High glycemic variability: An underestimated determinant of stroke functional outcome following large vessel occlusion.

BACKGROUND AND PURPOSE: Early glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion. METHODS: A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed. RESULTS: Among the 93 patients evaluated, 26 had early high GV (≥20.9mg/dl). High GV was associated with poor functional outcome (OR=8.00; 95%CI [1.34-47.89]; P=0.02) unlike admission glycemia and mean glycemia (OR=2.92; 95%CI [0.51-16.60]; P=0.23 and OR=0.36; 95%CI [0.05-2.6]; p=0.31, respectively). High GV was not associated with NIHSS at 24hours or hemorrhagic transformation. CONCLUSION: Acute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.

Saccharide-induced modulation of photoluminescence lifetime in microgels.

Sugar-responsive microgels were prepared by the covalent grafting of a poly(N-isopropylacrylamide) (pNIPAM) matrix with phenylboronic acid (PBA) as a saccharide sensing unit and a [Ru(bpy)3](2+) derivative (2,2'-bipyridine) as a luminescent reporter. Time-resolved emission studies reveal that the ruthenium complex has an unusually long lifetime (1.6 µs) and high quantum yield (∼0.17) in the PBA-microgel environment. In the presence of sugars, the microgels swell due to the formation of a sugar-boronate ester, leading to a more hydrophilic polymer chain. The swelling is accompanied by a decrease of the lifetime and the photoluminescence quantum yield, which cannot be explained solely by the swelling of the hydrogel. The emission properties of the ruthenium complex in PBA-functionalized microgels are compared to those in pNIPAM microgels lacking PBA moieties in various swelling states. The presence of PBA in the vicinity of [Ru(bpy)3](2+) is shown to have a predominant impact on its luminescence properties, mainly through a decrease of the polarity. Sugar-induced triggering of the boronate state thus leads to strong variations of the polarity and the luminescence characteristics.

Treatment of diabetes mellitus using an external insulin pump in clinical practice.

Before the initiation of insulin pump therapy, patients must be aware of the different aspects of this form of intensive insulin therapy. Most healthcare professionals recommend a sequential approach to inform patients about CSII. Factors that need to be considered in choosing an insulin pump include its safety features, durability of the device, tolerability and comfort of the catheter, user-friendliness, technical features and appearance. The initial insulin requirements need to be individualized for the given patient, using different methods to determine the appropriate dosages for the basal rate and prandial boluses. Glycaemic targets and algorithms for insulin dose adaptation need to be learned by the patients to enable them to avoid and/or correct hypo- and hyperglycaemia/ketosis episodes. Patients are also advised on how to carry out frequent self-monitoring of blood glucose-and of ketone bodies, if necessary. Insulin pumps are now able to deliver a range of basal rates and boluses that increase the flexibility of CSII. One specific issue is the approach to meal-planning, based on carbohydrate-counting or the equivalent: this method of so-called 'flexible insulin therapy' can improve metabolic control (for instance, by diminishing postprandial excursions) as well as the quality of life of patients. Evaluation of the knowledge and practices of the patient can be made through a continuous educational programme carried out by experienced nurses and physicians at the start of therapy and during follow-up. In addition, it may be necessary to identify the reasons for lack of improvement in metabolic control after several months of therapy, which include pump malfunction, cannula problems, miscalculated insulin dosages and insufficient metabolic control in specific clinical situations with a high risk of metabolic deterioration (illness, exercise, concomitant drugs). Annual assessment of the patient using an itemized checklist is required to verify the continued efficacy and safety of insulin pump therapy, two main factors of success with CSII treatment.

Bioelectronic organ-based sensor for microfluidic real-time analysis of the demand in insulin.

On-line and real-time analysis of micro-organ activity permits to use the endogenous analytical power of cellular signal transduction algorithms as biosensors. We have developed here such a sensor using only a few pancreatic endocrine islets and the avoidance of transgenes or chemical probes reduces bias and procures general usage. Nutrient and hormone-induced changes in islet ion fluxes through channels provide the first integrative read-out of micro-organ activity. Using extracellular electrodes we captured this read-out non-invasively as slow potentials which reflect glucose concentration-dependent (3-15 mM) micro-organ activation and coupling. Custom-made PDMS-based microfluidics with platinum black micro-electrode arrays required only some tens of islets and functioned at flow rates of 1-10 µl/min which are compatible with microdialysis. We developed hardware solutions for on-line real-time analysis on a reconfigurable Field-Programmable Gate Array (FPGA) that offered resource-efficient architecture and storage of intermediary processing stages. Moreover, real-time adaptive and reconfigurable algorithms accounted for signal disparities and noise distribution. Based on islet slow potentials, this integrated set-up allowed within less than 40 µs the discrimination and precise automatic ranking of small increases (2 mM steps) of glucose concentrations in real time and within the physiological glucose range. This approach shall permit further development in continuous monitoring of the demand for insulin in type 1 diabetes as well as monitoring of organs-on-chip or maturation of stem-cell derived islets.

