2-Butoxyethanol model of haemolysis and disseminated thrombosis in female rats: a preliminary study of the vascular mechanism of osteoarthritis in the temporomandibular joint.

Female rats develop haemolytic anaemia and disseminated thrombosis and infarction in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There is growing evidence that vascular occlusion of the subchondral bone may play a part in some cases of osteoarthritis. The subchondral bone is the main weight bearer as well as the source of the blood supply to the mandibular articular cartilage. Vascular occlusion is thought to be linked to sclerosis of the subchondral bone associated with disintegration of the articular cartilage. The aim of this study was to find out whether this model of haemolysis and disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six female rats were given BE orally for 4 consecutive days and the two control rats were given tap water alone. The rats were killed 26 days after the final dose. The mandibular condyles showed histological and radiological features consistent with osteoarthritis in three of the four experimental rats and in neither of the control rats. These results may support the need to explore the vascular mechanism of osteoarthritis further.

Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: a retrospective study in 700 patients.

Renal involvement as part of systemic lymphoma (LY) is quite frequent, however, primary extranodal renal non-Hodgkin's lymphoma (NHL) is extremely rare, and only about 65 cases have been reported in the world literature. In a retrospective study of renal manifestations in 700 patients with documented LY and chronic lymphocytic leukemia (CLL) seen at our hospital during 1986-95, 83 patients had signs of acute renal failure. Only five of these had proven renal infiltration, but none of them satisfied the criteria for primary renal LY. Glomerulonephritis (GN) has also rarely been reported in association with LY and CLL, and only 37 glomerular lesions in NHL and 42 in CLL have been documented, respectively. GN may precede, coexist, or follow the diagnosis of LY by several years. Of the 42 cases of CLL reported worldwide, 36 had nephrotic syndrome. Renal failure was seen in about one third. The most common glomerular lesion reported is membranoproliferative GN, followed by membranous GN. In our study, we found only five biopsy-proven cases with GN amongst the 700 patients seen. In this report we also briefly describe some rare interesting associated renal syndromes in CLL and NHL.

Bone mineral metabolism in adults with beta-thalassaemia major and intermedia.

Bone disease is an important cause of morbidity in older patients with beta-thalassaemia major and intermedia. We studied 27 women and 23 men with beta-thalassaemia major (37) and intermedia (13) whose mean age was 32.3 +/- 9.7 years. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius was determined by dual-energy X-ray absorbiometry (DXA). The longitudinal change in BMD over a mean of 5.6 years was determined in 19 patients. Serum 25-hydroxyvitamin D, insulin growth factor-1 (IGF-1), bone formation markers bone-alkaline phosphatase, osteocalcin and the resorption marker urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined. The BsmI vitamin D receptor (VDR) gene polymorphism was analysed. Reduced BMD (Z-score < -2) was present in 89%, 62% and 73% of patients in the spine, hip and radius respectively. Vitamin D deficiency was found in 62%, decreased IGF-1 in 72% and increased urinary NTx in 84% of patients. Serum IGF-1 correlated with spine and hip BMD (r = 0.4, r = 0.39, P < 0.01 respectively), and NTx correlated with the hip BMD Z-score (r = 0.35 P < 0.05). The mean annual percentage change in spine BMD was -1.36%. Patients with the VDR BB genotype had lower spine BMD than patients with the bb genotype. In conclusion, bone loss continues in adult thalassaemia patients and is associated with increased bone resorption and decreased IGF-1. The BsmI VDR gene polymorphism is associated with osteopenia in thalassaemia.

Abnormal low and high density lipoproteins in homozygous beta-thalassaemia.

The levels, structure and composition of plasma lipoproteins were determined in 67 patients with homozygous beta-thalassaemia and compared to healthy or heterozygous members of the same families and to patients with either sickle cell or iron deficiency anaemia. Plasma total and LDL and HDL cholesterol levels were low in patients with homozygous beta-thalassaemia and with sickle cell anaemia. Plasma triglycerides did not differ between subjects. The low plasma and lipoprotein cholesterol was independent of age, transfusion requirements and splenectomy. Abnormal structure and composition of lipoproteins was found in homozygous beta-thalassaemia. The LDL was of higher density and was triglyceride-rich and cholesterol ester-poor. HDL separated to three populations. HDL2 was prominent (in spite of low plasma HDL cholesterol). HDL3 was of normal density and an intermediate HDL population, not found in normal subjects, was identified and designated HDL2-3. All three HDL populations were enriched with triglycerides and poor in cholesterol ester content. The modified LDL and HDL particles may then be possibly cleared rapidly from the plasma by activated monocytes and macrophages.

Endometrial glandular haemosiderosis in homozygous beta-thalassaemia.

Female patients with beta-thalassaemia major usually suffer from hypogonadotropic hypogonadism associated with amenorrhea, anovulation and infertility, attributed to the deposition of haemosiderin in the pituitary gland as well as in the ovaries. Pregnancies are rare and, with few exceptions, occur mainly in patients with beta-thalassaemia intermedia. Our study presents histopathological evidence that deposition of haemosiderin occurs in the endometrial glandular epithelium of 3 patients with beta-thalassaemia major. This deposition is mainly evident in the apical part of these cells above the nuclei, and should be taken into consideration as a contributing factor to the infertility in these patients by altering endometrial receptivity for implantation. In 2 patients who received effective iron chelating treatment with desferrioxamine the endometrial haemosiderin deposits either disappeared (patient C.R.), or were significantly reduced (patient G.L.).

Deferoxamine improves left ventricular function in beta-thalassemia.

Serial echocardiographic examinations were made to study the changes in left ventricular (LV) function and wall mass in 35 patients with thalassemia followed up for 5.5 +/- 2 years (mean +/- SD). Twenty patients received deferoxamine sulfate for 2.0 +/- 0.6 years (drug group) and 15 patients did not (nondrug group). Repeated blood transfusions were used to maintain the pretransfusion hemoglobin levels at 9 g/dL (90 g/L). Deferoxamine therapy improved LV function and decreased LV wall mass. Percentage shortening of LV diameter improved in the drug group (5.0% +/- 3.9%) and deteriorated in the nondrug group (-6.8% +/- 5.6%). Similarly, the maximum velocity of LV posterior wall motion improved in the drug group (16.1 +/- 20.1 mm/s) and deteriorated in the nondrug group (-18.3 +/- 19.0 mm/s). Left ventricular wall mass decreased in the drug group when compared with the nondrug group. In a subset of the drug group, pathologic natural deterioration in LV systolic function was reversed by treatment. Correlation studies indicated that frequent blood transfusions together with chelation therapy reduced LV dilatation and wall thickness, but blood transfusions alone did not have the same effect. Thus, treatment of patients with thalassemia with modest blood transfusions and deferoxamine can prevent deterioration and may even improve their LV systolic function, associated probably with arrest and reversal of the pathologic process that increases LV wall mass.