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Biomedical subjects

S L Atkin

Publications and source records attributed to S L Atkin.

At least 19 recordsLinked to original sources
PubMed2006

How we do it: surgery should be considered equally with I131 and thionamide treatment as first-line therapy for thyrotoxicosis.

Radioiodine and thionamide treatment are the most frequently used treatment modalities for thyrotoxicosis in Europe and North America with surgery being reserved for selected cases. * In our clinic patients were offered all three modalities via simultaneous interview with an endocrinologist and a surgeon, with international risk benefit data for radioiodine and thionamide therapy, and local risk benefit data for total thyroidectomy provided. * When given the choice, at least 15% of patients opted for total thyroidectomy over the other modalities. * In our series of 100 consecutive surgical patients there was a 4% malignancy rate. * Total thyroidectomy should be offered equally, with radioiodine and thionamide treatment, as a first line treatment modality in the management of thyrotoxicosis.

Adolescent↗
PubMed2006

Dehydroepiandrosterone sulphate interferes with the Abbott Architect direct immunoassay for testosterone.

BACKGROUND: There are known difficulties in measuring testosterone in women using 'direct' (non-extraction) immunoassays. The positive bias encountered in many of these assays has been attributed to an unidentified interfering substance. We have evaluated the potential for dehydroepiandrosterone sulphate (DHEA-S) to cross-react in the Abbott Architect testosterone assay. METHODS: Samples (n = 81) from female patients who had DHEA-S, direct and extracted testosterone measured were examined retrospectively. Possible cross-reactivity was evaluated by spiking both testosterone free assay diluent and serum from a woman with exogenous DHEA-S. RESULTS: The retrospective patient analysis of the data demonstrated a relationship between interference and DHEA-S (r = 0.78, P < or = 0.0001). Spiking studies revealed a linear relationship between added DHEA-S and the measured testosterone concentration. Consistent with the retrospective study, for every 1 micromol/L increase in DHEA-S, 0.23 nmol/L of testosterone was measured in the diluent. Spiking DHEA-S into serum gave only a 0.12 nmol/L increase in measured testosterone for every 1 micromol/L rise in DHEA-S. CONCLUSION: DHEA-S cross-reacts in the Abbott Architect direct immunoassay for testosterone to a clinically significant effect. This cross-reactivity is likely to be responsible for much of the interference observed when measuring testosterone in women by this method.

Cross Reactions↗
PubMed2005

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium.

Angiogenesis is characterised by activation, migration and proliferation of endothelial cells and is central to the pathology of cancer, cardiovascular disease and chronic inflammation. Somatostatin is an inhibitory polypeptide that acts through five receptors (sst 1, 2, 3, 4, 5). Sst has previously been reported in endothelium, but their role remains obscure. Here, we report the expression of sst in human umbilical vein endothelial cells (HUVECs) in vitro, during proliferation and quiescence. A protocol for culturing proliferating and quiescent HUVECs was established, and verified by analysing cell cycle distribution in propidium-iodide-stained samples using flow cytometry. Sst mRNA was then quantified in nine proliferating and quiescent HUVEC lines using quantitative reverse transcriptase-polymerase chain reaction. Sst 2 and 5 were preferentially expressed in proliferating HUVECs. All samples were negative for sst 4. Sst 1 and 3 expression and cell cycle progression were unrelated. Immunostaining for sst 2 and 5 showed positivity in proliferating but not quiescent cells, confirming sst 2 and 5 protein expression. Inhibition of proliferating cells with somatostatin analogues Octreotide and SOM230, which have sst 5 activity, was found (Octreotide 10(-10)-10(-6) M: 48.5-70.2% inhibition; SOM230 10(-9)-10(-6) M: 44.9-65.4% inhibition) in a dose-dependent manner, suggesting that sst 5 may have functional activity in proliferation. Dynamic changes in sst 2 and 5 expression during the cell cycle and the inhibition of proliferation with specific analogues suggest that these receptors may have a role in angiogenesis.

