A new childhood T-cell lymphoma established in nude mice and in vitro.

A T-lymphoma cell line was established from a lymph node biopsy of a boy currently alive in complete remission. Neoplastic cells from this biopsy did not grow in vitro, whereas they formed a progressively growing s.c. tumor in splenectomized and sublethally irradiated nude mice and became serially transplantable in splenectomized and sublethally irradiated nude mice with a stable latency time. After the fourth transplant, cells were stored in liquid nitrogen and referred to as ST-4 cells. ST-4 cells display a membrane phenotype and a karyotype similar to that of the biopsy cells. After thawing, ST-4 cells grow both in splenectomized and sublethally irradiated nude mice and in vitro. They do not secrete interferon or interleukin 2, do not have natural killer activity, and do not respond to mitogen or alloantigen stimulation. The stable features of these T-lymphoma cells and the availability of normal autologous lymphocytes from the patient make this in vivo system quite unique and of importance for studies in tumor immunotherapy.

In vitro and in vivo susceptibility of human leukemic cells to lymphokine activated killer activity.

The susceptibility of human myeloid and lymphoid leukemic blasts to the lytic action of recombinant interleukin-2 (rIL-2)-generated lymphokine activated killer (LAK) cells was analyzed. With the exception of the K562 cell line, all 9 leukemic cell lines tested were resistant to the natural killer activity of freshly isolated peripheral blood lymphocytes (PBL) from healthy donors but were susceptible to the lytic action of PBL cultured for 3 days in the presence of rIL-2. Of the 32 primary myeloid and lymphoid acute leukemia samples investigated, the great majority were natural killer cell-resistant but were variably sensitive to LAK effectors. Variations in LAK activity were observed according to the donor of PBL, while little or no difference was documented in the capacity to elicit LAK activity of PBL cultured with 100 or 1,000 U of rIL-2/ml. Pretreatment of the leukemic target cells with neuraminidase did not increase substantially their sensitivity to LAK activity. LAK cells generated from the PBL of patients at the onset of the disease or in complete clinicohematological remission lysed Raji cells as efficiently as normal LAK effectors. Finally, LAK cells were capable of abrogating the tumor growth in nude mice of a human leukemic T cell line. These findings demonstrate the susceptibility in vitro and in vivo of human leukemic blasts to the lytic effect of LAK cells and point to a possible clinical exploitment of this new form of adoptive immunotherapy in the management of acute leukemia.

Serial transplantation of a human acute T lymphoblastic leukemia into nude mice.

A human acute T lymphoblastic leukemia line (PF-382) was serially transplanted into nude mice. No takes were observed in untreated nude mice, whereas solid tumors were observed in splenectomized and total body, sublethally irradiated mice. The minimal tumor-inducing dose and the latency time remained unchanged after the third and fifth serial transplants. Moreover, leukemic cells recovered from the 8th in vivo passages displayed the same differentiation antigens and chromosomal markers as the in vitro PF-382 cell line used for the first transplant. This stable and well-characterized experimental system could be a new model for T-lymphocyte differentiation and immune-reactivity against human leukemias.

[Changes in the phagocytic activity of human polymorphonuclear neutrophils induced in vitro by cefotiam vs 6 other antibiotics]. / Modifiche della attività fagocitaria dei polimorfonucleati neutrofili umani indotta in vitro da cefotiam vs altri 6 antibiotici.

The variation of granulocyte phagocytosis after antibiotic treatment has been studied. The conclusion is drawn that cephalosporins, piperacillin and aztreonam cause an increase of phagocytosis, while rifampicin and gentamicin induce a decrease of this activity.

[Cefixime. Microbiologic, kinetic and clinical profile]. / Cefixime. Profilo microbiologico, cinetico e clinico.

The microbiological, kinetic and clinical profile of cefixime, a IIIrd generation cephalosporin, administered orally, is presented. Cefixime is highly active versus Gram-negative aerobic bacteria while, with respect to Gram-positive bacteria, it is only active against Str. pneumoniae, Str. pyogenes, Str. agalactiae, and Str. bovis. It has no action against anaerobics. Endowed with good kinetics, cefixime possesses a favourable tissue distribution. Cefixime is highly indicated in infections of the upper and lower airways where the aethiology is prevalently due to Str. pneumoniae, H. influenzae and B. catarrhalis, that are extremely sensitive to the antibiotic. It is concluded that the therapeutic armamentarium has been enriched by a new, highly active antibiotic that, administered in a monodese/die, ca satisfy patient compliance.

