Tolbutamide-induced hemolytic anemia.

A 67-year-old female diabetic is presented who developed a Coombs'-positive hemolytic anemia after a year of treatment with tolbutamide. An IgG antibody was identified in the patient's serum that caused the agglutination of both the patient's red blood cells and tolbutamide-coated erythrocytes in the absence of complement. Such a reaction did not occur with the patient's erythrocytes when not exposed to tolbutamide. Agglutination of the patient's serum also occurred with erythrocytes treated with other sulfonylureas (chlorpropamide, glibenclamide, carbutamide) but not with phenacetin.

Erythroblastic islands in the bone marrow of rheumatoid arthritis with anaemia.

An increase of erythroblastic islands with recognizable central macrophages was observed in bone marrow of six rheumatoid arthritis (RA) patients suffering from anaemia. Since erythroblastic islands are more prominent in anaemic conditions associated with ineffective erythropoiesis, it is possible that this morphological finding might be an expression of the increased ineffective erythropoiesis observed in RA patients with anaemia.

An easy diagnostic approach to primary aldosteronism.

The infusion of 40 mEq potassium (aspartate) in 250 ml isotonic 1-fructose at a rate of 20 mEq/h into 5 patients (34-56 years old) with aldosteronoma and 2 patients with bilateral primary aldosteronism consistently raised their mean arterial pressure by 15-20 mmHg. Their pressure values returned to the baseline levels 4-5 h after the infusion. In contrast, in controls (10 patients with idiopathic arterial hypertension, matched for age, sex, and magnitude of the untreated hypertension, and 7 patients with inactive adrenal nodules as incidental findings on upper abdomen ultrasound or computerized tomography) the same procedure caused negligible arterial pressure changes. The cause of the rise in blood pressure observed uniquely in patients with primary aldosteronism after infusion of potassium (aspartate) cannot be accounted for by an increase in plasma aldosterone, blood volume, or plasma angiotensin II. The cause of this response thus remains obscure; nonetheless, this simple procedure may prove useful in differentiating primary aldosteronism from idiopathic hypertension, in excluding the adrenal disorder, and in revealing even its mildest forms.

Platyspondyly in treated beta-thalassemia.

Flattening of the vertebral bodies with a platyspondyly appearance is described in 14 patients selected for evaluation of short stature from 106 patients affected by thalassemia major, who received an intensive transfusion regimen combined with continuous chelation therapy. The vertebral body height/width ratio was decreased at the level of all the investigated tracts, namely, cervical and/or dorsal and/or lumbar. The flattening of the vertebral bodies may be due to suppression of intramedullary hematopoiesis by a high transfusion regimen. The reduced intravertebral pressure due to disturbed hemopoiesis could cause weight-bearing and other biological stresses to provoke a reduction in vertebral body height.

[Leucine arylamidase, lactate dehydrogenase and alkaline phosphatase activity of the urine of normal subjects of infant age]. / Attività enzimatiche di leucin arilamidasi, lattato deidrogenasi e fosfatasi alcalina nelle urine di soggetti sani di età infantile.

Urinary activity of Leucine arylamidase, lactate dahydrogenase and Alkaline phosphatase in 14 healt subjects, ranging from 2 to 10 years are described. Some correlations between enzymatic activities, ratios enzymatic activities/creatininuria and enzymatic activities/dayly proteic clearance are investigated.

[Clinico-radiologic aspects of calcium pyrophosphate dihydrate deposition disease]. / Aspetti clinico-radiologici della malattia da depositi di pirofosfato di calcio diidrato.

Calcium pyrophosphate dihydrate crystal deposition disease is a clinical condition characterised by Gout-like synovitis (pseudogout), calcification on and around the joints and an arthropathy that is radiologically similar to osteoarthritis (chronic pyrophosphate arthropathy). Though all these radiological clinical aspects may coexist in the same patient this is often not the case. An examination of the X-ray data on the 68 cases studied which were diagnosed on the basis of the criteria proposed by McCarty, shows that the disease is relatively common especially in the over-fifties. When chronic pyrophosphate arthropathy is the only clinical manifestation of the disease differential diagnosis from the osteoarthrosis so common in the elderly is difficult and depends on the greater severity and progression of the joint damage that may often affect joints not subjected to weight such as the shoulder, unlike what happens in osteoarthritis.

[Effect of antiblastic polychemotherapy (CMF) on the number of circulating monocytes in patients with breast cancer]. / Effetto della polichemioterapia antiblastica (CMF) sul numero dei monociti circolanti in pazienti affette da cancro della mammella.

The behaviour of the number of circulating monocytes has been studied in 34 patients suffering from breast cancer and subjected to antiblastic polychemotherapy in accordance with the CMF pattern. In 25 patients the absolute number of monocytes fell after treatment, while in 9 it rose. The percentage of monocytopenic patients rose from 29% to 50% of the total series. The pathogenetic mechanisms of this behaviour are discussed and it is emphasized that antiblastic treatment with cytostatic drugs can be included among the causes of monocytopenia.

