Guiding principles in choosing a therapeutic table for DCI hyperbaric therapy.

Hyperbaric therapy is the basis of treatment for pervasive development disorders. For this reason, the choice of the right therapeutic table for each case is critical. Above all, the delay in recompression time with respect to the first symptoms and to the severity of the case must be considered. In our experience, the use of low-pressure oxygen tables resolves almost all cases if recompression takes place within a short time. When recompression is possible almost immediately, the mechanical effect of reduction on bubble volume due to pressure is of remarkable importance. In these cases, high-pressure tables can be considered. These tables can also be used in severe spinal-cord decompression sickness. The preferred breathing mixture is still disputed. Heliox seems to be favored because it causes fewer problems during the recompression of divers, and above all, because nitrox can cause narcosis and contributes nitrogen. Saturation treatment should be avoided or at least used only in special cases. In cases of arterial gas embolism cerebral injury, it is recommended to start with an initial 6 ATA recompression only if the time between symptom onset and the beginning of recompression is less than a few hours.

Antiangiogenic metronomic chemotherapy and hyperthermia in the palliation of advanced cancer.

Among a large series of cancer patients treated with a combination of chemotherapy and sessions of hyperthermia, particular attention was given to a specific group of patients with advanced cancer who refused standard, aggressive, treatment. In these cases, hyperthermia was associated to low-dose (metronomic) chemotherapy. No toxicity was reported in any of our patients, while a marginal benefit in terms of tumour progression was observed. During therapy, we could detect a coagulative perturbation that deserves careful discussion. In our opinion, this experience should be matter of debate to conclude if current response criteria (WHO/UICC and RECIST) in treating cancer patients are really suitable tools to evaluate new, and non-aggressive anticancer strategies.

Activity of a nitroxylated analog of daunorubicin, ruboxyl, in B-lymphoproliferative disorders.

A nitroxylated analog of daunorubicin, ruboxyl (RBX), showed low toxicity but significant lympholytic effect in preclinical evaluations. A series of studies in vitro and in animals demonstrate that RBX is a putative agent in the treatment of many neoplasms. We report the results of a study in mice in which RBX showed selective B-lymphocyte immunosuppression. On the basis of this experience, RBX was administered to 3 patients with multiple myeloma and two patients with Waldenström's disease. The results of this pilot clinical study show that this compound has good activity and low myelotoxicity and cardiotoxicity, but seems to be characterized by a threatening immunosuppressive effect.

5-fluorouracil modulation in the chemotherapy of colorectal cancer.

More than ten years after the introduction into the clinic of Folinic Acid associated with 5-FU in the treatment of colorectal cancer, it appears that in terms of objective responses, associations with modulating agents are more effective than 5-FU alone. An improvement in survival has been observed in some studies, but this remains a debated subject. Results can probably be further improved by multiple modulation also using Interferon and by a more careful evaluation of drug scheduling. The data on the activity of modulated 5-FU in the adjuvant treatment of colon cancer await the publication of confirmatory trials, but they are already sufficiently convincing to assert that adjuvant treatment should be part of the standard approach to patients with locally advanced colon carcinoma. The comparison of reports from different groups emphasizes the need for protocol standardization and a better description of patients based not only on pathological staging, but also on the biological characteristics of the tumour.

Presence of interferon-gamma and interleukin-6 in colostrum of normal women.

Colostrum and blood samples were obtained on postpartum day 2 and 3 from 17 lactating, healthy women. After delipidation and molecular sieving fractionation of colostrum, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) could be readily measured by using a sensitive immunoassay. Antiviral activity could be also measured in some colostrum samples suggesting that interferon was biologically active. On the contrary, corresponding plasma samples showed negligible activity. These results expand previous data showing the presence of IL-1, tumor necrosis factor (TNF-alpha), and IL-6 in normal colostrum and are in line with the concept of a basal cytokine production in physiological conditions. All of these cytokines probably act on the oropharyngeal and gut-associated lymphoid tissue of the newborn and favor the development and maturation of the immune system.

Naloxone does not modify fenfluramine-induced prolactin increase in obese patients.

OBJECTIVE: To evaluate whether the supposed physiological interaction between serotoninergic and opioidergic pathways in the modulation of PRL release is preserved in human obesity, a pathological condition in which these two systems are greatly impaired. DESIGN: According to a single-blind randomized procedure, three tests were performed: test A (oral placebo + saline infusion over 5 hours), test B (fenfluramine, a well known serotoninergic drug, 60 mg orally + saline infusion over 5 hours) and test C (fenfluramine at the same dose + naloxone, an opiate receptor antagonist, infusion over 5 hours at a dose of 3 mg/h). PATIENTS: Ten obese women (body mass index 34.4 +/- 2.3 kg/m2, mean +/- SE) and ten normal-weight sex and age-matched subjects (body mass index 22.3 +/- 2.4 kg/m2) volunteered for the study. MEASUREMENTS: At each test, blood samples for PRL determination were collected in basal conditions (time 0) and every hour for 5 hours. Plasma PRL was determined by radioimmunoassay. RESULTS: In controls, naloxone significantly reduced the clear-cut PRL increase induced by fenfluramine. In obese patients, serotoninergic stimulation caused an increment in PRL levels similar to that in the controls, but opioid receptor blockade by naloxone did not affect this response. CONCLUSIONS: These findings confirm that there is a physiological relationship between the serotoninergic and the opioidergic systems in the control of PRL secretion and show that this interaction is not present in obese subjects. Our data provide indirect proof of the functional impairment of these two systems in human obesity.

