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PubMed1997

Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol.

People with NIDDM are resistant to insulin. The present studies sought to determine whether the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is impaired. To address this question, basal insulin concentrations were maintained constant with an exogenous insulin infusion, while endogenous hormone secretion was inhibited by somatostatin. The integrated glycemic response above baseline during identical prandial glucose infusions was greater (1,411 +/- 94 vs. 938 +/- 45 mmol/l per 5 h; P < 0.01) in the diabetic subjects than in the nondiabetic subjects, indicating a decrease in net glucose effectiveness. [6-3H]glucose also was infused to determine whether the decrease in net glucose effectiveness was due to a decrease in the ability of glucose to stimulate its own uptake and/or to suppress its own production. Despite identical rates of tracer infusion, the increment in plasma concentration of [6-3H]glucose was higher (4.50 +/- 0.29 vs. 3.16 +/- 0.21 x 10(5) dpm/ml per 5 h; P < 0.05) in the diabetic subjects than in the nondiabetic subjects. This was due to both a decrease (P < 0.05) in the ability of glucose to stimulate its own disappearance via mass action and to a greater (P < 0.01) inhibitory effect of glucose on its own clearance. The increase in glucose concentration resulted in prompt and comparable suppression of endogenous glucose production in both groups. Under these optimized conditions, indexes of glucose effectiveness calculated with both the "cold" and "hot" minimal models also were lower (P < 0.05) in the diabetic subjects than in the nondiabetic subjects and were highly correlated (r = 0.94-0.99; P < 0.001) with the indexes of glucose effectiveness calculated from the increments above baseline of glucose and [6-3H]glucose concentration. We conclude that the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is abnormal in people with NIDDM.

Blood Glucose↗
PubMed1982

Comprehensive kinetics of triiodothyronine production, distribution, and metabolism in blood and tissue pools of the rat using optimized blood-sampling protocols.

We have determined estimates for 24 physiological parameters of production, interpool transport, distribution, and metabolism of T3 in the major T3 pools of the unanesthetized male Sprague-Dawley rat, from blood-borne data and a comprehensive model and analysis of this system. Most of these indices have previously been unavailable. Whereas only 3% (2 ng/100 g BW) of the total body T3 pool (74 ng/100 g BW) is in plasma, the composite of slowly equilibrating (slow) tissue pools (e.g. muscle, skin, and brain) appears to contain most of the T3, 76% (57 ng/100 g BW) of the total. The composite of rapidly equilibrating (fast) tissue pools (e.g. liver and kidney) contains the remaining 19% (16 ng/100 g BW). The total body T3 production rate is 0.12 ng/100 g BW . min, and we estimate that about half of this emanates directly from T4 in the slow pools, whereas the remainder is derived from both thyroidal secretion and T4 to T3 conversion in the fast pools. Our results also indicate that T3 molecules spend an average of only 0.5 min in transit each time through plasma, whereas the single pass mean transit times in fast and slow tissue pools (the times available for hormone action) are 10 times and 200 times greater. In contrast, the mean residence time for T3 in the entire system is greater than 12 h despite the extremely rapid early disappearance of injected T3 from plasma. To obtain the required accuracy, we used a novel optimization approach for choosing blood-sampling schedules (1, 4, 44, 202, and 600 min), a remarkably small number of sample times, and each was adjustable by about +/- 20% without effect on optimized parameter accuracies.

Animals↗
PubMed2001

Evaluation of an optimal luteal phase support protocol in IVF.

SUBJECT: Luteal phase support has been shown in the past to be an essential part of ovarian stimulation protocols, especially the long protocol. It could be shown that hCG is as effective as is progesterone for luteal phase support but hCG is accompanied by a higher rate of complications. METHODS: Progesterone can be administered in several routes. The oral, intramuscular (i.m.) and vaginal routes have been chosen frequently in the past. The oral route is ineffective, since progesterone has a low oral bioavailability (<10%), and a high rate of metabolites, which may result in side effects such as somnolence etc. Intramuscular administration provides very high serum levels of progesterone and this route is effective with regard to pregnancy rates. Injection of progesterone, however, is painful and cannot be done by the patient herself. The vaginal route is also effective, progesterone can be administered by the patient herself and progesterone is delivered directly to the uterus, where high levels are achieved (first uterine pass effect). RESULTS: Several studies could show, in the past, that the vaginal administration of progesterone is effective also with regard to the downregulation of uterine contractions. Crinone 8% Vaginal Gel is especially designed for vaginal use with a special applicator and has to be administered once daily in the morning. It adheres to the vaginal epithelium, and leakage of the gel is substantially reduced as compared to other drugs like capsules or suppositories. CONCLUSIONS: Since progesterone is as effective as hCG for luteal phase support but provides a higher safety with regard to ovarian hyperstimulation syndromes, and vaginal progesterone is as effective as intramuscular progesterone, vaginal progesterone should be the standard choice for luteal phase support. Crinone 8% seems to be the most comfortable way of vaginal administration of progesterone for luteal phase support in IVF cycles.

