Calcitriol vs. dithranol in combination with narrow-band ultraviolet B (311 nm) in psoriasis.

BACKGROUND: Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. OBJECTIVES: To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. METHODS: Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. RESULTS: Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. CONCLUSIONS: Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed.

Dendritic cell-based vaccines: from mouse models to clinical cancer immunotherapy.

B and T lymphocytes are the effectors of specific immunity. However, their function is critically dependent on dendritic cells (DC). DC are professional antigen presenting cells that both initiate and modulate the immune response. The recent breakthrough in the generation of DC from their progenitors has stimulated research on DC in both fundamental and clinical immunology. Objective immune response induction has now been reported in clinical studies using DC. In this review we discuss the development and potential of DC-based vaccines to induce antitumor immunity.

Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model.

Tyrosinase-related protein (TRP) 2 belongs to the melanocyte differentiation antigens and has been implicated as a target for immunotherapy of human as well as murine melanoma. In the current report, we explored the efficacy of nonmutated epitopes with differential binding affinity for MHC class I, derived from mouse TRP2 to induce CTL-mediated, tumor-reactive immunity in vivo within the established B16 melanoma model of C57BL/6 mice. The use of nonmutated TRP2-derived epitopes for vaccination provides a mouse model that closely mimics human melanoma without introduction of xenogeneic or otherwise foreign antigen. The results demonstrate that vaccination with TRP2 peptide-loaded bone marrow-derived dendritic cells (DCs) results in activation of high avidity TRP2-specific CTLs, displaying lytic activity against both B16 melanoma cells and normal melanocytes in vitro. In vivo, protective antitumor immunity against a lethal s.c. B16 challenge was observed upon DC-based vaccination in this fully autologous tumor model. The level of protective immunity positively correlated with the MHC class I binding capacity of the peptides used for vaccination. In contrast, within this autologous model, vaccination with TRP2 peptide in Freund's adjuvant or TRP2-encoding plasmid DNA did not result in protective immunity against B16. Strikingly, despite the observed CTL-mediated melanocyte destruction in vitro, melanocyte destruction in vivo was sporadic and primarily restricted to minor depigmentation of the vaccination site. These results emphasize the potency of DC-based vaccines to induce immunity against autologous tumor-associated antigen and indicate that CTL-mediated antitumor immunity can proceed without development of adverse autoimmunity against normal tissue.

Generation and functional characterization of mouse monocyte-derived dendritic cells.

Dendritic cells (DC) are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. As a result, DC are currently used in clinical studies to induce immunity against infectious disease and malignant cells. However, multiple DC subsets exist and it has been suggested that the type of DC may affect the immune response induced. The vast majority of DC used in experimental mouse tumor models is derived from bone marrow progenitors. In contrast, most in vitro as well as in vivo human studies involve the use of DC generated from adherent peripheral blood-derived monocytes in the presence of GM-CSF and IL-4. In the current report, we describe for the first time the generation and characterization of mouse monocyte-derived DC (MODC). The results indicate that mouse MODC display similar morphology, phenotype and immunostimulatory activity as compared to bone marrow-derived DC. Both DC subsets were able to efficiently take up and subsequently cross-present protein antigen to cytotoxic T cells. Moreover, we demonstrate that vaccination with peptide-loaded MODC mediates induction of tumor-reactive immunity in vivo. The isolation and characterization of mouse MODC will provide a valuable research tool to investigate fundamental aspects of DC biology and which DC subsets are most suitable to induce anti-tumor immunity.

Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration.