[The use of thymopentin in preventing acute infectious relapses in elderly subjects with COPD]. / Uso della timopentina nella prevenzione delle riacutizzazioni infettive in soggetti anziani affetti da BPCO.

In this study the authors considered the effectiveness of thymus hormone in the prevention of acute infections within a group of elderly subjects affected by COPD. Ten subjects were considered, nine males and one female in the age included between 65 and 89 years (medium age = 70.2 +/- 6.96 years), with clinical evaluation and altered functional respiratory tests (FEV1 < 70%). The patients were treated with timopentina 50 mg s c three times a week for a month. The following parameters were considered: leucocytes/mm3; lymphocytes/mm3 in standard conditions, in the first and in the second month after the therapy start, contagious episodes two months before and two months after the beginning of therapy. The Authors noticed a real reduction in the relapses of the infectious episodes (11 relapses in the months before therapy and 2 relapses after therapy had begun). Leucocytes/mm3 rates were reduced (8.070 +/- 3.414 in standard conditions, 6.420 +/- 1.041 after 60 days; 0.2 < P < 0.1). Lymphocytes/mm3 rates were increased, 1.579 +/- 752 in standard conditions, 2103 +/- 491 after 60 days 0.2 < P < 0.1). These preliminary data seem to show in the small number of cases considered, the effectiveness of the thymus hormone (thymopentina) in elderly subjects affected by COPD.

[Secretory IgA. Recent progress]. / IgA secretorie. Recenti acquisizioni.

After a brief introduction on the role of the immune system, the paper illustrates the methods of IgA production and their local protective functions. Those pathologies in which the monitoring of IgA levels plays a diagnostic and prognostic role are also described. In conclusion, the current methods used for the correct evaluation of IgA2 titres are discussed: RIA and competitive immunoenzymatic and immunofluorescent tests, although the latter can only be used on biopsy tissue.

[Bacampicillin vs amoxicillin in respiratory pathology]. / Bacampicillina vs amoxicillina in patologia respiratoria.

Clinical research was conducted to evaluate the comparative therapeutic efficacy in respiratory pathology of 800 mg X 2 per diem bacampicillin v. 1000 mg X 2 per diem amoxicillin, both orally administered. The results were more or less identical and are interpreted as indicating the better constant absorption of the precursor, hence its higher concentration gradient that produces a higher antibiotic concentration in the lungs.

[Clinico-epidemiologic findings in a group of patients with acute viral hepatitis]. / Rilievi clinico-epidemiologici su una casistica di epatite virale acuta.

Certain clinical and epidemiological findings among 2262 AVH patients are reported. The patients were all admitted to the A. di Savoia Hospital for Infectious Diseases in Turin over a two-year period.

[Cefoperazone: microbiological, kinetic and clinical studies]. / Cefoperazone: ricerca microbiologica, cinetica e clinica.

In vitro cefoperazone proved more active against the tested gram-negative bacteria than either piperacillin or mezlocillin. When administered in 1 g venous bolus the antibiotic achieved high plasmatic concentrations that were still adequate after 8 hours. 33.2% was excreted by the kidneys and a considerable amount by the biliary way. Cefoperazone produced a clinical cure in 35/36 patients (97.22%). A disulfiram-like effect was noted in 18.18%.

[Cefotiam, a new cephalosporin. Microbiological research, preliminary evaluation of its effect on phagocytosis and clinical multicenter research]. / Cefotiam, nuova cefalosporina. Ricerca microbiologica, valutazione preliminare dell'interferenza sulla fagocitosi e ricerca clinica policentrica.

