Reduced Th1, but not Th2, cytokine production by lymphocytes after in vivo exposure of healthy subjects to endotoxin

Endotoxin (lipopolysaccharide [LPS]) tolerance is characterized by a reduced capacity of monocytes to produce proinflammatory cytokines upon restimulation in vitro. To determine whether LPS exposure induces a change in lymphocyte cytokine production and whether this results in a shift in the T-helper 1 (Th1)/Th2 balance, whole blood obtained from seven healthy subjects before and after an intravenous injection of LPS (4 ng/kg) was stimulated in vitro with the T-cell stimulus anti-CD3/CD28 or staphylococcal enterotoxin B. Whole-blood production of the Th1 cytokines gamma interferon (IFN-gamma) and interleukin-2 (IL-2) was markedly reduced at 3 and 6 h, while the production of the Th2 cytokines IL-4 and IL-5 was not influenced or was slightly increased. The IFN-gamma/IL-4 ratio was strongly decreased at 6 h. Serum obtained after LPS exposure could slightly inhibit the release of IFN-gamma but increased IL-4 production during stimulation of blood drawn from subjects not previously exposed to LPS. Normal serum also inhibited IFN-gamma production, albeit to a lesser extent. LPS exposure influences lymphocyte cytokine production, resulting in a shift toward a Th2 cytokine response, an effect that may be mediated in part by soluble factors present in serum after LPS administration in vivo.     

Activation of ion transport by combined effects of ionomycin,forskolin and phorbol ester on cultured HT-29cl.19A human colonocytes

The differentiated clone 19A of the HT-29 human colon carcinoma cell line was used as a model to study the intracellular electrophysiological effects of interaction of the cAMP, the protein kinase C (PKC) and the Ca²⁺ pathways, (a) A synergistic effect between ionomycin and forskolin was observed. From intracellular responses it was concluded that the synergistic effect is caused by activation of an apical Cl^– conductance by protein kinase A and a basolateral K⁺ conductance by Ca²⁺. (b) A transient synergistic effect of ionomycin and the phorbol ester phorbol dibutyrate (PDB) was found. The decrease of the response appeared to be due to PKC-dependent inactivation of the basolateral K⁺ conductance. The synergism is caused by PKC-dependent increase of the apical Cl^– conductance and Ca²⁺-dependent increase of the basolateral K⁺ conductance. (c) The effects of carbachol and PDB were not fully additive presumably because of their convergence on PKC activation, (d) Forskolin and PDB, when added in this order, had a less than additive effect. Results of cell-attached patch-clamp studies, presented in the accompanying paper, showed a synergistic effect of forskolin and PDB on non-rectifying small-conductance Cl^– channels. Assuming that these channels are involved in the transepithelial responses it is suggested that forskolin and PDB induce a modulatory, synergistic increase of the apical Cl^– conductance when both pathways are activated simultaneously. (e) The HT-29cl.19A cells differ from T₈₄ cells in that the latter did not respond with an increase of the short-circuit current to addition of phorbol ester. This may be due to a very low expression of PKC.     

Home care after early discharge: Impact on healthy mothers and newborns

Objective

to compare early discharge with home care versus standard postpartum care in terms of mothers' sense of security; contact between mother, newborn and partner; emotions towards breast feeding; and breast-feeding duration at one and three months after birth.

Design

retrospective case-control study.

Setting

a labour ward unit in Stockholm, Sweden handling both normal and complicated births.

Participants

96 women with single, uncomplicated pregnancies and births, and their healthy newborns.

Intervention

early discharge at 12–24 hours post partum with 2–3 home visits during the first week after birth. The intervention group consisted of women who had a normal vaginal birth (n=45). This group was compared with healthy controls who received standard postnatal care at the hospital (n=51).

Instruments

mothers' sense of security was measured using the Parents' Postnatal Sense of Security Scale. Contact between mother, child and father, and emotions towards breast feeding were measured using the Alliance Scale, and breast-feeding rates at one and three months post partum were recorded.

Findings

women in the intervention group reported a greater sense of security in the first postnatal week but had more negative emotions towards breast feeding compared with the control group. At three months post partum, 74% of the newborns in the intervention group were fully breast fed versus 93% in the control group (p=0.021). Contact between the mother, newborn and partner did not differ between the groups.

Conclusion

early discharge with home care is a feasible option for healthy women and newborns, but randomised controlled studies are needed to investigate the effects of home care on breast-feeding rates.     