Practical implementation, education and interpretation guidelines for continuous glucose monitoring: A French position statement.

The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.

VEGF in physiological process and thyroid disease.

Angiogenesis is a physiological process involving the growth of new vessels from pre-existing vasculature. Vascular endothelial growth factor (VEGF) is an important regulator of both benign and malignant disease processes in the thyroid gland. The VEGF family includes seven members respectively named VEGF-A, also known as VPF (vascular permeability factor), VEGF-B, VEGF-C, VEGF-D, all described in mammals, VEGF-E (found in Parapoxviridae), VEGF-F (also called svVEGF, for snake venom VEGF, found in viper venom) and PlGF (placental growth factor). Thyrocytes are able to synthesize and secrete VEGF. VEGF-A is implicated in tumour growth and metastasis via blood vessels while VEGF-C and VEGF-D, involved in lymphangiogenesis, favour metastasis to the cervical lymph nodes in papillary thyroid carcinomas. High levels of VEGF expression in thyroid tumour cells may correlate with a poorer outcome in papillary thyroid carcinomas. Because of its important role in malignant angiogenesis, VEGF is the preferential target of a new variety of therapeutic agents called angiogenesis inhibitors.

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Indication, organization, practical implementation and interpretation guidelines for retrospective CGM recording: A French position statement.

AIM: The benefits of retrospective continuous glucose monitoring (retroCGM) recording have been widely explored in clinical studies, and many diabetes physicians routinely use this examination. However, the method of interpretation of CGM recordings has never been precisely described. METHOD: An expert French panel of physicians met for two days to discuss several aspects of retroCGM use and to produce a position statement. RESULTS: The guidelines cover the indications for retroCGM, the general organization and practical implementation of CGM recordings, a description of the different devices available and guidelines for the interpretation of retroCGM recordings. CONCLUSION: This consensus document should help clinicians in the proper use of retroCGM.

Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome.

SRIF receptor scintigraphy (SRS) has been proposed for the localization of ectopic ACTH-secreting tumors responsible for Cushing's syndrome. However, in most cases reported, the tumors were also visible using conventional imaging. Therefore, the usefulness of SRS in localizing truly occult ectopic ACTH-secreting tumors remains unknown. We report the results of SRS in 12 patients with ectopic ACTH syndrome (EAS) and in whom the source of ACTH was occult at presentation despite carefully performed conventional imaging. The diagnosis of EAS was made by identification of an ACTH-secreting tumor during follow-up in 5 patients or given a pituitary-to-peripheral ACTH ratio of 1.9 or less during petrosal sinus sampling combined with CRH injection and a negative pituitary magnetic resonance imaging (MRI). Whole-body planar SRS, using (111)In-pentetreotide, was performed 19 times in the 12 patients during initial workup and/or follow-up. Axial tomography imaging (single-photon emission-computed tomography) was performed in 7 of these. Conventional imaging was performed within a month of SRS, allowing comparison of the two approaches for the localization of the ACTH-secreting tumors. In addition, the response of plasma cortisol, after a single injection of 200 microg octreotide, was studied in 6 patients. Five patients had negative SRS and conventional imaging studies. The source of ACTH secretion remains occult despite 10-55 months of follow-up in four of these, whereas a 2-cm ileal carcinoid tumor, with liver micrometastases, was found at laparotomy in one patient, 14 months after presentation. SRS was positive in 4 of 12 patients. It was false-positive in 1 patient with follicular thyroid adenoma. Nineteen months after presentation, SRS identified liver metastasis that was also visible using MRI in one patient, but the primary tumor remains occult. SRS identified a 10-mm pancreatic tumor that became detectable, using computed tomography (CT) scanning 9 months later, in 1 patient; and 2 mediastinal lymph nodes of 10 mm, previously ignored by MRI, in another patient, whereas no tumor was detectable within the parenchymal lung. SRS had little influence on therapeutic options in these 2 patients, in whom no final diagnosis could be made. Repetition of SRS during the follow-up of patients with previously negative scintiscans was useless. Conventional imaging was positive in 6 of 12 patients. In the 2 patients with pancreatic tumor and isolated mediastinal lymph nodes, conventional imaging studies were interpreted as positive only after the results of SRS. One patient had liver metastasis that was also visible using SRS. Thin-section CT scanning visualized ACTH-secreting bronchial tumors and metastatic mediastinal lymph nodes of 10-15 mm in diameter in 3 patients after 14-72 months of follow-up, whereas SRS was negative. There was no evident relationship between the endocrine status (hyper- or eucortisolism) and the results of SRS. The in vivo response of plasma cortisol to octreotide correlated to the results of SRS in 4 of 6 cases. In conclusion, both imaging procedures had a low diagnostic yield in this series. However, the sensitivity of SRS for the detection of bronchial carcinoids was lower than that of thin-section CT scanning. We therefore advocate the use of conventional imaging, including thin-section CT scanning of the chest, analyzed by experienced radiologists, as the first-line investigation in patients with occult EAS. SRS should not be repeated during the follow-up in patients with a previously negative scintigram.

Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation.

Triple A (3A) syndrome, a rare autosomal recessive disorder, is characterized by adrenocorticotropic hormone-resistant adrenal insufficiency, achalasia of the cardia, alacrima, and variable autonomic and neurologic dysfunction. The gene responsible, AAAS, recently has been identified. We describe the neurologic phenotype of the first adult case of 3A syndrome presenting bulbospinal amyotrophy as the prominent sign in association with a homozygous nonsense mutation identified in the AAAS gene.

Optimized radioiodine therapy of Graves' disease: analysis of the delivered dose and of other possible factors affecting outcome.

The best approach to radioiodine dose selection in the treatment of Graves' hyperthyroidism remains highly controversial. The formula to calculate the individual dose of (131)I to be delivered has been used for half a century and takes into account the thyroid mass, the effective half-life and the maximum uptake of (131)I. The objective of the present study was to evaluate the accuracy of this formula by determining the relationship between the administered dose of (131)I calculated to deliver a target dose of 50Gy to the thyroid and the actual exact organ dose. We further analyzed if therapeutic success, defined by euthyroidism following the individually calculated dose, can be predicted by different pretreatment parameters and particularly by organ dose. One hundred patients with a first episode of Graves' disease and who had received optimal thyroid irradiation after precise dosimetry were retrospectively reviewed. The patients were categorized according to their thyroid function (plasma free thyroxine (T(4)) serum concentration) as eu-, hyper- or hypothyroid during and 1 year after treatment. The relationship between the administered dose and organ dose was assessed by simple regression. We compared free T(4), free tri-iodothyronine, thyroid weight, the number of patients with antithyroperoxidase antibodies and TSH receptor autoantibodies, 24h urinary iodine excretion, (131)I uptake, and the exact dose of (131)I delivered to the thyroid as pretreatment variables. Although we found a correlation between administered dose (mCi) and organ dose (Gy) (r=0.3, P=0.003), the mean coefficient of variation for organ dose was 45%. Individualized radioiodine therapy enabled euthyroidism in 26% of patients and failed in 74% of patients (33% had persistent or recurrent hyperthyroidism and 41% permanent hypothyroidism). (131)I uptake was significantly higher in the hyperthyroidism group in comparison with the euthyroid group. However, organ dose and other pretreatment variables did not differ among the three groups. In conclusion, these results confirm the low performance of individual dosimetry using what are established ratios, since the delivered dose to the gland, although correlated to the intended dose, is highly variable. The finding that other usual pretreatment variables are not different between groups, gives little hope for improving the way of calculating the ideal dose of radioiodine. We suggest to those not yet ready to give a standard or an ablative dose for Graves' hyperthyroidism that they abandon this way to calculate the (131)I dose.

Experience with the Biostator for diagnosis and assisted surgery of 21 insulinomas.

