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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.

It is well known that osteoporosis is more common in chronic alcoholists than in age-matched controls. Possible aetiological factors could be: malabsorption of calcium and vitamin D, liver disease, abnormal parathyroid function. With this study, the authors investigated parathyroid hormone (PTH) behaviour in thirteen selected patients with alcohol abuse, free from any clinical or humoral sign of hepatopathy, and in ten healthy subjects as a control group. In alcohol abusers a significant reduction of plasmatic PTH, compared to normal calcium levels were found. A possible direct interaction effect between ethyl alcohol and PTH may be suggested, even if further studies are required.

Even if the well-known predisposing factors play an essential role in the realization of cerebrovascular accidents, in these last years the possible importance of the hemoreologic parameters is still a topic under discussion. The authors found a significant increase of the considered hemoreologic parameters (HT, Hb, RBC) in the patients hospitalized for cerebrovascular accidents compared to controls, without differences for gender, even if this increase remained into the limits of normal range. Conversely, no significant differences were found concerning the considered metabolic parameters.

Nifedipine has been shown to increase heart rate and plasma catecholamines, due to an adrenergic activation. Two healthy male subjects, after a period of sinchronization, have self-measured heart rate (HR) every 30 min for two consecutive days through a portable, non invasive, automatic device. The data were then analysed by means of chronobiologic procedures, to verify their personal HR acrophase. Forty-eight hours later, the same subjects repeated the trial, assuming 20 mg of sublingual nifedipine just one hour before their calculated HR acrophase, and data were analysed at the same way. After drug assumption, both HR acrophases and mesors failed to show any modification.

Red cell carbonic anhydrase isoenzymes I and II have been measured by means of cellulose acetate membrane electrophoresis in patients with chronic renal failure and dependent on periodic hemodialysis; these patients showed a chronic anemia due to many factors. Carbonic anhydrase isoenzymes were higher in uremic and anemic patients than in the controls. Since hemoglobin can act as a protons acceptor from the active site of carbonic anhydrase during the hydratation of CO2 (and vice-versa), the increase of carbonic anhydrase can facilitate, via the Bohr effect, the transfer of the oxygen to the peripheral tissues. Therefore an increase of red cell carbonic anhydrase can constitute a compensating mechanism of anemic hypoxia in uremic patients.

An epidemiologic retrospective study was conducted from January 1984 to December 1988 on subjects admitted into the Institute of Semeiotica Medica of the University of Ferrara (as a general medicine, unselective department) and presenting a stroke. Year, month and hour of onset of symptoms in 141 patients (all resident in Ferrara, mean age 74.3 +/- 8.3 years) were carefully recorded. The definition of precise clock hour was reached only in 108 cases. The data were then analyzed by means of Halberg's single cosinor. Time series analysis showed a seasonal pattern of disease onset, characterized by a circannual rhythm with acrophase in late winter - early spring (-83.9 degrees). A significant circadian rhythm was found too, with acrophase at afternoon (-242.8 degrees).

An anomalous (because of the advanced age of its onset) case of isthmic coarctation of the aorta in preductal site observed at the persistence of hypertensive symptomatology associated with cephalgic and lipothymic attacks is reported. Instrumental examinations confirmed the clinical suspicion and resective-reconstructive surgical treatment led to complete resolution of both cause and effect.

A case of acute myelomonocytic leukema is described, which was characterized cytogenetically by the presence of centromeric elongations, somatic crossovers, selective endoreduplication figures, and multiple chromosomal clusters. The demonstration of these phenomena by selective staining techniques for the chromosome bands (Q, C, G and S) and the nucleolar areas (acridine-orange, amido black B 10) raises some biological aspects involved in the proliferation of leukemic cells, such as nucleolar persistance during the metaphase and the non-separation of chromatids in the clusters during the anaphase. These structural abnormalities may represent the background for the explanation of the appearance of subclones in neoplastic disorders.

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.

