Clonal expansion of CD8+ BV8 T lymphocytes in bone marrow characterizes thymoma-associated B lymphopenia

A subgroup of thymoma patients is affected by severe immunodeficiency clinically resembling an HIV infection (Good syndrome). These individuals are characterized by B lymphopenia with B-lymphopoiesis deficiency. To investigate the pathogenesis of this unique condition, we studied the T-cell repertoire in blood and bone marrow samples by heterogeneity length analysis of CDR3 beta variable regions of the T-cell receptor (spectratyping). While no alterations were found in the peripheral blood, we detected an oligoclonal population of beta variable 8 (BV8) CD8(+) T cells in 5 of 5 bone marrow samples. No lymphocyte expansions were found in the bone marrow of 2 thymoma patients with normal B-cell counts, 2 healthy donors, and 3 patients with diseases unrelated to thymoma. These data suggest that an immune response toward an unknown antigen is taking place in the bone marrow of B-lymphopenic thymoma patients. We propose that BV8 CD8(+) T cells may play a role in the pathogenesis of this immunodeficiency syndrome.     

Effect of combining ACE inhibitor and statin in severe experimental nephropathy

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor therapy given soon after disease induction uniformly prevents proteinuria in virtually all models of disease progression. This does not necessarily apply to patients with proteinuric nephropathies, who might be referred late in the course of their disease. Here we used a severe rat model of passive Heymann nephritis (PHN), which may mimic advanced phases of human membranous nephropathy, to study the response to ACE inhibitor alone or in combination with a HMG CoA reductase inhibitor (statin) that independently of the cholesterol-lowering effect influences pathways involved in inflammatory and fibrogenic processes. Therapies started when animals had massive proteinuria and renal lesions. METHODS: PHN was accelerated by uninephrectomy seven days after IV injection of rabbit anti-FX1A antibody. Four months later, when massive proteinuria and renal lesions were present, the rats were divided into five groups and daily given orally: vehicle; lisinopril 40 mg/L; lisinopril 400 mg/L; simvastatin 2 mg/kg b.i.d; or lisinopril 40 mg/L plus simvastatin. Six normal rats served as controls. Animals were sacrificed at 10 months. RESULTS: By the end of the study three PHN rats died in the vehicle group, four in the group given lisinopril at 40 mg/L and two in the group at 400 mg/L, whereas all rats on simvastatin or combined therapy were alive. Blood pressure increased during time in PHN and was normalized by treatment with ACE inhibitor and combined therapy. Even at the high dose lisinopril failed to reduce proteinuria. Simvastatin only partially affected proteinuria. However, combining lisinopril with simvastatin had a remarkable antiproteinuric effect, such that at 10 months the urinary proteins were comparable to pre-treatment values and significantly lower than either the vehicle or lisinopril groups. Hypercholesterolemia of PHN rats was limited by combined therapy, and a positive correlation was found between serum cholesterol and proteinuria. Renal function was only partially ameliorated by simvastatin but significantly improved by combined therapy. Drug combination significantly limited glomerulosclerosis, tubular damage and interstitial inflammation, compared to vehicle or drugs alone. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) mRNA in PHN kidneys was not affected by lisinopril, it was inhibited by 30% after simvastatin, and almost completely normalized by lisinopril plus simvastatin. CONCLUSIONS: These data suggest that a combined ACE inhibitor and statin approach could represent a therapeutic option for patients with advanced renal disease in whom ACE inhibitors alone fail to lower proteinuria and injury to any substantial extent.     

Temperament and character in obese women with and without binge eating disorder

Obesity is a serious disorder and its treatment involves dietitians, psychologists, and psychiatrists, often with a poor outcome. The role of psychiatric issues in obesity is equivocal, and so is the fact whether emotional and behavioral disturbances are causes or consequences of an individual's overweight condition. We performed a study that included 120 obese women (59 with binge eating disorder [BED] and 61 with non-BED) according to specific selection criteria, and compared to 80 healthy controls. Body mass index (BMI) was calculated for all patients and they were assessed with the Temperament and Character Inventory (TCI). Despite the fact that obese patients with BED and without BED display a similar personality profile, those with BED show lower scores in Self-Directedness (SD). Both groups of obese patients differ from nonobese controls in Novelty Seeking (NS), Harm Avoidance (HA), Cooperativeness (C), and SD. SD seems to be the strongest predictor for the development of BED. The idea that two distinct groups of obese patients exist is supported. Moreover, as regards personality, a lower SD and a higher risk of Personality Disorders were found in obese BED patients. Different severities of overweight do not seem to relate to a specific personality susceptibility.     

S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study

Cerebral damage remains one of the hazards related to cardiac surgery with cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be of practical value. We investigated the plasma release patterns of S-100 protein and neuron-specific enolase (NSE) during the intervention and their relationship with the development of neuropsychological deficits assessed 6 months after the intervention in 16 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and postoperatively. Significant correlations were found between values measured at several time points and impaired performance in a few tests at the 6-month follow-up. A stratification into two age subgroups led to the hypothesis that age might have a confounding or a modifying effect on the association between S-100 and NSE levels, and cognitive impairment.     

