An experimental pilot study of tacalcitol activities during modulation of parakeratotic skin features

Establishing guidelines and experimental models preclinical and clinical evaluations of new agents for treatment, and/or prevention of human diseases has become a task of crucial importance. Psoriasis is such one disease holding great interest for dermatology owing to its high rate of incidence and complexity of treatment. However the absence of psoriatic lesions in animals and the inability to induce them, calls for experimental techniques both in vitro and in vivo. The purpose of this study was to evaluate experimentally the effects of tacalcitol on cell proliferation and differentiation process. Thereafter a human pilot study on psoriatic patients has been developed.     

Na/K pump current in guinea pig cardiac myocytes and the effect of Na leak

INTRODUCTION: Steady-state Na/K pump current (Ip) in adult guinea pig ventricular myocytes was studied to determine the effect on the Na/K pump of transmembrane Na leak, membrane potential, and pipette Na concentration. METHODS AND RESULTS: Using conventional whole cell, patch clamp techniques, Ip was identified as either Ko-sensitive or ouabain-sensitive current when most other membrane currents were inhibited. Control experiments showed that there were no Ko-sensitive currents other than Ip under the conditions of our experiments. Ip was found to be similar to that reported by others being voltage dependent between -130 and 0 mV and having a half maximal activation by Nai of 28 mM. Ouabain sensitivity was also measured, and it was found that there were two binding sites with the high affinity site comprising 5% to 10% of the total and having an apparent affinity 1000-fold higher than the low affinity site. Apparent affinity of both sites was shifted about 10-fold (higher affinity) by increasing Nai from 10 to 85 mM. When internally perfused with 0 Na solution, Na leak through the membrane was found to be linearly related to Na/K pump activity. In contrast to prior suggestions, Ip was not correlated with series resistance when there was a large transmembrane Na gradient. CONCLUSION: These data suggest that, under conditions of high transmembrane Na gradient, Na leak through the membrane plays a significant role in determining Na/K pump activity.     

Small-signal modeling and control of the quasi-square-wave boostconverter

Sampled-data techniques are used to examine the dynamic characteristics and closed-loop performance of the quasi-square-wave boost converter. Direct duty-ratio control and current-mode control are considered. With direct duty-ratio control, the system poles remain well damped under all load conditions, and there is no zero in the control-to-output transfer function. Good closed-loop performance is therefore achieved. Under current-mode control, the requirement for a stabilizing ramp is seen to depend on load conditions, and the achievable voltage control-loop bandwidth is smaller than that using direct duty-ratio control; however, there is a significant reduction in the magnitude of the DC source to output-voltage frequency response     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

3 cases of post-stapedectomy labyrinthine fistula

Three cases are presented of labyrinthine fistula which suddenly arose in patients who had undergone stapedectomy interposing a vein graft from the back of the hand. These patients had all enjoyed 12-15 years apparently problem free period before the fistula occurred. In all three cases the fistula was accompanied by objective dizziness and varying degrees of sensorineural or mixed hearing loss. The patients underwent revision surgery which identified the fistula and the endolymph oozing out of the graft from the previously installed prosthesis. The authors present the cases, describe how the symptoms arose and the results obtained with revision surgery. Finally, they discuss the need to first perform stapedotomy with a platinar hole; they indicate that the number of cases of total or partial stapedectomy should be limited only to those cases characterized by anatomical variations and/or whenever complications arise during surgery.     

Communication network protocol for real-time distributed controland its LSI implementation

A new token-passing mechanism, priority token passing, which features real-time access and fast detection and recovery of transmission errors, is discussed in detail in comparison with standard token-passing protocols, and its large-scale integration (LSI)-oriented design concept is described. Priority token passing includes only a small performance overhead, due to its switching functions, which can change network topology from ring to broadcast medium. A token-holding node passes the token to another node after determining the successor through priority comparison. Errors occurring during token passing can, thus, be detected and corrected simply and promptly. Priority token passing has a simple hardware implementation, requiring only small additions to the frame control circuitry, and has a small implementation overhead. The priority token-passing protocol and two other important network communication functions, dual ring network reconfiguration and high-level data link control (HDLC) normal response mode-based message transmission, are designed as a single finite-state machine, and implemented into a compact LSI chip. This integrated instrument network (IINET) chip provides complete network communication services and requires only three additional external electronic components for operation     