Surgical removal is the treatment of choice for insulinomas. Definitive biochemical diagnosis of organic hyperinsulinism has to be established before surgery. These tumors are sometimes undetected by preoperative imaging investigations and, in addition, surgical management may also be complicated by the absence of palpable tumors or the presence of multiple tumors. We report the value of the euglycemic clamp technique for diagnosis and surgical treatment in 21 patients with confirmed insulinomas. Data were compared with 12 controls, and nine patients were retested after surgery. During the euglycemic hyperinsulinic clamp, the mean C-peptide value was 3.6+/-2.2 ng/ml and it remained high (3.8+/-2.5 ng/ml), despite exogenous hyperinsulinemia (1762.7+/-233.2 microU/ml for the highest plateau). In contrast, the C-peptide concentration declined in 12 control patients (0.3+/-0.1 ng/ml, P < 0.001) and after successful surgery in nine retested patients (0.3+/-0.2 ng/ml, P < 0.01). During continuous glucose monitoring, successful removal of the insulin-secreting tumor was accompanied by an increase in plasma glucose concentrations and a loss of requirement for endogenous glucose within 36 min (range 28-43 min). The continuing requirement for glucose after the ablation of the tumor revealed the existence of additional and initially undetected tumors in four patients, among whom two had the multiple endocrine neoplasia type I (MEN I) syndrome. We conclude that the euglycemic hyperinsulinic clamp is a reliable and convenient diagnostic test for insulinoma, as it is both safe (no hypoglycemia) and relatively brief (3 x 90 min). Glucose monitoring and glucose clamping provide a reliable indicator of complete removal of insulin-hypersecreting tissue, especially in patients with occult or multiple tumors.

Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas.

OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.

Glucose profiles in a type 1 diabetic patient successively treated with CSII using regular insulin, lispro and an implantable insulin pump.

The delayed subcutaneous insulin absorption makes stable blood glucose difficult to achieve in patients with type 1 diabetes, and there is a high risk for severe hypoglycemia. The human insulin analogs demonstrated to circumvent this major limitation of rapid-acting insulin particularly in the context of a continuous subcutaneous insulin infusion (CSII). As insulin profiles generated by implantable insulin pump (IP) are similar to lispro, we studied glucose profiles and the risk for severe hypoglycemia assessed by the low blood glucose index (LBGI) in a patient successively moved from CSII using regular-acting insulin to CSII using lispro and finally to an IP. Insulin delivery with the IP, and to a lesser extent CSII using lispro tend to reduce the average glycemia in comparison with CSII using regular-acting insulin (114.2+/-53.0, 131. 6+/-56.8 and 140.7+/-81.5 mg/dl, respectively). Reduction of glycemic fluctuations assessed by area under the curves was more pronounced during IP therapy in comparison with lispro and with rapid-acting insulin in CSII (789.5, 798.2 and 891.5 h.mg.dl-1, respectively). LBGI remained in the moderate range with IP and CSII using lispro (4.3+/-6.8 and 4.0+/-5.7 respectively), while LBGI was in the high range with rapid-acting insulin (5.5+/-10.2). In conclusion our case report suggests that IP tends to reduce the average glycemia and affect the amplitude of glycemic fluctuations in comparison with CSII using lispro, with an equivalent risk for severe hypoglycemia. A prospective randomized study is needed to compare these two modes of insulin replacement.

Comparison of blood glucose stability and HbA1C between implantable insulin pumps using U400 HOE 21PH insulin and external pumps using lispro in type 1 diabetic patients: a pilot study.

BACKGROUND: To assess the efficacy on blood glucose control of continuous peritoneal insulin infusion from implantable pump (CPII) compared with continuous subcutaneous infusion using insulin lispro (CSII-IL) in type 1 diabetic patients. METHODS: Fourteen type 1 diabetic patients (5 males and 9 women, age 50.6 +/- 12.8, diabetes duration 28.0 +/- 13.4 years) were treated with CSII-IL and CPII. Capillary blood glucose (BG) was monitored and recorded at least 4 times per day during 2 study periods of 45 days: using CSII-IL (period A), and from 45th to 90th day after implantation (period B). HbA1C was measured at the end of each period. RESULTS: Both daily BG levels (145 +/- 18 vs 153 +/- 17 mg/dl, p<0.01) and preprandial BG levels (139 +/- 20 vs 147 +/- 22 mg/dl, p<0.05) were lower in period B. Although postprandial BG values tended to be lower in period B, this reduction did not reach statistical significance (149 +/- 20 vs 157 +/- 16 mg/dl, p=0.07). Meanwhile, SD of all BG values was lower with CPII (69 +/- 11 vs 79 +/- 17 mg/dl, p<0.01) and HbA1c levels were lower at the end of period B (7.3 +/- 0.9 vs 7.8 +/- 0.9%, p=0.04). Low blood glucose index was comparable during both periods (2.8 +/- 1.6 vs 3.1 +/- 1.5, p=0.4). CONCLUSION: CPII may provide a better BG control and stability than CSII-IL. However, a long-term randomized prospective study is needed to confirm these improvements.

A randomized study comparing blood glucose control and risk of severe hypoglycemia achieved by non-programmable versus programmable external insulin pumps.

