Search

A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years.Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years.The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF.All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

The clinical observation that the laparoscopic surgical approach lessens postoperative pain and shortens hospital stay [1, 2] when compared to open surgery, might lead one to postulate that laparoscopy is accompanied by a diminished postoperative physiologic stress response. Indeed, the very term “minimally invasive surgery” indirectly suggests this possibility. However, it is not yet clear that laparoscopy lessens the complex neurohormonal stress response which accompanies conventional surgery. There is an increasing body of research on the physiological changes which occur with pneumoperitoneum, as well as a growth of data on the related condition of an acute rise in intra-abdominal pressure and the abdominal compartment syndrome (ACS) [3–9].

The aim of this study was to characterize the circadian variation of oral tacrolimus disposition in 8 stable liver allograft recipients. In the steady state, a total of 23 blood samples was taken before and after tacrolimus administration during a 24-hr period and the pharmacokinetic parameters were compared. The area under the curve (AUC) of tacrolimus after the morning dose was significantly larger than after the evening dose (211+/-43 ng x hr/ml [morning] vs. 179+/-45 ng x hr/ml [evening], P=0.02). The time to peak (Tmax) was significantly shorter after the morning dose than after the evening dose (1.6+/-0.7 hr [morning] vs. 2.9+/-0.6 hr [evening], P=0.002). The peak (Cmax) was significantly higher after the morning dose than after the evening dose (32.2+/-10.2 ng/ml [morning] vs. 19.1+/-4.3 ng/ml [evening], P=0.003). However, the trough (Cmin) was not significantly different between the morning dose and the evening dose (13.1+/-3.9 ng/ml [morning] vs. 13.3+/-4.4 ng/ml [evening], P=0.4). This study demonstrated that tacrolimus disposition in liver transplant patients was determined by administration time.

A target rotator and a target wobbler, both using a minimum of space in the scattering chamber, have been designed and built. All adjustments can be made from outside the chamber and targets can be traferred to and from target holders without breaking the vacuum.

Proton spectra from the /sup 37/Cl(/sup 3/He,p)/sup 39/Ar reaction were taken at bombarding energies of 17 MeV and 19 MeV at angles between 5/sup 0/ and 40/sup 0/. A total of 28 states were observed below 5 MeV, most of which can be identified with states reported in other reactions. Between 5 and 7 MeV, 19 more peaks were seen, and it is probable that many of these do not correspond to a single level. Dominating the spectrum is the transition to the 9.078 MeV level, which is the analog of the /sup 39/Cl ground state. The antianalog of the 9.078 MeV level is predicted to lie at about 2.4 MeV and, in the simplest shell model picture, should be strongly fed. However, no such transition was found. Evidence is presented that suggests that the 3.383 MeV state, which is fed much more weakly than the analog, contains much of the antianalog configuration with some fragmentation to higher energies indicated. This state appears to belong to the class of multiparticle, multihole states of unstretched isospin that lie at a higher than expected energy, but the reason for the existence of this class remains unclear. The analog and several other states,more » including the suspected antianalog, exhibit an L = 0 angular distribution. Distorted-wave Born approximation calculations give a fair fit to both the ground- and the first excited state transitions when wave functions from a shell model calculation are used.« less

At the temperature and radiation levels expected in the core region of some projected reactor plants, conventional radiation sensors, such as fission chambers, suffer severe radiation damage. On the other hand, remote location of sensors introduces geometry effects. These circumstances emphasize the need for a power level sensor which is highly resistant to the hostile environment and still responds directly to power level changes. Such a detection channel has been proposed. It is based on sensing the gamma flux above some energy threshold, thus discriminating against gamma radiation associated with decay. In addition, the proposed system dispenses with cables and voltages applied across damageable insulators, through sensing the light transmitted along a cylindrical duct. The detecting medium is the gas with which the duct is filled; the light signal is the Cherenkov radiation generated by relativistic Compton recoil electrons. Cherenkov radiation intensity increases sharply from an electron velocity threshold, which depends on the index of refraction of the medium. For gases, this threshold can be continuously varied by adjusting the gas pressure. On the other hand, electrons with subthreshold velocities can generate (background) light through scintillation processes. In order to assay the overall discrimination available from the choice of gas, pressure, and geometry, a series of tests has been under way with 3-MeV electron pulses from a Van de Graaff accelerator.

By the use of a simple instrument of original design, a condition of enophthalmos or exophthalmos can be ascertained with a reasonable degree of accuracy in the normal as well as in the anesthetized dog. Pentothal sodium, sodium amytal, pentobarbital, and chloralose administered intravenously cause a marked enophthalmos, while surgical ether anesthesia produces a slight exophthalmos. Sympathomimetic drugs cause little or no change in the position of the eye of the unanesthetized dog. In animals anesthetized with sodium amytal and related drugs, ephedrine and tyramine when administered intravenously cause the eye to advance almost to the position held before anesthesia. Thus the so-called “exophthalmos” reported in the literature as resulting from injections of sympathomimetic drugs is more correctly explained as an advancement of the eye to its normal position from a condition of enophthalmos. The eyes of animals made thyrotoxic behaved in every respect as did those of normal controls. From the Division of Experimental Medicine of the Mayo Foundation.

SummaryAdrenal-demedullated rats responded like normal animals in respect to the coagulability of blood following emotional excitation and following ether anesthesia.

A resistive impedance matching circuit for splitting fast pulses with unequal attenuations e,η can be constructed with 1− e = 2 η (1− η ). With uneven splitting an additional resistor is required shunting the weaker signal to ground in order to maintain constant impedance throughout.

In 1948 Bost, Percefull, and Leming 1 published a paper reviewing 54 cases of tularemia seen at this hospital, half of whom had been seen before streptomycin was available and half of whom had been treated with this antibiotic. The present paper is a study of 44 additional patients treated at this hospital during a three year period ending Dec. 31, 1950. A report of these cases may seem unimportant per se, but we feel that the ineffectiveness of aureomycin that we encountered should be brought to the attention of the medical profession. Foshay, 2 who with Pasternack 3 first reported the successful clinical use of streptomycin in tularemia, has recently recommended streptomycin and dihydrostreptomycin as the drugs of choice, but he states that aureomycin appears to have been effective in a few cases of averages severity. He adds that chloramphenicol (chloromycetin®) has been used experimentally and gives good indication

1.1. Determinations of the hemoglobin content, and the number and volume of erythrocytes in the blood of dogs and rabbits, indicate that hemoconcentration does not occur incident to hypoglycemic reactions resulting from injections of nonfatal or fatal doses of insulin. 2.2. Visceral evidences of capillovenous congestion and increased capillary permeability were not seen in animals after death by insulin hypoglycemia. 3.3. The mechanism of death resulting from large doses of insulin is not the same as that of shock. The term "insulin shock" is confusing and should be abandoned. 4.4. The leucocytosis recorded in previous reports on insulin hypoglycemia was confirmed.