Activity-composition relations of MnO in MnO-CrO x -CaO-SiO2-containing melts

The MnO activities in (MnO-CrO _x -CaO-SiO₂)-containing melts, which were saturated with the (Mn, Cr)₃O₄ spinel phase, were determined at 1500 °C under an oxygen partial pressure of 10^−8.99 atm. This was done by equilibrating the samples with platinum. The activity of MnO in the melt was then calculated from the activity coefficient of manganese in the resultant Pt-Cr-Mn alloy. Darken’s quadratic formalism for ternary metallic solutions was used to calculate the activity coefficient of manganese in the Pt-Cr-Mn system, in which platinum was considered to be the solvent. It was found that an increase in the concentration of MnO in the melt increases both the MnO activity and the activity coefficient of MnO. For a constant MnO concentration in the (MnO-CrO _x -CaO-SiO₂)-containing melts, the activity of MnO can be increased by increasing the basicity of the melt. In order to obtain high-manganese recoveries from (MnO-CrO _x -CaO-SiO₂)-containing melts into an alloy phase, basic slags in which the activity coefficient of MnO is high should therefore be used.     

Infrequent association: massive inguinoscrotal bladder hernia, multiple scrotal lithiasis, and bilateral obstructive uropathy]

BACKGROUND AND AIMS OF THE STUDY: Surgical treatment of functional tricuspid regurgitation associated with advanced valvular disease remains controversial, mainly due to the difficulty in choosing between valve replacement or reconstructive surgery. Failure to correct tricuspid regurgitation during valvular surgery carries a poor prognosis, as reoperation may represent a significant risk to the patient. Thus correct tricuspid valve surgery is vital to achieve improved early and long-term clinical results. METHODS: A total of 142 patients underwent concomitant tricuspid annuloplasty with mitral valve replacement and their clinical outcome was assessed. RESULTS: Overall hospital mortality rate was 11.3%. Seven patients died during follow up. The overall actuarial survival rate for 10 years was 74.1 +/- 14.2%. Postoperatively, 75.8% of the patients had no residual tricuspid insufficiency, while 24.2% had first- or second-degree tricuspid insufficiency and were treated medically. All patients were in NHYA functional class I or II postoperatively. CONCLUSION: Clinically, it is important to assess the severity of functional tricuspid insufficiency before and/or during the operation. Bicuspidalization annuloplasty for functional tricuspid insufficiency has provided good results, with a low incidence of reoperation and significant clinical improvement. The technique could be used in most patients with functional tricuspid regurgitation.     

Biochemical alterations of the tunica albuginea in impotence

PURPOSE: The objectives of this study were to quantify the immunohistochemical stainings of collagen types I, III and IV, and investigate the value of glycohistochemical staining with 3 lectin types specific to a particular glycan structure, Arachis hypogaea, Triticum vulgare and concanavalin A, as a method of defining possible changes in the collagen structure of the tunica albuginea in potent and impotent patients. MATERIALS AND METHODS: The study involved 4 normal men, 4 with pure venous leakage and 4 with pure arterial disease. Collagen types I, III and IV, and lectins Arachis hypogaea, Triticum vulgare and concanavalin A were studied using a cell image processor. The labeling index relates to the percentage of staining and mean optical density relates to the staining intensity. RESULTS: Mean labeling index values for the 3 types of collagen and lectins were similar (p > 0.05). Mean optical density value relating to collagen type I was significantly higher in the arteriogenic group than in the other groups (p < 0.05), while mean optical density value of collagen type IV was significantly higher in the venogenic group than in the 2 other groups (p < 0.05). Mean optical density values relating to the 3 lectin types were similar in the 3 clinical groups (p > 0.05). CONCLUSIONS: An alteration in the distribution and structure of the various collagen types and lectins in the tunica albuginea of impotent patients has been shown that may interfere with normal function and lead to impotence.