After a brief review of the data on cefotiam in the literature the report presents the results of microbiological research, a preliminary study into the drug's possible actions on phagocytosis and a polycentric clinical study of 93 cases of broncho-pleuro-pulmonary pathology and one sinusitis of the jaw. In vitro cefotiam was found to have an excellent inhibitory effect on gram positive and gram negative bacteria with MICs50 and 90 respectively 0.2 and 0.8 mcg/ml V. Staph. aureus, Str. pyogenes. E. Coli, K. pneumoniae and Pr. mirabilis. A dose-dependent increase in phagocytosis was noted. The clinical response was excellent with 90.43% (88/94) of the cases achieving clinical and radiological cure or very much improved. Cefotiam was very well tolerated with the appearance of 2/94 skin rashes (2.12%). The liver and kidney parameters showed no change at the end of treatment. No increase in enzymuria was noted during treatment with cefotiam.

[Cephalosporins and enzymuria]. / Cefalosporine ed enzimuria.

Urinary enzyme excretion was studied in 56 patients treated with cephalosporins in order to evaluate their potential nephrotoxicity. Only in 4 out of 56 patients (7%) was increased NAG, gamma-GT, AlP excretion seen. A rapid return to normal values was observed just after the end of the therapy.

[Variations in serum kininase II activity in acute jaundice]. / Variazioni dell'attività sierica kininasica II negli itteri acuti.

An assay of Kininase II activity in the serum of 92 jaundice patients revealed a significant difference between the group with viral hepatitis (268.48 +/- 70.93 U/ml), that with biliary obstructions (133.05 +/- 37.64 U/ml) and with cirrhosis (173.76 +/- 79.56 U/ml). The increase encountered in patients with medical jaundice correlates well with total bilirubinaemia but not with cytolysis enzymes. This suggests failed demolition of ACE by the hepatocyte during cellular stress.

[Social class, mode of admission, severity of illness and hospital mortality: an analysis with "All patient refined DRG" of discharges from the Molinette hospital in Turin]. / Classe sociale, modalità di ricovero, gravità clinica e mortalità ospedaliera: un'analisi con "All Patient Refined--DRG" dei dimessi dall'ospedale Molinette di Torino.

Data available from the standard hospital discharge database (SDO) allow us to explore differences in health conditions according to different indicators of socioeconomic status (SES). We analysed all the patients aged 30-59, discharged from the S. Giovanni Battista (Molinette) hospital (the main general hospital in Turin, Italy) during three years (1996-1998) (n = 49949). Three health indicators were used as outcomes: a) emergency admission; b) severity of illness (according to the "All Patient Refined DRGs" subclasses); c) hospital mortality. Patients were compared for each outcome according to two different SES indicators: a) level of education; b) employment status. Logistic regression models (both conditional and unconditional) were used to adjust for several potential confounders. Patients with lower education (up to 5 years of schooling), compared to those with 13 or more years of schooling, showed a higher probability of being admitted through the emergency ward (29.1% vs 23.3%), with an odds ratio (OR) = 1.56-95% confidence interval (95% CI) = 1.45-1.68; of being classified in higher severity subclasses of illness (23.3% vs 17.7%, OR = 1.14; 95% CI = 1.07-1.22) and of dying in hospital (2.3% vs 1.6%). However, after adjustment for other prognostic factors (as severity of illness and specific expected mortality), this association disappeared (OR = 1.05, 95% CI = 0.84-1.32). Similar, but somewhat stronger, associations were observed when comparing the unemployed versus the employed. The corresponding figures (ORs; 95% CI) were 1.57 (1.42-1.74) for emergency admission; 1.31 (1.18-1.45) for severity of illness and 1.55 (1.10-2.16) for hospital mortality. In conclusion, this study showed that SES differentials in health are clearly measurable through routine hospital information systems, and documented that patients of low SES, particularly unemployed, experienced a delayed access to hospital, were admitted in poorer general health conditions and had a more unfavourable prognosis.

[Quality of data or quality of care? Comparison of diverse standarization methods by clinical severity, based on the discharge form, in the analysis of hospital mortality]. / Qualità dei dati o qualità dell'assistenza? Confronto tra diversi metodi di standardizzazione per gravità clinica, basati sulla scheda di dimissione, nell'analisi della mortalità ospedaliera.

