biopsies and the age of the patients. RESULTS: A better yield of olfactory ensheathing cells was obtained from areas of the septum that were more superior and posterior in position. The yield was not related to the size of the biopsy or the patient's age. CONCLUSION: Septal mucosa is a possible source of olfactory ensheathing cells, although the yield may be smaller than that which may be obtained from mucosa of the lateral nasal cavity and superior turbinate.

Research paper thumbnail of Torticollis after electrocution

Movement Disorders, 1993

... Communication. Torticollis after electrocution. Carlo Colosimo 1 ,; Roman S. Kocen 1 ,; Micha... more ... Communication. Torticollis after electrocution. Carlo Colosimo 1 ,; Roman S. Kocen 1 ,; MichaelPowell 1 ,; Andrew J. Lees 1 ,; Adnan Abdallat 2. Article first published online: 12 OCT 2004. DOI: 10.1002/mds.870080121. Copyright © 1993 Movement Disorder Society. Issue. ...

Research paper thumbnail of Identification of Adrenocorticotropin Receptor Messenger Ribonucleic Acid in the Human Pituitary and Its Loss of Expression in Pituitary Adenomas

The Journal of Clinical Endocrinology & Metabolism, 2003

The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that i... more The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that includes five seven-transmembrane G protein-coupled receptors and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short-loop feedback within the pituitary. ACTH-secreting adenomas are characterized by resistance to glucocorticoid feedback, and they may have dysregulated ACTH feedback. We therefore investigated the ACTH-R in normal and adenomatous human pituitary tissue. We report here the identification of ACTH-R mRNA in the human pituitary gland, which was confirmed by direct sequencing. We studied the expression of the ACTH-R in 23 normal pituitary specimens and 53 pituitary adenomas (22 ACTH-secreting, nine GH-secreting, eight prolactin-secreting, one TSH-secreting, one FSH-secreting, 10 nonfunctioning, and two silent corticotroph adenomas), using the sensitive technique of real-time quant...

Research paper thumbnail of Prolactinomas resistant to dopamine agonists

Current Opinion in Obstetrics and Gynecology, 1994

Research paper thumbnail of UK guidelines for the management of pituitary apoplexy

Clinical Endocrinology, 2010

Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone may... more Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone maybe life saving. It is a clinical syndrome characterized by the sudden onset of headache, vomiting, visual impairment and decreased consciousness caused by haemorrhage and/or infarction of the pituitary gland. It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. If diagnosed patients should be referred to a multidisciplinary team comprising, amongst others, a neurosurgeon and an endocrinologist. Apart from patients with worsening neurological symptoms in whom surgery is indicated, it is unclear currently for the majority of patients whether conservative or surgical management carries the best outcome. Post apoplexy, there needs to be careful monitoring for recurrence of tumour growth. It is suggested that further trials be carried out into the management of pituitary apoplexy to optimize treatment.

Research paper thumbnail of PPAR-? expression in pituitary tumours and the functional activity of the glitazones: evidence that any anti-proliferative effect of the glitazones is independent of the PPAR-? receptor

