[Carbamazepine-induced agranulocytosis. Apropos of 2 cases]. / Agranulocitosi indotta da carbamazepina. A proposito di due casi.

Carbamazepine-induced agranulocytosis (CIA) is a rare event. We report on two cases, highlighting the wide variability of the bone marrow, which may show pseudohypercellularity with disappearance of neutrophils and excess of immature cells (myeloblasts and promyelocytes), thus mimicking the features of acute myeloid leukemia. Although its pathogenesis is still unclear, CIA must be considered as an idiosyncratic hemopathy and moreover it appears to be an unpredictable complication among patients taking the drug. It should be clearly distinguished from the benign neutropenia frequently associated with carbamazepine therapy and often self-limiting. Anyhow a careful clinical and hematological monitoring is the only mean to recognize promptly this life-threatening disease and to treat it with the withdrawal of the drug and the administration of an adequate anti-infectious therapy.

[2 cases of acute cholestasis caused by ticlopidine]. / Due casi di colestasi acuta da ticlopidina.

We report the case of two patients suffered from cholestatic jaundice occurred 3-4 weeks after starting ticlopidine therapy. In both cases the diagnosis was made by ruling out any other known cause of acute hepatitis or cholestasis. One patient underwent liver biopsy, which showed a typical intralobular cholestatic pattern and a slight lymphocytic infiltration of the portal tracts. The other patient, a 29 year-old woman, was taking ticlopidine as the sole drug, further to an ischemic stroke occurred while she was taking oral contraceptives; she presented a diffuse itchy dermatitis, fever and slight eosinophilia besides cholestasis. In both patients ticlopidine was discontinued and liver tests returned to normal values within 4-8 weeks; no rechallenge was attempted and ticlopidine was replaced with another antiplatelet drug. To the best of our knowledge 19 cases of ticlopidine-related cholestatic disease have been described so far in the literature. Its pathogenesis is still unknown, although some clinical findings and experimental results from patients with acute enteropathy or agranulocytosis induced by ticlopidine suggest that the drug may act through a toxic mechanism, perhaps mediated by prostaglandins.

[Primary thrombocythemia in a female carrier of IgA deficiency]. / Trombocitemia primitiva in portatrice di deficit di IgA.

We describe a case of essential thrombocythemia observed in a 67-year-old woman with severe IgA-deficiency. The the best of our knowledge, this is the first report concerning the onset of a chronic myeloproliferative disease (CMPD) in a patient affected with primary immunodeficiency, in particular IgA-defect. The association may be merely coincidental; otherwise hemopoietic growth factors acting on myeloid progenitor cells could play a role in this relationship. It has recently been shown that serum levels of many cytokines are elevated in patients with CMPD and probably contribute to enhance proliferation of the malignant clones; on the other hand interleukin-6 seems to account for reactive thrombocytosis, and significant amounts of circulating interleukin-4 and interleukin-6 have been detected in IgA-deficient patients. Overproduction of the two cytokines may depend on recurrent infections, but it could also represent a primary abnormality, with a putative role in the pathogenesis of the immune defect. These findings suggest that high levels of growth factors could induce myeloid hyperproliferation and so expose stem cells to genetic mutations responsible for malignant transformation.

[Myocardial infarction caused by accidental electrocution. Apropos of a case with an 8-year follow-up]. / Infarto miocardico da elettrocuzione. A proposito di un caso seguito per 8 anni.

We report on a case of non-fatal myocardial infarction (MI) after electrocution. The diagnosis was made on the basis of electrocardiographic and enzymatic changes and was supported by the results of two-dimensional echocardiogram and radio-nuclide scans, showing segmental hypoperfusion and wall motion abnormalities. The patient was followed for over 8 years, evaluating the evolution of cardiac damage with the above tests. MI associated with electrical injury is very likely overestimated, owing to the low specificity of classical diagnostic criteria, such as ECG changes and CK-MB elevation, and the short monitoring of survivors. We suggest that non-invasive functional methods, exploring myocardial perfusion and ventricular kinesis, and a longer follow-up can reliably assess the prevalence of this complication.

[Immune hemolytic anemia and acute kidney failure due to rifampicin]. / Anemia immunoemolitica e insufficienza renale acuta da rifampicina.

A case is reported of hemolytic anemia following rifampicin administration and complicated by acute renal failure. Furthermore clotting analyses suggested a slight disseminated intravascular coagulation, very likely activated by hemolysis products. Both hemolysis and renal function impairment subsided spontaneously, after the sole withdrawal of rifampin. Direct antiglobulin test became negative within a few days, while an indirect Coomb's test was demonstrated persistently with the patient's serum using red blood cells sensitized in vitro with the drug. Otherwise from all reports in the literature, the patient developed an acute hemolytic anemia while on daily therapy and as many as twenty years after a previous treatment with rifampicin. Mechanisms of drug-induced immune hemolytic anemia and acute nephropathy are discussed (formation of drug-antibody complexes, which adhere on the red blood cells surface and are able to fix complement and induce intravascular hemolysis; tubular necrosis due to hemoglobinuria or immuno-mediated interstitial nephritis).

