Alterations in erythrocyte rheology in patients with severe peripheral vascular disease: 1. Cell volume dependence of erythrocyte rigidity

The erythrocyte rigidity of patients suffering from severe peripheral vascular disease (PVD) was measured by a filtration method using 3 microns pore size filters. Filtration pressures for both PVD patients and normal subjects showed a cell volume dependency, and patient filtration pressures were normalized to cell volume to evaluate intrinsic, ie, nonvolume dependent, abnormalities in erythrocyte deformability. A significant (p less than 0.001) increase in cell rigidity was found in 44 of 54 PVD patients in comparison with volume-matched normal controls. No significant difference was found between patient mean corpusculer hemoglobin (MCH) and normal MCH at any given mean corpuscular volume (MCV), indicating that observed increases in erythrocyte rigidity are not attributable to changes in patient MCH. Therefore, the mechanism of increase in erythrocyte rigidity for PVD patients still needs further investigation into such parameters as levels of adenosine triphosphate,2,3-DPG, and membrane fluidity (calcium- and/or protein-binding membrane, cholesterol and phospholipid content of membrane, etc), as well as other aspects of erythrocyte physiology.     

Histopathological observations in new and classic models of experimental Schistosoma haematobium infections

The authors present marsh rat Holochilus brasiliensis, jirds Meriones shawi and M. unguiculatus as new models of Schistosoma haematobium infection. Histological findings were compared with those of classic models mouse Mus and hamster Mesocricetus. In new models, embryonated eggs were seen in the stool from 90 days post infestation (DPI) and active disease developed from 117 to 175 DPI. Seven out of 10 rodents presented granulomatous and/or chronic cystitis, fibrosis, polyps and urothelial changes: squamous metaplasia, precancerous dysplasia and squamous cell carcinoma of the urinary bladder. In the digestive tract of all new models, granulomas eroded the mucosa, formed inflammatory polyps, infiltrated the wall and accumulated into bilharziomas. In the liver, granulomatous hepatitis surrounded by bilharzial pigment deposit was apparent. Pipe-stem fibrosis involved 4 rodents with precirrhotic changes in 1 and portal hypertension in 2. One female Meriones suffered from granulomatous endometritis and salpingitis. All new models developed pulmonary granulomatosis with associated vascular lesions: giant cell arteritis in 1 rodent, thromboses in 3 and pulmonary hypertension in 4 others. In classic models, 1 Mus presented a squamous cell carcinoma of the urinary bladder while Mesocricetus displayed diverse lesions in digestive and genital tracts, liver and lungs. All tissue lesions, resembling those seen in humans in all points, were far more frequent and severe in new models than in classic ones. Those involving the urinary bladder have never been reported in other models such as monkeys: Pan troglodytes, Cercopithecus aethiops and Cebus apella. A comparison was carried out between different models on the basis of experimental conditions: definitive hosts, number of cercariae used, type and duration of infection. This study clearly demonstrated that Holochilus brasiliensis, Meriones shawi and M. unguiculatus are perfectly adequate models in terms of laboratory facilities. They are helpful in investigating the pathogenic mechanism of some disorders in S. haematobium infection, particularly tumours of the urinary bladder, and this may enhance therapeutic assays.     

Therapy-induced preleukaemia in patients treated for Hodgkin''s lymphoma: clinical and therapeutic relevance of sequential chromosome banding studies

Between January 1978 and December 1982 successful sequential chromosome analyses were carried out on bone marrow cells of five patients previously treated for Hodgkin's lymphoma (HL) presenting unexplained cytopenia or pancytopenia during follow-up. All patients had concurrent morphological examination of bone marrow specimens showing signs of dysplasia and/or hypoplasia, without leukaemic infiltrate. Six other patients treated for HL who had normal haematological parameters served as controls. All the patients with unexplained cytopenias had clonal chromosome abnormalities; monosomy for chromosome No. 5 was the most frequent. No abnormalities were detected in the control group. Two patients have evolved to resistant leukaemia, one died of sepsis before leukaemic conversion while severely neutropenic, and two are in full marrow and cytogenetic recovery after aggressive anti-leukaemic treatment in the pre-leukaemic phase. Our data suggest that cytogenetic studies may be of crucial value in detecting therapy-induced preleukaemia (t-PL) at an early stage of its evolution and in planning appropriate therapy before the establishment of overt leukaemia.     

Bilateral renal embolism during thrombolytic therapy with tissue-type plasminogen activator in a patient with thrombosis of the left ventricle

The authors report a case of bilateral renal embolism during thrombolytic treatment in the acute phase of myocardial infarction in a 77 year old patient in whom echocardiography had shown a left ventricular thrombus. After reviewing the literature, the risk of embolic complications of thrombolytic therapy would seem difficult to evaluate because of the difficulty of diagnosis, but they exist irrespective of the type of thrombolytic agent used.     

Inflammation and Vascular disease: the role of C-reactive protein

Inflammation is an important component of active atherosclerotic disease. C-reactive protein (CRP)is a non-specific inflammatory marker that is increased in inflammatory conditions. Newer more sensitive assays (high sensitivity CRP) can detect the low levels of inflammation associated with vascular disease. CRP levels can give further risk assessment to individuals beyond predictions from traditional risk factors. This measurement is most useful in helping to discriminate risk in intermediate risk patients such as metabolic syndrome patients. Exercise and weight loss have been shown to significantly lower CRP levels. Lipid lowering therapies, especially with the statin class of medications, also lower CRP levels. A reduction in inflammation may be an important component of plaque stabilization and contribute to cardiovascular risk reduction.     

Inflammation and Hras signaling control epithelial–mesenchymal transition during skin tumor progression

Epithelial–mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%–30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic inflammation causes a dramatic reduction in classical papillomas and squamous cell carcinomas (SCCs), but the mice still develop highly invasive carcinomas with EMT properties, reduced levels of Hras and Egfr signaling, and frequent Ink4/Arf deletions. Deletion of Hras from the mouse germline also leads to a strong reduction in squamous tumor development, but tumors now acquire activating Kras mutations and exhibit more aggressive metastatic properties. We propose that invasive carcinomas can arise by different genetic and biological routes dependent on exposure to chronic inflammation and possibly from different target cell populations within the skin. Our data have implications for the use of inhibitors of inflammation or of Ras/Egfr pathway signaling for prevention or treatment of invasive cancers.