Administration, Intravaginal↗
PubMed1996

The use of vibratome sections for the ruthenium tetroxide protocol: a key for optimal visualization of epidermal lipid bilayers of the entire human stratum corneum in transmission electron microscopy.

In this paper we describe a preparative procedure which allows maximal visualization of all lipid bilayers in the human stratum corneum (SC). We used 50-microns-thick vibratome sections of paraformaldehyde/glutaraldehyde-fixed human skin. The sections were post-fixed in 1% osmium tetroxide and 0.5% ruthenium tetroxide. The vibratome sections were dehydrated only in 70% ethanol in order to prevent dissolution of the lipids. Lipid bilayers, including the alternating electron-dense and electron-lucent lamellae, were visible between all cell layers of the SC. In addition, this preparative procedure also appeared to be excellent for the ultrastructural preservation of lamellar bodies.

Epidermis↗
PubMed2000

Optimization of TEOAE recording protocols: a linear protocol derived from parameters of a time-frequency analysis: a pilot study on neonatal subjects.

Linear and non-linear TEOAE protocols were compared in terms of nine parameters in order to define the protocol producing recordings with the highest signal quality (lowest noise and highest signal-to-noise ratio). The pilot project acquired data using ILO-92 apparatus from 220 neonates (397 ears) at the second/third day after birth in three European laboratories. A Gabor spectrogram time-frequency representation of the recordings showed considerable frequency dispersion in TEOAE latencies >4.0 ms. The data, analysed with a Wilcoxon test, indicated that a linear TEOAE protocol: (i) generates recordings of a lower noise and a higher signal-to-noise (S/N) ratio in the 2.0, 3.0, 4.0 kHz TEOAE bands; (ii) the increase in the S/N ratio can result in a decrement of the required number of TEOAE sweeps; (iii) the higher values of S/N can be used in the estimation of more robust pass-fail criteria, minimizing the percentage of false positives and negatives.

Acoustic Stimulation↗
PubMed1985

Quantification of contrast in clinical MR brain imaging at high magnetic field.

The relative contrast between two tissues in a magnetic resonance (MR) image is shown to be quantifiable for any combination of pulse timing parameters, provided the intrinsic parameters are known. Based on multiple inversion-recovery and spin echo images, a region-of-interest T1, T2 and density analysis was conducted at 1.4T in selected patients with diagnosed neuropathology for various brain tissues. The resulting tissue parameters subsequently served to calculate the contrast-to-noise (C/N) ratio for typical tissue interfaces as a function of the operator-variable pulse timing parameters and the data were compared with the images. Although such calculations may be useful as a protocol selection aid, it is obvious that an optimized pulse protocol can only be established for a single tissue interface. The data also reveal that a T2-discriminating pulse sequence like Carr-Purcell-Meiboom-Gill with long repetition time, generally advocated as clinically most effective, may not always be ideal.

Brain Diseases↗
PubMed1999

Optimization of the immunosuppressive protocol after lung transplantation.

BACKGROUND: The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart transplantation led us to investigate regimens including this agent at our center for lung transplantation. METHODS: From 1991 to 1998, 86 patients underwent lung transplants at our center and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilymphocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone. RESULTS: The number of acute rejection episodes per 100 patient days was 1.5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the incidence of refractory acute rejection per 100 patient days was lower in both Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejection was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/Aza). Freedom from recurrent acute rejection was significantly higher in both Tac groups (P=0.027 Tac/ Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza). The incidence of infections per 100 patient days was similar (0.8, 0.5, and 0.8) in all three treatment groups, with a similar distribution of fungal, bacterial, and viral infections. Freedom from infection also showed no difference. The survival rate was significantly higher for the Tac population, with actuarial 1- and 3-year survival rates of 93% and 71%, compared with the CsA group (71% and 51%, respectively, P=0.04). Prevalence of renal dysfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was lower in the CsA group than in the Tac-Aza group (15% vs. 27%, P<0.05). CONCLUSIONS: Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection rates and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.

