Surviving decentralisation? Impacts of regional autonomy on health service provision in Indonesia

The paper aims to assess the impacts of decentralisation and privatisation reforms on access to and quality of health services in Indonesia. The research draws on qualitative and quantitative data from interviews, focus group discussions, and household surveys in four selected districts. The main conclusions are three-fold; the local administration of health care services is without transparency and accountability, health centres are turned into profit centres, and the increasing roles of private actors tend to reduce concerns over preventive health care and the conditions for poor people. Our policy recommendations include increased government spending to maintain public efforts in environmental and preventive health and in maintaining a minimum health service for the poor.     

Immunization against a low-frequency human platelet alloantigen in fetal alloimmune thrombocytopenia is not a single event: characterization by the combined use of reference DNA and novel allele-specific cell lines expressing recombinant antigens

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal immunization against a fetal platelet (PLT) alloantigen. In cases of FNAIT attributed to low-frequency PLT alloantigens, the laboratory diagnosis is often hampered by the lack of adequate PLTs. STUDY DESIGN AND METHODS: Three families with maternal immunization against fetal PLT antigens were analyzed. In Family 1, previous immunization of another female or woman has been observed. In Families 2 and 3, newborns presented with the typical clinical picture of FNAIT. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing with reference to DNA from Epstein-Barr virus-transformed B-lymphoblastoid cell lines. Antibodies were characterized by glycoprotein (GP)-specific immunoassay with a panel of stable Chinese hamster ovary cell lines expressing low-frequency alloantigens. RESULTS: In three families, maternal immunization associated with the low-frequency alloantigens human PLT antigen (HPA)-8bw (Sra), HPA-11bw (Groa), and HPA-13bw (Sita) was identified. Maternal serum samples showed positive reactions in an antigen capture assay with cell lines carrying recombinant GP IIb/IIIa (HPA-8bw and -11bw) or GPIa/IIa (HPA-13bw), respectively. These results could be confirmed by genotyping analysis of fathers and newborns. CONCLUSION: This study demonstrates that cases of FNAIT attributed to low-frequency PLT alloantigens cannot be regarded as single events. The availability of reference DNA and cell lines expressing recombinant PLT alloantigens can facilitate their identification.     

Functional heterogeneity of alloantibodies against the human platelet antigen (HPA)-1a

The integrin alphaIIbbeta is the major fibrinogen receptor on the platelet membrane and plays a crucial role for platelet aggregation. The beta3-subunit carries the human platelet alloantigen (HPA)-1a, which is the main target for alloantibodies (alloabs) responsible for foetal and neonatal alloimmune thrombocytopenia (FNAIT) and post-transfusion purpura (PTP). Whereas PTP is almost invariably associated with severe bleeding, the clinical presentation of FNAIT ranges from mild thrombocytopenia to severe haemorrhagic diathesis. However, this clinical heterogeneity is not fully understood as it is not explained solely by the variability of the platelet count. Here, we examined the ability of HPA-1a alloabs from mothers with FNAIT (n = 43) and PTP patients (n = 8) to inhibit cell adhesion to fibrinogen and asked if this inhibition was correlated with the heterogeneity of the clinical picture. Stably transfected cells expressing HPA-1a (beta3-Leu33) and -1b (beta3-Pro33) isoforms were incubated with sera containing HPA-1a alloabs and were allowed to adhere to immobilised fibrinogen. The inhibitory activity was measured as percentage of cell adhesion in the presence of patient sera versus normal AB serum. Only two FNAIT sera specifically inhibited the adhesion of HPA-1a, but not HPA-1b cells. Two other FNAIT sera blocked the adhesion of HPA-1a as well as HPA-1b cells. Interestingly, all four neonates with inhibitory HPA-1a alloabs (9% of all sera) suffered severe bleeding. In comparison, the majority of PTP sera (75%) inhibited cell binding to fibrinogen, four PTP sera selectively inhibited the adhesion of HPA-1a cells whilst 2 sera impaired the binding of both allotypes. Our observations indicate that 1) HPA-1a alloabs are heterogeneous in their ability to interfere with fibrinogen binding, and 2) inhibition of the alphaIIbbeta3 fibrinogen receptor by HPA-1a alloabs may contribute to pronounced bleeding in patients with alloimmune thrombocytopenia.     

Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation

Leukocyte extravasation is a finely tuned process, in which transmigration is the final step. Transmigration depends on molecules located at borders of endothelial cells; e.g., junctional adhesion molecules (JAM-A, -B and -C). In vivo blockade of JAM-A lead to decreased migration of monocytes into the skin. In contrast, the role of JAM-B and -C in development of cutaneous inflammation is unknown. We therefore elicited an allergic contact dermatitis in mice using 2,4-dinitro-1-fluorobenzene. RT-PCR and immunofluorescent staining of healthy skin revealed a constitutive JAM-B (66.4%+/-6.7% of all vessels) and -C expression (88.6+/-13.2%), which remained constant after induction of contact dermatitis. Functional studies, in which either JAM-B or -C neutralizing antibodies were injected into sensitized mice prior to allergen challenge showed a concentration-dependent reduction of the contact dermatitis. Decreased ear swelling was accompanied by reduction of leukocyte infiltration as analyzed by hematoxylin and eosin (H&E) histology and enzyme activity. Combined antibody treatment at doses of 1.25 mg per kg bodyweight lead to additive inhibition of allergic contact dermatitis, indicating that JAM-B and -C may have distinct functions. In conclusion, interactions with JAM-B and -C are essential for development of cutaneous inflammation.     