Clinical Endocrinology, 2006

Objective It has been reported that both normal pituitary and pituitary tumours express PPAR-γ , ... more Objective It has been reported that both normal pituitary and pituitary tumours express PPAR-γ , a nuclear hormone receptor, the expression being more abundant in pituitary tumours, and that this is the basis for the reported antiproliferative effects of the thiazolidinedione, rosiglitazone, in animal models. However, the mechanisms for the responsivity to rosiglitazone have remained unclear. Design and measurements To investigate this further, 'real-time' PCR was used to assess PPAR-γ mRNA expression, and Western blotting and immunohistochemistry to study its protein expression, in 46 human pituitary tumours and normal pituitary tissue. Cell proliferation of the GH3 pituitary cell line was assessed by [ 3 H]thymidine-incorporation after 48 h rosiglitazone and pioglitazone (10 − 4 -10 − 10 ) treatment alone, or rosiglitazone in combination with the PPAR-γ antagonist GW9662. Results PPAR-γ mRNA and protein was found to be expressed in normal pituitary and was variably expressed in pituitary tumours, but were increased specifically in nonfunctioning pituitary adenomas. However, very little staining was observed with immunohistochemistry, with only occasional cell nuclei stained, and no difference was detectable between controls and tumours. Rosiglitazone at 10 − 4  and 10 − 5  concentrations inhibited cell proliferation (10 − 4  14•0% ± 1•5% and 10 − 5  67% ± 4% [mean ± SEM] vs Control 100% ± 3%, P < 0•0001) while lower concentrations showed no significant effect. Following withdrawal of rosiglitazone 10 − 5  , the cells fully recovered at a further 48 h, while lower doses showed a 'rebound' of stimulation. Pioglitazone was of similar potency to rosiglitazone in inhibiting proliferation. The PPAR-γ antagonist did not show a significant reversal of the antiproliferative effect of rosiglitazone, and indeed suppressed proliferation on its own. Conclusions Our data suggest that the antiproliferative action of rosiglitazone is probably not via PPAR-γ .

Research paper thumbnail of The outcome of hypophysectomy for prolactinomas in the era of dopamine agonist therapy

Clinical Endocrinology, 1996

Dopamine agonists are the primary therapeutic modality for the majority of patients with prolacti... more Dopamine agonists are the primary therapeutic modality for the majority of patients with prolactinomas, with pituitary surgery reserved for those patients intolerant of or resistant to these agents. Most published surgical series, however, contain patients treated by surgery as the primary therapeutic modality. Previous exposure to dopamine agonists or the selection of patients with prolactinomas resistant to conventional therapy may potentially compromise the surgical success rate. The purpose of this study was to evaluate the efficacy and safety of pituitary surgery for prolactinomas in a tertiary referral centre where the majority of patients were operated on after treatment with dopamine agonists. A retrospective review of the outcome of pituitary surgery for prolactinomas performed at a tertiary neurosurgical centre by a single neurosurgeon. Twenty-three patients underwent excision of a macro and 11 excision of a micro-prolactinoma. Pituitary tumour diameter was determined by CT or MRI imaging. Pre and post-operative measurements were made of serum PRL concentration (off dopamine agonist therapy), free T4, free T3, LH and testosterone (males). Post-operative restoration of a menstrual cycle was taken to indicate resolution of hypogonadism in female patients. The majority (73.9%) of the patients with macro and all with micro-prolactinomas had received dopamine agonists preoperatively. Of the 23 patients with macroprolactinomas, in whom the median preoperative PRL concentration was 13255 mU/l, 17 (73.9%) had radiological evidence of suprasellar extension and 5 (21.7%) cavernous sinus invasion. Only 4 (17.4%) of the patients with macroprolactinomas had a normal serum PRL post-operatively, although there was an improvement in visual fields in 66% of those with preoperative defects. The median preoperative PRL concentration was 4309 mU/l in the patients with microprolactinomas, significantly lower than in the macroprolactinoma group (P = 0.02). Despite a significant fall in serum PRL postoperatively (median PRL 860 mU/l, P = 0.0001), only 45.5% of patients had a normal serum PRL concentration after surgery. The cure rate following pituitary surgery for prolactinomas in a tertiary referral centre was low when compared with previous series in which surgery was used as the primary therapeutic modality. We suggest this may result both from dopamine agonist pretreatment and the referral of prolactinomas resistant to conventional therapy. The outcome is probably a more realistic reflection of the results of pituitary surgery for prolactinomas as currently practised in the majority of neuroendocrine centres.

Research paper thumbnail of Sir Victor Horsley (1857–1916): lessons for the modern clinician

British Journal of Neurosurgery, 2011

Sir Victor Horsley is well known for his pioneering work as a neurological surgeon but his vital ... more Sir Victor Horsley is well known for his pioneering work as a neurological surgeon but his vital contributions to the regulation and advancement of the medical profession are less well understood. This archived literature review of The Horsley collection of papers (UCL Special Collections Library) documents Sir Victor&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s campaign for the autonomy of the stagnating medical profession of over a century ago. These lessons should empower modern clinicians to retain the professionalism they worry about losing.