Acute Disease↗
PubMed2003

Electrotransfer at MR imaging: tool for optimization of gene transfer protocols--feasibility study in mice.

PURPOSE: To test, by using an electrotransfer protocol for the transfection of skeletal muscle with naked plasmid complementary DNA, whether in vivo magnetic resonance (MR) imaging can help delineate either the spatial extent of the electric field when contrast agent is injected intraperitoneally or the transfection area when contrast agent is injected locally. MATERIALS AND METHODS: Three groups of five mice each were examined at 4 T. Gadopentetate dimeglumine was injected intraperitoneally before electroporation in group 1 and after electroporation in group 2. In group 3, gadopentetate dimeglumine was coinjected in situ with plasmid pCMV-beta Gal in the gastrocnemius muscle before electroporation. MR imaging and muscle preparation for histologic examination were performed 3 days later. On T1-weighted images, increase of muscle signal intensity was determined in regions of interest (ROIs) of treated legs and compared with contralateral ROIs. Comparison of signal intensity increase between groups 1 and 2 was performed with Kruskal-Wallis test. RESULTS: In groups 1 and 3, T1-weighted images of treated muscle showed zones of strongly increased signal intensity. In corresponding ROIs of groups 1, 2, and 3, the mean T1-weighted signal intensity increase at day 3 was 1.64 +/- 0.20 (SD), 1.16 +/- 0.06, and 1.58 +/- 0.17, respectively. The difference between groups 1 and 2 (ie, gadopentetate dimeglumine injected before and after electrotransfer) was significant (P <.001) both without and with correction for T2 variation (1.47 +/- 0.19 and 1.04 +/- 0.09, respectively). In group 3, after in situ coinjection of gadopentetate dimeglumine and plasmid, the area of increased signal intensity revealed at ex vivo MR imaging of the muscle showed a reasonable concordance with the transfected area revealed with beta-galactosidase on histologic sections. CONCLUSION: In vivo and ex vivo results indicate that atraumatic visualization of the permeabilized and transfected area is possible.

Animals↗
PubMed2001

[Magnetic resonance imaging in the evaluation of parametrial invasion of carcinoma of the cervix uteri: optimization of the study protocol].

PURPOSE: To determine the efficacy of three different MR sequences in the evaluation of parametrial invasion by early-stage cervical cancer. MATERIAL AND METHODS: Eighteen consecutive patients with cervical cancer clinically assessed as stage IB1 underwent MR imaging examination with the use of the following sequences: FSE T2-weighted, FSE fat-suppressed T2w, and SE fat-suppressed Gadolinium-enhanced T1w. In all cases, the presence or absence of parametrial invasion on both sides per each sequence used was evaluated. Subsequently all the sequences have been considered together for the evaluation of tumor invasion. Gold standard of the study was the histopathologic analysis of the surgical specimens. RESULTS: At histological examination, parametrial invasion by tumor was found in 6 out of 36 parametria evaluated. The accuracy achieved with each of the sequences used was as follows: 94% with FSE T2w; 86% with FSE fat-suppressed T2w; and 67% with SE fat-suppressed Gadolinium-enhanced T1w. The simultaneous evaluation of all 3 sequences obtained an accuracy level similar to that achieved with FSE T2w. The difference between the accuracy of T2w sequences and that of fat-suppressed contrast-enhanced T1w sequences was statistically significant (p<0.01). DISCUSSION AND CONCLUSIONS: Our data suggest that the MR imaging protocol for the evaluation of parametrial tumor invasion could be restricted to FSE T2w sequences. These proved to have the highest negative predictive value (97%) which allows a reliable selection of patients who can be surgically treated.

Adenocarcinoma↗
PubMedDate not supplied

Optimizing brain MR imaging protocols with gadopentetate dimeglumine: enhancement of intracranial lesions on spin-density- and T2-weighted images.