Micturition syncope during pregnancy

BACKGROUND: Micturition syncope is a relatively uncommon cause of sudden and temporary loss of consciousness. Most prevalent in older males, this condition is extremely rare in women. CASES: Two pregnant women presented with recurrent syncope. The syncopal events were more common in the early morning and were precipitated by the presence of a distended bladder, urinary urgency, assuming a standing position after either being supine or sitting, or associated with travel motion. Extensive neurology and cardiology evaluations were negative, and the events were considered consistent with micturition syncope. Both patients responded favorably to conservative voiding behavior modification measures throughout the remainder of pregnancy. CONCLUSION: Micturition syncope during pregnancy may not be a rare occurrence. This potentially dangerous condition is amenable to voiding behavior modification measures.     

Reduced endothelial cell migratory signal production by endometrial explants from women using Norplant contraception

Bleeding problems can be one of the major reasons for womento discontinue the use of hormonal contraceptives.Causes ofendometrial bleeding can include disturbances in endometrialregeneration and angiogenesis. Endothelial cells migrate andproliferate rapidly as part of the angiogenic process underthe influence of appropriate stimuli.The aim of this study isto investigate the production of endothelial cell migratorysignals by endometrial explants from women receiving Norplantand to compare it to that of those with a normal menstrual cycle.The subjects were selected from Norplant users with an exposureof 3-9 months. The endothelial cell migratory signal productionwas assayed using the Folkman method (1989), modified by Rogers(1992). Blood serum concentrations of oestradiol,progesteroneand sex hormone binding globulin were monitored for 2 weeksprior to endometrial biopsy.Endothelial cell migration towardendometrial explants of 30 women as control and 46 Norplantacceptors was assayed. The results showed that endothelial cellmigratory activity toward endometrial explants from the controlgroup was significantly higher than toward those from Norplantacceptors (z = -3.89, P < 0.001). There were no differencesbetween endometrial endothelial cell migratory activities inNorplant acceptors with bleeding or withoutbleeding problems.     

Human platelet alloantigens Br/Br are expressed on the very late activation antigen 2 (VLA-2) of T lymphocytes

We report the molecular localization of the human platelet alloantigens Br^a/Br^b on activated T lymphocytes. By radioimmunoprecipitation anti-Br^a precipitated two proteins from T lymphocytes of Br(a+) donors after long-term activation (24 days), but not from resting or short-term-activated T lymphocytes (4 days). No bands could be precipitated with anti-Br^a from T lymphocytes of Br(a−) donors, but the same two bands were seen with anti-Br^b. The apparent molecular weights of unreduced molecules were 155 and 130 kDa, respectively. Monoclonal antibody Gi14 directed against an epitope on the platelet membrane glycoprotein Ia/IIa complex precipitated the same two bands with long-term-activated T lymphocytes, whereas MoAb TS2/7 directed against very late antigen (VLA)-1 molecules precipitated two bands with M_r 180 and 130 kDa (₁β heterodimer). The physicochemical properties of these two bands precipitated by anti-Br^a, anti-Br^b or monoclonal antibody Gi14 with molecular weights of 155 and 130 kDa, respectively, correspond to VLA ₂ and β chains and fit defined criteria for the VLA-2 antigen. These results were corroborated by an assay employing monoclonal antibody for antigen immobilization showing that Br^a and Br^b antigens were present only on long-term activated T lymphocytes. Our results provide evidence for the expression of the Br^a/Br^b platelet alloantigen system on VLA-2 antigens of activated T lymphocytes and demonstrate a genetic polymorphism of VLA-2 molecules on both cell lines.     

Workshop Report on the Genotyping of Blood Cell Alloantigens

The immunization against alloantigens present on platelets, granulocytes and red blood cells (RBCs) is responsible for various clinical syndromes. Since the molecular basis of these antigens has become clear during the last decade, genotyping is nowadays used in several laboratories. However, many DNA-based techniques still have to be evaluated. We therefore organized a workshop on the genotyping of the most relevant alloantigens on platelets and granulocytes as well as on selected RBC alleles. DNA was isolated from peripheral blood lymphocytes or from B-lymphoblastoid cell lines (B-LCL). We distributed samples for the identification of platelet (n = 7), granulocyte (n = 6) and RBC (n = 4) polymorphisms, respectively. There were 33 institutions in Germany, Austria and Switzerland, which participated in at least one part of the workshop. Twenty-four laboratories reported results on HPA-1, and 23 laboratories on HPA-2, -3, and -5 typing. In addition, five laboratories typed for HPA-4 and -6. The HNA-1a/b (NA1/NA2) alleles were identified by eight laboratories, one of which also typed for HNA-1c (SH). The most frequent genes of the ABO (A1, B, O) and Rh (D, C, c, E, e) systems were typed by 12 participating laboratories, and an additional four laboratories restricted their RBC typing to the RHD gene. The typing technique mainly used for all three cell lineages was the polymerase chain reaction with sequence-specific primers. Other techniques were restriction fragment length analysis, oligonucleotide ligation assay, enzyme-linked mini-sequence assay or direct sequence analysis. The following typing errors were observed: HPA: 15/1442 (1.0%), HNA: 4/108 (3.7%), ABO: 5/96 (5.2%) RH 1/320 (0.3%). Our workshop demonstrated the existence of a number of reliable techniques for the genotyping of blood cell alloantigens and a high standard in the participating laboratories. In addition, we could show the usefulness of B-LCL as a source of reference DNA. However, the 5.2% rate of mistyping in the ABO system demonstrated that further efforts are needed to improve the precision of the genotyping techniques. Future workshops will have to challenge methods and participants with rare variants of RBC genes to guarantee reliable genotyping, e.g. in prenatal diagnosis of fetomaternal incompatibility.