Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

Determining when to start antiretroviral treatment (ART) is vitally important for people living with HIV. Yet the optimal point at which to start to maximize clinical benefit remains unknown. In the absence of randomized studies, current guidelines rely on conflicting observational data and expert opinion, and consequently diverge on this point. In the USA, ART is recommended irrespective of CD4 cell count. The World Health Organization now recommends starting ART at a CD4 cell count of 500 cells/µL, while the threshold for the UK and South Africa remains at 350 cells/µL. The Strategic Timing of AntiRetroviral Treatment (START) study, one of the largest clinical trials on the treatment of HIV infection, will answer this question. START compares two treatment strategies: immediate treatment at a CD4 cell count of 500 cells/µL or higher versus deferring treatment until the CD4 cell count decreases to 350 cells/µL or until AIDS develops. START includes seven substudies, five of which will clarify the relative contributions of HIV and ART in common comorbidities. START is fully enrolled and expected to be completed in 2016. HIV advocates support the study's design and have been involved from inception to enrolment. The trial will produce rigorous data on the benefits and risks of earlier treatment. It will inform policy and treatment advocacy globally, benefitting the health of HIV-positive people.

[Tietze's syndrome in the elderly: description of a case and review of the literature]. / La sindrome di Tietze in età avanzata: descrizione di un caso e revisione della letteratura.

A case of Tietze's syndrome in a 62-year-old man and a critical up-to-date review of the literature are reported. Although the etiology of the disease is unknown, it has been suggested that recurrent microtrauma of the anterior chest wall may be implied in the development of characteristic degenerative changes involving single or multiple upper costochondral junction. The syndrome described by Tietze has been more commonly found in older people than previously reported and it seems to be no sex or side prevalence. Because of the benign nature of this disease and its excellent prognosis, the treatment is usually symptomatic. The accumulated data stress the importance of a thorough clinical investigation and the need to exclude severe and lifethreatening conditions in the elderly.

[The clinico-diagnostic and therapeutic considerations in carcinoma of the male breast]. / Considerazioni clinico-diagnostiche e terapeutiche nel carcinoma della mammella maschile.

Three cases of male breast cancer, observed during the last 10 years at the III Surgical Department of the University of Rome "La Sapienza", out of a total of 282 operations performed for mammary carcinoma are reported. In agreement to what reported in the literature the M/F ratio was 1:100. It is pointed out how male breast cancer compared to the female one, involves older subjects. Furthermore, since the disease in males reaches its most advanced stages quite rapidly a radical surgical treatment such as the traditional Halsted operation is mandatory. The prevalence of the histopathological form of invasive ductal carcinoma and the high frequency of intratumoral estradiol and progesterone receptors are confirmed. The latter in many cases allows for adjuvant hormonal therapy and represents, in association with polychemotherapy, a valid alternative to traditional endocrino-surgical therapy, both in terms of long term prognosis and quality of life.

Viral hepatitis: modern aspects of clinical diagnosis.

In these years, more light has been brought into the field of hepatitis viruses, particularly with regard to their biology and etiopathogenesis. Besides, first attempts of specific therapy have been done, thanks to the introduction of interferons. This paper wants to give the main guidelines of up-to-date diagnosis and treatment of hepatitis supported by viral infection.

Effect of SAS 650 (Furofenac) on malondialydehyde production by platelets.

The activity of SAS 650, a new anti-inflammatory drug, on ex vivo and in vitro MDA production by platelets was compared to that of aspirin. The drug induced dose-dependent inhibition of in vitro MDA production by rat and guinea-pig platelets and also had good activity after 30 second of incubation in rat platelets, quicker than aspirin. SAS 650 preincubation reduced the in vitro inhibitory effect of ASA, as shown also by ex vivo experiments. The results of the present study support the involvement of SAS 650 in the platelet cyclooxygenase pathway.

E-rosette positive acute lymphoblastic leukaemia in adolescents and adults.

E-rosetting of leukaemic blast cells is one of the markers of T-cell acute lymphoblastic leukaemia (ALL). In children, E+ ALL has a bad prognosis. In adults, data are scarce. This report provides information on 25 E+ ALL adult patients who have a minimum follow-up time of 36 months. Twenty-two of 25 patients (88%) achieved complete remission (CR) (median duration 16 months), and six of them were alive, relapse-free, and off therapy after 36-81 months, with a 26% projected 6-year relapse-free survival. In 97 patients with E-SmIg- ALL, who were treated at the same Institutions, over the same period of time, and by the same modalities, the outcome of therapy was almost identical: CR 80%, median duration of first CR 15 months, projected 6-year relapse-free survival 15%. The white blood cell (WBC) count at presentation influenced significantly and to the same degree first CR length in both E+ and E- cases. In this adult series, WBC count was not as high as in children. Moreover, a high Hb concentration, a very high WBC count, lymphadenomegaly, and mediastinal involvement, were found more frequently in adolescents and young adults than in adults. Based on these data, it is suggested that in adults E-rosetting as such is not a marker of a poorer prognosis, that some of the typical features of children E+ ALL weaken with age, and that in adults the disease can have a less aggressive character.

Long-term survival in adolescent and adult acute lymphoblastic leukemia.