Research paper thumbnail of Loss of vision from pituitary tumours causing chiasmal compression

Acta Neurochirurgica, 2010

Research paper thumbnail of A memorable patient: Keep looking for a reason

Research paper thumbnail of The Association between Calcitonin Gene-Related Peptide (CGRP), Substance P and Headache in Pituitary Tumours

Pituitary, 2004

Objectives: To determine if the differential expression of calcitonin gene-related peptide (CGRP)... more Objectives: To determine if the differential expression of calcitonin gene-related peptide (CGRP) or substance P (SP) in a range of pituitary tumours was related to the presence or absence of headache. Methods: Using recognised immunohistochemical techniques we examined twenty-six consecutive pituitary adenoma specimens for the presence of CGRP and SP. We included one normal post mortem pituitary specimen for comparison. A separate observer divided the patients into two groups: headache and non-headache. The association between the presence of CGRP, SP and headache was observed. Results: We observed CGRP in seven specimens (27%) and SP in six tumour specimens (23%), with cytoplasmic staining being the predominant morphological picture. CGRP and SP were co-expressed in the same tumour specimen in five cases. There was no significant association between the presence of CGRP and headache (χ 2 0.86; P = 0.35). We did not observe CGRP or SP in the control specimen. There was no correlation between tumour subtype and the presence of CGRP or SP. Conclusions: The mechanism of pituitary tumour-associated headache remains undetermined. The significance of the presence of CGRP and SP in pituitary tumours is unknown but does not appear to be related to headache or endocrine activity of the tumour.

Research paper thumbnail of Relapsing intracranial Rosai-Dorfman disease

Journal of Neurology, Neurosurgery & Psychiatry, 2001

Two patients presenting with recurrent visual impairment due to relapsing intracranial Rosai-Dorf... more Two patients presenting with recurrent visual impairment due to relapsing intracranial Rosai-Dorfman disease are described. In both patients a preoperative diagnosis of meningioma was made. Histological examination disclosed the characteristic picture of S100 and CD68 positive histiocytosis with prominent lymphophagocytosis. In both patients complete tumour removal by surgery was impossible with residual tissue being the origin of relapsing disease. Low dose radiation led to partial recovery of vision and resolution of the intracranial mass. Review of the literature on intracranial Rosai-Dorfman disease leads to the suggestion that postoperative radiotherapy may be advisable in all cases.

Research paper thumbnail of Characterization of SNARE Proteins in Human Pituitary Adenomas: Targeted Secretion Inhibitors as a New Strategy for the Treatment of Acromegaly?

The Journal of Clinical Endocrinology & Metabolism, 2013

Context:Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins ... more Context:Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins engineered from botulinum toxin, represent a novel approach for treating diseases with excess secretion. They inhibit hormone secretion from targeted cell types through cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) proteins. qGHRH-LHN/D is a TSI targeting pituitary somatotroph through binding to the GHRH-receptor and cleavage of the vesicle-associated membrane protein (VAMP) family of SNARE proteins.Objective:Our objective was to study SNARE protein expression in pituitary adenomas and to inhibit GH secretion from somatotropinomas using qGHRH-LHN/D.Design:We analyzed human pituitary adenoma analysis for SNARE expression and response to qGHRH-LHN/D treatment.Setting:The study was conducted in University Hospitals.Patients:We used pituitary adenoma samples from 25 acromegaly and 47 nonfunctioning pituitary adenoma patients.Outcome:Vesicle-SNARE (...

Research paper thumbnail of Drug points: Intranasal chlorhexidine resulting in anaphylactic circulatory arrest

BMJ, 1997

was 12.6 weeks and at counselling 15.3 weeks. Three out of four further couples referred to the s... more was 12.6 weeks and at counselling 15.3 weeks. Three out of four further couples referred to the specialist centre had prenatal diagnosis (at 11, 11.3, and 17.3 weeks). No fetus was diagnosed as affected, but one pregnancy miscarried. One woman declined prenatal testing because of a poor obstetric history, and she later miscarried. Two out of 17 liveborn children had a sickle cell disorder. Overall, 1 in 10 affected pregnancies was detected prenatally and terminated.

