An anti-CD44 antibody does not enhance engraftment of DLA-identical marrow after low-dose total body irradiation

920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings.     

Ductus aneurysm as a rare cause of inspiratory stridor in the newborn infant

A paralysis of the left vocal cord was seen by laryngoscopy in a 3-days-old boy with inspiratory stridor. A ductus aneurysm was established by angiocardiography, which was believed to be the cause of the vocal cord paralysis. Within 8 days after the angiocardiography the aneurysm became smaller and the stridor disappeared. Twelfth months later the control-angiocardiography showed the total obliteration of the ductal aneurysm.     

Cognitive reserve and mortality in dementia: the role of cognition, functional ability and depression

OBJECTIVE: This study examined whether dementia patients with greater cognitive reserve had increased mortality rates, and whether this association was different across strata of cognition, functional ability and depression. METHODS: In the community-based Amsterdam Study of the Elderly, 261 non-institutionalized dementia patients, identified using the Geriatric Mental State Schedule (GMS), were followed for an average of 55.5 months after which mortality data were obtained. Cognitive reserve was indicated by years of education and pre-morbid intelligence (measured using the Dutch Adult Reading Test). Cognition, functional ability and depression were indicated by Mini-Mental State scores, ADL and IADL measurements and GMS depressive syndrome, respectively. RESULTS: During the follow-up 146 persons (55.9%) died. Cox regression analyses showed that more highly educated dementia patients had higher mortality rates, only if they had low MMSE scores or if they had a concurrent depression. Pre-morbid intelligence was associated with a higher mortality rate, independent of cognition, but this association was much stronger among patients with depression. The positive association between education or intelligence and mortality was not modified by functional disabilities. CONCLUSIONS: The results suggest that dementia patients with greater cognitive reserve have increased mortality rates, only if the disease has progressed to such an extent that clinical symptoms are more severe. In this respect, the reserve hypothesis needs a modification. Depression in dementia patients with greater cognitive reserve may reflect a subgroup of patients with poor prognosis.     

Effect of low levels of serum vitamin B12 and folic acid on cognitive performance in old age: a population-based study

We studied the effect of low levels of vitamin B12 and folic acid, alone or combined, on cognitive performance in a population-based sample of 698 older adults (mean age = 68.7 years). No evidence was found for a vitamin-related memory deficit, but research participants with low levels of vitamin B12 exhibited reduced information processing speed relative to participants with normal vitamin B12 levels.     

Glycosylphosphatidylinositol-specific phospholipase D immunoreactivity is present in islet amyloid in type 2 diabetes

Numerous apolipoproteins associate with amyloid plaques. A minor high-density lipoprotein-associated protein, glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), has recently been described by the authors and others. Since GPI-PLD is synthesized by, and secreted from, pancreatic islet beta cells, the present study examined the hypothesis that GPI-PLD associates with islet amyloid. GPI-PLD immunoreactivity was examined in pancreatic tissues from type 2 diabetic and non-diabetic humans. GPI-PLD binding to heparan sulphate proteoglycan was determined in the absence or presence of heparan sulphate or heparin. Fibril formation from human islet amyloid polypeptide was determined in the absence or presence of GPI-PLD. In non-diabetics, GPI-PLD immunoreactivity was present and co-localized with insulin, as opposed to co-localizing with amyloid in diabetics. No immunoreactivity for apolipoprotein A-I was present in islet cells or islet amyloid. Heparan sulphate proteoglycan, which is commonly present in most amyloid, bound GPI-PLD in vitro. GPI-PLD inhibited the formation of amyloid fibrils from synthetic islet amyloid polypeptide in vitro. GPI-PLD is therefore present in islet amyloid and appears to derive from local production from islets. This localization likely derives from interaction between GPI-PLD and heparan sulphate proteoglycan. Since GPI-PLD also inhibited islet amyloid polypeptide fibril formation in vitro, it is concluded that GPI-PLD may play a role in islet amyloid formation in type 2 diabetes.     

Risk factors for depression in later life; results of a prospective community based study (AMSTEL)

BACKGROUND: Depression in the elderly was found to be associated with a variety of risk-factors in cross sectional designs. Based on the vulnerability-stress model, etiologic pathways for depression have been suggested, with vulnerability modifying the effect of stress factors. The current prospective study tests an etiologic model for depression incidence, by assessing modifying effects of three types of vulnerability: genetic/familial vulnerability, organic vulnerability, and environmental vulnerability. METHODS: 1940 non-depressed community-living elderly were interviewed at baseline, and at follow-up three years later. Bivariate and multivariate relationships between risk factors and incident depression (GMS-AGECAT) were studied. RESULTS: Higher age, personal history of depression, death of spouse, health related factors and comorbid organic or anxiety syndrome showed significant bivariate associations with depression incidence. In multivariate analysis, the effect of stress factors on incident depression was not modified by a genetic/familial vulnerability, nor by an organic vulnerability. Effect modification by environmental factors was however evident; having a marital partner, and if unmarried having social support, significantly reduced the impact of functional disabilities on the incidence of depression. LIMITATIONS: The study consisted of two measurements with a three years interval, depressive episodes with a short duration may be under-represented. CONCLUSIONS: In the elderly, the effect of stress on incident depression is modified by environmental vulnerability. No evidence was found of effect modification by either genetic/familial or organic vulnerability. The results have implications for both recognition and treatment of late-life depression.     

Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation.

The reported incidence of grades II to IV acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation with HLA-identical sibling donors has increased considerably during the past 15 to 20 years at our center. The purpose of this study was to evaluate the potential reasons for this change. We reviewed organ stages and overall grades of GVHD for 2220 patients who received a first marrow or peripheral blood cell transplant from an HLA-identical sibling or an HLA-allele-matched unrelated donor with the use of a posttransplantation immunosuppressive regimen that included both methotrexate and cyclosporine between 1985 and 2001. The most striking change was an increased incidence of stage 1 gut involvement from 10% to 20% before 1992 to 50% to 60% since 1992, both with related and unrelated donors. This change increased the incidence of grade II GVHD with sibling donors, such that the overall incidence of grade II to IV GVHD is now 60% to 70%. Among patients with chronic myeloid leukemia in chronic phase, the increasingly frequent diagnosis of acute GVHD since 1992 has not been associated with decreased survival. A high diagnostic sensitivity and increased awareness that gut GVHD can occur without skin involvement account for the increased incidence of acute GVHD at our center.