Search

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.

Staphylococcus aureus is a major human pathogen. An effective anti-S. aureus vaccine remains elusive as the correlates of protection are ill-defined. Targeting specific T cell populations is an important strategy for improving anti-S. aureus vaccine efficacy. Potential bottlenecks that remain are S. aureus-induced immunosuppression and the impact this might have on vaccine-induced immunity. S. aureus induces IL-10, which impedes effector T cell responses, facilitating persistence during both colonization and infection. Thus, it was hypothesized that transient targeting of IL-10 might represent an innovative way to improve vaccine efficacy. In this study, IL-10 expression was elevated in the nares of persistent carriers of S. aureus, and this was associated with reduced systemic S. aureus-specific Th1 responses. This suggests that systemic responses are remodeled because of commensal exposure to S. aureus, which negatively implicates vaccine function. To provide proof of concept that targeting immunosuppressive responses during immunization may be a useful approach to improve vaccine efficacy, we immunized mice with T cell-activating vaccines in combination with IL-10-neutralizing antibodies. Blocking IL-10 during vaccination enhanced effector T cell responses and improved bacterial clearance during subsequent systemic and subcutaneous infection. Taken together, these results reveal a potentially novel strategy for improving anti-S. aureus vaccine efficacy.

Controlled substance dependence (CSD) among anesthesiology personnel, particularly residents, has become a matter of increasing concern. Opinions vary as to the effectiveness of controlled substances (CS) accountability in deterring, identifying, or confirming CSD. A survey of program directors of American anesthesiology training programs was conducted in the summer of 1990 to determine the level of CS dispensing and accountability within their programs. The survey demonstrated that CS dispensing and accountability varied considerably among programs, among hospitals associated with individual programs, and within geographically distinct anesthesia delivery areas within the separate hospitals. Nevertheless, most institutions were moving toward improved methods of CS dispensing and providing more and better CS accountability. The presence of significant CSD, particularly among anesthesiology residents, was reconfirmed. We were unable to correlate the level of accountability of CS with the incidence of CSD. It remains to be seen to what extent CS accountability will continue to develop and whether CSD prevalence will then be changed.

The results of a survey on the use of surgical satellite pharmacies in hospitals with anesthesiology training programs are reported. In June 1990 a questionnaire was mailed to 158 directors of anesthesiology training programs for physicians. The questionnaire solicited information on the presence of surgical satellite pharmacies in the training hospitals and the nature of the services provided, including accounting for controlled substances. Responses were received from 102 program directors and their designees, for a 65% response rate. Some respondents returned questionnaires completed by affiliated hospitals; a total of 137 responses were accumulated. Surgical satellite pharmacies were present in 46 (34%) of the 137 hospitals. Of those 46 satellite pharmacies, only 14 dispensed all controlled substances to anesthetic-administration areas. Most of the satellite pharmacies provided services at least eight hours per day. All 46 pharmacies dispensed controlled substances, 31 provided i.v. admixtures, and 12 dispensed all i.v. solutions. Accountability for controlled drugs was provided through a daily inventory count (45 satellite pharmacies), daily comparison of agents received and returned (36), review of the anesthesia record (31), random audits of individual providers (18), or quantitative or qualitative analysis of residual drugs (16). Accountability was considerably better in hospitals with surgical satellite pharmacies than in hospitals without them. Surgical satellite pharmacies provided increased accountability for controlled substances in institutions with anesthesiology training programs but did not use all the available methods for preventing drug diversion.

Protein binding of thiopental was studied in 21 samples of neonatal serum (from placental blood) and compared with protein binding in ten healthy volunteers. These infants ranged between 32 and 43 weeks of gestational age (mean, 37.7 weeks) and the adult age range was from 27 to 54 years (mean, 35.4 years). Because the unbound fraction of the drug is responsible for its pharmacologic effect, a marked difference in the protein binding between neonates and adults may be relevant to the clinician. Blood obtained from freshly delivered placentas or from adult volunteers was allowed to clot and the serum separated from the sample. A portion of the serum was sent for protein and bilirubin analysis and the remainder retained for study. This latter serum was combined with four concentrations of thiopental. These specimens were then ultrafiltered and the amount of thiopental in the ultrafiltrate (unbound) compared with the prefiltered amount (total), as measured by reverse-phase high-performance liquid chromatography. The binding studies were repeated at pH 7.2, 7.4, and 7.6 in both the adult and neonatal serum. Total protein and albumin are significantly less in neonatal serum, whereas bilirubin (total and direct) is significantly higher in neonatal serum than in adult serum (P less than 0.01). Neonatal serum was associated with significantly more unbound thiopental than adult serum at all levels of pH studied (P less than 0.005). Increasing the pH resulted in less free drug in both groups, but this reached statistical significance only in the adult group (P less than 0.025). Drug concentration had no effect on binding in the range examined.(ABSTRACT TRUNCATED AT 250 WORDS)

The occurrence of a bleeding placenta praevia in a young woman, with a viable fetus and an acutely obstructed Lillehei-Kaster valve, provided serious difficulties in priorities and decision making. This has prompted an analysis of the problems which others may encounter.

This review attempts to deal with the basic principles required to interpret the ever-increasing clinically relevant pharmacokinetic studies. Factors governing drug absorption, distribution and elimination are discussed, as are the terms pharmacodynamics, exponentials, half-life and clearance.

The Pierre Robin syndrome consists of micrognathia, pseudo-macroglossia, glossoptosis and a high arched or cleft palate. Difficult intubation of the trachea and associated abnormalities such as congenital heart disease are well known complications of this syndrome. Intraoral surgery (such as cleft palate repair and palatoplasty) can also be technically difficult for the surgeon resulting in prolonged retraction on the tongue with a mouth gag to provide adequate surgical exposure. We report a case where massive lingual oedema following a cleft palate repair resulted in life-threatening airway obstruction.

In eight patients, following carotid angiography under neuroleptanalgesia, a radiopaque dye was instilled into the pharynx. The chest was x-rayed 15 min later. All eight patients were observed to have aspirated the dye. The technique of neuroleptanalgesia described should not be used without safeguarding the airway in patients liable to regurgitate and inhale gastric contents.

Halothane or isoflurane was used to induce anesthesia in children scheduled for outpatient surgical procedures. Both agents were administered at predetermined rates until comparable concentrations in end-expired air were reached. Induction of anesthesia, as well as the time taken before tracheal intubation was possible, was protracted in patients given isoflurane. In the recovery period, the times taken to respond to pharyngeal suction, to tracheal extubation, and to the first cry were similar for both anesthetic agents.

A standard 50-mg dose of tilidine hydrochloride (Valoron) was administered to 20 patients in the postoperative phase of open-heart surgery. No significant change in respiratory status, as measured by arterial blood gas analysis, was demonstrated with this dosage.