Experiences of relatives of donors with the donation procedure; comparison between 1995 and 1998

OBJECTIVE: To determine the experience of the relatives of organ and tissue donors, immediately before, during and soon after the donation procedure. DESIGN: Questionnaire. METHOD: At two national one-day meetings at which about 10% of the families of donors between 1991 and 1998 were represented, the participants completed a questionnaire with questions about their appreciation of the communication with the different health care professionals. The appreciation was scored on a 7-point scale. RESULTS: Most relatives looked back with satisfaction on the events in the hospital and soon thereafter; the appreciation was 'a little satisfied' to 'satisfied'. The relatives in non-heart-beating kidney transplantation were more satisfied compared to those confronted with the brain death transplantation, with regard to the conversation in which the death was announced as well as to the conversation regarding the donation procedure. Relatives in 1998 were more positive about some specific aspects than in 1995, notably concerning explanation of the phenomenon of brain death. Satisfaction was primarily influenced by the way in which the news of death was conveyed and the aftercare by the transplant coordinator. The moment donation was addressed and the moment the relatives said 'good-bye' to their beloved were the next important factors.     

Loss of transforming growth factor counteraction on interleukin 1 mediated effects in cartilage of old mice

OBJECTIVE: To investigate if a difference exists between young and old mice in the response of articular cartilage to interleukin 1 (IL1) and transforming growth factor beta (TGFbeta) alone or in combination. METHODS: The interaction of IL1 and TGFbeta was studied in cartilage of young (three months) and old mice (18 months) both in vivo and in vitro. Therefore, IL1, TGFbeta, or IL1 together with TGFbeta was injected into the knee joints of mice on days 1, 3, and 5 before harvest of the patellae on day 6. Alternatively, isolated patellae were stimulated with IL1, TGFbeta, or IL1 together with TGFbeta in culture for 48 hours. Proteoglycan (PG) synthesis and nitric oxide (NO) production were measured. RESULTS: IL1 inhibited PG synthesis and increased NO production in cartilage of both young and old mice. On the other hand, TGFbeta stimulated PG synthesis and reduced NO production in both age groups. Importantly, TGFbeta was able to counteract IL1 mediated effects on PG synthesis and NO production in young but not in old mice. CONCLUSIONS: Contrary to the findings in young mice, the cartilage of old animals does not antagonise IL1 effects via TGFbeta. This loss of responsiveness to the pivotal cytokine TGFbeta on effects of IL1 can be important in the initiation and progression of osteoarthritis (OA).     

A woman with a lobar infiltrate due to psittacosis detected by polymerase chain reaction

This report presents a case of community-acquired pneumonia due to Chlamydia psittaci presenting with a lobar infiltrate and diagnosed by a newly developed ompA gene-based polymerase chain reaction (PCR). This gene encodes a specific C. psittaci major outer membrane protein. This kind of PCR could reduce antibiotic consumption and expedite outbreak management.     

The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families

The frame-shifting mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene (CHEK2) has been reported to be associated with familial breast cancer in families in which mutations in BRCA1 and BRCA2 were excluded. To investigate the role of this variant as a candidate breast cancer susceptibility allele, we determined its prevalence in 237 breast cancer patients and 331 healthy relatives derived from 71 non-BRCA1/BRCA2 multiple-case early onset breast cancer families. Twenty-seven patients (11.4%) were carrying the CHEK2*1100delC variant. At least one carrier was found in 15 of the 71 families (21.1%). There was no evidence of cosegregation between the variant and breast cancer, but carrier patients developed breast cancer earlier than did noncarriers. We studied CHEK2 protein expression in 111, and loss of heterozygosity at CHEK2 in 88 breast tumors from these patients. Twelve of 15 tumors from carriers showed absent protein expression as opposed to 3 of 76 tumors from noncarriers (P < 0.001). CHEK2 loss of heterozygosity was associated with absence of protein expression but not with 1100delC carrier status. Thus, selecting for breast cancer cases with a strong familial background not accounted for by BRCA1 or BRCA2 strongly enriches for carriers of CHEK2*1100delC. Our results support a model in which CHEK2*1100delC interacts with an as yet unknown gene (or genes) to increase breast cancer risk.     

