Clinical characteristics of people experiencing biochemical hypoglycaemia during an oral glucose tolerance test: cross-sectional analyses from a UK multi-ethnic population.

AIMS: People who experience biochemical hypoglycaemia during an oral glucose tolerance test (OGTT) may be insulin resistant, but this has not been investigated robustly, therefore we examined this in a population-based multi-ethnic UK study. METHODS: Cross-sectional data from 6478 diabetes-free participants (849 with fasting insulin data available) who had an OGTT in the ADDITION-Leicester screening study (2005-2009) were analysed. People with biochemical hypoglycaemia (2-h glucose <3.3mmol/l) were compared with people with normal glucose tolerance (NGT) or impaired glucose regulation (IGR) using regression methods. RESULTS: 359 participants (5.5%) had biochemical hypoglycaemia, 1079 (16.7%) IGR and 5040 (77.8%) NGT. Biochemical hypoglycaemia was associated with younger age (P<0.01), white European ethnicity (P<0.001), higher HDL cholesterol (P<0.01), higher insulin sensitivity (P<0.05), and lower body mass index (P<0.001), blood pressure (P<0.01), fasting glucose (P<0.001), HbA1C (P<0.01), and triglycerides (P<0.01) compared with NGT and IGR separately in both unadjusted and adjusted (age, sex, ethnicity, body mass index, smoking status) models. CONCLUSIONS: Biochemical hypoglycaemia during an OGTT in the absence of diabetes or IGR was not associated with insulin resistance, but instead appeared to be associated with more favourable glycaemic risk profiles than IGR and NGT. Thus, clinicians may not need to intervene due to biochemical hypoglycaemia on a 2-h OGTT.

Perinatal testosterone exposure and maternal care effects on the female rat's development and sexual behaviour.

Natural variations in maternal care have profound influences on offspring behaviour, brain activity and hormone release. Measuring the amount of time that a rat dam spends licking/grooming (LG) her pups during their first week of life allows for characterisation of distinctive Low, Mid and High LG phenotypes. We have previously found that female offspring of High LG mothers are less sexually receptive, less motivated to mate and show a later onset of puberty relative to Low LG offspring. Given that High LG females are exposed to greater levels of testosterone in utero, we hypothesise that differences in sexual behaviour between High and Low LG female offspring are driven in part by differences in prenatal hormone exposure. To test this hypothesis, pregnant dams pre-characterised as Low, Mid, or High LG mothers were implanted with testosterone or placebo on gestational day (GD) 16. Offspring body weight and anogenital index were assessed at GD 21 and in adulthood. Age of vaginal opening and oestrous cyclicity were assessed to determine the timing of pubertal onset. Testosterone exposure removed the difference between LG phenotypes in pubertal onset by delaying vaginal opening and the appearance of first pro-oestrus. In adulthood, sexual behaviour in a paced mating chamber after sham surgery or ovariectomy with steroid-replacement was examined. Our findings show that Low, Mid and High LG female offspring are differentially affected by perinatal testosterone exposure, and that this exposure removes the precocial pubertal onset of Low LG offspring and increases the sexual proceptivity and receptivity of High LG offspring. These results suggest that maternal programming of the female reproductive system may be mediated, in part, through differences in perinatal testosterone exposure, instead of solely through maternal behaviour.

Cluster headache secondary to macroprolactinoma with ipsilateral cavernous sinus invasion.

We present a 25 year-old man with episodic cluster headache that was refractory to all standard pharmacological prophylactic and abortive treatments. Because of the lack of response, an MRI brain was performed which showed a large pituitary tumour with ipsilateral cavernous sinus invasion. The serum prolactin was significantly elevated at 54,700 miU/L (50-400) confirming a macro-prolactinoma. Within a few days of cabergoline therapy the headache resolved. He continues to be headache free several years after starting the dopamine agonist. This case highlights the importance of imaging the pituitary fossa in patients with refractory cluster headache, It also raises the potential anatomical importance of the cavernous sinus in pituitary-associated headache.

