Leucocyte Migration Test and Hypersensitivity to Glafenin

The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.     

Clinical modulation of epirubicin resistance by lonidamine in patients with advanced soft-tissue sarcomas

To determine if lonidamine (LND) could reverse anthracycline resistance In patients with advanced, soft-tissue sarcomas, thirty-six patients were treated with epirubicin (EPI) 120 mg/m(2) i.v. every 3 weeks. Progressive patients were given the same chemotherapy regimen on day 4 in combination with oral LND, 150 mg on day 1, 300 mg on day 2, and 450 mg on days 3 to 5. Among 35 evaluable patients there were 2 complete responses and 3 partial responses (PR) for an overall response rate of 14%. In the group treated with EPI+LND (24 evaluable patients) 2 PR were observed, lasting 3 and 10 months respectively. The overall survivall was 11.5 months. The most common side-effects were myelotoxicity, nausea and vomiting. Clinical cardiotoxicity was. not observed. Only in one patient a >20% decrease in LVEF from baseline was recorded. LND related toxicities were mild to moderate myalgia and photophobia. In a pharmacokinetic study performed parallel to the clinical study, no difference was observed between the parameters derived from EPI and EPI+LND curves except for Vapp. This study indicates that LND may circumvent clinical resistance in some cases without altering chemotherapy related toxicity.     

Doppler echography in the intraoperative assessment of the liver circulation: an experimental study in swine

In this experimental study the authors report an experience in the evaluation of hepatic blood flow with intraoperative echo-Doppler during orthotopic liver transplantation and side-to-side or end-to-side portacaval shunt. Doppler ultrasonography studied the flow of portal vein, hepatic artery and inferior vena cava before the recipient hepatectomy, and after reperfusion during liver grafting. Furthermore echo-Doppler of the portal system was performed to confirm portacaval shunt efficacy. Usually intraoperative Doppler ultrasonography may give informations about the patency of the shunt and regarding the development of early hepatic artery thrombosis during liver transplantation, but often unclear is the exact evaluation of the velocity of the blood flow through the liver. Further experimental studies and clinical evaluations need to find safe parameters and markers of vascular alteration using this superior diagnostic procedure.     

Current data on GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) in acute myeloid leukemia]

GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) activates neutrophil, eosinophil, granular, and macrophage precursors through binding to specific receptors. GM-CSF receptor is a member of the "cytokine receptor superfamily", which displays a particular transmembrane structure. It is expressed in small amounts on normal mature blood or medullary cells, with a high affinity. On acute myeloid leukemia blasts (18 patients), our results agree with the review of the literature: GM-CSF receptors are in small amounts, of two types (high and low affinity), with no relation to the FAB classification of leukemias.     

Invivo control of tumor-growth by lonidamine and radiations - influence of the timing and sequence of drug administration and irradiation treatment

It has been well established that Lonidamine (LND), [1,(2,4 dichlorobenzyl)-1H-indazol-3-carboxylic acid], affects tumor growth and enhances the effect of X-ray both in vitro and in vivo. Nevertheless, difficulties arise if the available experimental data should be utilized to design clinical trials since schedules, routes of administration as well as dosages greatly differ from those currently employed in the clinic. With the aim to overcome these difficulties, experiments with modalities similar to those employed in the current clinical practice have been undertaken to evaluate: (i) the influence of the LND dosage on the antitumor effect; (ii) the time lenght of its administration for the optimal effect; (iii) the best schedule of treatment when LND is associated with radiations. The results may be summarized as follows: (i) antitumor effectiveness of LND, in terms of growth delay, increases with LND dosage. Moreover, the drug administered from the day of transplant significantly decreases the tumor takes. (ii) to exert the antineoplastic effect LND must be administered continuosly because if the treatment is interrupted the tumor regrows like an untreated one. (iii) the maximal response of the association X-ray-LND is elicited when the drug is given after irradiation treatment.     

Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.