Searching for dose-response in HF clinics.

The study of Strömberg and colleagues¹is one of the firststudies to describe the effectiveness of a nurse-led heart failureclinic in decreasing mortality. Although several studies onheart failure management programmes have shown promising resultsin decreasing readmission and     

Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis

To elucidate the molecular basis of band 3 deficiency in a recently defined subset of patients with autosomal dominant hereditary spherocytosis (HS), we screened band 3 cDNA for single-strand conformation polymorphism (SSCP). In 5 of 17 (29%) unrelated HS subjects with band 3 deficiency, we detected substitutions R760W, R760Q, R808C, and R870W that were all coinherited with the HS phenotype. The involved arginines are highly conserved throughout evolution. To examine whether or not the product of the mutant allele is inserted into the membrane, we studied one HS subject who was doubly heterozygous for the R760Q mutation and the K56E (band 3sMEMPHIS) polymorphism that results in altered electrophoretic mobility of the band 3 Memphis proteolytic fragments. We detected only the band 3MEMPHIS in the erythrocyte membrane indicating that the protein product of the mutant, R760Q, band 3 allele is absent from the red blood cell membrane. These findings suggest that the R760Q substitution, and probably the other arginine subsitutions, produce band 3 deficiency either by precluding incorporation of the mutant protein into the red blood cell membrane or by leading to loss of mutant protein from differentiating erythroid precursors.     

Autism as a Natural Human Variation: Reflections on the Claims of the Neurodiversity Movement

Neurodiversity has remained a controversial concept over the last decade. In its broadest sense the concept of neurodiversity regards atypical neurological development as a normal human difference. The neurodiversity claim contains at least two different aspects. The first aspect is that autism, among other neurological conditions, is first and foremost a natural variation. The other aspect is about conferring rights and in particular value to the neurodiversity condition, demanding recognition and acceptance. Autism can be seen as a natural variation on par with for example homosexuality. The broad version of the neurodiversity claim, covering low-functioning as well as high-functioning autism, is problematic. Only a narrow conception of neurodiversity, referring exclusively to high-functioning autists, is reasonable. We will discuss the effects of DSM categorization and the medical model for high functioning autists. After a discussion of autism as a culture we will analyze various possible strategies for the neurodiversity movement to claim extra resources for autists as members of an underprivileged culture without being labelled disabled or as having a disorder. We will discuss their vulnerable status as a group and what obligation that confers on the majority of neurotypicals.     

Activation of human platelets by immune complexes prepared with cationized human IgG

The present study shows that the ability of soluble immune complexes (IC), prepared with human IgG and rabbit IgG antibodies against human IgG, to trigger platelet activation was markedly higher for IC prepared with cationized human IgG (catIC) compared with those prepared with untreated human IgG (cIC). CatIC induced platelet aggregation and adenosine triphosphate release in washed platelets (WP), gel-filtered platelets (GFP), or platelet-rich plasma (PRP) at physiologic concentrations of platelets (3 x 10(8)/mL) and at low concentrations of catIC (1 to 30 micrograms/mL). On the contrary, under similar experimental conditions, cIC did not induce aggregation in PRP, WP, or GFP. Low aggregation responses were only observed using high concentrations of both WP (9 x 10(8)/mL) and cIC (500 micrograms/mL). Interestingly, catIC were also able to induce platelet activation under nonaggregating conditions, as evidenced by P-selectin expression. Cationized human IgG alone did not induce platelet aggregation in PRP but triggered either WP or GFP aggregation. However, the concentration needed to induce these responses, was about eightfold higher than those required for catIC. The responses induced either by catIC or cationized human IgG were completely inhibited by treatment with heparin, dextran sulphate, EDTA, prostaglandin E1, or IV3, a monoclonal antibody against the receptor II for the Fc portion of IgG (Fc gamma RII). The data presented in this study suggest that IgG charge constitutes a critical property that conditions the ability of IC to trigger platelet activation.     

Balloon angioplasty of coarctation of the aorta: a safe alternative for surgery in adults: immediate and mid-term results.

Patients with coarctation of the aorta can be treated either with surgery or with balloon angioplasty. So far, the last method has proved to be successful in children, but results of this treatment in (young) adults are virtually unknown. The aim of this study was to evaluate the immediate and mid-term follow-up results of balloon angioplasty of native coarctation in (mainly young) adults. Coarctation of the aorta was diagnosed by means of ultrasound or angiography, and defined as a stenosis with a pressure gradient greater than 20 mm Hg. The balloon angioplasty-procedure was carried out under complete anesthesia, and was considered to be successful, if the pressure gradient was reduced to less than 20 mm Hg. Nineteen consecutive adults (12 males, 7 females; aged 14-67 years, median 29) with native coarctation were treated from 1995-99. Mean pressure gradient decreased from 49.3+/- 20.8 to 4.8+/-8.2 mm Hg (P<0.0001). One patient showed a suboptimal result with a residual pressure gradient of 28 mm Hg. In one other patient a stent was placed on request of the referring physician. Follow-up was 100% complete and ranged from 3-47 months (mean 20.2+/- 12.9). At 1-year follow-up mean systolic blood pressure was reduced from 159.4+/-19.5 to 132.5+/-17.6 mm Hg (n = 18; P<0.0001), and mean ankle-arm pressure index improved from 0.73+/-0.09 to 0.96+/-0.05 (n = 18; P<0.0001). Anti-hypertensive medication could either be reduced or stopped in 7 patients (53.8%). With ultrasound or angiography or MRI, no patients had signs of aneurysm formation or worsening restenosis during follow-up. In adult patients with uncomplicated native coarctation of the aorta, balloon angioplasty (without stenting) would seem to be an excellent and safe alternative for surgery. In our hospital it has completely replaced surgical correction in such patients.     

Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease

We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T- cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.