Accuracy of two continuous glucose monitoring systems: a head-to-head comparison under clinical research centre and daily life conditions.

AIMS: To assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems. METHODS: We studied the Dexcom®G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6-h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points ≥15 min apart. RESULTS: The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Δ) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Δ = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [≤3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Δ 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%. CONCLUSIONS: During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL.

External trial deep brain stimulation device for the application of desynchronizing stimulation techniques.

In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

Investigation of human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble/highly permeable drug (efavirenz).

Human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble, highly permeable, micronized drug (efavirenz) was investigated. The tablets and capsule, prepared with samarium oxide and neutron activated to produce radioactive samarium-153, were evaluated for their in vivo disintegration and gastrointestinal (GI) transit in healthy subjects under fasted condition. Scintigraphic images were acquired to coincide with blood sampling times to assess the plasma concentration-time profile in relation to in vivo disintegration and GI transit. The mean gastric emptying times were approximately the same for all three formulations. Although in vivo dosage form disintegration was faster for Tablet A as compared to Tablet B and was similar between Tablet A and the capsule, Tablet A showed a slower rate and extent of drug absorption than Tablet B and the capsule. The results of this study eliminated the initial hypothesis that the difference in in vivo performance between the two tablet formulations is due to a different rate of in vivo disintegration and suggest that for this drug the in vivo dissolution rate of the drug from its disintegrated dosage form was a more important factor affecting the rate and extent of drug absorption.

Bioequivalence study of stressed and nonstressed hard gelatin capsules using amoxicillin as a drug marker and gamma scintigraphy to confirm time and GI location of in vivo capsule rupture.

PURPOSE: Evaluate if crosslinked hard gelatin capsules (HGCs) having different in vitro dissolution profiles changed in vivo release times or altered bioavailability of a drug marker; assess if a two-tier dissolution test (with and without enzyme) predicted in vivo performance. METHODS: Two classifications of stressed HGCs were artificially produced by exposure to formaldehyde (HCHO). HGCs were categorized as, a) pass/pass (p/p) which met in vitro dissolution criterion (75% drug dissolution at 45 min), b) moderately crosslinked fail/pass (f/p) which failed dissolution criterion in the absence of enzymes and passed in the presence of enzymes, and c) severely crosslinked fail/fail (f/f) which failed in vitro standards with or without enzymes. A six-way, single dose bioequivalence study (n = 10) administered the three HGCs under the fasted and fed condition. In vivo capsule rupture and GI transit were monitored via gamma scintigraphy, and blood samples were collected through six hours. RESULTS: Each crosslinked HGC was bioequivalent to the control p/p capsule when using AUC(0-infinity) and Cmax for comparison. Mean in vivo disintegration of the p/p capsule was 7 +/- 5 min for the fasted condition and 11 +/- 7 min for the fed condition. In vivo rupture for the f/p capsule was 22 +/- 12 min and 23 +/- 11 min for the fasted and fed studies, respectively, while the f/f HGC ruptured at 31 +/- 15 min and 71 +/- 19 min under the fasted and fed condition, respectively. Onset of amoxicillin absorption was dependent on in vivo HGC rupture and subsequent entry of the released radioactive marker into the small intestine. Consequently, fasted Tmax values were significantly later for the f/p HGC (1.62 +/- 0.53 hr) and f/f HGC (1.85 +/- 0.58 hr) as compared to the p/p HGC (1.17 +/- 0.30 hr). Fed Tmax values were statistically different only for the f/f capsule (2.55 +/- 0.44 hr) where Tmax values for the p/p and f/p HGCs under the fed condition were 1.50 +/- 0.47 hr and 1.60 +/- 0.46 hr, respectively. CONCLUSIONS: A two-tier dissolution procedure that retested a crosslinked hard gelatin capsule with addition of gastric or intestinal enzymes provided an adequate in vitro indicator of the formulation's in vivo performance. The observed delays in the onset of amoxicillin absorption and Tmax for the severely crosslinked f/f HGC was attributed to delayed in vivo capsule rupture, however, this delay did not adversely change AUC(0-infinity) nor Cmax.

In vivo evaluation of the absorption and gastrointestinal transit of avitriptan in fed and fasted subjects using gamma scintigraphy.

The study was conducted to assess the bioavailability of avitriptan after a standard high fat meal, in relation to gastrointestinal transit. Six healthy male subjects were enrolled in a four-period study with a partial replicate design where each was administered 150-mg avitriptan capsule (i) after an overnight fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a standard high fat breakfast. The treatment administered in Period 3 was repeated in Period 4 to assess intrasubject variations in pharmacokinetics and gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with nonradioactive samarium chloride hexahydrate which was neutron-activated to gamma-emitting samarium before dosing. Serial blood samples were collected for analysis of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained to assess the plasma concentration-time profile in relation to the GI transit of the avitriptan capsule contents. Bioavailability of avitriptan was reduced when administered in the fed condition but only the decrease in AUC(INF) was statistically significant. Tmax was significantly delayed between the fed conditions and the fasted condition. Qualitative appearance of plasma concentration-time profiles for avitriptan could be related to the manner in which the drug emptied from the stomach. It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment. Thus, when gastric emptying was interrupted and then resumed, the net result was a double peak in some of the individual plasma concentration profiles. Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine. In the fed state, gastric emptying was slow and continuous resulting in extended absorption and a lower occurrence of double peaks. Qualitatively, the intrasubject variability in Cmax and AUC could be explained by the intrasubject variability in gastric emptying in both fasted and fed conditions.