Maternal death reviews at a rural hospital in Malawi

ObjectiveTo analyze maternal deaths at Nkhoma Church of Central Africa Presbyterian (CCAP) Hospital and identify factors causing delays in care.MethodsMaternal death audits are performed after every maternal death at Nkhoma CCAP Hospital. Information regarding the care provided at the health facility, the referral process, and any delays in the community was collected by an audit team using a structured approach. Data from August 2007 to September 2011 were analyzed retrospectively.ResultsIn total, 61 maternal deaths occurred during the study period, of which 58 were analyzed. Most deaths were categorized as indirect (n = 34 [58.6%]). Non-pregnancy-related infections were the leading cause of indirect death (n = 22), with meningitis the most common (n = 13). Most patients experienced a delay in seeking care (n = 37 [63.8%]), a transport delay (n = 43 [74.1%]), or a delay in receiving adequate care (n = 34 [58.6%]).ConclusionMost maternal deaths had indirect causes and were associated with delays in all phases. An audit makes clear which part of the referral chain needs to be strengthened. Nkhoma CCAP Hospital has taken steps to address all phases of delay.     

Reliability and responsiveness of the Juvenile Arthritis MRI Scoring (JAMRIS) system for the knee

Objectives

To assess the reliability and responsiveness of a new Juvenile Arthritis MRI Scoring (JAMRIS) system for evaluating disease activity of the knee.

Methods

Twenty-five juvenile idiopathic arthritis (JIA) patients with clinical knee involvement were studied using open-bore 1-T MRI. MRI features of synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions were independently scored by five readers using the JAMRIS system. In addition, the JAMRIS system was determined to be a follow-up parameter by two readers to evaluate the response to therapy in 15 consecutive JIA patients.

Results

Inter-reader (ICCs 0.86–0.95) and intra-reader reliability (ICCs 0.92–1.00) for the scoring of JAMRIS features was good. Reliability of the actual scores and changes in scores over time was good for all items: ICCs 0.89–1.00, 0.87–1.00, respectively. Concerning therapy response, the mean synovial hypertrophy scores decreased significantly (mean 1.1 point; P?<?0.001, SRM?=??0.65). No change was observed with respect to bone marrow change, cartilage lesion and bone erosion scores.

Conclusions

The JAMRIS proved to be a simple and highly reliable assessment score in the evaluation of JIA disease activity of the knee. The JAMRIS system may serve as an objective and accurate outcome measure in future research and clinical trials.

Key Points

? MRI is increasingly used to diagnose and assess juvenile idiopathic arthritis. ? A simple and reliable scoring method would help monitor progress and research. ? The Juvenile Arthritis MRI Scoring (JAMRIS) system provides reliable objective measures. ? JAMRIS evaluates synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions. ? The JAMRIS system can detect therapeutic response and should help future research.     

Timing of psychiatric consultations: the impact of social vulnerability and level of psychiatric dysfunction

The authors examined the timing of patient referrals to a psychiatric consultation-liaison service in relation to the patient's social vulnerability and level of psychiatric dysfunction. One hundred consecutive patients were assessed with the INTERMED, a method to document biopsychosocial and health care-related aspects of disease. Although 30% of patients were referred within the first day of admission, 19% of requests for referrals were made after 2 weeks. Late referral was associated with high social vulnerability and early referral with severe psychiatric dysfunction. The authors illustrate the disadvantages of a psychiatric liaison model focusing on psychopathology alone and demonstrate the need for an integrated patient assessment in the general hospital, focusing on detecting frail elderly patients.     

Preconditioning of rat hearts by adenosine A1 or A3 receptor activation

A reduction in airway beta-adrenoceptor density has been reported in cystic fibrosis lung but the mechanism underlying this defect remains unclear. In this study, we have investigated whether the decrease in beta2-adrenoceptor associates with altered G protein-coupled receptor kinase (GRK) levels. We assessed GRK activity by rhodopsin phosphorylation, and beta2-adrenoceptor and GRK at the mRNA and protein levels by Northern and Western blotting in peripheral lung samples from normal donors and patients with cystic fibrosis. GRK activity was significantly increased in peripheral cystic fibrosis lung with parallel increases in GRK2/5 mRNAs and protein expression. Functionally, isoproterenol-stimulated adenylyl cyclase activity was also diminished by 65% in cystic fibrosis lung homogenates. These data suggest that the increase in GRK activity may be one of the mechanisms underlying alterations in the coupling between beta2-adrenoceptor and adenylyl cyclase via G-protein and may thus contribute to the downregulation of beta2-adrenoceptor in cystic fibrosis lung.