Combination salvage chemotherapy with MIZE (ifosfamide-mesna, idarubicin and etoposide) for relapsing or refractory lymphoma.

In this study, 54 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory disease's patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.

Antinociceptive and behavioral effects of synthetic deltorphin analogs.

A possible correlation of behavioral, antinociceptive and cataleptic responses with central delta- and mu-opioid receptor stimulation was tested for in the rat by i.c.v. injections of some synthetic deltorphin analogs. At doses ranging from 0.1 to 3.0 nmol/rat, the selective delta-opioid receptor agonist, [D-Ala2,Glu4]deltorphin (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), induced a dose-dependent stereotyped pattern of locomotor activity, reaching the maximum in the first 30 min; doses higher than 30 nmol induced early and fleeting antinociception. The replacement of Glu4 by Gly, Ala, Val, His or Asn yielded peptides with a lower delta-selectivity because of a gain in mu-affinity. [D-Ala2,Ala4]deltorphin (0.14-4.0 nmol) induced negligible behavioral stimulation but a rapidly appearing and long-lasting analgesia and catalepsy. The other four synthetic peptides induced biphasic effects: low dosages stimulated locomotion whereas higher doses initially suppressed, then increased locomotor activity. At doses ranging from 1 to 70 nmol all the peptides induced analgesia and catalepsy. In experiments examining the locomotor and antinociceptive effects induced by 14 nmol of [D-Ala2,Gly4]deltorphin in rats pretreated with mu and delta antagonists, the non-selective mu-opioid receptor antagonist, naloxone (1 mg/kg i.p.), reduced analgesia and abolished the initial hypolocomotion. The delta-selective antagonist, naltrindole (10 mg/kg i.p.), abolished locomotor activity without affecting analgesia. The mu1 -selective antagonist, naloxonazine (10 mg/kg i.v.), seemed to prolong analgesia and immobility. Hence this peptide appears to activate, in addition to delta-receptors, mainly the opioid receptor mu2-subtype, which mediates catalepsy in the rat. We suggest that the mu2- and delta-opioid receptors of the rat brain modulate locomotor behavior by activating functionally opposed responses. [D-Ala2,Ala4]deltorphin had an antinociceptive and cataleptic potency higher than would have been expected from its mu-affinity. A possible explanation might be a mu/delta-opioid receptor interaction.

Behavioural effects of deltorphins in rats.

When given i.c.v. in rats deltorphins induced a syndrome of behavioural stimulation consisting of increased locomotion rearing and sniffing. The increased locomotor activity and rearing were dose-related over the range of 0.13 to 3.8 nmol/rat for [D-Ala2]deltorphin II (DADELT II) and 1.04 to 20.8 nmol/rat for deltorphin. The delta-selective antagonist, naltrindole (10 mg/kg i.p.), completely abolished the behavioural stimulation induced by 1.3 nmol/rat of DADELT II and shifted the dose-response curve to the right, without decreasing the maximum effect. The mu-preferring antagonist, naloxone, was able to antagonize the DADELT II-induced locomotor activity but only at very high doses (10 and 20 mg/kg i.p.). The i.v. administration of a large dose (10 mg/kg) of the mu 1-selective antagonist, naloxonazine, did not affect the DADELT II response. At doses up to 38 nmol/rat, the i.c.v. injection of DADELT II never induced analgesia. At doses over 20.8 nmol/rat, deltorphin always induced spontaneous controlateral barrel rotations and circling, responses which were not blocked by prior administration of naloxone or haloperidol. In studies performed on the social behaviour of rats, i.c.v. administration of 0.38 nmol/rat of DADELT II was ineffective, while 1.3 nmol/rat increased the number of social contacts. Regression analysis showed that the increase in social contacts was a primary effect of the peptide, not correlated with the increased locomotor activity.

Effects of sauvagine, urotensin I and CRF on food intake in rats.

Sauvagine (SV) is a forty amino acid peptide, isolated from the skin of the South American frog Phyllomedusa sauvagei and structurally related to fish Urotensin I (U1) and to mammalian corticotropin releasing factor (CRF). Intracerebroventricular (ICV) injections of SV (0.3-2.0 micrograms/rat), CRF (1.0-15.0 micrograms/rat) and U1 (0.5-2.0 micrograms/rat) inhibited feeding in 18 hr food deprived rats. By subcutaneous (SC) route, only SV (3.0-10.0 micrograms/kg) and U1 (10.0-20.0 micrograms/kg) exhibited anorexogenic effects, CRF being completely inactive up to a dose of 200 micrograms/kg. Vagotomy did not prevent the feeding inhibition by SC SV. In ICV injected rats, CRF increased grooming in comparison with both food deprived and satiated controls, while SV and U1 increased grooming only in comparison with fasted controls. Compared to satiated animals, food deprived rats when injected ICV with anorexogenic doses of the peptides showed decreased resting and increased moving. Rats given SC injections of SV and U1 significantly decreased grooming in comparison with both food deprived and satiated controls, while increased resting only in comparison with fasted controls. CRF by the SC route did not affect the behaviour of the rat.

[Phage typing of the "Staphylococcus epidermidia" (author's transl)]. / La tipizzazione fagica dello "Staphylococcus epidermidis".

Serious infections due to hospital-transmitted Staphylococcus epidermidis strains have become more and more important and frequent. Therefore, a need for typing methods which characterize St. epidermidis strains for epidermiological purpose is increasing. Only a few data are available for the phage typing of those strains and the aim of our paper has been to set them up.

["Staphylococcus saprophyticus": a little known Staphylococcus (author's transl)]. / Lo "Staphylococcus saprophyticus": uno stafilococco poco noto.

Enzymatic patterns, antibiotic sensitivity, penicillinase, production, mercury ion resistance have been studied in St. saprophyticus strains in comparison with St. epidermidis, both isolate from urinary infections of hospital patients. The St. saprophyticus has shown to have a lower number of virulence factors, to be more sensitive to antibiotics and to have a lower potential epidemiological value.