[Adaptation to changing needs in mental health care: mental health centers]. / Aanpassing aan veranderende zorgbehoefte in de ggz: mentale gezondheidscentra.

BACKGROUND: The increasing healthcare needs in the Netherlands lead to increasing healthcare costs and waiting lists and warrants sufficient (staff-)capacity. The current market-driven organization of care affects qualitative, accessible, and affordable care. Whether the Dutch mental healthcare system can adapt efficiently is questioned in this article. AIM: Gaining insight into the developments and bottlenecks that can contribute to the realization of appropriate care in mental health. METHOD: An overview of literature is given regarding developments and necessary adjustments in mental healthcare. RESULTS: Appropriate care is value-driven, focused on health (instead of the absence of illness), based on management of health of the client and his network, is accessible, affordable and is offered at the right time and place. The collaborative innovation of Mental Healthcare Centers, in which GGz Breburg (specialized mental health care), Indigo Brabant (general mental health care), and health insurance company, form a sustainable coalition which is presented as a solution for manageability of the mental healthcaresystem. This coalition aims to improve the public values of mental healthcare as a response to the required paradigm shift and future model of mental healthcare. CONCLUSION: As a regional network model, the Mental Healthcare Centers offer a desirable answer to the demand for an appropriate and future-proof mental healthcare. w.

The use of different methods for rapid determination of the ESR induces DAS28 misclassification in clinical practice.

OBJECTIVES: Monitoring of disease activity using DAS28 is more effective than routine RA care, but the ESR measurement is time consuming. Alternative rapid ESR determination methods can be used but effects on DAS28 classification are unknown. METHODS: Alternative rapid ESR methods, including the Starrsed 30-minute mode and Alifax Roller Test-1TH, were compared to the Westergren method. Mean difference, limits of agreement (LoA) and intraclass correlation coefficients (ICC) were calculated. Based on these results, using a longitudinal design the percentage of DAS28 misclassification for the Alifax Roller Test-1TH was measured. RESULTS: The Alifax showed acceptable ICCs, but LoA were large. ICC was 0.67 (0.56-0.76), LoA -43;34. The longitudinal study on the Alifax (n=125) showed an ICC of 0.93, a kappa of 0.61, but disease activity was misclassified in 26% of the patients. Use of the ESR from the previous visit resulted in comparable levels of misclassification. CONCLUSIONS: ESR measured by automated analysers like Alifax show acceptable ICC but LoA are large compared to the Westergren ESR. The Alifax Roller Test-1TH is very rapid but DAS28 misclassification is considerable and even as large as when using the ESR of the previous visit.

Measurement characteristics of a new rapid anti-CCP2 test compared to the anti-CCP2 ELISA.

OBJECTIVE: Anti-cyclic citrullinated peptide (CCP)2 antibody status is an important diagnostic tool in the work-up of undifferentiated arthritis (UA)/early rheumatoid arthritis (RA) but the results of the enzyme-linked immunosorbent assay (ELISA) are only available a few days after the test. The aim of this study was to assess the measurement characteristics of a rapid anti-CCP2 test compared to the usual anti-CCP2 ELISA test. METHODS: In the first phase, rapid anti-CCP2 (CCPoint) tests were performed in capillary blood obtained by finger puncture (CAP), in venous blood from a clot tube (CLOT) and in serum (SERUM) in consenting RA patients. Anti-CCP2 measured in serum using the anti-CCP2 ELISA (ELISA) was set as the gold standard (reference). In the second phase of the study, specificity versus RA was confirmed in consenting non-RA patients and healthy controls. The anti-CCP2 results were negative (no visible line or anti-CCP2<25 U/mL) or positive (visible line or anti-CCP2> or =25 U/mL). RESULTS: A total of 880 subjects (109 RA patients, 351 non-RA patients and 420 healthy controls) were enrolled in this study. For the RA patients, 5%, 15%, and 1% of CAP, CLOT and SERUM tests, respectively, were inconclusive. The sensitivity and specificity of CAP compared with ELISA were 95% (95% CI 90-100) and 95% (95% CI 89-100), respectively, and the corresponding values for SERUM were 97% (95% CI 93-100) and 98 (95% CI 94-100). The specificity for RA versus non-RA and healthy controls was 99% (95% CI 97-100) and 99% (95% CI 98-100), respectively. CONCLUSION: The CCPoint test is a fast, valid and reliable anti-CCP2 test in both capillary blood and serum but not directly in venous blood.

Development of ELISAs for quantification of HMFG1-specific human anti-mouse IgG and IgM antibodies.

The aim of this study was to develop and validate ELISAs for quantification of HAMA-IgM and HAMA-IgG in serum of patients with ovarian cancer who enrolled in a large international randomized phase III trial of intraperitoneal Yttrium-90-labeled HMFG1 murine monoclonal antibody therapy. The capture antibody of these 2 assays was the murine antibody HMFG1, while mouse anti-human IgM-HRP or mouse anti-human IgG(Fc)-HRP served as tracer antibodies. A pool of HAMA-positive serum samples was used to prepare a series of assay standards and another pool served as reference preparation. The analytical sensitivity of the HAMA-IgM assay was 2.5 arbitrary units per mL (AU/mL) and 4.7 AU/mL for the HAMA-IgG ELISA. Diluted serum samples showed good parallelism with the HAMA-IgM and HAMA-IgG standard dose-response curves. Within-assay coefficient of variation was 7.5% for HAMA-IgM and 6.5% for HAMA-IgG. Between-assay variation was 14.2% for HAMA-IgM and 15.3% for HAMA-IgG. The developed HAMA-IgM and HAMA-IgG ELISAs show satisfactory reliability criteria (sensitivity, parallelism and precision) and are suitable for monitoring of HAMA-IgM and HAMA-IgG responses in ovarian cancer patients. These ELISAs will be used to monitor the development of HAMAs in patients who received radioimmunotherapy with murine HMFG1.