To determine whether long TR MR imaging is best performed before or after IV administration of gadopentetate dimeglumine, we obtained spin-density- and T2-weighted images before and after contrast administration in 21 patients with known intracranial enhancing lesions. Of 25 lesions demonstrating enhancement on T1-weighted sequences, 21 showed mild or moderate enhancement on spin-density-weighted sequences and 20 showed mild enhancement on T2-weighted sequences. Importantly, no spin-density or T2 information was obscured by the administration of gadopentetate dimeglumine, and no T2 shortening effects were visible. Two new foci of enhancement were visible on postcontrast spin-density- and T2-weighted images that were missed on postcontrast T1-weighted images and on precontrast spin-density- and T2-weighted studies. Visualization of new areas of enhancement is the main advantage provided by the long TR images obtained after IV injection of gadopentetate dimeglumine. The most likely reason for the appearance of these newly visualized lesions is thought to be delayed enhancement. This imaging protocol also allows the display of adjacent edema or gliosis and enhancing lesions on a single image. Additionally, in three cases, posterior fossa phase-shift artifacts raised the suspicion of an enhancing lesion on postcontrast T1-weighted images, but the cerebellum was shown to be normal on the postcontrast spin-density- and T2-weighted studies. On the basis of our results, we recommend obtaining long TR images after rather than before the administration of gadopentetate dimeglumine in patients with intracranial enhancing lesions.

Astrocytoma↗
PubMedDate not supplied

Signal intensity artifacts in clinical MR imaging.

Signal intensity artifacts are often encountered during magnetic resonance (MR) imaging. Occasionally, these artifacts are severe enough to degrade image quality and interfere with interpretation. Signal intensity artifacts inherent in local coil imaging include intensity gradients and local intensity shift artifact. The latter can be minimized but not eliminated with optimal coil design and tuning. Improper coil or patient positioning can produce subtle or, in some cases, severe signal intensity artifacts, and each is easily corrected. Signal intensity artifacts and image degradation can also occur in a perfectly functioning coil if protocols are not optimized. Failure of decoupling mechanisms can produce signal intensity artifacts that will not respond to protocol optimization and will worsen with gradient imaging. Improper coil tuning manifests as a shading artifact that can mimic other findings. Signal-degrading artifacts may be caused by a ferromagnetic foreign body in the imager. Signal intensity artifacts can also result from performing ultrafast imaging with coils that were not designed for this type of imaging or from MR imaging system malfunction. Familiarity with the various causes of signal intensity artifacts is necessary to maintain optimal image quality and should be required as part of any MR imaging quality assurance program.

Artifacts↗
PubMed1990

Design and control of the atrio-aortic left ventricular assist device based on O2 consumption.

The left ventricular assist device (LVAD) is used in parallel with the left ventricle to temporarily assist patients with diminished cardiac function for the purpose of minimizing heart workload and to maintain systemic arterial perfusion. The proper adjustment and timing of the pneumatic LVAD is important such that this goal is achieved. Previous investigations into the left ventricular assist device are inconclusive regarding the optimal utilization of this device. This paper documents a protocol for optimal timing of the LVAD. Timing is studied using a closed-loop analog model of the heart, vascular system, and the LVAD. The model is tested for basic representation of the physiological system. The LVAD is incorporated into the model to discover its interaction with cardiac preload and afterload. Heart workload is computed via the pressure-volume-area method. The normal and impaired heart are modeled, in each case the pump control variables are adjusted. A protocol for adjustment of the LVAD is proposed based on reduced heart oxygen consumption. It was found that the pump should begin ejection immediately after the close of the aortic valve and that the pump filling pressure should be set to a value which produces maximum filling of the pump. Although aortic pressure and flow could be improved at pump rates above the heart rate, oxygen utilization of the heart could only be minimized for synchronous pumping. The adjustment of the pump ejection pressure is a tradeoff between d/dt (LVO2) and stroke volume and mean arterial pressure. The LVAD should be designed to minimize inflow and outflow resistance and to maximize pump compliance. The process of weaning the patient from the LVAD is considered. The overall results provide quantitative guidance for the use of the AA-LVAD.

Animals↗
PubMed2001

Simultaneous optimization of cryoprobe placement and thermal protocol for cryosurgery.

We demonstrate that it is possible to simultaneously optimize multiple cryoprobe placements and their thermal protocol for one freeze-thaw cycle. A numerical optimization algorithm is used and three different forms of objective function are examined in terms of algorithm convergence rate, minimum value of the chosen objective function, temperature-volume histograms and isotherm distributions. The optimization results depend on the initial values of the variables, the form of the objective function, optimization goals and the mathematical method adopted for gradient calculation. The proposed optimization model offers significant advantages over the previously reported semi-empirical approach to conformal cryotherapy, such as the ability to handle an unlimited number of variables and eliminating the need for the user input between iterations, thereby reducing, if not removing, the subjectivity of cryosurgery treatment planning.