Research paper thumbnail of Sir Victor Horsley—an inspiration

BMJ, 2006

see as particularly important. The company could be profit led (any drug would do, provided it ra... more see as particularly important. The company could be profit led (any drug would do, provided it raised money), disease led (focusing on drugs that target a particular disease, tuberculosis perhaps), or drug led (developing biotech products, or drugs from products now used as folk or herbal medicines, for example).

Research paper thumbnail of The lasting legacy of Sir Victor Horsley

Acta Neurochirurgica, 2013

Research paper thumbnail of Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

The Journal of Clinical Endocrinology & Metabolism, 2015

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same... more Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

Research paper thumbnail of Pituitary Volume and Headache

Archives of Neurology, 2004

Background: Pituitary tumors are commonly associated with disabling headache. The accepted mechan... more Background: Pituitary tumors are commonly associated with disabling headache. The accepted mechanisms for headache are dural stretch and cavernous sinus invasion. Objective: To determine if there is a relationship between pituitary tumor size and the report of headache. Design: We prospectively studied 63 patients who were initially seen with pituitary tumors. Clinical headache scores, pituitary tumor volume, and the extent of cavernous sinus invasion were obtained for each patient. Results: The prevalence of headache was 70%. There was no positive correlation the between clinical headache score and pituitary volume (r=−0.32, P=.01, Spearman rank correlation). There was also no association between cavernous sinus invasion and headache. There was a strong association between pituitary-associated headache and a family history of headache (2 =8.36, P=.004). Conclusions: These data suggest that a pituitary tumorassociated headache may not simply be a structural problem. Other factors such as family history of headache, and the endocrine activity of the tumor may be equally important determinants of headache. Elucidating these mechanisms will aid in the treatment of these patients and further our understanding of other headache syndromes.

Research paper thumbnail of The clinical characteristics of headache in patients with pituitary tumours

Brain, 2005

The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache we... more The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitaryassociated headache is given.

Research paper thumbnail of Correlation of target site with histology and cell culture in CT-directed stereotactic biopsy

Biology of Brain Tumour, 1986

38 suspected brain tumours were biopsied using the Brown Roberts Wells stereotactic CT guided sys... more 38 suspected brain tumours were biopsied using the Brown Roberts Wells stereotactic CT guided system. Multiple target sites were biopsied in each lesion including the tumour centre and edge as defined by CT. Histology and cell culture were studied at each site. 34 tumours were identified. In 16 there was histological variation between the centre and the periphery as defined by CT. In 11 of these the enhancing edge was histologically free of tumour. 8 of these 11 were from the glioma series including 7 malignant gliomas. Cell culture studies were less conclusive but confirm that culture is feasible from small samples. Two types of short term culture were seen, those with malignant features and those without.

Research paper thumbnail of A Prospective Observational Study of the Yield of Olfactory Ensheathing Cells Cultured from Biopsies of Septal Nasal Mucosa

Neurosurgery, 2008

We sought to study the yield of olfactory ensheathing cells from biopsies of the mucosa of the na... more We sought to study the yield of olfactory ensheathing cells from biopsies of the mucosa of the nasal septum. These specialized cells encourage regeneration of nerves of the central nervous system and may be of value for spinal cord and nerve injuries. METHODS: We undertook a prospective observational study of biopsies of nasal mucosa by endonasal dissection of the mucosa of the nasal septum during the approach for routine transsphenoidal surgeries. Samples were cultured in the laboratory, and the yield of olfactory ensheathing cells was compared as to the location, size, and weight of the biopsies and the age of the patients. RESULTS: A better yield of olfactory ensheathing cells was obtained from areas of the septum that were more superior and posterior in position. The yield was not related to the size of the biopsy or the patient's age. CONCLUSION: Septal mucosa is a possible source of olfactory ensheathing cells, although the yield may be smaller than that which may be obtained from mucosa of the lateral nasal cavity and superior turbinate.