[Sarcomatous degeneration in Paget disease of bone. Apropos of a clinical case]. / Degenerazione sarcomatosa nella malattia ossea di Paget. A proposito di un caso clinico.

Sarcomatous degeneration is the most dreaded complication of Paget's disease of bone: this case report offers an opportunity for underlining the difficulties of differential diagnosis in a case of pulmonary metastatization in the presence of osteitis deformans. Immunohistochemical assay applied to the cytology of pulmonary needle-aspiration and surgical biopsy targeted to the suspected neoplastic lesion allowed correct diagnosis. This case confirms the very poor prognosis of this kind of neoplasm: the rapidity of the fatal outcome was not significantly influenced even by the most aggressive polychemotherapy. This poor prognosis appears to be related to a more aggressive growth of the neoplasm and to the reduced immunologic resistance of the elderly.

[The emergency treatment of supraventricular tachyarrhythmias: the efficacy and safety of intravenous propafenone]. / II trattamento d'emergenza delle tachiaritmie sopraventricolari: efficacia e sicurezza del propafenone endovena.

One hundred patients, admitted to the Emergency Unit for paroxysmal supraventricular tachycardia (SVT) with 1:1 AV conduction, atrial fibrillation (af) and flutter (AF) of recent onset (less than 72 hours) were treated with intravenous propafenone (P). The drug was administered at the dose of 70 mg over 5 min, repeated after 10 min if sinus rhythm (SR) was not restored and eventually followed by continuous infusion (0.35-0.50 mg/min) until conversion to SR or during the next 48 hours. Exclusion criteria were ventricular rate < 100/min, R-R intervals > 1 s, clinical signs of heart failure or asthma. Termination of SVT within 30 min was obtained in 94% of the patients, while reversion to SR occurred in 79% with af and in 55% with AF. For af and AF conversion was achieved within 30 min in 49% of overall responders (R), between 30 min and 6 hours in 27% and between 6 hours and 48 hours in 24%. The efficacy of P was significantly influenced by the duration of arrhythmia and left atrial size, measured by 2D-echocardiography. On the contrary, no difference was observed between R and non-R in mean age and in the percentage of primary or relapsing arrhythmias. Adverse effects were encountered in 7 patients: in 1 case worsened arrhythmia and in 6 patients, with long-lasting arrhythmias, congestive heart failure. Neither conduction disturbance nor extra-cardiac complications occurred. In conclusion, P provides effective and safe treatment for paroxysmal atrial tachyarrhythmias, so that it can be considered among the drugs of first choice even in non-intensive care units.

[Severe ventricular arrhythmia secondary to indapamide-induced hypopotassemia]. / Aritmie ventricolari gravi secondarie a ipopotassiemia indotta dall'indapamide.

We report on two patients, treated with indapamide for mild hypertension, who developed life-threatening ventricular arrhythmias. The former showed severe hypokalemia, QT interval prolongation and "torsade de pointes": the latter, who suffered from ischemic heart disease, had slightly decreased serum potassium and ventricular fibrillation. In both cases no other cause accounting for hypokalemia and ventricular arrhythmia was found. Therefore we stress that serum potassium and ECG must be carefully monitored during indapamide therapy, mainly in patients with cardiac disease.

Cold agglutinin hemolytic anemia in a patient with adult-onset Still's disease.

We report on a patient with adult Still's disease who developed, at the onset of her illness, an autoimmune hemolytic anemia (AHA) due to cold agglutinin (CA). Hemolysis spontaneously subsided and CA disappeared before starting therapy with aspirin and prednisone. The occurrence of AHA in patients affected with collagen diseases is currently explained by a loss of tolerance, leading to the emergence of multiple autoreactive clones. In our case the self-limiting course of AHA leads us to propose another interpretation, i.e. that the cold reactive autoantibody might have been related to a transient infection able to play a pathogenetic role in the systemic disease, as suggested by several authors.

[Acute hybrid leukemia. Review of the literature and presentation of a case]. / La leucemia acuta ibrida. Rassegna della letteratura e illustrazione di un caso.

In the last years, the development of immunophenotypic and molecular analyses allowed to recognize several cases of hybrid acute leukemia (AL), whose blast cell display both lymphoid and myeloid features. Hybrid, or mixed-lineage, AL seems to have distinct clinical manifestations and hematological findings, and is mainly characterized by resistance to chemotherapy and poor prognosis. We report on a patient with AL, which showed a very rapid switch from the lymphoblastic phenotype exhibited at presentation to a myelomonoblastic one, appeared at first relapse, and lastly progressed to an undifferentiated leukemia in the terminal phase. Together with this morphologic and cytochemical evolution, leukemic cells expressed, besides the primary early-B antigens, new immunological markers related to T-lymphocytic and myeloid lineages. Based on this observation and current understanding of the ontogenesis of hematologic malignancies, we discuss biological mechanisms which are likely to underlie hybrid leukemia.

[Polycythemia vera and hemoregulator hormones. Considerations on an unusual clinical case]. / Policitemia vera e ormoni emoregolatori. Considerazioni su di un caso clinico insolito.