Antineoplastic Agents, Hormonal↗
PubMed2005

Does thyroid subspecialization alter practice and outcome? A completed 4-year audit loop.

OBJECTIVE: To assess the effect of subspecialization on thyroid surgical practice and outcome. DESIGN: The multidisciplinary thyroid clinic was established in November 2000. A retrospective study of all thyroid surgery covering the period November 1998 to November 2000 was carried out. Best practice principles were implemented and prospective data were collected over a further 2 years to complete the audit loop. Practice and results were compared. SETTING: The project was carried out through the Hull and East Yorkshire Multidisciplinary Thyroid Clinic, a tertiary referral clinic for the management of thyroid disease. PARTICIPANTS: All patients who underwent thyroid surgery through the Department of Otolaryngology Head and Neck Surgery for 2 years before the establishment of the thyroid clinic (39 patients) and all patients who underwent thyroid surgery through the department for 2 years after the establishment of the clinic (108 patients) were included. MAIN OUTCOME MEASURES: Referral patterns, preoperative workup, types of surgery, histopathological diagnosis and complications rates were compared. RESULTS: The audit loop revealed that permanent vocal cord palsy rates had fallen from 8% to 0%, haematoma rates had fallen from 5% to 2% and permanent hypoparathyroidism rates had fallen from 8% to 2%. In addition, caseload had markedly increased, preoperative investigations were reduced and types of surgery standardized. CONCLUSION: It is clear that thyroid subspecialization is beneficial as far as overall outcome is concerned. However, this may lead to increased throughput which must be borne in mind for future activity planning.

Ambulatory Care Facilities↗
PubMed2005

Improvement of glycaemic control with rebound following orlistat initiation and cessation associated with minimal weight change.

A 57-year-old Caucasian woman with Type 2 diabetes treated for seven years with diet and oral combination hypoglycaemic therapy was referred because of the progressive deterioration of glycaemic control. She was obese (77 kg, BMI = 39.9), hypertensive, hypercholesterolaemic with marked osmotic symptoms (HbA(1c) 12.2%), therefore she was started on insulin (Human Mixtard 30 b.d.) with metformin therapy. Dietary counselling, recommendations to increase physical activity, and supervised self-injection technique with titration of her insulin were also provided. She was routinely followed-up to assess her progress. Two years later, her glycaemic control remained suboptimal. Average HbA(1c) was 10.4% despite an increasingly high dose of insulin (94 units/day) although it improved when metformin was increased to 1 g t.d.s. (HbA(1c) = 9.3%). Her BMI progressively rose from 39.9 to 42.1 (77 to 82.5 kg) despite dietary advice. A trial of orlistat (three months) was commenced, after intensive dietary counselling, that reduced her body weight by 1.5 kg (2% reduction, BMI 41.3). However, her HbA(1c) improved by 0.5% (from 9.3 to 8.8%). Six months after orlistat was stopped her HbA(1c) rose to 10.5% and weight increased to 81.8 kg (BMI 41.8). Despite the orlistat treatment broaching NICE guidelines should it have been continued?

Diabetes Mellitus, Type 2↗
PubMed2005

Thyroidectomy does not cause globus pattern symptoms.

Post-thyroidectomy patients often complain of globus pharyngeus type symptoms. One of the organic pathologies recognized as causing globus pattern symptoms is goitre. We conducted a prospective questionnaire-based study in the thyroid clinic at Hull Royal Infirmary to examine the relationship between goitre, thyroidectomy and globus pattern symptoms by using the Glasgow-Edinburgh Throat Scale. A questionnaire-based study in which 41 consecutive patients due to undergo thyroidectomy prospectively completed the questionnaire pre-operatively and 12 months post-operatively. A subset of 25 randomly selected patients also completed the questionnaire three months post-operatively. Globus symptoms were not worsened by thyroidectomy at three or 12 months. Indeed two of the questioned parameters were significantly improved at three months, and six at one year (p < 0.023). In conclusion, thyroidectomy does not exacerbate globus pharyngeus symptoms. Indeed, in the absence of other clinical causes, when a patient has a World Health Organization (WHO) 2 goitre or greater, thyroidectomy may improve them.