Research paper thumbnail of Torticollis after electrocution

Movement Disorders, 1993

... Communication. Torticollis after electrocution. Carlo Colosimo 1 ,; Roman S. Kocen 1 ,; Micha... more ... Communication. Torticollis after electrocution. Carlo Colosimo 1 ,; Roman S. Kocen 1 ,; MichaelPowell 1 ,; Andrew J. Lees 1 ,; Adnan Abdallat 2. Article first published online: 12 OCT 2004. DOI: 10.1002/mds.870080121. Copyright © 1993 Movement Disorder Society. Issue. ...

Research paper thumbnail of Identification of Adrenocorticotropin Receptor Messenger Ribonucleic Acid in the Human Pituitary and Its Loss of Expression in Pituitary Adenomas

The Journal of Clinical Endocrinology & Metabolism, 2003

The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that i... more The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that includes five seven-transmembrane G protein-coupled receptors and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short-loop feedback within the pituitary. ACTH-secreting adenomas are characterized by resistance to glucocorticoid feedback, and they may have dysregulated ACTH feedback. We therefore investigated the ACTH-R in normal and adenomatous human pituitary tissue. We report here the identification of ACTH-R mRNA in the human pituitary gland, which was confirmed by direct sequencing. We studied the expression of the ACTH-R in 23 normal pituitary specimens and 53 pituitary adenomas (22 ACTH-secreting, nine GH-secreting, eight prolactin-secreting, one TSH-secreting, one FSH-secreting, 10 nonfunctioning, and two silent corticotroph adenomas), using the sensitive technique of real-time quant...

Research paper thumbnail of Prolactinomas resistant to dopamine agonists

Current Opinion in Obstetrics and Gynecology, 1994

Research paper thumbnail of UK guidelines for the management of pituitary apoplexy

Clinical Endocrinology, 2010

Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone may... more Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone maybe life saving. It is a clinical syndrome characterized by the sudden onset of headache, vomiting, visual impairment and decreased consciousness caused by haemorrhage and/or infarction of the pituitary gland. It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. If diagnosed patients should be referred to a multidisciplinary team comprising, amongst others, a neurosurgeon and an endocrinologist. Apart from patients with worsening neurological symptoms in whom surgery is indicated, it is unclear currently for the majority of patients whether conservative or surgical management carries the best outcome. Post apoplexy, there needs to be careful monitoring for recurrence of tumour growth. It is suggested that further trials be carried out into the management of pituitary apoplexy to optimize treatment.

Research paper thumbnail of PPAR-? expression in pituitary tumours and the functional activity of the glitazones: evidence that any anti-proliferative effect of the glitazones is independent of the PPAR-? receptor

Clinical Endocrinology, 2006

Objective It has been reported that both normal pituitary and pituitary tumours express PPAR-γ , ... more Objective It has been reported that both normal pituitary and pituitary tumours express PPAR-γ , a nuclear hormone receptor, the expression being more abundant in pituitary tumours, and that this is the basis for the reported antiproliferative effects of the thiazolidinedione, rosiglitazone, in animal models. However, the mechanisms for the responsivity to rosiglitazone have remained unclear. Design and measurements To investigate this further, 'real-time' PCR was used to assess PPAR-γ mRNA expression, and Western blotting and immunohistochemistry to study its protein expression, in 46 human pituitary tumours and normal pituitary tissue. Cell proliferation of the GH3 pituitary cell line was assessed by [ 3 H]thymidine-incorporation after 48 h rosiglitazone and pioglitazone (10 − 4 -10 − 10 ) treatment alone, or rosiglitazone in combination with the PPAR-γ antagonist GW9662. Results PPAR-γ mRNA and protein was found to be expressed in normal pituitary and was variably expressed in pituitary tumours, but were increased specifically in nonfunctioning pituitary adenomas. However, very little staining was observed with immunohistochemistry, with only occasional cell nuclei stained, and no difference was detectable between controls and tumours. Rosiglitazone at 10 − 4  and 10 − 5  concentrations inhibited cell proliferation (10 − 4  14•0% ± 1•5% and 10 − 5  67% ± 4% [mean ± SEM] vs Control 100% ± 3%, P < 0•0001) while lower concentrations showed no significant effect. Following withdrawal of rosiglitazone 10 − 5  , the cells fully recovered at a further 48 h, while lower doses showed a 'rebound' of stimulation. Pioglitazone was of similar potency to rosiglitazone in inhibiting proliferation. The PPAR-γ antagonist did not show a significant reversal of the antiproliferative effect of rosiglitazone, and indeed suppressed proliferation on its own. Conclusions Our data suggest that the antiproliferative action of rosiglitazone is probably not via PPAR-γ .

