The short insulin tolerance test for determination of insulin sensitivity: a comparison with the euglycaemic clamp.

The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate KITT in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non-insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose KITT over the period 3-15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mumol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.     

Relation between ventricular repolarization duration and cardiac cycle length during 24-hour Holter recordings. Findings in normal patients and patients with long QT syndrome.

BACKGROUND. The interval from the R wave to the maximum amplitude of the T wave (RTm) contains the heart rate dependency of ventricular repolarization. METHODS AND RESULTS. A computer algorithm was developed to quantify the RTm and preceding RR intervals for each of more than 50,000 beats on 24-hour ambulatory electrocardiographic (Holter) recordings to evaluate the dynamic relation between repolarization duration and cycle length. The relation of RTm to the preceding RR interval (RTm/RR slope) was determined by the best-fit linear regression equation between these two parameters. Eleven normal subjects and 16 patients with long QT syndrome (LQTS) were investigated. Six of the normal subjects had Holter recordings obtained before and after beta-blocker therapy. beta-Blockers were associated with a significant (p = 0.005) reduction in the RTm/RR slope from 0.13 +/- 0.02 to 0.10 +/- 0.02. The mean value of the RTm/RR slope was significantly (p = 0.003) larger in the LQTS patients (0.21 +/- 0.08) than in normal subjects (0.14 +/- 0.03). CONCLUSIONS. These findings indicate that 1) quantification of the dynamic relation between ventricular repolarization and RR cycle length can be obtained on a large number of Holter-recorded heart beats; 2) beta-blockers reduce the RTm/RR slope in normal patients; and 3) LQTS patients have an exaggerated delay in repolarization at long RR cycle lengths.     

Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.     

Original lithotomy positioning for transperineal extracorporeal shockwave lithotripsy for distal ureteric calculi with Tripter X1.

Extracorporeal shockwave lithotripsy (ESWL) has been initially designed for stones located in the kidney and the upper ureter. Our lithotripter is no exception. Its components (the table and the orientation of the semi-ellipsoid reflector) are adapted for the treatment of kidney or lumbar ureter stones. However, the elements forming the unit of treatment (the table, the C-arm and the Tripter) can be modified in such a way that focalization of stones of the lower ureter becomes possible through a perineal exposure. The aim is to avoid the pelvic bone shield while a good focalization of the stone is realized. From June 1989 to March 1991, 35 patients were treated for distal ureteric stones by ESWL in this original positioning.     

Light and electron microscopic immunocytochemical localization of glutamine synthetase in the superficial pineal gland of the rat.

Glutamine synthetase (L-glutamate:ammonia ligase; EC 6.3.1.2), an enzyme catalysing the ATP-dependent formation of glutamine from glutamate and ammonia, was detected immunocytochemically only in glial (interstitial) cells of the superficial pineal gland of the rat. The results show the important role of pineal glial cells in the metabolism of the presumptive neurotransmitters, glutamate and gamma-aminobutyric acid (GABA) as well as in detoxification of ammonia.