Adult↗
PubMed2004

Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome.

The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.

Adult↗
PubMed2004

Nateglinide alone or with metformin safely improves glycaemia to target in patients up to an age of 84.

AIM: To assess the effect of nateglinide on efficacy [fasting plasma glucose (FPG), postprandial plasma glucose (PPG) plasma glucose and HbA1c], tolerability and safety in patients with type 2 diabetes mellitus (T2Dm) on diet alone or on metformin in subjects up to an age of 84. METHODS: In an open-labelled 12-week, parallel study of 358 patients, aged 35-84 years with T2Dm, nateglinide was given as either monotherapy in patients previously on diet alone or low-dose sulfonylureas, which required washout before the study (group 1), or as an addition therapy in patients on steady dose of metformin (group 2). Nateglinide 120 mg was given before main meals. HbA1c, FPG and PPG values were taken at the time of breakfast at the beginning and the end of the study. RESULTS: HbA1c fell by a mean of 0.83%, 95% confidence interval (CI) (-0.97, -0.69) (p < 0.001) in group 1, and 0.67%, 95% CI (-0.77, -0.58) (p < 0.001) in group 2. There was a significant improvement in PPG in group 1 by a mean reduction of -3.47 mmol/l, 95% CI (-4.08, -2.87) (p < 0.0001) and in group 2 of -2.41 mmol/l, 95% CI (-2.84, -1.99) (p < 0.0001). There was an improvement in FPG of -1.2 mmol/l, 95% CI (-1.49, -0.81) (p < 0.0001) and -0.8 mmol/l, 95% CI -(1.07, -0.53) (p < 0.0001) in group 1 and 2 respectively. 44% of patients in group 1 and 34% in group 2 achieved target of HbA1c < 7.0 and 66% in group 1 and 59% in group 2 achieved of HbA1c < 7.5%. Only one subject on nateglinide and metformin was withdrawn due to the side effect of hypoglycaemia. No patient required third-party assistance nor was admitted to hospital due to hypoglycaemia. CONCLUSION: These data demonstrate that nateglinide is a safe and effective agent in treatment to target in patients with T2Dm up to an age of 84 years.

Adult↗
PubMed2004

The immunohistochemical localisation of somatostatin receptors 1, 2, 3, and 5 in acoustic neuromas.

AIMS: Acoustic neuroma is a benign tumour, which develops through an overproliferation of Schwann cells along the vestibular nerve. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane bound receptor subtypes. The aim of this study was to determine whether somatostatin receptor subtypes (SSTRs) 1, 2, 3, and 5 are present in acoustic neuromas. METHODS: The expression of SSTRs 1, 2, 3, and 5 was studied in both the Schwann cells and blood vessels of eight acoustic neuroma specimens, by means of immunohistochemistry using novel rabbit polyclonal antibodies raised against human SSTR 1, 2, and 5 subtype specific peptides, and a commercial anti-SSTR3 antibody. RESULTS: SSTR2 was the most prevalent subtype in Schwann cells (seven of eight), with intermediate expression of SSTR3 (six of eight), and lower expression of SSTRs 1 and 5 (four of eight and five of eight, respectively). There was ubiquitous vascular expression of SSTR2, with no evidence of SSTR 1, 3, or 5 expression in blood vessels. CONCLUSION: SSTRs 1, 2, 3, and 5 are differentially expressed in acoustic neuromas. Somatostatin analogues may have a therapeutic role in the management of this rare and challenging condition.

Adult↗
PubMed2004

Somatostatin analogues have no role in the treatment of advanced differentiated thyroid cancer.