Algorithms↗
PubMed1981

A visual field screening protocol for glaucoma.

In this prospective evaluation of the reliability and efficiency of an optimized visual field screening protocol for glaucoma, we tested 145 eyes (73 patients) with increased intraocular pressures to determine the location of early glaucomatous visual field defects. The field examination, which was used as a control, and protocol testing were performed on a manual Goldmann perimeter using kinetic and suprathreshold static techniques, respectively. Of the 145 eyes tested, kinetic Goldmann perimetry detected 43 eyes with glaucomatous defects. The screening protocol detected 39 defective eyes. There were four false-negative tests and one false-positive test. The false-negative rate of just under 10% was within the range predicted from earlier data. The computer-generated optimal protocols performed as predicted and provided an excellent screening technique for the detection of early glaucomatous visual field defects.

Clinical Trials as Topic↗
PubMed1992

Optimization and standardization of an enzyme-linked immunosorbent assay protocol for serodiagnosis of Actinobacillus pleuropneumoniae serotype 5.

An indirect enzyme-linked immunosorbent assay protocol has been optimized with special emphasis given to assay standardization and quality control. Technical aspects such as choice of a microplate, antigen immobilization, buffer composition, optimal screening dilution of sera, and kinetics of the enzymatic reaction were studied and evaluated in order to design a standard protocol offering maximal analytical sensitivity and specificity, as well as to obtain minimal within- and between-plate variability. Among the 27 plates tested, the Nunc 475-094 and 269-620 immunoplates were found to be the best in terms of high positive-to-negative ratio and low variability. No significant differences in antigen immobilization were found by using buffers of various compositions or pHs; however, the presence of magnesium ions (Mg2+; 0.02 M) resulted in a twofold increase in nonspecific background. An optimal screening dilution of sera was established at 1:200. A 1-h incubation period for test serum was found to be optimal. Maximum enzymatic activity for peroxidase was obtained by adjusting both substrate (H2O2) and hydrogen donor [2,2' -azinobis(3-ethylbenz-thiazoline sulfonic acid)] concentrations to 4 and 1 mM, respectively. To control between-plate variability, a timing protocol was adopted. Within-plate variability was also controlled by using a sample placement configuration pattern. Sliding scales were determined by repeated testing of a cross section of samples to set acceptance limits for both within- and between-plate variability. These limits were used in a quality control program to monitor assay performance. The results obtained suggest that this standardized protocol might be useful in the serodiagnosis of Actinobacillus pleuropneumoniae serotype 5.

Actinobacillus Infections↗
PubMed1998

Effect of hyperbaric oxygen on a rat transverse rectus abdominis myocutaneous flap model.

The single-pedicle transverse rectus abdominis myocutaneous (TRAM) flap is frequently associated with partial flap necrosis. Hyperbaric oxygen has previously been shown to increase the survival of skin flaps, although there has been no investigation of possible beneficial effects of hyperbaric oxygen on survival of the TRAM flap. The present study compares the effectiveness of hyperbaric oxygen therapy, normobaric 100% oxygen, a hyperbaric air-equivalent mixture, and no treatment at all (control group), in the prevention of TRAM flap necrosis in a rat model. Forty-eight animals were randomly assigned to one of the four above-mentioned groups. The surviving area of the flap was evaluated 7 days after surgery. The hyperbaric oxygen treatment protocol consisted of five 9-minute sessions breathing 100% oxygen at a pressure of 2.5 atmospheres absolute during the first 48 hours, starting within 1 hour of surgery. The areas of surviving skin paddles ranged from 38.5 percent in the control group to 52.5 percent in the group treated with hyperbaric oxygen. One-way analysis of variance indicated that flap area survival was significantly greater in the hyperbaric oxygen group (F = 2.69, p = 0.05). Tukey's pairwise comparison and the two-sample t test indicated that the group treated with hyperbaric oxygen differed significantly from the control group (Tukey's critical value = 3.8, rejection level = 0.05, t test p = 0.01). Our results suggest that the hyperbaric oxygen treatment protocol used improves survival in the rat TRAM flap. However, the optimal treatment protocol to achieve this objective even in the rat seems to be variable, and further studies are required before extrapolating these data to human applications.

Animals↗