The challenges with NOTES retroperitoneal access in humans.

BACKGROUND: Animal studies have supported natural orifice transluminal endoscopic surgery (NOTES) retroperitoneal access. NOTES also may offer unique retroperitoneal access in humans. OBJECTIVES: This study was designed to assess the feasibility of endoscopic transgastric and transrectal retroperitoneal access in a cadaver model using prone and supine positioning, and to compare NOTES retroperitoneal examination with endoscopic ultrasound. METHODS: Using a multidisciplinary team, this institutional review board-approved study evaluated transgastric and transrectal retroperitoneal examination in six cadavers (3 male, 3 female; body mass index range, 25-37 kg/m(2)). Endoscopic ultrasound retroperitoneal examination preceded NOTES access. Transgastric Access: Using a prototype dual channel endoscope, a needle knife gastrotomy was created on the preantral posterior gastric wall. Retroperitoneal examination specifically targeted the pancreas and surrounding structures with the cadaver supine and prone. Transrectal Access: Using the same endoscope, a posterior needle knife rectotomy distal to the upper valve of Houston provided extraluminal access. Retroperitoneal examination proceeded with the cadaver prone and supine. Open dissection followed procedure completion. RESULTS: Access into the retroperitoneum succeeded at all sites. Significant challenges locating identifiable landmarks were faced-mostly transrectal and improved transgastric prone. All cadavers, despite body mass index or sex, had significant retroperitoneal adipose tissue limiting the endoscopic view. CONCLUSIONS: Although porcine studies have highlighted successful NOTES retroperitoneal procedures, the abundant human retroperitoneal adipose tissue challenged the translation of porcine research to humans. Additionally, although access to the retroperitoneal space and dissection within this space were accomplished easily, the appearance of cadaveric tissue and lack of blood flow made confident landmark identification impossible. Further study should continue in this area and focus on confident landmark identification for directed dissection. In a cadaveric model, this would best be improved by pre-NOTES anatomic marking or active perfusion of vasculature along with consideration of direct entry into the retroperitoneum from a targeted intraperitoneal site in clinical patients.

Endoscopic retrograde cholangiopancreatography using a single-balloon enteroscope in patients with altered Roux-en-Y anatomy.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is challenging to perform in patients with postsurgical gastrointestinal anatomy. We assessed the diagnostic and therapeutic success rates using single-balloon enteroscopy in patients with Roux-en-Y anastomosis. PATIENTS AND METHODS: Patients who underwent single-balloon ERCP between April 2008 and February 2010 were retrospectively identified using a computerized endoscopy database. Diagnostic success was defined as successful duct cannulation or securing the diagnosis, and therapeutic success was defined as the ability to successfully carry out endoscopic therapy. Complications of ERCP were defined according to standard criteria. RESULTS: A total of 50 patients (34-male, mean age 57 years, range 19 - 85 years) with Roux-en-Y anastomosis underwent ERCP using a single-balloon enteroscope on 56 occasions. Indications for ERCP were cholestasis, acute cholangitis, recurrent primary sclerosing cholangitis with strictures, and choledocholithiasis. Overall diagnostic success was achieved in 39 / 56 cases (70 %). Therapeutic success was achieved in 21/23 cases (91 %). In 16 cases therapeutic intervention was not required. Therapeutic interventions included balloon dilation of strictures (n = 14), retrieval of retained biliopancreatic stents (n = 5), biliary stone extraction (n = 2), insertion of biliopancreatic stents (n = 4), and biliary and pancreatic sphincterotomy (n = 5). No major complications occurred. Importantly, in 22 / 56 procedures (39 %) a prior attempt at ERCP failed using conventional colonoscopes; single-balloon ERCP was successful in 15 / 22 (68 %) of these cases. CONCLUSIONS: Single-balloon ERCP is feasible in patients with complex postsurgical Roux-en-Y anastomosis, allows diagnostic evaluation and therapeutic intervention in patients with pancreaticobiliary disease, and is a useful salvage technique in the majority of patients in whom ERCP using colonoscopies has failed.