[Phagocytic lymphocyte-like elements (PLLE) and irradiation in vitro]. / Elementi simil-linfocitari fagocitanti (E.S.L.F.) e irradiazione in vitro.

The peripheral blood of rats contains lymphocyte-like phagocytes after intracardial injection of India ink. In vitro irradiation of whole blood (1000 r - 60Co), causes marked reduction in whole lymphocytes but does not modify the number and morphological integrity of the phagocytes, which can therefore be held to be comparatively radioresistant: as such, they could belong either to the mononucleate phagocyte system or to the lymphatic system (T4 lymphocytes). Since T-lymphocytes are not capable of phagocytosis, the former hypothesis would appear the most probable.

[Radioanalytical methods of determination in vitro of folates and vitamin B 12: diagnostic use in disorders of absorption and utilization]. / Le metodiche radioanalitiche di dosaggio "in vitro" dei folati e della vitamina B12: utilità diagnostica nei difetti di assorbimento ed utilizazione

The blood concentrations of vitamin B12 and folate, which are very useful in diagnosis of megaloblastic anemia and of these factors' dificiencies, are actually measured by precise, rapid, and specific competitive binding radioassays. Futher clinical advantages can be reached with the application of other in vitro radioisotope techniques, such as radioassay of IF, of antibodies anti-IF, of transcobalamins, and of FABP (folic acid binding protein). The major impact of the vitamin B12, folates and other related radioassays has been to permit more Hospitals and laboratories to do these determinations, replacing the more time-consuming, relatively imprecise, and often artifactual microbiological assays.

Growth plate injury of the long bones in treated beta-thalassemia.

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50-80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.

[The evolutionary effects of therapy on the skeletal lesions in beta-thalassemia]. / Effetti dell'evoluzione della terapia sulle lesioni scheletriche nella beta-talassemia.

Up to the mid-1960s, beta-thalassemia was treated with blood transfusions as frequent as needed to keep symptoms under control and to prevent transfusional hemosiderosis. In the following years, high transfusion regimens and iron chelation therapy with desferrioxamine were used. Because of these different treatment modalities, skeletal findings in thalassemia have markedly changed. In the past, thalassemic patients treated with a low transfusion regimen and without chelation therapy developed osteopenia--with widened medullary spaces, cortical thinning and trabecular atrophy--secondary to chronic expansion of red marrow, due to increased erythropoietin response to chronic anemic hypoxia. Typical radiographic patterns in the skull included widened diploic space, atrophic-especially outer--tables and, in some patients, the "hair-on-end" pattern. As for the face, obliteration of the paranasal sinuses and the typical "rodent facies" were observed. In the ribs, bulbous expansion of the posterior and anterior segments and the "rib within a rib" patterns were observed. As for the spine, coarse trabecular arrangement was seen. The "cobweb" pattern was seen in the pelvis and finally the lack of the normal concave outline was observed in the long bones. In the patients treated with high transfusion regimens and iron chelation therapy over the last 30 years, both skull anomalies and disfigurement are less frequent. The skull is almost normal, with the exception of osteopenia and thickened diploic space in the frontal bone only; the paranasal sinuses are usually not obliterated. The hands and rib are normal, just like long bones, pelvis, scapulae and vertebral bodies. Nevertheless, in some adequately treated patients new skeletal features have been recently observed in the long bones, which are similar to those occurring in rickets and/or scurvy, and in the vertebral bodies, resembling platyspondylia. These abnormal features might be caused by several factors--i.e., marrow expansion, transfusion regimens, direct/indirect effects of desferrioxamine, iron load, endocrine abnormalities, deficiency of some minerals and finally dysvitaminoses. Nevertheless, osteopenia remains the main negative factor of thalassemia.

The "lamellated" skull in beta-thalassaemia.

The skull in homozygous beta-thalassaemia may present several abnormalities, such as osteopenia, widening of the diploic space, and a "hair-on-end" appearance. In some cases it presents also a particular stratified appearance caused by a variable number of osseous lamellae, parallel with the inner table. This "lamellated skull" was observed in 16 out of 150 patients affected by the disease (10.6%). Possible mechanisms are discussed. The lamellar osseous changes could be due to repeated periosteal osteoblastic reactions to the sinusoidal neovascularization associated with marrow hyperplasia in poorly transfused patients.

Association between diffuse idiopathic skeletal hyperostosis and multiple myeloma.

OBJECTIVE: To determine whether an association exists between multiple myeloma and diffuse idiopathic skeletal hyperostosis (DISH). DESIGN AND PATIENTS: Radiologic studies were performed over a 26-month period in a series of 97 consecutive patients with multiple myeloma (56 male and 41 female, aged 42-91 years). RESULTS: Both myelomatous bone lesions and hyperostosis similar to DISH were found in these patients. The prevalence of DISH in association with multiple myeloma (21 male and 8 females patients) was higher (29.8%) than in our control group (973 patients, 449 male and 524 female) or in the general population (15-20%). The involved segments of the column were thoracic in 11 males and 7 females, cervical in 8 males and 2 females, and lumbar in 5 males and 4 females. Ossifying enthesopathy in the pelvis ("whiskering") was observed in 7 males and 1 female. CONCLUSIONS: The pathogenesis of hyperostosis remains unknown. It is possible that the coexistence of DISH and multiple myeloma is merely an association. For this reason, it is important for the real prevalence of DISH in the general population to be defined.

