Thrombotic complications in inflammatory bowel diseases.

Inflammatory bowel disease (IBD), Crohn's Disease (CD) and Ulcerative Colitis (UC) are associated with an increased risk of arterial and venous thromboembolism. A 2 to 3 time fold increased risk of developing thromboembolic complications was reported for IBD patients compared to general population. A systematic literature search was conducted using PubMed, Medline, Scopus, Cochrane database. The key words were: "Inflammatory Bowell Disease", "Crohn's Disease and Thrombosis", "Ulcerative Colitis and Thrombosis", "Thrombosis" and "Inflammatory Bowel Diseases and Thrombosis". Full articles and abstracts were included. Studies such as case reports, letters and commentaries were excluded from the analysis if appropriate data could not be extracted. Although no randomized controlled trials (RCTs) have been established to evaluate the efficacy of thromboprophylaxis in patients with IBD due to the incidence of VTE and PE in such patients, it is highly recommended the adoption of thromboprophylactic measures. Available prophylaxis and treatment options include pharmacological anticoagulant therapy (LMWH-Low Molecular Weight Heparin, Fondaparinux and UH-Unfractionated Heparin) and mechanical prophylaxis. In case of acute VTE patient must be treated with fibrinolytic agents and in selected non-responsive cases vascular surgery. IBD patients have an increased risk of VTE complications. Prophylaxis for VTE should be recommended in all patients who do not show contraindications to treatment.

Alterations of erythropoiesis in chronic uremic patients treated with intermittent hemodialysis.

The in vitro growth of the blood burst-forming cells (BFU-E) of 9 chronic uremic patients, treated with intermittent hemodialysis three times a week has been studied at the time of maximum and minimum level of retained nitrogen catabolites. The effect of uremic sera on the vitro growth of normal BFU-E was also studied. The in vitro growth of blood BFU-E was shown to be greatly reduced in all uremic patients and dialysis did not modify their growth. The sera of uremic patients significantly inhibited the in vitro growth of normal blood BFU-E when it was taken at the time of maximum retention of nitrogen catabolites. However, inhibition of normal BFU-E growth was not seen when uremic sera were taken at the time of minimum retention of nitrogen catabolites. These data seem to indicate a long lasting suppression of BFU-E in chronic uremia due to serum inhibitor/s.

Correlation between blood granulocyte progenitor cells and polymorphonuclear leukocytes. A tentative pathophysiological subgrouping of neutropenic and neutrophilic patients.

Blood granulocyte-macrophage progenitors (CFU-GM) were studied in 116 normal, 32 neutropenic and 22 neutrophilic subjects through a double layer agar culture system. The neutropenic group showed significantly lower than normal mean value of CFU-GM per ml of blood, the blood concentration of CFU-GM being within normal limits in 25/32 subjects (78.1%). The neutrophilic group showed significantly higher than normal mean value of blood CFU-GM, and a normal blood concentration of CFU-GM was found in 17/22 patients (77.3%). Within the neutropenic group the concentration of blood CFU-GM was lower than normal in 5/11 (45.4%) patients with less than 1.1 x 10(9) polymorphonuclear leukocytes (PMN) and only in 2/21 (9.5%) patients with more than 1.1 x 10(9)/1 PMN. Within the neutrophilic group the concentration of blood CFU-GM was normal in all 12 subjects having less than 10.5 x 10(9)/1 PMN, while 5/10 (50%) patients with more than 10.5 x 10(9)/1 PMN had higher than normal blood concentration of CFU-GM. The mean leukocyte CSA of the normal, neutropenic and neutrophilic groups did not differ significantly. Within the neutropenic group the CSA was lower than normal in 3/11 (27%) patients with less than 1.1 x 10(9)/1 PMN and in 2/20 (10%) patients with more than 1.1 x 10(9)/1 PMN. Within the neutrophilic group the CSA was normal in all patients with less than 10.5 x 10(9)/1 PMN and it was higher than normal in 2/10 (20%) patients with more than 10.5 x 10(9)/1 PMN. A pathophysiological approach to both neutropenia and neutrophilia, according to PMN and CFU-GM blood concentration, is discussed.

Comparison between diurnal changes and changes induced by hydrocortisone and epinephrine in circulating myeloid progenitor cells (CFU-GM) in man.

A significant increase from 8 AM to 3 PM was found in both myeloid progenitor cell (CFU-GM) and polymorphonuclear leukocyte (PMN) blood concentration in 45 normal subjects. Diurnal blood (CFU-GM and PMN changes were significantly correlated. Spontaneous diurnal changes in blood CFU-GM levels and in PMN were compared with the changes induced by i. v. administration of hydrocortisone (16 normal volunteers) and of epinephrine (10 normal volunteers). Diurnal changes in CFU-GM and PMN seem to follow a pattern similar to that induced by epinephrine administration. These findings suggest that diurnal changes in CFU-GM reflect mainly a shift of these cells between different blood compartments.

