Mechanism of induction of complement susceptibility of erythrocytes by spider and bacterial sphingomyelinases

We have recently shown that the sphingomyelinase toxins P1 and P2 from the venom of the spider Loxosceles intermedia induce complement (C)-dependent lysis of autologous erythrocytes by induction of the cleavage of cell surface glycophorins through activation of an endogenous metalloproteinase facilitating the activation of the alternative pathway of C. Phospholipase D (PLD) from Corynebacterium pseudotuberculosis shows some degree of homology with the spider sphingomyelinases and can induce similar clinical symptoms to those observed after spider envenomation. The aim of this study was to investigate if the bacterial PLD-induced haemolysis of human erythrocytes was C dependent and if cleavage of glycophorins occurred. We show here that haemolysis of both PLD- and P1-treated human erythrocytes was C dependent, but while PLD-mediated haemolysis was dependent on activation of the classical pathway of C, P1 induced lysis via both the classical and alternative pathways. P1, but not PLD, induced cleavage of glycophorins and no change in expression of complement regulators was induced by either of the toxins. In both cases, annexin V binding sites were exposed, suggesting that the membrane asymmetry had been disturbed causing exposure of phosphatidylserine to the cell surface. Our results suggest that C susceptibility induced by L. intermedia and C. pseudotuberculosis PLD is a result of exposure of phosphatidylserine, and the higher potency of P1 toxin can be explained by its additional effect of cleavage of glycophorins.     

Identification of isolated and early prostatic adenocarcinoma in radical prostatectomy specimens with correlation to biopsy cores: clinical and pathogenetic significance

Prostatic adenocarcinoma (PAC) is a multifocal disease. In this study, we identified isolated and small foci of PAC (ISPAC) in radical prostatectomy specimens, described the histopathologic features, investigated their zonal distribution in the prostate and their relationship with large tumor nodules, and correlated the findings with those of preceding biopsy cores. One hundred and thirty radical prostatectomy specimens performed for PAC or for urothelial carcinoma of the urinary bladder with incidental PAC were reviewed for identification of ISPAC. Prostates were serially sectioned in the horizontal plane and submitted in toto for microscopic examination. ISPAC were defined as foci of PAC measuring less than 3 mm in maximum diameter. There were 461 ISPAC identified in 114 cases. They were distributed in the transitional zone (TZ) (18 foci), the apex (73 foci), the anterior horn of the non-TZ (NTZ) (118 foci), the base (8 foci), and the remaining NTZ (244 foci). ISPAC usually consisted of groups of small acini with a GS ranging from 2 to 7 (3 + 4). GSs of ISPAC consisted of single grade or two consecutive grades equal to or lower than those of the main PAC. ISPAC were more often located in close proximity to large tumor nodules. The number of ISPAC increased with the tumor volume up to 3 cm3, then decreased as the PAC became more extensive (p value = 0.02, statistically significant). Prostates with NTZ PAC <1.5 cm3 and TZ PAC or prostates containing 4 or more than 4 ISPAC tended to be frequently associated with small foci of PAC in biopsy cores In this study, we identified ISPAC that likely represent foci of PAC in early development and account for the multicentricity and heterogeneity of PAC. ISPAC in the NTZ were common and may account for small foci of PAC or atypia in biopsy cores. Although these small foci of PAC or atypia in biopsy cores without accompanying higher GS PAC were often associated with significant PAC, they may also occasionally represent insignificant or vanishing PAC in subsequent radical prostatectomies.     

Guidelines for management of glycogen storage disease type I—European study on glycogen storage disease type I (ESGSD I)

Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods of dietary and pharmacological treatment. Based on the data of the European Study on Glycogen Storage Disease Type I, discussions within this study group, discussions with the participants of the international SHS-symposium ‘Glycogen Storage Disease Type I and II: Recent Developments, Management and Outcome’ (Fulda, Germany; 22–25th November 2000) and on data from the literature, guidelines are presented concerning: (1) diagnosis, prenatal diagnosis and carrier detection; (2) (biomedical) targets; (3) recommendations for dietary treatment; (4) recommendations for pharmacological treatment; (5) metabolic derangement/intercurrent infections/emergency treatment/preparation elective surgery; and (6) management of complications (directly) related to metabolic disturbances and complications which may develop with ageing and their follow-up.Conclusion: In this paper guidelines for the management of GSD I are presented.     

Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I)

Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods of dietary and pharmacological treatment. Based on the data of the European Study on Glycogen Storage Disease Type I, discussions within this study group, discussions with the participants of the international SHS-symposium 'Glycogen Storage Disease Type I and II: Recent Developments, Management and Outcome' (Fulda, Germany; 22-25th November 2000) and on data from the literature, guidelines are presented concerning: (1). diagnosis, prenatal diagnosis and carrier detection; (2). (biomedical) targets; (3). recommendations for dietary treatment; (4). recommendations for pharmacological treatment; (5). metabolic derangement/intercurrent infections/emergency treatment/preparation elective surgery; and (6). management of complications (directly) related to metabolic disturbances and complications which may develop with ageing and their follow-up. CONCLUSION: In this paper guidelines for the management of GSD I are presented.     

Morphometric study of the spleen in chronic Chagas' disease

There is frequently an increase in spleen size in infectious systemic and chronic venous congestion. The aim of this report was to perform a comparative study of the spleen tissue of chagasic or nonchagasic autopsied patients with or without congestive heart failure. Evaluations were made of 111 cases. Connective tissue intensity, follicular density and area, and follicular arterioles wall area were determined through the morphometric study. The connective tissue was similar in all groups. The density of the lymphoid follicles was significantly less among the chagasic cases (P = 0.032). The follicular area was larger among the chagasic cases and in the chagasic group with congestive heart failure. The chagasic group without congestive heart failure presented a greater area of follicular arteriole walls. Therefore, the spleen modifications in chronic Chagas' disease could be a consequence not only of the heart failure but also of the Chagas infection itself.     

The effect of plasma caeruloplasmin levels on the sensitivity for activated protein C

The effect of caeruloplasmin levels on the sensitivity for activated protein C (APC), measured by a clotting assay based on the activated partial thromboplastin time, was investigated in a large group of healthy individuals without factor V Leiden. A modest inverse association between caeruloplasmin and normalized APC sensitivity ratio was found (regression coefficient beta = -0.33 x 10-2; 95% confidence interval, -0.42 x 10-2 to -0.24 x 10-2). After adjustment for sex and oral contraceptive use, this association weakened (beta = -0.19 x 10-2; 95% CI: -0.34 x 10-2 to -0.05 x 10-2). After additional adjustment for factor VIII levels, which are known to influence the assay, the effect of caeruloplasmin on APC sensitivity completely disappeared.     

Osteosarcoma of the temporomandibular joint: report of 2 cases

The aim of this article is to report 2 cases of osteosarcoma of the mandibular condyle, a rare pathological condition, and to emphasize and discuss the usefulness of different imaging modalities in the diagnosis and evaluation of osteosarcoma of the temporomandibular joint. In our assessment of the different imaging modalities, we found that 2-dimensional computed tomograms provide excellent detection of tumor calcification, cortical involvement, and in most instances, soft tissue and intramedullary extension, whereas 3-dimensional computed tomography vascular protocol can help to define the extension of the lesion, improving the visualization of the lesion's relationship to the adjacent anatomical structures. Magnetic resonance imaging is more effective in demonstrating the intramedullary and extraosseous tumor components on T2 weighted images. Because metastasis from body tumors to the maxillofacial region occurs occasionally, it is useful to examine the oral cavity when symptoms first appear and devote special attention to the subtle changes that may indicate early metastatic involvement.     

Corns and calluses resulting from mechanical hyperkeratosis

The formation of corns and calluses can be caused by mechanical stresses from faulty footgear (the wearing of poorly fitting shoes), abnormal foot mechanics (deformity of the foot exerting abnormal pressure), and high levels of activity. Corns and calluses result from hyperkeratosis, a normal physiologic response of the skin to chronic excessive pressure or friction. Treatment should provide symptomatic relief and alleviate the underlying mechanical cause. The lesions will usually disappear following the removal of the causative mechanical forces. Most lesions can be managed conservatively by the use of properly fitting shoes and padding to redistribute mechanical forces. Surgery is only indicated if conservative measures fail and should be aimed at correcting the abnormal mechanical stresses.