Somatostatins are neuropeptides that have a downregulatory effect on various physiological processes. Their use in the management of certain endocrine tumours is well recognized. Their use in thyroid cancer is not established, although there is some evidence to suggest that they have a role in advanced metastatic disease. We report a case of a patient with advanced metastatic follicular thyroid cancer which demonstrated strong octreotide uptake with reduced avidity for I(131). Treatment with the somatostatin analogue octreotide, however, failed to achieve a significant response. We feel this case is important as it suggests that although octreotide provides a useful further imaging modality in differentiated thyroid cancer, it has no therapeutic role.

Antineoplastic Agents, Hormonal↗
PubMed2003

Fluvastatin induces apoptosis of vascular endothelial cells: blockade by glucocorticoids.

Statins block de novo synthesis of cholesterol by inhibiting the enzyme, HMG CoA reductase. The product of this reaction, mevalonic acid, is also a precursor of isoprenoids, molecules required for the activation of signaling G-proteins, such as Ras. Signal transduction pathways involving Ras are important for cell survival and this may be why statins induce apoptotic death of several cell types. Given that statins are used to treat vascular disease, surprisingly no studies have been conducted on vascular endothelial cells. Here we show that fluvastatin (FS), at concentrations from 1-2 microM, blocks growth and induces apoptosis of the endothelial cell line, EA.hy 926. Considerable redundancy is known to exist in cell signaling and in vivo toxicity of FS might be prevented by other signaling pathways, like those activated by adrenal or sex steroids. RT-PCR analysis revealed the expression of the androgen and glucocorticoid receptor in EA.hy 926 cells. Although the androgen, dihydrotestesterone (DHT) had no effect, the glucocorticoid, dexamethasone (Dex), blocked FS-induced apoptosis. Cell cycle analysis revealed that 24 h exposure to FS prevented cells from leaving G(1) and 24-48 h later a marked sub-G(1) peak was observed. Dex was able to reduce the sub-G(1) peak, but it failed to block accumulation of cells in G(1), indicating that it's effect was specific for blockade of apoptosis, and not specific to an effect on FS alone. This study strongly suggests that glucocorticoids have a role to play in preventing vascular injury and they may provide the reason why statins are not inherently toxic to vascular endothelial cells, in vivo.

Anticholesteremic Agents↗
PubMed2003

The expression of somatostatin receptors 1 and 2 in benign, pre-malignant and malignant laryngeal lesions.

The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane-bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre-malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre-malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low-to-moderate levels in only 2/6 (33%) pre-malignant and 3/12 (25%) malignant specimens (P < 0.01). This 'loss' of epithelial SSTR2 expression may provide a growth advantage in pre-malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre-malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.

Adult↗
PubMed2003

The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance.

This study was designed to assess the biological variability of total testosterone and SHBG in polycystic ovarian syndrome (PCOS) and to determine the use of SHBG as a surrogate marker of insulin resistance in PCOS. Fasting blood samples were collected at 4-d intervals on 10 consecutive occasions from 12 PCOS patients and 11 age- and weight-matched controls. Duplicate samples were analyzed for SHBG, testosterone, and insulin in a single batch, and insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR). The PCOS group had higher testosterone (mean +/- SD, 3.9 +/- 0.8 vs. 3.2 +/- 1.3 nmol/liter; P = 0.001), lower SHBG (28.6 +/- 17.1 vs. 57.6 +/- 30.2 nmol/liter; P = 0.001), and greater HOMA-IR (5.85 +/- 5.3 vs. 1.67 +/- 0.63 U; P = 0.001) than the controls. In contrast to HOMA-IR (1.09 vs. 0.48 U; P = 0.001), the intraindividual variation in SHBG was lower in the PCOS group (mean, 3.4 vs. 6.3 nmol/liter; P = 0.041). The index of individuality for SHBG and testosterone in PCOS was 0.49 and 0.69, respectively. This study shows that for patients with PCOS, SHBG is an integrated marker of insulin resistance that may be of use to identify insulin-resistant individuals for targeted treatment with insulin-sensitizing agents. However, SHBG and testosterone concentrations measured in isolation are inherently unsuitable for use as tests to detect hyperandrogenemia.