Dendritic cells (DCs) are professional antigen-presenting cells, well equipped to initiate an immune response. Currently, tumor antigen-derived peptide loaded DCs are used in clinical vaccination in cancer patients. However, the optimal dose and route of administration of a DC vaccine still remain to be determined. Using indium-111-labeled DCs, we investigated whether the route of administration does affect the biodistribution of DCs in lymphoid organs and whether it influences the outcome of DC vaccination in the B16 mouse melanoma tumor model. The results demonstrate that i.v. injected DCs mainly accumulate in the spleen, whereas s.c. injected DCs preferentially home to the T-cell areas of the draining lymph nodes. Using tyrosinase-related protein-2-derived peptide-loaded DC vaccination in a fully autologous B16 melanoma tumor model, we observed a delay in tumor growth, improved survival as well as increased antitumor cytotoxic T-cell reactivity after s.c. vaccination as compared to i.v. vaccination. These data demonstrate that optimal induction of antitumor reactivity against the autologous melanocyte differentiation antigen tyrosinase-related protein-2-derived peptide occurs after s.c. vaccination and correlates with the preferential accumulation of DCs in the T-cell areas of lymph nodes.

An overhead specimen handling system for variable workloads.

This unique overhead specimen handling system requires virtually no floor space and only a minimal amount of bench space. It uses state-of-the-art conveyors suspended near the ceiling to transport, log-in and sort blood specimens in standard specimen containers. Specimens placed into the system at bench-level bins are automatically singulated and loaded onto cleated conveyors and lifted to the main conveyor belt near the ceiling. The barcoded labels are then read as the containers are rotated under an optical scanner. The specimens are then diverted to the appropriate branch conveyor and lowered back to the bench level by cleated conveyors. The specimen handling system is rapid and accurate, requires no special containers, allows laboratorians to move unimpeded below it, and is inexpensive by automation standards. Studies show no adverse effect upon the specimens.

The combination of specimen tracking with an advanced AutoLog in a laboratory information system.

The ability to provide timely laboratory results is an important aspect of quality which must be continually monitored. In order to complete all testing before the maximum turnaround time requirements are exceeded, laboratorians need to have immediate and automatic access to the location of specimens and the status of tests ordered on each specimen. Any such automated approach must be able to monitor continually the status of work in progress, while simultaneously linking it to a specimen tracking (history) system that allows real-time tracing of the path of specimens through all laboratory operations. The authors have greatly advanced the capabilities of the AutoLog technology and have added to it a tracking system that captures specimen movement with minimum user assistance. This has been accomplished without the need to implement total process automation.

LabLink--the key to multi-computer interfacing.

The growing complexity of computing environments requires creative solutions to prevent the gain in productivity promised by computing advances from being swallowed up by the necessity of moving information from one environment to another. LabLink is an interfacing tool for accomplishing such transfers in a clinical laboratory environment. It handles the automated data transfer among four systems, as well as providing substantial back-up capacity for critical operations when systems are down for saves or maintenance.

Migrating a clinical laboratory information system between technologies.

The technical revolution that has strongly driven events in the clinical laboratory for the last thirty years is now threatening to make obsolete what has become the central pillar of operation in many laboratories, the minicomputer-based laboratory information system. Some of its functions could easily be absorbed by the personal computers which are proliferating in the laboratory, but any single step leap between systems risks replacing order with chaos. Appropriate use of networking tools, together with essential software development, can provide a systematic migrational path for both the administrative and technical computer support from one environment to another without the trauma of a massive replacement step.

Long-term data storage in a clinical laboratory information system.

The clinical laboratory is pressured on one side by physicians and regulators who want the laboratory to keep more detailed patient records available for longer periods and on the other side by physical space and cost constraints which favor rapidly transferring such records to Medical Records or a warehouse from which retrieval is slow and difficult. Various forms of inactive data storage and archiving in machine-readable form are available to address this dilemma, yet these solutions can create even more difficult problems. Two different approaches were developed within the framework of Relational LABCOM to address both the intermediate and long-term storage of data. In this paper we examine the two methods as solutions to the problems, discuss their limitations, and determine why one is superceding the other in the installation base.

Computer aided manual leucocyte differential counting.