Radiolabeled chemotactic cytokines: new agents for scintigraphic imaging of infection and inflammation.

Several radiopharmaceuticals are currently used for diagnosis of inflammatory and infectious diseases in patients. Most inflammatory and infectious processes can be visualized with radiolabeled autologous leukocytes, currently considered to be the most appropriate radiopharmaceutical for this purpose. This agent is very well capable to delineate most inflammatory and infectious foci in a relatively short time after injection. The time-consuming and intricate labeling procedure and the handling of potentially contaminated blood, however cause that there is a great interest in the development of new radiopharmaceuticals comprising the same imaging qualities but without these disadvantages. Besides radiolabeled leukocytes several other radiopharmaceuticals, such as (67)Ga-citrate, radiolabeled anti-granulocyte antibodies and FDG are used to image infection and inflammation. These agents accumulate in infectious and inflammatory lesions in a non-specific manner or have suboptimal diagnostic characteristics. Nowadays, there is a great interest in the development of radiolabeled chemotactic and chemokinetic cytokines that accumulate and are retained in infectious and inflammatory foci by specific interaction with infiltrated inflammatory cells. In this review we describe the specific characteristics of the chemotactic and chemokinetic compounds that are currently studied as potential radiopharmaceutical to visualize infectious and inflammatory foci. The characteristics of a series of cytokines (IL-1, IL-2), chemokines (IL-8, PF-4, MCP-1, NAP-2), complement factors (C5a, C5adR), chemotactic peptides (fMLF) and other chemotactic factors (LTB4) are described. The potentials of these compounds to serve as an imaging agent are discussed.

A 3-step pretargeting strategy to image infection.

UNLABELLED: A new 3-step approach to imaging infectious and inflammatory foci was developed and optimized in a rat model. The approach relies on the nonspecific localization of an anti-diethylenetriaminepentaacetic acid (DTPA) antibody in inflamed tissue. In this study, the 3-step strategy was optimized by selecting the most suitable radiolabeled hapten and tuning the dosing schedule. METHODS: Wistar rats with Staphylococcus aureus infection in the left calf muscle were primed with the anti-DTPA antibody DTIn-1 (0.67, 2, or 6 nmol per rat). In the second step (1-24 h later), the anti-DTPA activity in the circulation was blocked with unlabeled bovine serum albumin DTPA-In (0.3, 1, or 3 nmol per rat). In the third step (5-30 min later), the radiolabeled hapten (monovalent or bivalent 111In-DTPA) was administered. The in vivo distribution of the radiolabel was monitored by scintigraphic imaging and by ex vivo counting of dissected tissues. RESULTS: Scatchard analysis revealed that the affinity of DTIn-1 for bivalent DTPA-111In (111In-diDTPA) was 6 times higher than the affinity for monovalent 111In-DTPA (K(a) = 0.87 x 10(-9) mol/L vs. 5.3 x 10(-9) mol/L). The uptake of the bivalent chelate in the abscess was 2.5-fold higher than that of monovalent 111In-DTPA. Most important, the bivalent chelate was completely retained in the abscess over time. Using the bivalent chelate, the optimal dosing scheme was determined with respect to the DTIn-1 dose (2 nmol per rat), the blocking agent dose (1 nmol per rat), and radiolabeled chelate dose (40 pmol per rat). The procedure was rapid; the infectious focus was clearly visualized 1 h after injection of the 111In-labeled diDTPA, which was 5 h after administration of the anti-DTPA antibody. The nontargeted radiolabel rapidly cleared to the urine, only being retained in the abscess and the kidneys (4-6 percentage injected dose). Finally, an N2S2 core was attached to the diDTPA compound, allowing the use of 99mTc. CONCLUSION: This 3-step approach enables rapid imaging of infectious foci with minimal uptake in noninflamed tissues.

The amino-acid sequence of troponin C from frog skeletal muscle.

The primary structure of the troponin C from skeletal muscle of the frog Rana esculenta has been determined. The amino acid sequence was deduced from amino acid determinations of peptides obtained after cleavage with cyanogen bromide. Overlapping peptides were isolated from tryptic digests of performic-acid-oxidized troponin C and phthalylated performic-acid-oxidized troponin C. All overlaps have been determined except for the Arg-Ile sequence at position 103--104, which has been obtained by comparison with homologous troponins C. Frog troponin C consists of one polypeptide chain containing 152 amino acids. The calculated molecular weight is 18299. There is a single cysteine residue at position 101 and a single tyrosine residue at position 112. No histidine or tryptophan residues are present. The amino-terminal amino acid is N-acetylated. The homology of frog troponin C with other skeletal and cardiac troponin C is briefly discussed.

Determination of the complete amino acid sequence of bovine cardiac troponin C.

The amino acid sequence of bovine cardiac troponin C has been completely determined. The protein was cleaved by cyanogen bromide and the resulting peptides were isolated. All of the 161 residues of the protein could be accounted for in 12 cyanogen bromide peptides. Overlapping peptides were generated by tryptic digestion of citraconylated troponin C and isolation of the resulting five peptides. The primary structure of cardiac troponin C was elucidated by sequential manual Edman degradation of these peptides. It consists of four homologous regions, one of which probably has lost the ability to bind calcium ions. By comparing the amino acid sequence of cardiac troponin C with the sequence of skeletal troponin C, it was found that the mutation rate of the region that does not bind calcium is almost twice as high as the mutation rate of the three homologous regions that do bind calcium.