Among 164 patients with acute lymphoblastic leukemia (ALL) (age greater than 11 years) induced into complete remission at four hospitals in Italy and The Netherlands between 1971-1977, 49 survived for more than three years in continuous complete remission. Features at diagnosis of the 49 long-term survivors were compared with those of the parent group. The long-term survivors presented with significantly lower leukocyte counts and were slightly younger. Late relapses occurred in nine patients after 37-91 months from remission. Of the 45 patients who had all treatment stopped after 24-60 months of continuous remission, seven have relapsed. Relapses, mainly in the marrow, occurred 4-32 months after cessation of therapy, the risk of relapse being greatest in the first year and dropping to zero by the fourth year. ALL appears curable in approximately one fifth of adolescents and adults entering complete remission with adequate chemotherapy.

Adolescent and adult acute lymphoblastic leukemia: prognostic features and outcome of therapy. A study of 293 patients.

The case histories of 293 adolescent and adult patients with acute lymphoblastic leukemia (ALL) first seen and treated between 1969 and 1979 are reviewed. A complete remission (CR) was achieved in 79% of cases. Male sex, advanced age (greater than or equal to 30 yr old), and early CNS involvement were the major determinants of remission failure. Median duration of first CR was 16 mo, with 23 patients (actuarial proportion 25%) alive and relapse-free at 5 yr. The major determinant of first CR length was white blood cell (WBC) count (best cut-off value at 35 X 10(9)/liter). First CR length was also negatively affected by early CNS involvement, morphological FAB L3 subtype, and B-cell (Smlg+) leukemia, but these features were significantly associated with a high WBC count. First CR length in patients 11-15 yr old did not differ significantly from that of patients 16-59 yr old. The negative prognostic value of T-cell (E+) leukemia was not confirmed in this adult series. CNS prophylaxis provided an effective protection against CNS relapse. Maintenance chemotherapy was apparently more effective when 4 or more than 4 drugs were employed. "Low risk" patients (WBC count less than 35 X 10(9)/liter still relapsed rather frequently (32% at 1 yr, 49% at 2 yr), with 33% of them alive and relapse-free at 5 yr. "High risk" patients (WBC count greater than or equal to 35 X 10(9)/liter +/- early CNS involvement +/- morphological L3 subtype +/- B-cell leukemia) relapsed very quickly (50% at 6 mo. 70% at 1 yr), with only 6% of them relapse-free at 5 yr.

Vindesine effect in myeloid leukemia.

Vindesine (VDS), a semisynthetic vinca alkaloid derivative, was given weekly at a dose of 3 mg/m2 as single-agent chemotherapy to seven patients with chronic myeloid leukemia (CML), 17 patients with chronic myeloid leukemia in blastic metamorphosis (CML/BM), and 12 patients with acute nonlymphocytic leukemia (ANLL). A substantial and rapid decrease of leukemic cells was obtained in 31 of 36 patients, and this was independent of cell phenotype and morphology. VDS may improve the results of polychemotherapy of ANLL, and is useful for palliative treatment of CML/BM.

Rectal absorption of some glycosaminoglycan sulphates and heparin in rats.

A standardized extract of glycosaminoglycan sulphates containing heparin, with a low affinity for antithrombin III, and a commercial heparin were administered to rats, by the rectal route. When the glycosaminoglycan sulphates were given in oil emulsion with sodium laurylsarcosinate as surfactant, 1 mg kg-1 and 3 mg kg-1 were sufficient for the clearing and anticoagulant activities, respectively. The rectal absorption of glycosaminoglycans after dosing with a suitable 'promoter' produced dose-dependent effects and their kinetics were comparable to those obtained after intramuscular administration. The oil emulsion improved the bioavailability of glycosaminoglycan sulphates at least 20 times.

Staging of chronic myeloid leukaemia.

The prognostic value of nine clinical and haematological features, recorded at diagnosis in chronic myeloid leukaemia (CML), was analysed in two distinct series of patients. One series (116 cases) was collected at a single hospital over a 12-year period. The second series (139 cases) was collected from a multicentre trial over a 20-month period. Six features were associated with a poor prognosis: splenomegaly (more than 15 cm below the costal margin), hepatomegaly (more than 6 cm below the costal margin), thrombocytopenia (< 150 X 10(9)/l) or thrombocytosis (> 500 X 10(9)/l), a leucocyte count above 100 X 10(9)/l, peripheral blood non-granulated precursors (blast cells) above 1%, and peripheral blood granulated precursors (promyelocytes and myelocytes) above 20%. Depending on the number of negative prognostic factors, patients were divided into three categories: group I (0 or 1 factor), group II (2 or 3 factors) and group III (4,5 or 6 factors). Survival was significantly different in the three groups (P < 0.0005), and this was independent of age (below and above 50). The prognostic value of the classification was confirmed in a third series of 153 patients. We suggest that this classification provides a useful tool to identify prognostic categories in CML, and thus allows a proper allocation of patients to different therapies.

Defibrination in adult acute lymphoblastic leukaemia. Report of four cases.

Defibrination is a rare event in acute lymphoblastic leukaemia (ALL). This paper describes four cases of acute defibrination in a series of 52 adult patients with ALL. All four patients had blood clotting tests consistent with or suggesting defibrination prior to therapy, but haemorrhages and unequivocal laboratory evidence of defibrination developed only after leukaemic blast cells had been destroyed early during therapy for remission induction. All patients received supportive therapy, and three of them were also given a continuous IV heparin infusion. Haemorrhages were controlled and blood clotting tests were improved within 12--48 h.