Circadian variation in the occurrence of fatal pulmonary embolism. Differences depending on sex and age.

Published studies have indicated a circadian variation in the occurrence of several acute cardiovascular events, e.g., myocardial ischemia, myocardial infarction, sudden cardiac death and cardiac arrest. The aim of this study was to determine if there is a circadian variation in the occurrence of fatal pulmonary embolism, and to evaluate possible differences in the temporal pattern in relation to sex and age. 230 cases of fatal pulmonary embolism (74 out-of-hospital and 156 hospitalized) observed in a general hospital over a 9-year period were considered. The total sample was stratified both by sex and into four groups by age including, respectively, subjects aged less than 60 years (group A), between 60 and 69 (group B), between 70 and 79 (group C) and 80 years and over (group D). The data were analyzed by the single cosinor method. A significant morning pattern was found for the total population (p = 0.011), females (p = 0.033), and age subgroups C and D (p = 0.015 and 0.008), with respective acrophases at 11.57, 11.23, 10.54 and 13.24. A morning pattern in the onset of fatal pulmonary embolism is confirmed for the total population, although sex and age seem also to play an important role.

Sudden death in diabetic subjects: evidence for a peculiar circadian variation in occurrence.

Anatomo-physiopathological and chronobiological features of 59 diabetic subjects out of 610 non hospitalized individuals observed for sudden death (SD) in an Emergency Room, over an 8-year period, were studied. Mean age and anatomopathological causes of SD were not different between diabetic (DMs) and non-diabetic subjects (NDs). However the frequency of DMs was higher among subjects who died from circulatory failure death (CFD), rather than from arrhythmic death (AD). Diabetics presented a prevalent peak incidence of SD in the afternoon-late evening; whereas in NDs two peaks were present, respectively in the morning and in the afternoon. According to anatomo-physiopathological causes, DMs presented a higher incidence of acute myocardial infarction (AMI) and CFD between 21:01 and 24:00, whereas in NDs the prevalent peak of AMI was observed in the early afternoon (13:01 to 16:00). Moreover, in DMs SD from acute myocardial failure prevalently occurred in the early afternoon (13:01 to 16:00), whereas in NDs it was uniformly distributed throughout the day. The present study seems to indicate that different anatomo-physiopathological causes of SD may present specific temporal patterns in diabetics.

[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.

Hypoparathyroidism in chronic alcohol intoxication: a preliminary report.

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.

[A "plethora", minor and transient, as an immediate cause of a cerebrovascular accident]. / Una "pletora", minima e fugace, come concausa immediata degli episodi di accidenti vascolari cerebrali.

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.

[Arterial hypertension and syncope in an adult patient with coarctation of the aorta]. / Ipertensione arteriosa e sincope in adulto portatore di stenosi istmica dell'aorta.

An uncommon case of aortal coartactation in an adult patient treated, since five years, for hypertension and faintness is described. The surgical treatment led to complete resolution of her symptomatology without drug therapy.

Acute sublingual nifedipine and adrenergic activation: a chronobiologic attempt of optimized administration in healthy subjects.

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.

[Erythrocyte carbonic anhydrase in subjects on periodic hemodialysis]. / Anidrasi carbonica eritrocitaria in soggetti sottoposti ad emodialisi periodica.

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.

Temporal organization of cerebrovascular accidents: a retrospective, preliminary study about stroke in Ferrara, Italy.

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).

[Isthmic coarctation of the aorta. Description of an anomalous case]. / Coartazione istmica dell'aorta. Descrizione di un caso anomalo.

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.

[Findings in relation to serum and urinary iron in heterozygotic beta-thalassemia]. / Indagine intorno al ferro sierico ed urinario nella beta-talassemia eterozigote.

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.

[The "lamellar cranium": a particular radiologic feature of Cooley's disease]. / Il "cranio lamellare": un particolare aspetto radiologico del morbo di Cooley.

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.

[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.

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.

[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.

[Aseptic necrosis of the head of the femur in Cooley's disease]. / La necrosi asettica della testa del femore nel morbo di Cooley.

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.