The role of endoscopic ultrasound for loco-regional staging of rectal cancer.

Rectal cancer is projected to have the 10th highest incidence of cancer in the United States in 2009, with 40 870 estimated new cases this year. The prognosis for patients with rectal cancer is directly related to several factors, with the most important, based on current data, the extent of primary tumor invasion, the number of lymph nodes involved, involvement of the circumferential resection margin, and the presence of metastases. Contemporary therapy is dependent upon pre-surgical diagnostic imaging modalities, which influence the indication for neoadjuvant therapy and the decision process concerning the appropriate surgical approach. A comprehensive overview based on the currently available evidence of endoscopic ultrasound imaging in the loco-regional assessment of primary de novo rectal cancer evaluation following neoadjuvant therapy and post operative disease surveillance is presented. Relevant ano-rectal anatomy, staging systems for rectal cancer and alternative radiological staging strategies are also presented.

Frequency of visualization of presumed celiac ganglia by endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Celiac ganglia can be visualized by endoscopic ultrasound (EUS). It is unknown how often ganglia are visualized during EUS, and what clinical factors are associated with ganglion visualization. The aim of this study was to prospectively evaluate the frequency of visualization of presumed celiac ganglia by EUS and to identify factors that predict their visualization. PATIENTS AND METHODS: Clinical, demographic, EUS, and cytologic data were collected prospectively from 200 unselected patients who were undergoing EUS in a tertiary referral centre. When presumed celiac ganglia were visualized, their size, number, location, and echo features were noted. When presumed ganglia were aspirated, the results of cytology were recorded. RESULTS: The most common indication for EUS was investigation of a pancreatic mass or cyst (25 %). Presumed celiac ganglia were identified in 81 % of patients overall. Logistic regression analysis determined that female sex and having no prior history of gastrointestinal surgery were independently associated with ganglion visualization. Among patients whose ganglia were visualized, more ganglia were seen per patient with linear echo endoscopes (2, range 0 - 5) than with radial echo endoscopes (1, range 0 - 4) ( P = 0.001). Presumed celiac ganglia were aspirated in 10 patients; and cytologic examination revealed neural ganglia in all of these. CONCLUSIONS: Celiac ganglia can be visualized by EUS in most patients who undergo upper gastrointestinal EUS examinations, and are best seen with linear-array echo endoscopes. Ganglia can usually be differentiated from lymph nodes on the basis of their endosonographic appearance.

The relationship between neuropeptide Y expression and headache in pituitary tumours.

Patients with pituitary tumours often present with disabling headache but there is no clear relationship between tumour size and headache. Neuropeptide Y (NPY) has been identified in pituitary tumours and may serve as a biochemical marker of the propensity for headache. Using immunohistochemical techniques we examined 27 consecutive pituitary adenoma specimens for NPY (including one normal postmortem control anterior pituitary specimen). A separate observer divided the patients into two groups: headache and non-headache. The association between the presence of NPY and headache was tested. NPY positive immunoreactivity was seen in 13 tumour specimens (50%, 13 of 26 pituitary tumour specimens), characterized by cytoplasmic and nuclear staining patterns. There was no significant association between the presence of NPY and headache (chi(2) = 0.9, P = 0.34). We did not observe NPY in the normal anterior pituitary control specimen. NPY was present in four of five (80%) growth hormone-secreting tumours and two of two (100%) prolactinomas, compared with four of 11 (36%) non-functioning adenomas. The mechanism of many pituitary tumour-associated headaches remains undetermined. The significance of NPY positivity in pituitary tumours is unknown, although the results of this study may implicate this peptide in the control of somatotroph and lactotroph activity. Our data do not support a clear role for NPY pituitary tumour-associated headache.

The clinical characteristics of headache in patients with pituitary tumours.

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 pituitary-associated headache is given.