Using discharge abstract data, we analysed hospital mortality comparing four different methods of risk adjustment. All patients discharged from the S. Giovanni Battista (Molinette) hospital in Turin (Italy) between January 1996 and June 1999 (n = 169,746) were classified with All Patient Refined--Diagnosis Related Groups (APR-DRG). A first analysis evaluated the time trend of hospital mortality by semester. A second analysis compared hospital mortality during the last 12 months among eight units of internal medicine (n = 5592). All comparisons were made through logistic regression models. As the quality of discharge abstracts increased during time and showed variation among units with similar patients, all comparisons were repeated using four models, characterised by increasing predictivity and sensitivity to quality of data. In addition to crude comparisons (A), the other models included as risk factors: B) age and emergency admission; C) same as 'B' plus expected mortality by APR-DRG; D) same as 'B' plus expected mortality by APR-DRG and risk of death subclass. If no risk factors were considered (A), hospital mortality showed an increasing trend, with an odds ratio (OR) of 1.02 by semester, with a 95% confidence interval (CI) between 1.01 and 1.03. The association was weakened when age and mode of admission were taken into account (B) and disappeared when the APR-DRG expected mortality was also considered (C) (OR = 1.00; CI = 0.98-1.01). Finally, if the comparisons were adjusted also for the expected mortality by APR-DRG and risk of death subclass (D) a reversed trend appeared (OR = 0.95; CI = 0.94-0.97). The comparison among the units of internal medicine gave discordant results according to the method used to adjust for confounders. The most striking variations were detected for those units with the best and the worst clinical data. The unit with the poorer clinical data (average number of diagnoses per patient = 2.9) showed a crude OR of 1.38 (CI = 0.99-1.93) and an adjusted OR (D) of 1.71 (CI = 1.10-2.66); the unit with the best quality of data (average number of diagnoses per patient = 4.4) changed the OR from 1.55 (CI = 1.06-2.26) (A) to 0.66 (CI = 0.37-1.17) (D). In conclusion, these results confirm the high sensitivity of the APR-DRG classification to the quality of data and, more in general, suggest to be prudent when using powerful instruments like this to assess quality of care, especially if the quality of data among the units compared is less than optimal or not homogeneous.

Single-dose treatment of lower urinary tract infections with fosfomycin trometamol: preliminary experiences.

In recent years many clinical trials were carried out in order to evaluate the efficacy of single dose therapy in lower urinary tract infections (UTIs). In this trial we treated 26 patients (5 M and 21 F) suffering from lower UTI with an single oral dose of 3 g of fosfomycin trometamol, a new phosphonic acid derivative. The overall cure rate four weeks after treatment was 77% (20 out of 26 patients). A cure rate of 89% (16 out of 18 patients) was observed in adult females with uncomplicated UTI. No patients complained of side effects due to fosfomycin trometamol.

Fluctuations of NK activity in human volunteers receiving vitamin A or a placebo daily.

This paper examines the effect of prolonged daily administration of Vitamin A on NK activity. A placebo and a pill containing 50,000 IU retinol acetate (RA) were taken daily for 120 days by 5 and 6 healthy volunteers respectively. NK activity was determined on days -45, -40, -30 and -10 to calculate each volunteer's inherent variability and then twice a month throughout the administration period. To minimize the experimental variability, an internal control was inserted in each assay. This consisted of two lymphocyte preparations from two healthy individuals divided into cryopreserved aliquots. The cytotoxicity percentage in each assay was corrected against these reference standards and converted into NK values by angular transformation. No increase in NK activity was noted during the study in the group receiving RA. A marked individual variability, however, was noted in both groups.

In vitro and in vivo immunomodulatory activity of an N-9 arginyl hypoxanthine derivative (PCF-39).

A new synthetic derivative, N-alpha-5 (1,6-dihydro-6-oxo-9-purinyl) pentyloxy-carbonyl-L-arginine (PCF-39) has been evaluated in vitro and in vivo in order to clarify its immunopharmacologic profile. In vitro, PCF-39 did not modify spleen cell functions, whereas parenteral administration in mice of 2.5 and 25 mg/kg (50 and 500 micrograms/mouse) induced an increase in spleen and lymph node cellularity that resulted in a significant resistance to the growth of two distinct syngeneic transplanted tumors. These in vivo findings show that PCF-39 is a potent immunotherapeutic agent with an antitumor effect.