Adult↗
PubMed2002

Localisation of somatostatin and somatostatin receptors in benign and malignant ovarian tumours.

Somatostatin has been identified as having anti-proliferative, anti-angiogenic and pro-apoptotic actions in many tumour systems, and these effects are mediated through a family of five transmembrane G-protein coupled SRIF receptors. Ovarian cancer is the commonest gynaecological malignancy in the UK and maintenance therapy is urgently required. Native somatostatin expression and its receptors sst(1,2,3 and 5) were studied with immunohistochemistry in 63 malignant and 35 benign ovarian tumours of various histological types. Fifty-seven out of 63 (90%) of malignant and 26/35 (74%) benign tumours expressed somatostatin. Receptors sst(1,2,3 and 5) were expressed variably in epithelial, vascular and stromal compartments for both benign and malignant tumours. Somatostatin was found to correlate significantly with stromal sst(1) (P=0.008), epithelial sst(1) (P<0.001), stromal sst(2) (P=0.019), vascular sst(2) (P=0.026), epithelial sst(3) (P=0.026), stromal sst(5) (P=0.013) and vascular sst(5) (P=0.038). Increased expression of native somatostatin correlating with somatostatin receptors in malignant ovarian tumours raises the possibility that either synthetic somatostatin antagonists or receptor agonists may have therapeutic potential.

Adenocarcinoma↗
PubMed2002

Somatostatin receptor 2 expression in the human endometrium through the menstrual cycle.

OBJECTIVE: Somatostatin mediates its many inhibitory functions through five G-protein-coupled receptors (sstr1-5); however, it is not known whether somatostatin or its receptors are present in the endometrium. DESIGN: We have used immunohistochemistry on formalin-fixed paraffin-embedded sections of normal human endometrium from the menstrual (n = 6), proliferative (n = 15) and secretory (n = 10) stages of the endometrial cycle to determine the pattern of expression of somatostatin receptor (sstr) subtype 2. In addition, we have used quantitative polymerase chain reaction (PCR) to determine the level of expression of the sstr2 mRNA in 17 samples of normal human endometrium. PATIENTS: Endometrial tissue had been removed from patients undergoing dilation and curettage (D&C) for menorrhagia and had been determined to be normal histologically. MEASUREMENTS: Immunostaining in the epithelium, endothelium and the stroma of the endometrial sections was characterized and was scored positive or negative. The PCR results were analysed using the software provided to standardize the expression of sstr2 against that of constitutively expressed beta-glucoronidase in the same sample. A final percentage value of the level of sstr2 expression was then determined. RESULTS: sstr2 was expressed variably throughout all the stages of the menstrual cycle in the epithelium, the endothelium and the stroma. In particular, the position of sstr2 expression varied in the epithelial cells surrounding the endometrial glands from being basal or diffuse in the proliferative and secretory phase to being lumenal in the menstrual stage. Quantitative PCR showed that 15 of 17 samples expressed sstr2 mRNA and the level of expression between individual samples varied dramatically. CONCLUSIONS: These data show that sstr2 is present in the endometrium and its location seems to vary through the menstrual cycle.

Adult↗
PubMed2002

Somatostatins and their role in thyroid cancer.

Somatostatins are neuropeptides that exert a downregulatory effect on various physiological processes. Somatostatin analogues are used in the imaging and management of various tumour types. Their role in thyroid cancer has not as yet been fully elucidated. A systematic review of the literature using the keywords thyroid, cancer and somatostatin revealed 263 references. This paper summarizes the current knowledge of the role of somatostatins in thyroid cancer and assesses their future potential.

Antineoplastic Agents↗
PubMed2002

Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size.

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 microg, 3 times daily, increased to 200 micro g three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 microg/liter). Five-point GH profiles were performed at 0, 4, 12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).

Acromegaly↗