[Monoarthritis]. / Le monoartriti.

By definition, monoarticular arthritis means one-joint involvement, even though, in fact, such a condition is often an oligoarthritis because as many as two or three separate joints will be involved. Arthritis is often limited and may regress, so that it is frequently misdiagnosed. Sometimes, a monoarticular condition may be a polyarthritis onset (i.e., rheumatoid arthritis). Monoarticular arthritis can be caused by many factors, such as infections (septic arthritis), nonspecific inflammatory processes (reactive arthritis), crystals deposition (gout, CPPD crystal deposition disease), trauma, neoplasm (pigmented villonodular synovitis), immunologic conditions (amyloidosis) and hormonal changes (parathyroid disease). Its onset is usually acute and sometimes dramatic, with fever, pain and joint swelling, so that a decision must be made promptly to stop rapid illness evolution and to prevent the irreversible destruction of cartilage and bone (especially in septic arthritis). Diagnostic studies are performed with mono-bilateral radiographs of the joint. Radiographic findings (i.e., soft tissue swelling, joint effusion, widening and thinning of joint spaces, bone erosions and destruction of bone surface) are typical of the disease, but some findings (e.g., type of evolution and progression), laboratory tests, synovial biopsy and arthroscopy can differentiate infectious from inflammatory forms. Scintigraphy can depict isotopic joint uptake, before articular abnormalities are demonstrated with radiography, thanks to its high sensitivity; nevertheless, because of its low specificity, scintigraphy may miss some kinds of lesions (including osteoarthritis) and cannot easily differentiate osteomyelitis from septic arthritis. CT and MRI play a secondary, though not negligible, role, especially to study such deep infections as psoas abscesses, which may mimic arthritides.

[Osteoporosis and the thalassemia "trait"]. / Osteoporosi e "trait" talassemico.

The authors evaluated the prevalence of the thalassemia trait in a general population affected with femoral neck fractures. Our research was aimed at assessing whether hemoglobinopathy might affect osteoporosis, which is responsible for femoral fractures. Two hundred and thirty-eight patients admitted to St. Anna Hospital, Ferrara, for proximal femoral fractures, were retrospectively studied. The patients were 68 males and 170 females, aged 58 to 83 years (mean age: 70.4 years). The thalassemia trait was seen in 11.76% of cases, versus in 7-8% of the general population. The high prevalence of heterozygous beta-thalassemic subjects probably means that the beta-thalassemia condition is a further "variable" which is responsible for the more frequent occurrence of fractures of the proximal femur and is certainly related to an osteopenic condition much more severe than usual.

Circumscribed lytic lesions of the thalassaemic skull.

Solitary or multiple circumscribed osteolytic areas are described in seven patients, selected from 250 patients with homozygous beta-thalassaemia (Cooley's anaemia). On X-ray examinations, these areas appear as purely osteolytic lesions with well-defined margins not associated with sclerosis. The possible mechanisms are discussed.

[Ochronotic arthropathy in alkaptonuria. Radiological manifestations and physiopathological signs]. / L'artropatia ocronotica dell'alcaptonuria. Manifestazioni radiologiche e cenni di fisiopatologia.

Alkaptonuria is a rare autosomal recessive metabolic disease, due to the lack of homogentisic acid oxidase. The following accumulation of homogentisic acid brings about a black discoloration of both the urine (alkaptonuria) and connective tissue (ochronosis). The ochronotic alterations into joint cartilages cause degenerative arthropathy and osteopenia. The radiological features of three unrelated cases of alkaptonuria are reported. Radiographic abnormalities of ochronotic arthropathy are found in both the spine and the extraspinal joints. In the spine, the progressive calcification and "vacuum" phenomenon of disc spaces are the most characteristic findings. Disc space narrowing is associated with calcification and marginal sclerosis of vertebral bodies and is accentuated by osteopenia. Osteophytes are usually absent or of small size; nevertheless progressive formation of marginal intervertebral bridges and obliteration of disc spaces at multiple levels ("pseudoblock vertebrae") may occur. In extraspinal sites, space narrowing, bone sclerosis and fragmentation may also be observed. Diagnosis of ochronotic arthropathy is often suggested by radiographs of the spine, and it is confirmed afterwards by clinical and laboratory findings. The characteristic radiological findings of ochronotic spondylitis, in the final stage, include narrowing of at least four lumbar disc spaces, associated with their calcification and "vacuum" phenomenon, "pseudoblock vertebrae", marginal sclerosis and osteopenia of vertebral bodies.