Over the last two decades numerous ways have been devised for automating the recording of the results of the leucocyte differential, ranging from computer-readable cards to very costly automated cell counters. The growing availability of inexpensive personal computers makes it possible to improve the counting and reporting of the manual differentials which still account for the bulk of these counts. This report describes the development of a system using a personal computer, either as a standalone device or integrated into a larger laboratory system, to assist the technologist in performing the differential count and in completely describing the results. It permits complete flexibility in function assignments and in information structuring to match the constraints of the laboratory host computer system.

Effects of system tuning and RAM disk on the performance of a clinical laboratory information system.

Improvements in the performance of a laboratory computer system do not necessarily require the replacement of major portions of the system and may not require the acquisition of any hardware at all. Major bottlenecks may exist in the ways that the operating system manages its resources and the algorithm used for timesharing decisions. Moreover, significant throughput improvements may be attainable by switching to a faster storage device if substantial disk activity is performed. In this study the fractions of time used for each of the types of tasks a laboratory computer system performs (e.g. applications programs, disk transfer, queue cycler) are defined and measured. Methods for reducing the time fractions of the various types of overhead are evaluated by doing before and after studies. The combined results of the three studies indicated that a 50% improvement could be gained through system tuning and faster storage without replacement of the computer itself.

The development of a third generation system for entering microbiology data into a clinical laboratory information system.

Increased demands on technologists' time and the desire to have electronic storage of patient information have led to numerous computer-based efforts to manage microbiology data. Our approach to the design of a new microbiology subsystem has been to maximize the functionality without requiring unusual input devices. DEC VT100-compatible terminals are used for data entry and display. Data are displayed taking advantage of such features of these terminals as reverse video, highlighting, and scroll windowing. Numerous single-key instructions for invoking functions and changing cursor positions have been implemented to minimize keystrokes and to anticipate the entry sequences of the technologists. A program that allows the quick location and display of specimens and results is also included in the package.

Implementation of a multirule, multistage quality control program in a clinical laboratory computer system.

We developed a computer subsystem that permits users to implement multirule, multistage quality control procedures. The subsystem runs as a task in the RelationaLABCOM information system and permits the collection of data from on-line instruments, as well as through manual (keyboard) entry. The choices of control rules and their combinations are at the discretion of each laboratory section, with the system automatically administering the chosen protocols for all the technologists working with the computer. Retrospective data analysis and statistics are available for review by laboratory personnel. The subsystem provides a significant improvement in the availability of real-time quality control at the bench.

Coordinated computer reporting of clinical microbiology data.

The importance of the incorporation of microbiology information into the laboratory cumulative report implies that continuing efforts need to be made to enhance the readability and style of such reports. In addition, the optimizing of laboratory work flow around a computer record-keeping system in microbiology is essential to guarantee technologist satisfaction with and usage of the system. The efforts and results of extending a commercially available system in the microbiology laboratory are discussed and compared with another approach using the same system base. The project led to smooth laboratory work flow and highly successful combined reports. Necessary software modifications are summarized.

A computer-based record system for a hospital transfusion service.

An on-line, real-time system for recording transfusion service activities was added to an existing LABCOM general laboratory computing system. The new programs monitor the blood inventory, crossmatches performed, units issued and final disposition of all units of blood. The computer prints the final patient record of units crossmatched and transfused, generates the patient bill, and tallies the workload. The system has reduced the manual clerical operations from 12 to 14 man-hours per day to eight or less. Acceptance by the medical technologists has been excellent.

Trend detection in control data: optimization and interpretation of Trigg's technique for trend analysis.

A method for trend detection, Trigg's technique [Oper. Res. Q. 15, 271 (1964)], has been investigated for use in monitoring trends in control data produced by multitest continuous-flow analyzers. Simulated trend data were used to optimize the method. Actual control data were analyzed retrospectively to determine the frequency of trends and the accuracy of several parameters obtained from Trigg's method. The prospective use of the technique has successfully uncovered important trends. Criteria for the interpretation of the Trigg's trend data are suggested and an algorithm for the computer implementation of Trigg's calculations is included.