Biodegradable indium-111 labeled microspheres for in vivo evaluation of distribution and elimination.

Short-lived gamma emitting radioisotopes can be incorporated into polylactide/glycolide polymeric microspheres with various specific activities for possible use in understanding the in-vivo deposition, distribution and clearance of microparticulate drug carrier systems. The incorporated radiolabel is stable with negligible leaching out of the microspheres. These microspheres are suitable for studying the oral uptake of particles, lung distribution after inhalation delivery and evaluation of in-vivo fate following parenteral administration in systemic circulation or in specific tissue compartments.

[The effect of the pipe material of the drinking water system on the frequency of Legionella in a hospital]. / Zum Einfluss von Rohrmaterialien des Trinkwassernetzes auf die Legionellenhäufigkeit in einem Klinikum.

In this paper the prevalence of Legionella in water samples from cold and warm water supply systems made of copper, iron and polyethylene was determined. Water supplied by copper pipes revealed to be nearly free of Legionella (only 2% of probes positive), but water from iron (90%) or polyethylene pipes (65% probes positive) proved to be heavily contaminated. The 82 isolates were identified as Legionella pneumophila, one from serogroup 1, the others from serogroup 4.

Animal model for chronic-abscess-forming peritonitis: histology and microbiology.

Clinical experience gives evidence of the increasing importance of chronic-abscess-forming peritonitis with a general physical impairment in spite of a well-controlled abdominal situation. The number of unsolved problems led us to develop a standardized and reproducible experimental animal model, using Wistar rats. We induced peritonitis by intraperitoneal injection of a mixture containing a capsulated strain of Bacteroides fragilis and DEV agar. The histologic changes in the parietal and visceral peritoneum, lymphnodes and liver were recorded in the course of the disease. The data largely correlate with those recorded in human peritonitis. Bacteriologic examinations gave evidence of bacteria passing through the intestinal wall into the abdomen. This is the first model for peritonitis which is defined by its histological and bacteriological course. It enables one to examine pathophysiological problems and the consequences of harm and stress for the course of the disease.

Analyzing the service contract when buying equipment.

When purchasing equipment, financial managers must consider how much maintenance and repair will cost in addition to the initial purchase price. Equipment service contracts can help ease the cost of equipment maintenance. But before signing a contract, financial managers should carefully analyze the agreement, considering such factors as vendor qualifications, covered equipment, and the term, coverage, conditions, and cost of the agreement.

[New therapeutic aspects in the treatment of diffuse peritonitis]. / Neue therapeutische Aspekte in der Behandlung der diffusen Peritonitis.

The diffuse peritonitis is a syndrome during the course of which biochemical reactive chains are activated according to a cascade principle. Most of these biochemical reactive chains develop within an acid environment. The solutions applied for abdominal lavage so far had neutral pH value. The present acute peritonitis experiment has shown that a peritoneal pH increase during lavage therapy stopped the septic reactive chain and thus improved significantly the rate of survival in the test animals. These experimental findings ar now subject for clinical examination.

[Perioperative prophylaxis in elective colorectal surgery]. / Untersuchungen zur perioperativen Prophylaxe in der elektiven colorectalen Chirurgie.

The effects of perioperative antibiotic prophylaxis in elective colon surgery was evaluated in a prospective study on 100 patients. Bowel cleansing was done by orthograde lavage. The patients were divided into 5 groups receiving equally cefotaxime 3 x 2 g, lamoxactam 3 x 2 g, cefmenoxime 3 x 1 g, mezlocillin 3 x 5 g an piperacillin 3 x 4 g. Mucosa biopsies of the resected colon were taken for aerobic and anaerobic cultures. Further mucosal serum probes were frozen immediately for determination of tissue and serum levels of the antibiotics. Our results show that bacterial growth of the colon mucosa was significantly reduced. Anaerobes were identified in only 8%. The tissue concentrations exceeded the MIC-levels of the identified bowel organisms many times over. The clinical infection rate was 4%. All administered antibiotics can be recommended without reservation.

Hyperinsulinism after removal of a pheochromocytoma.

The finding of hypoglycemia after the surgical removal of a pheochromocytoma in two patients in a previous study led to monitoring of the serum glucose and plasma C-peptide levels in two other patients with a pheochromocytoma and one with unilateral adrenocortical hyperplasia. In the two patients with a pheochromocytoma endogenous insulin secretion, as measured by a C-peptide assay, was suppressed before removal of the tumours and resumed immediately after removal. The serum glucose levels decreased in these patients, but sufficient intravenous administration of glucose prevented postoperative hypoglycemia. In the patient with adrenocortical hyperplasia the plasma C-peptide level was not decreased before tumour removal, nor did it increase abruptly following removal. It therefore seems likely that the rapid fall in the serum glucose level following removal of a pheochromocytoma is caused by prompt resumption of beta-cell activity, with rebound hyperinsulinism.