Multiple coronary artery aneurysms in a child with neurofibromatosis type 1

A number of frequently unrecognised vascular manifestations have been described in patients with neurofibromatosis type 1 (NF1), including involvement of the great vessels, cerebral, visceral and renal arteries. Rarely, changes in the coronary arteries have been reported in adults with NF1. We report on a 16-year-old boy affected by NF1 with dysmorphic features and three aneurysms in the mid-portion of the left descending coronary artery disclosed by chance during investigation for a malignant peripheral nerve sheath tumour. Molecular analysis detected a gross de novo deletion in the NF1 gene. The boy had had no previous cardiac symptoms but died suddenly after developing signs and symptoms suggestive of myocardial infarction. Conclusion To the best of our knowledge, this represents the first report of multiple lesions in the coronary arteries in a child affected by neurofibromatosis type 1 with a known deletion of the neurofibromatosis type 1 gene. Received: 11 November 1999 and in revised form: 9 January 2000 / Accepted: 9 January 2000     

High rate of recurrence in renal transplant recipients after a first episode of venous thromboembolism

BACKGROUND: No data are available about the optimal duration of oral anticoagulant therapy (OAT) after an episode of venous thromboembolism (VTE) occurring in renal transplant (RT) recipients. Our study was undertaken to evaluate the risk of VTE recurrence in patients developing a first episode of VTE after RT. METHODS: Among 484 RT patients, 34 (7%) developed a first VTE: 28/34 VTE patients (Group 1) were prospectively studied, after stopping OAT. Group 1 was compared with a group of 84 patients without history of renal disease who had suffered from a first episode of VTE matched for age, sex and type of thrombotic event (Group 2) and with a matched group of 84 RT recipients with no history of VTE (Group 3). After OAT withdrawal, blood samples were obtained for thrombophilia and clotting activation markers (prothrombin fragment 1+2 (F1+2) and D-dimer plasma levels). RESULTS: During follow-up, 14/28 patients of Group 1 and 8/84 patients of Group 2 experienced VTE recurrence (P < 0.0005). Homocysteine, F1+2 and D-dimer plasma levels were significantly higher in Group 1 than in Group 2 and 3 (P < 0.0001 and <0.05 respectively) for all the three parameters. CONCLUSIONS: Our data outline the high risk of VTE recurrence in RT recipients. Strategies for VTE recurrence prevention are needed; Prolonged OAT, in spite of the high bleeding risk of RT patients, should be considered in this respect.     

Extension of myocardial necrosis differently affects MIBG retention in heart failure caused by ischaemic heart disease or by dilated cardiomyopathy

Purpose This study aims to investigate the relationship between cardiac sympathetic nervous function (CSNF) and myocardial perfusion/function in patients with heart failure (HF) due to dilated cardiomyopathy (DCM) or ischaemic heart disease (CAD).Methods Twenty patients (10 DCM, 10 CAD, 17 males, age 69±5 years) with NYHA class IIIb HF were studied. CSNF was evaluated by early/delayed ¹²³I-metaiodobenzylguanidine (MIBG) uptake and regional washout (WO). Myocardial perfusion and function were evaluated by ^99mTc-tetrofosmin gated single-photon emission tomography (G-SPECT) using a 20-segment model for 400 segments. In each segment, regional MIBG WO was computed as (count density in early images–count density in delayed images/count density in early images)×100.Results DCM and CAD showed similar summed rest perfusion score (6.7±5 vs 9.5±5, p=NS) and mean ejection fraction values (29±7% vs 30±9%, p=NS). By contrast, the summed thickening score was higher in DCM than in CAD patients (26±7 vs 17±6, p<0.05). QGS analysis identified akinesis/dyskinesis in 129/137 (94%) severely hypoperfused segments which were considered as damaged. According to the underlying aetiology of HF, marked differences in regional MIBG WO were observed. In fact, within the CAD group, regional MIBG WO was lower in reference than in damaged segments (38±21% vs 46±19%, p<0.05). By contrast, in DCM patients, regional MIBG WO was faster in reference than in damaged segments (49±18% vs 41±30%, p<0.05). When the two groups were directly compared, regional MIBG WO from damaged areas was similar irrespective of the underlying disease, while it was faster in DCM than in CAD patients from reference segments.Conclusion These data confirm the hypothesis that the presence of myocardial necrosis in HF due to CAD and the consequent loss of neuronal endings cause alterations in regional MIBG WO different from those observed in DCM.     

Catheter-induced straightening of external iliac tortuosity: a cause of pseudostenosis to be borne in mind

Reversible vascular obstructive lesions, i.e. pseudostenoses, may pose significant threats to interventional cardiologists as they can be mistaken for obstructive lesions and prompt inappropriate revascularization procedures. We hereby report for the first time in the literature a case of external iliac artery pseudostenosis due to catheter straightening of significant underlying vessel tortuosities. Despite the initial angiographic image obtained from retrograde catheterization of the right external iliac artery which was strongly suggestive for significant stenosis, a thorough review of clinical history, physical examination and a second-look angiography by means of contralateral catheterization and contrast injection showed the absence of any significant lesion in the tortuous left external iliac artery, thus avoiding an unnecessary and potentially harmful vascular intervention. This clinical vignette emphasizes the importance of a thorough clinical examination and angiographic assessment for the appropriate diagnosis and management of reversible stenoses.