Renal hemodynamics and proteinuria in running and swimming beagle dogs

Summary In beagle dogs swimming, in contrast to treadmill running, was found to cause an increase in urine flow and urinary protein excretion. Renal blood flow measured by electromagnetic flow probes decreased by 13.0±4.9% when the treadmill gradient was 15% and arterial pressure was elevated by 11.6±4.9%. Immersion resulted in an immediate decrease in renal blood flow of 8.8±5.1% and a 24.6±6.9% increase in arterial pressure. Acid-base status indicated a respiratory alkalosis in all running experiments, no net change in five swimming experiments in which hyperventilation occured, but a metabolic acidosis in eight swimming experiments without hyperventilation. During running there was a threefold increase in oxygen consumption. We conclude that swimming possibly induces more sympathetic nervous activity than treadmill running in dogs, while an alkalosis is consistently present during running, but acid-base response is variable during swimming.     

An IL-13 promoter polymorphism associated with increased risk of allergic asthma

IL-13 plays a crucial role in the development of allergic asthma by several mechanisms, including induction of IgE antibodies, airway eosinophilia and hyper-reactivity. We previously established a deregulated production of IL-13 by T cells from allergic asthma patients. In this report we describe the identification of a novel IL-13 promoter polymorphism (C to T exchange) at position -1055. The IL-13 -1055 TT genotype is associated with allergic asthma (P = 0.002), altered regulation of IL-13 production (P < 0.002), and increased binding of nuclear proteins to this region. We postulate that the presence of this polymorphism predisposes to the development of allergic asthma.     

The selective antigen-presenting cell capacity of activated B lymphocytes in HLA-II-restricted responses of CD4+ T lymphocytes

We examined the role of antigen-presenting B lymphocytes using panels of antigen-specific CD4+8-T-lymphocyte clones (TLC). All 19 TLC showed a class II major histocompatibility complex-encoded (HLA-II) restricted proliferation to antigen presented by antigen-presenting cells (APC) from the monocyte fraction of peripheral blood. Only six TLC were effectively activated by antigen presented by autologous B lymphocytes activated by EBV transformation. This failure of B lymphocytes was not due to: (i) a high degree of cell surface sialic acid; (ii) a low expression of the cell surface proteins HLA-II, ICAM-1 or LFA-3 that restrict antigen presentation; (iii) lack of secretion of the cytokine IL-1 or other soluble factors that may be required as secondary signals; or (iv) induction of incomplete T-cell activation resulting in the production of growth factor interleukin-2 (IL-2) or the expression of receptors for IL-2 only. These data suggest the involvement of another cell surface interaction in antigen presentation acting besides the interactions known so far.     

Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis.

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.     

Development of osteoarthritic lesions in mice by "metabolic" and "mechanical" alterations in the knee joints

Male, 10-week-old C57B1 10 mice received a single intraarticular injection in the knee joints with papain, iodoacetate, or collagenase. This led to osteoarthritic lesions, such as matrix depletion, chondrocyte proliferation, and osteophyte formation, in the injected knee joints within several weeks. After injection of iodoacetate and papain, the main osteoarthritic alterations were localized in the femoropatellar joint, whereas injection of collagenase led to marked osteoarthritic lesions in the femorotibial joint. The mechanism of induction of these alterations appears to differ for iodoacetate and papain on one site and collagenase on the other site. Data are presented that collagenase injection, by way of damaging ligaments and tendons, destabilizes the knee joint eventually leading to osteoarthritic alterations. In contrast, injection of papain or iodoacetate directly interferes with cartilage metabolism resulting in osteoarthritic changes.