[Transient loss of consciousness: a frequent and difficult problem in emergency service. Retrospective analysis of 391 cases]. / Perdita transitoria di coscienza: un frequente e difficile problema nel pronto soccorso. Analisi retrospettiva di 391 casi.

The present study was designed to evaluate the patients with transient loss of consciousness who are seen in the emergency room and the ways in which they are currently triaged and evaluated, to determine the risk factors influencing their prognosis, and to analyze the aspects of diagnostic evaluation that are most useful. We made a retrospective study of 391 patients with transient loss of consciousness seen at the emergency room of S. Martino hospital. The causes of loss of consciousness, admission decision, diagnostic tests ordered, initial and final diagnoses and mortality are evaluated. The admission decision was influenced by three factors: cause of loss of consciousness, presence of chronic disease, and patient age. The same factors were shown to influence mortality. Full concordance between initial and final diagnosis was only 50 per cent. In 18.6 per cent of patients the cause of loss of consciousness was not identified at dismissal. The history and physical examination were crucial elements in the evaluation of most patients, and only in selected cases did tests such as electrocardiogram, Holter monitoring, electroencephalogram, computerized tomography scan provide diagnostic information.

[Heart arrest]. / L'arresto cardiaco.

Cardiac arrest is one of the leading causes of mortality in industrialized countries and is mainly due to ischemic heart disease. According to ISTAT estimates, approximately 45,000 sudden deaths occur annually in Italy whereas according to the World Health Organization, its incidence is 1 per 1000 persons. The most common cause of cardiac arrest is ventricular fibrillation due to an acute ischemic episode. During acute ischemia the onset of a ventricular tachyarrhythmia is sudden, unpredictable and often irreversible and lethal. Each minute that passes, the probability that the patient survives decreases by 10%. For this reason, the first 10 min are considered to be priceless for an efficacious first aid. The possibility of survival depends on the presence of witnesses, on the heart rhythm and on the resolution of the arrhythmia. In the majority of cases, the latter is possible by means of electrical defibrillation followed by the reestablishment of systolic function. An increase in equipment alone does not suffice for efficacious handling of cardiac arrest occurring outside the hospital premises. Above all, an adequate intervention strategy is required. Ambulance personnel must be well trained and capable of intervening rapidly, possibly within the first 5 min. The key to success lies in the diffusion and proper use of defibrillators. The availability of new generation instruments, the external automatic defibrillators, encourages their widespread use. On the territory, these emergencies are the responsibility of the 118 organization based, according to the characteristics specific to each country, on the regulated coordination between the operative command, the crews and the first-aid means. Strategies for the handling of these emergencies within hospitals have been proposed by the Conference of Bethesda and tend to guarantee an efficacious resuscitation with a maximum latency of 2 min between cardiac arrest and the first electric shock. The diffusion of external automatic defibrillators is a preventive measure. Such equipment has permitted early defibrillation by non-medical first-aid personnel. These instruments contain software capable of recognizing an arrhythmia which may be defibrillated and of instructing the operator whether and when to press the defibrillation button. The latest instruments deliver the shock by means of a biphasic wave necessitating a lesser amount of energy which can be provided by lighter condensers. Thus such equipment weighs just a couple of kilograms. As suggested by ILCOR, for reasons of priority, such instruments should not only be available within hospitals and in ambulances but also on the territory, in particular in more crowded places. The availability of external automatic defibrillators in such places should reduce the time latency before intervention and thus increase survival. The ILCOR guidelines have suggested the constitution of an itinerary team well equipped for defibrillation and composed of trained personnel of State Institutions such as the Municipal Police, Traffic Police and the Fire Brigades. With regard to the majority of arrhythmias amenable to defibrillation which occur at home or in less crowded places, other strategies, such as primary prevention and training programs for categories at increased risk, must be employed. Antiarrhythmic drugs have long been considered the best solution for the prevention and treatment of ventricular tachyarrhythmias. However, the approach to these pathologies has drastically changed during the last few years owing to accumulating evidence in favor of defibrillators which may be implanted for the primary and secondary prevention of malignant ventricular arrhythmias. For patients with previous cardiac arrest, randomized studies have proven the advantages of such an approach compared to medical therapy. On the basis of the above, the guidelines for the use of antiarrhythmic implants have been modified. In most western countries, the laws regarding this aspect of medicine have recently been renewed. In the United States, where there is the "Law of the Good Samaritan", in order to protect and acquit persons who give first-aid, many states have adopted new laws which promote the use of external automatic defibrillators. Following recent dispositions by the President of the United States that defibrillators should be present in all Federal properties and on civil aircraft, a new Federal Law is about to pass. Italy lacks legislation regarding the use of defibrillators: in order to rectify this position, which is still anchored to existing dispositions of the civil and penal codes including those regarding the omission of first-aid, a bill entitled "The definition and modalities of the use of the external cardiac defibrillator" has recently been presented.