Research paper thumbnail of The outcome of hypophysectomy for prolactinomas in the era of dopamine agonist therapy

Clinical Endocrinology, 1996

Dopamine agonists are the primary therapeutic modality for the majority of patients with prolacti... more Dopamine agonists are the primary therapeutic modality for the majority of patients with prolactinomas, with pituitary surgery reserved for those patients intolerant of or resistant to these agents. Most published surgical series, however, contain patients treated by surgery as the primary therapeutic modality. Previous exposure to dopamine agonists or the selection of patients with prolactinomas resistant to conventional therapy may potentially compromise the surgical success rate. The purpose of this study was to evaluate the efficacy and safety of pituitary surgery for prolactinomas in a tertiary referral centre where the majority of patients were operated on after treatment with dopamine agonists. A retrospective review of the outcome of pituitary surgery for prolactinomas performed at a tertiary neurosurgical centre by a single neurosurgeon. Twenty-three patients underwent excision of a macro and 11 excision of a micro-prolactinoma. Pituitary tumour diameter was determined by CT or MRI imaging. Pre and post-operative measurements were made of serum PRL concentration (off dopamine agonist therapy), free T4, free T3, LH and testosterone (males). Post-operative restoration of a menstrual cycle was taken to indicate resolution of hypogonadism in female patients. The majority (73.9%) of the patients with macro and all with micro-prolactinomas had received dopamine agonists preoperatively. Of the 23 patients with macroprolactinomas, in whom the median preoperative PRL concentration was 13255 mU/l, 17 (73.9%) had radiological evidence of suprasellar extension and 5 (21.7%) cavernous sinus invasion. Only 4 (17.4%) of the patients with macroprolactinomas had a normal serum PRL post-operatively, although there was an improvement in visual fields in 66% of those with preoperative defects. The median preoperative PRL concentration was 4309 mU/l in the patients with microprolactinomas, significantly lower than in the macroprolactinoma group (P = 0.02). Despite a significant fall in serum PRL postoperatively (median PRL 860 mU/l, P = 0.0001), only 45.5% of patients had a normal serum PRL concentration after surgery. The cure rate following pituitary surgery for prolactinomas in a tertiary referral centre was low when compared with previous series in which surgery was used as the primary therapeutic modality. We suggest this may result both from dopamine agonist pretreatment and the referral of prolactinomas resistant to conventional therapy. The outcome is probably a more realistic reflection of the results of pituitary surgery for prolactinomas as currently practised in the majority of neuroendocrine centres.

Research paper thumbnail of Sir Victor Horsley (1857–1916): lessons for the modern clinician

British Journal of Neurosurgery, 2011

Sir Victor Horsley is well known for his pioneering work as a neurological surgeon but his vital ... more Sir Victor Horsley is well known for his pioneering work as a neurological surgeon but his vital contributions to the regulation and advancement of the medical profession are less well understood. This archived literature review of The Horsley collection of papers (UCL Special Collections Library) documents Sir Victor&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s campaign for the autonomy of the stagnating medical profession of over a century ago. These lessons should empower modern clinicians to retain the professionalism they worry about losing.

Research paper thumbnail of Loss of vision from pituitary tumours causing chiasmal compression

Acta Neurochirurgica, 2010