Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.     

Age- and gender-specific risk of death after first hospitalization for heart failure

Background  

Hospitalization for heart failure (HF) is associated with high-in-hospital and short- and long-term post discharge mortality. Age and gender are important predictors of mortality in hospitalized HF patients. However, studies assessing short- and long-term risk of death stratified by age and gender are scarce.     

Implementation by simulation; strategies for ultrasound screening for hip dysplasia in the Netherlands

Background  

Implementation of medical interventions may vary with organization and available capacity. The influence of this source of variability on the cost-effectiveness can be evaluated by computer simulation following a carefully designed experimental design. We used this approach as part of a national implementation study of ultrasonographic infant screening for developmental dysplasia of the hip (DDH).     

Age-related cognitive effects of ECT and ECT-induced mood improvement in depressive patients

This explorative study investigated the interaction between electroconvulsive therapy (ECT) treatment-effect, reduced depression, and neuropsychological outcome in relation to age. Follow-up neuropsychological assessment was conducted with depressive patients treated with ECT. From a potential sample of 45 patients, the neuropsychological measures (pre-ECT, three times post-ECT, up to 12 months) and clinical data from the remaining 21 patients who completed all assessments were evaluated (mean age=56.76; SD=14.12; range, 33-79). ECT resulted in a decrease in the depression scores. A distinct impact of ECT and depression decrease on cognitive domains was found. Depression alleviation was mainly associated with improvement in cognitive domains such as memory, information processing, and executive function. ECT improved cognitive domains such as information processing and perception. Short-term cognitive improvement was greater in older patients but showed an increase similar to that at long-term follow-up in younger patients (<60). Current findings provide evidence that ECT may improve cognitive functioning in nondemented elderly, which has strong clinical relevance concerning the use of ECT.     

Effects of An Oral Mixture Containing Glycine,Glutamine and Niacin on Memory,GH and IGF-I Secretion in Middle-aged and Elderly Subjects

Abstract

Aging is associated with declining activity of the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis and with a decrease in cognitive function. The stimulatory effect of an orally administered nutritional supplement, mainly containing glycine, glutamine and niacin on the GH-IGF-I axis and on mood and cognition was investigated. Forty-two healthy subjects (14 men and 28 women, aged 40-76 years) were enrolled in a randomised, double blind, placebo-controlled trial. They received 5 g of a nutritional supplement or placebo, twice daily orally for a period of 3 weeks. At baseline and after 3 weeks, blood was collected for measurement of serum GH and IGF-I levels and mood and cognitive function were tested. The nutritional supplement ingestion for 3 weeks was found to increase serum GH levels with 70% relatively to placebo, whereas circulating IGF-I levels did not change. Mean GH (±SD) increased in this group from 3.23 (±4.78) to 4.67 mU/l (±5.27) (p=0.03). GH increase was not associated with improvement in mood or memory. Correlation analyses, however, revealed that individual increases in IGF-I, but not GH, were associated with improved memory and vigour. It is concluded that an oral mixture of glycine, glutamine and niacin can enhance GH secretion in healthy middle-aged and elderly subjects.     

Extensive nodular cutaneous amyloidosis: an unusual presentation

Amyloidosis is characterized by the deposition of a group of unrelated proteins leading to changes in tissue architecture and function. The nodular variant is the rarest form of the cutaneous amyloidoses. We report a patient with localized nodular amyloidosis without systemic amyloid involvement or paraproteinaemia after 6 years of follow-up. The unusual aspects of our case were a plaque presentation rather than nodular, and the disseminated pattern observed.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction

P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable angina. We investigated the P-selectin gene as a possible candidate for myocardial infarction (MI). The P-selectin gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17 exons. The sequences of the 5'-flanking region and exons of 40 alleles from patients with MI were screened for polymorphisms using polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing. Thirteen polymorphisms were identified: five in the 5'-flanking and eight in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp, Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of the P- selectin protein. All P-selectin polymorphisms as well as a common E- selectin polymorphism, Ser128Arg which has been reported as being associated with an increased risk of premature coronary heart disease (CHD), and is in tight linkage disequilibrium with several P-selectin polymorphisms, were investigated in 647 patients with MI and 758 control subjects from four regions of France and Northern Ireland (the ECTIM study). The entire set of P-selectin polymorphisms provided a heterozygosity of 91%. The polymorphisms were tightly associated with one another and displayed patterns of linkage disequilibrium suggesting the existence of highly conserved ancestral haplotypes. The five polymorphisms in the 5'-flanking region of the gene were unrelated to MI or any relevant phenotype measured in the ECTIM study. We inferred that the four missense variants identified in the coding region predicted eight common forms of the P-selectin protein. The Pro715 allele which characterizes one of these forms was less frequent in France than in Northern Ireland ( P < 0.002) and in cases than in controls ( P < 0.002; P < 0.02 after correction for the number of tests). We conclude that the P-selectin gene is highly polymorphic and hypothesize that the Pro715 variant may be protective for MI. Whether this variant affects the properties of the P-selectin protein in a way which is compatible with this hypothesis needs to be checked experimentally.