Alterations of granulopoiesis in chronic uremic patients treated with intermittent hemodialysis.

Granulocyte-macrophage progenitor cells (CFU-GM), leukocyte colony-stimulating activity (CSA), granuloblast differentiation and proliferation and the effect of uremic serum on the in vitro growth of normal CFU-GM have been studied in 8 chronic uremic patients treated with intermittent hemodialysis three times a week. The studies were performed in the postabsorptive state twice in each patient, that is at the longest and shortest dialytic interval. CFU-GM growth in agar and leukocyte CSA did not differ significantly from the normal level in uremic subjects. The granulocytic and macrophagic differentiation in a liquid culture system was significantly reduced in uremic patients, notwithstanding the appearance of high numbers of undifferentiated blastic cells. The serum of uremic patients had no effect on normal CFU-GM and leukocyte CSA.

Disorders of granulopoiesis in patients with untreated Graves' disease.

Total and differential leucocyte countings, mobilization of the marrow granulocyte reserve with hydrocortisone and growth of blood colony-forming cells (CFU-C) in agar culture have been evaluated in 17 patients with Graves' disease before therapy. Moreover, the myeloid differentiation of blood CFU-C in liquid culture has been studied in 4 patients. Neutropenia was found in only 1 patient (5.9%), while the marrow granulocyte reserve was reduced in 7 out of 15 patients (46.7%). Blood concentration of CFU-C and myeloid differentiation in liquid culture were normal in all patients studied. These data show an abnormal granulopoiesis in a high percentage of patients with untreated Graves' disease. The mechanisms accounting for the reduction of the marrow granulocyte reserve in patients with Graves' disease are discussed.

Mobilization of colony-forming cells (CFU-C) into the peripheral blood of man by hydrocortisone.

The effect of hydrocortisone on blood CFU-C has been studied in six normal subjects through a double layer agar culture system. Increased numbers of CFU-C appeared in the peripheral blood reaching a maximum 366% to 631% increase 5-8 hours after the i.v. administration of the hormone. Contemporary lymphopenia caused a 4 to 10 fold enrichment in the proportion of CFU-C to lymphocytes. Hydrocortisone added in vitro somewhat inhibited the colony growth. The results suggest that the increase of blood CFU-C is due to mobilization from the bone marrow. Hydrocortisone, when compared to other agents, appears to offer some advantages in increasing the blood CFU-C for clinical purposes.

Influence of the spleen on the blood distribution of the colony-forming cells (CFU-C) in man.

The incidence of the blood committed granulocyte progenitor cells (CFU-C) before and after epinephrine administration has been studied in 10 normal, 16 splenomegalic and 8 splenectomized subjects through a double-layer agar culture system. A significant increase of the mean values of CFU-C per milliliter of blood has been observed after epinephrine administration in normal and in splenomegalic subjects. In splenectomized patients the baseline mean values of CFU-C per milliliter of blood were higher than those observed in the other groups of subjects, but they did not increase after epinephrine infusion. The concentration of CFU-C per 10(6) total blood leukocytes was the same in all three groups of subjects and it was not modified by epinephrine administration. Our results seem to indicate that the CFU-C are distributed in two blood compartments, the spleen representing an important section of the marginal compartment of the blood CFU-C.

[Modifications of enzyme activities in rat liver plasma membrane after carbon tetrachloride poisoning]. / Modificazioni dell'attivita' di enzimi di membrana plasmatica nel fegato di ratto intossicato con tetracloruro di carbonio.

Adenylate Cyclase activity is increased in the liver of animals treated with CCl4 (250 ul/100g body wt.) after 30 min. The maximum increase is observed 2 hours after administration of the hepatotoxin. Whereas, 3',5'-nucleotidephosphodiesterase decreases significantly throughout all the experiments. Our results present evidence that there is relationship between Adenylate Cyclase and Phosphodiesterase activity and suggest that intracellular calcium ion may mediate a regulation of the synthesis and degradation of cyclic nucleotides. It is difficult to determine the exact role Ca2+ plays in regulating these two opposing reactions. Thus, in the near future the work in this laboratory will be to define carefully the effects of the CCl4 on ions on these two systems.

Blood granulocyte-macrophage progenitor cell concentrations and differentiation in vitro in patients with hepatic cirrhosis.

Blood granulocyte-macrophage progenitor cells (CFU-GM) and myeloid differentiation were studied in 16 patients with hepatic cirrhosis by culturing blood mononuclear cells in semisolid and in liquid medium. The numbers of CFU-GM from normal and cirrhotic subjects were not significantly different, even when increased numbers of monocyte-macrophagic colonies and decreased numbers of granulocytic colonies were observed in cirrhotic patients. Significantly reduced granulocytic growth and increased monocyte-macrophagic cell growth were found in liquid culture of cirrhotic patients. These data seem to indicate that in hepatic cirrhosis, besides granulocyte sequestration within the spleen, there is a disorder of granulocytic versus monocyte-macrophagic differentiation.