OBJECTIVE: To compare a non-programmable and a programmable insulin external pump using regular insulin on glycemic stability, the risk of severe hypoglycemia and metabolic control in type 1 diabetic patients. MATERIAL AND METHODS: Ten type 1 diabetic patients were involved in a randomized, crossover study comparing two periods of 3 months with continuous subcutaneous insulin infusion (CSII) either with a non-programmable insulin pump or a programmable insulin pump. Comparisons were made among mean blood glucose values before and after meals, at bedtime and at 2: 00 a.m.; the risk of severe hypoglycemia assessed by the low blood glucose index (LBGI); and HbA1c. RESULTS: Mean average blood glucose (BG) measurements were significantly lower with the programmable in comparison with the non-programmable insulin pump (respectively 157+/-78 vs. 165+/-79, p=0.034). While postprandial values for BG were not different between the two pumps, the use of the programmable pump resulted in a significant decrease in mean preprandial BG levels (140+/-68 vs. 150+/-73 mg/dl p=0.039). Conversely mean BG level was lower at 2 a.m. with the non-prgrammable pump (125+/-81 vs. 134 +/-93 mg/dl, p=0.02) but with a higher incidence of hypoglycemia. Mean LBGI was comparable with the two pumps (3.1+/-8.6 vs. 2.8+/-6.9, p=0.1). There was a 0.2% decrease in HbA1c during the programmable pump period that did not reach statistical significance (p=0.37). CONCLUSIONS: The present study suggests that programmable external insulin pumps, although more complex and more expensive than non-programmable insulin pumps, significantly reduce fasting glycemia during the day without increasing the risk of severe hypoglycemia and are safer during the night.

Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience.

OBJECTIVE: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter. RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation. RESULTS: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study. CONCLUSION: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

Evaluation of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients with negative radioiodine scintigraphy.

The follow-up of patients who underwent thyroidectomy for differentiated thyroid carcinoma is based on the combination of serum thyroglobulin (Tg) measurement and radioiodine total-body scan (ITBS). The diagnostic strategy to be used in patients with elevated serum Tg level but negative ITBS remains debatable. Somatostatin receptor scintigraphy (SRS) has been proposed. Our objective was to compare the results of SRS and conventional radiological imaging (CRI) for the diagnosis of recurrent disease and/or metastases in 15 patients who had had thyroidectomy for differentiated carcinoma (14 papillary, 1 Hurthle cell carcinoma) and who displayed elevated Tg levels (10 to 65000 ng/mL) together with negative ITBS performed after 100 mCi. All patients underwent SRS and CRI within 3 months, allowing comparison of the 2 approaches for the identification of thyroid carcinoma metastases. CRI first included a chest x-ray and ultrasonography of the neck. It was followed by computed tomography (CT) scanning and/or magnetic resonance imaging (MRI) of the neck, chest and occasionally abdomen, and 99mTc bone scintigraphy in case of negative results. In 6 patients with Tg levels ranging from 65 to 65000 ng/mL, CRI detected 12 histologically proven metastases among 9 organs. Among these patients, SRS identified only 6 metastases. SRS identified 1 case of mediastinal recurrence that was not detected by CRI. In another patient with a Tg level of 51 ng/mL, a cervical node was identified using both SRS and CRI but proved to be a false-positive (inflammatory cervical node). In the other 8 patients with Tg levels ranging from 10 to 580 ng/mL, SRS and CRI were negative, and the source of Tg secretion remains unknown. The results of SRS did not correlate with serum Tg level. In conclusion, the diagnostic accuracy of SRS in this study was disappointing and clearly lower than that of CRI. Our results do not support the use of SRS as a guide conventional imaging modalities in patients operated on for differentiated thyroid carcinoma who display elevated Tg levels together with negative ITBS.

Homocysteine, hypothyroidism, and effect of thyroid hormone replacement.

Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate.

[Treatment of macroprolactinomas with quinagolide (Norprolac)]. / Traitement des macroprolactinomes par le quinagolide (Norprolac).

Quinagolide is a non-ergot dopaminergic agonist recently available on the French market. The endocrine and tumoral efficacy as well as the safety and tolerability of quinagolide in the treatment of macroprolactinomas are reviewed. In this situation, plasma prolactin levels are normalized in about 60% of patients and in about one third of those who are resistant to bromocriptine. A significant decrease in pituitary tumor size is demonstrated by radiographic studies in 58 to 69% of patients. About one third of patients show more than 50% tumor shrinkage. The tolerability of quinagolide is satisfactory in most cases and clearly better than that of bromocriptine. Thus, quinagolide is a useful tool in the treatment of macroprolactinomas.