Lysis of human monocytic leukemia cells by extracellular adenosine triphosphate: mechanism and characterization of the adenosine triphosphate receptor

The present study shows that extracellular adenosine triphosphate (ATP) has the capacity to mediate dose-dependent lysis of the monocytic leukemia cell line THP-1. The lysis, assessed by 51Cr release, was found to be selective for ATP, because adenosine diphosphate (ADP) or other nucleotides were less effective in their ability to lyse the cells. The amount of 51Cr released was particularly enhanced by the stimulation of the cells with 1,000 U/mL of interferon gamma (IFN-gamma) for 3 days, and the sensitivity was time and dose dependent. Analysis of the mechanism of lysis indicated that the fully ionized form, ATP4-, mediated the lysis, because the addition of cation chelators or the absence of the divalent cations, Ca2+ and Mg2+, in the culture medium of a 6-hour 51Cr release assay increased the percent specific lysis. Therefore, the ATP receptors on THP-1 cells were classified as P2Z purinoceptors. Moreover, it is shown here that the Ca2+/calmodulin complex plays a role in the regulation of the lysis by extracellular ATP of THP-1 cells, because antagonists of this complex, such as trifluoperazine or KN-62, were found to inhibit the ATP-mediated cell lysis.     

Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit

OBJECTIVE: The initially well-fixed implants of total hip replacement (THR) are in the long-term subject to aseptic loosening. Many cytokines can contribute to osteolysis due to osteoclast recruitment and/or activation. However, in this respect tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role, because it upregulates interleukin-1 and 6 and granulocyte-macrophage colony stimulating factor. The aim of this study was to assess the eventual presence, cellular localization and extent of expression of TNF-alpha in the synovial-like membrane at the implant or at the cement to bone interface compared to control synovial membrane. METHODS: Twenty samples from the synovial-like membrane of the periprosthetic tissues were compared to control samples. TNF-alpha containing cells were visualized using an avidin-biotin-peroxidase complex (ABC) method and analyzed by light microscopy, double labelling and image analysis. RESULTS: TNF-alpha was found in the periprosthetic tissues in fibroblasts and vascular endothelial cells, but mainly in the macrophages was it found to coincide with areas containing implant-derived debris. TNF-alpha containing cells were more numerous in the synovial-like membrane in the interface tissue from the proximal stem area (2816 +/- 318 cells) than in the control synovial membrane (565 +/- 93 cells, p < 0.01). Interestingly, similarly high TNF-alpha expression (3452 +/- 582 cells) was also seen in the synovial-like membrane of the pseudocapsule. CONCLUSION: These findings suggest that the foreign body-type host reaction caused by THR is characterized by the high expression of TNF-alpha. Because such expression occurred in the interface tissue between the implant and surrounding bone, TNF-alpha, due to its pivotal direct and indirect role in the activation and recruitment of osteoclasts, may contribute to periprosthetic osteolysis and to the loosening of THR.     

Community resources for clients with mobility problems

Clients are leaving the hospital "quicker and sicker," and they frequently have acute care needs that must be met by resources outside the hospital setting. Community resources are diverse, vary widely from place to place, and have no central administration. Thus, using them can be challenging for both the nurse, client, and family. Reimbursement mechanisms underlie a person's ability to use resources and receive health care. By presenting two actual case scenarios where clients have mobility problems commonly seen by orthopaedic nurses, the authors discuss the community resources available, avenues of access to them, and their reimbursement mechanisms.     

Total throidectomy in the management of Graves' disease. A review of 282 cases

Antithyroid drugs, radioactive iodine, and surgery, either alone or in various combination, are used in the management of Graves' disease. If surgery is selected as the treatment of choice for Graves' disease than nothing less than total thyroidectomy should be performed.     

Comparison of 4- and 24-hr thyroid scans with 123I: concise communication

Thyroid scans were performed at 4 and 24 hr after administration of Na123I solution in 124 examinations. The 4-hr and 24-hr scans were found to be of equal diagnostic value. Thus, in individuals with structural thyroid abnormalities, one can effectively reduce the time required for scan evaluation from the standard 24 hr to 4 hr.     

Sex typing and androgyny: further explorations of the expressive domain

Previous research by Bem has indicated that androgynous individuals of both sexes display "masculine" independence when under pressure to conform as well as "feminine" nurturance when interacting with a kitten. In contrast, sex-typed individuals were low in one or both of these behaviors. The two studies reported here were designed to replicate the low nurturance of the masculine male and to clarify the unexpected finding that feminine females were low in both independence and nurturance. In the first study subjects interacted with a human infant, and in the second study they listened to a lonely student. Taken together, the results of these two studies conceptually replicated the low nurturance of the masculine male and demonstrated that the low nurturance of the feminine female does not extend to her interaction with humans. Finally, evidence was presented in support of Spence, Helmreich, and Stapp's distinction between "androgynous" individuals, who are high in both masculinity and feminity, and "undifferentiated" individuals, who are low in both of these characteristics.     

The radiology of transsphenoidal hypophysectomy: a review of 100 cases

This report describing the radiology of transsphenoidal hypophysectomy based on a review of 100 consecutive surgical procedures. Preoperative laminographic evaluation of the sphenoid sinus is an important aid in planning the most direct surgical approach to the pituitary. It is also useful in defining the many anatomic structures that may be injured inadvertently at the time of surgery. Intraoperative radiography or fluoroscopy is helpful in identifying the sella floor and as an aid in preventing loss of orientation within a capacious sinus. Various changes occur within the sphenoid sinus following surgery, some transient and others persistent. The surgical defect is usually difficult to identify on routine roentgenograms but is clearly visible on lateral laminography. A persistent soft tissue mass within the sinus is usually a manifestation of fascia and fat placed as a seal within the sinus.     

The mixed kidney cell-lymphocyte reaction in rats

Optimal conditions for obtaining the proliverative response in mixed kidney cell-lymphocyte culture (MKLC) have been determined in rats. The addition of 2-mercaptoethanol to the culture medium was essential for successful stimulation of lymphocytes by allogeneic kidney cells. Proliferative responses by standard MLC and MKLC were compared in rats with the same or a different Ag-B locus. In most strain combinations, there was a significant correlation between MLC and MKLC reactions, However, the DA-ACI combination, compatible at the Ag-B locus, consistently showed negative MLC and positive MKLC reactions. This suggested the possibility that this technique allowed the expression of kidney specific antigens.