The incidence of aseptic necrosis of femoral head in homozygous beta-thalassaemia (Cooley's anaemia)--which is indeed significantly high--is not satisfactorily referred in late literature regarding haemolytic syndromes. Therefore, 4 cases of osteonecrosis of femoral head, recently recognized in a series of 280 patients affected by Cooley's anaemia (14.5 0/00) are presented, and a review of hypotheses about the pathogenesis of the lesions is considered. In Cooley's anaemia, the skeletal lesion (osteoporosis) must be believed as a propitious state, in which some other pathogenetic events (i.e. local ischemia, bony age, etc.) and microtraumas overlap. In any case, characteristic blood circulation of the femoral head is the "conditio sine qua non" in developing osteonecrosis.

A case of Mönckeberg's arteriosclerosis associated with Raynaud's phenomenon and diabetes is reported. It is probable that Mönckeberg's arteriosclerosis could provoke a Raynaud's phenomenon when predisposing local conditions, such as microvasculature and/or haemorheological alterations, are present. Finally our findings seem to demonstrate that xeroradiographic investigation is most important for the early diagnosis of the disease.

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.

Since anaemia of varying degree is a quite common finding in heterozygous beta-thalassaemia, a research was done to see if beta-thalassaemia heterozygotes occupationally exposed to long-term continuous external radiation should be more susceptible to haematopoietic damage than non thalassaemic subjects. We examined peripheral haematological findings of 20 beta-thalassaemia heterozygotes previously exposed to a mean of 10.7 mSv, compared with 22 non thalassaemic subjects exposed to 6 mSv, and with 50 not exposed beta-thalassaemia heterozygotes. The obtained results suggest that whole-body external irradiation--with the mean doses reported--does not cause noteworthy changes in beta-thalassaemia heterozygotes.

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.

Mean reticulocyte volume (MRV) and reticulocyte/nonreticulated erythrocyte (R/E) area ratio were determined by a planimetric method in normals and in heterozygous beta-thalassaemia subjects. The MRV in beta-thalassaemia group was significantly less, whereas no difference in the R/E area ratio was observed. These data suggest that in both groups the extent of splenic surface remodeling of the red cells should overlap, whereas the small reticulocyte size of beta-thalassaemia is determined by some alteration of bone marrow function. We suggest that a small MRV in beta-thalassaemia trait could also account for ineffective erythropoiesis, a major bone marrow feature of heterozygous beta-thalassaemia.

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.

The skull in homozygous beta-thalassemia (Cooley's anemia) may present with 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 aspect owing to a variable number of osseous lamellae, arranged so as to be parallel to the inner table. This "lamellated skull" was observed in 16 patients, selected from 150 patients with Cooley's anemia (10.6%). The possible mechanisms are discussed. The pluristratified lamellar osseous production could be brought about by repeated periosteal osteoblastic reaction to the sinusoidal neovascularization associated with marrow hyperplasia in poorly or not at all transfused patients.

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.

The liver macrophages behaviour after cyclophosphamide or total-body irradiation (1000 rads - 60Co) has been studied in the mouse previously injected with colloidal carbon. In these conditions an early increase of carbon-laden macrophages in the central zone of the liver lobules has been observed. Carbon-containing mononuclear cells were also observed in the lumina of the hepatic collecting system. Possible implications of these findings are discussed; a migration of macrophages from the liver to elsewhere is suggested.

Iron status (expressed as serum ferritin and iron levels) has been compared in normal and in heterozygous beta-thalassemic subjects. A higher serum ferritin concentration has been found in beta-thalassemic males, showing, therefore, a shift towards super-normal values of the balance between tissue iron and serum ferritin levels. In beta-thalassemic subjects the serum ferritin levels have been found in the normal range and this seems to be correlated with an adequate and ready iron supply by protein transferrin to hyperplastic bone marrow. The higher urinary iron values in normal male subjects can be explained in this way: a large iron supply from the transferrin to the thalassemic erythroid cells limits the contribution from this protein to the urinary iron.