The case is reported of a patient with polycythemia vera, who developed an anterior panhypopituitarism, due to an adenoma, some years later. The endocrine deficiency caused the return of the hemoglobin count and global red cell volume to the normal range. The finding suggests that in polycythemia vera the neoplastic growth is still partially responsive to normal hemoregulator factors.

[Myocardial infarct following a negative maximal exercise test: apropos of a case]. / Infarto miocardico dopo prova da sforzo massimale negativa. A proposito di un caso.

A 63-year-old patient, with effort angina diagnosed 3 months previously, suffered a myocardial infarction 6 minutes after a maximal exercise stress test which had given a normal result. Intravenous streptokinase, nitrates and calcium-antagonist treatment were performed immediately, but they failed to achieve myocardial re-perfusion. The patient refused coronary arteriography, but one year later underwent a further maximal exercise test, which gave a completely negative result. Here, we discuss hemodynamic mechanism likely to be involved in this rare event, and suggest that coronary arterial spasm might play an important role in inducing delayed myocardial ischemia.

Adrenal failure due to bilateral metastases as the sole manifestation of relapsing lung carcinoma. Report of two cases.

We describe two patients with lung carcinoma in whom adrenal glands were the sole site of tumor relapse, revealed by the appearance of Addison's disease. Both patients showed bilateral adrenal masses on US and/or CAT scans and received hormone replacement therapy, with rapid improvement of their general conditions. One of them, with small-cell carcinoma, could also be treated with further chemotherapy and achieved a second remission. Therefore, we stress that patients with lung carcinoma should be periodically screened for adrenal deposits by US or CAT and undergo prophylactic steroid maintenance whenever metastatic involvement of the glands is detected.

A case of Waldenström macroglobulinemia terminating in acute lymphoblastic leukemia.

A case of acute lymphoblastic leukemia occurring in a patient with Waldenström macroglobulinemia more than 6 years after the onset of the disease is reported. At the time of acute transformation, bone marrow and peripheral blood lymphoid populations were almost entirely represented by lymphoblasts; the serum monoclonal peak had disappeared and no cells bearing surface or intracytoplasmic immunoglobulins were found. This observation suggests that the blast crisis might be derived from a dedifferentiative process within the lymphatic clone of the chronic phase.

[Juvenile myocardial infarct. A description of 2 cases occurring before 20 years of age and a review of the literature]. / L'infarto miocardico giovanile. Descrizione di due casi manifestatisi prima dei 20 anni e revisione della letteratura.

Authors report two cases of myocardial infarction occurred before the age of twenty: the former in a man without risk factors, who had 12 years later a cerebral embolic stroke, caused by a left-ventricular thrombus; the latter in a young woman who was taking oral contraceptives. The review of the literature shows that the prevalence of myocardial infarction in juvenile age is not negligible. Especially in those cases occurred before the age of 35, risk factors, clinical features, coronary angiographic findings and possible pathogenetic mechanisms are quite different from those generally observed in elderly patients. Cigarette smoking and estro-progestinic drugs represent the main risk factors; myocardial infarction is often the first event of ischaemic heart disease and usually effort angina is lacking; several patients have patent coronary arteries or minor (single vessel) lesions and collaterals are generally absent; coronary spasm and/or intravascular thrombosis probably play a predominant pathogenetic role.

[Plasma cell leukemia originating with pleural effusion]. / Leucemia plasmacellulare esordita con versamento pleurico.

A case of plasma cell leukemia, secreting light kappa chains, is reported. It arose in a 62 year old man and was diagnosed on the basis of a bilateral pleural effusion, which showed many plasma cells and plasmoblasts. The patient also presented multiple osteolytic lesions, no adenopathies, or signs of hepatic or splenic infiltration. Cytological, cytochemical, immunological findings and serum beta 2-microglobulin assays demonstrated a highly aggressive plasmacytic proliferation. The clinical and hematological data, particularly the onset of the disease with pleural effusions, identify the case as an intermediate form between the typical plasma cell leukemia reported in the literature and anaplastic myeloma.

Measurement of glomerular filtration rate by impulse synthesis: clinical validation and optimization.

Impulse synthesis is a technique which relies upon the logic of continuous infusion but extracts the clearance value from single-injection data by shifting and adding them until an asymptotic value is attained. This study has been aimed at validating and optimizing clinically the measurement of glomerular filtration rate by impulse synthesis. A single intravenous injection of 51Cr-EDTA has been made in 32 patients and plasma activity monitored over the next 6 h. Glomerular filtration rate computed by a single-exponential fit method (GFR-SEF) has been shown to be significantly (p less than 0.001) overestimated when compared with the glomerular filtration rate obtained by the impulse synthesis technique (GFR-IS) in spite of an excellent (r = 0.989) linear correlation between the two sets of data. On the other hand, the comparison between GFR-IS and 24-h creatinine clearance has not shown any significant difference. Moreover, we have found that in patients with severe renal failure GFR-IS is overestimated when the sampling time span is shortened to 3 h. On the other hand, GFR-IS is slightly underestimated in patients with severe renal failure when the convolution time interval is increased over a few minutes.