5-Fluorouracil (FU) with folinic acid (FA) and mitomycin C (MMC) in the adjuvant treatment of colorectal carcinoma. Part I. Evaluation of toxicity.

Ninety-six patients with colorectal cancer (stage B2-C) were randomized to the control arm or to receive adjuvant chemotherapy with folinic acid, FU and MMC. Ninety-three patients are evaluable. The median follow up is 12 months. The average time between surgery and the start of therapy is 28 days. Toxicity is evaluable in 36 of 41 treated patients. Four patients (10%) failed to complete the projected treatment due to toxicity. Toxicity observed in 208 courses of therapy was mostly gastrointestinal and hematological. No cases of treatment related death or cancer-associated hemolytic uremic syndrome (C-HUS) were reported. The average relative dose intensity (rDI) of the projected treatment was 82.6%. Our study is ongoing and further patients are required to achieve statistically significant results.

[The heart and central nervous system. Benzodiazepines in cardiovascular psychosomatic medicine]. / Cuore e sistema nervoso centrale. Le benzodiazepine in psicosomatica cardiocircolatoria.

In certain clinical situations, a close correlation between CNS alterations and changes in the normal functioning of the cardiovascular apparatus has been well documented. Thus, it has been shown that a certain type of behavior, termed type A, is significantly associated with coronary disease and other cardiovascular disorders. Stress, too, by activating complex neurohormonal mechanisms can become an important factor in the pathogenesis of these disorders. Systematic management of these disorders has not yet been worked out but centrally acting drugs, and especially benzodiazepines, have been found useful in reducing the stress reaction and the consequent psychosomatic cardiovascular involvement. Some molecules of this class of drugs have been shown to possess marked affinity for the cardiac muscle and to act effectively in control and suppression of the cardiovascular disorders following upon the neuro-hormonal activation caused by stressful events.

Anthracycline in colorectal carcinoma: an in vitro short-term assay to predict drug sensitivity. Preliminary results.

The chemosensitivity of 26 non-pretreated colorectal carcinomas (primary tumors and/or colorectal metastases) was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. Our results correlate with the response rate obtained in clinical studies with monochemotherapy and justify the possibility of a future prospective study using individually tailored chemotherapy regimens. Doxorubicin-analogues, with an overall in vitro efficacy in 16.0% and 14.3% for 4-epidoxorubicin (epi-DX) and 4-deoxydoxorubicin (deo-DX), respectively, seem to deserve a modest role in the treatment of colorectal cancer, provided that a careful selection of patients is performed. Variability in anthracycline activity is indeed evident, also in our study, in relation to the different neoplastic picture of the various patients.

Calcium homeostasis in the first days of life in relation to feeding.

Determinations of serum calcium (Ca), phosphorus (P), magnesium (Mg), calcitonin (CT) and parathyroid hormone (PTH) were carried out in full term newborn infants during the first 168 h of life. The infants were randomly assigned to two different diets: glucose and breast feeding (BF) only or early formula feeding (F). The Ca serum levels decreased from birth to the 24th h; after that time they increased until the 72nd h. The values of serum Ca at the 48th and 72nd h were significantly lower in the F than in the BF group. In contrast, the P serum levels increased from birth to the 48th h and then they decreased; the values of serum P at the 48th h were significantly higher in F than in the BF group. The CT serum levels increased from birth to the 24th h and then they decreased. No difference between the F and BF groups was found during the first 48 h, while at the 72nd h the F group demonstrated significantly higher values of serum CT. PTH serum levels also increased from birth to the 24th h with significantly higher values at the 72nd h in the F group. The results of this investigation demonstrate that the difference in feeding in the first hours of life affects the calcium homeostasis and the secretion of hormones involved in the regulation of serum Ca levels.

Calcitonin and parathyroid hormone in newborn infants with fracture of the clavicle.

Determinations of serum calcium (Ca), phosphorus (P), calcitonin (CT), and parathyroid hormone (PTH) were carried out in 36 full-term newborn infants with fracture of the clavicle (CF) and in 46 normal neonates (N). At the 6th hour of life the CF neonates demonstrated lower serum Ca and higher serum CT in comparison with normal infants. In the hours following, no significant differences between the two groups for the Ca levels were found, whereas serum CT remained significantly higher in the CF newborns at the 24th, 48th, and 72nd hour of life. Significant differences between normal and CF infants in the PTH serum levels were detected only at the 48th hour, when PTH was lower in the CF newborns. The results of this investigation indicate that the fracture of the clavicle is a significant and peculiar factor in stimulating CT secretion. Serum Ca level appeared to be controlled by CT rather than auto-regulating the secretion of the hormone.