Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

BACKGROUND: This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day. METHODS: A prospective study of 100 Italian repeat blood donors was undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin supplementation. All subjects were randomised into four groups: [A] folic acid (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500 mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21 (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF levels were significantly (P<0.01) increased in all supplemented subjects. The median Hcy level was significantly (P=0.008) reduced in subjects supplemented with FA and significantly (P=0.01) increased in those supplemented with vitamin C alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.

Carboxylic acids and skeletal muscle chloride channel conductance: effects on the biological activity induced by the introduction of methyl groups on the aromatic ring of chiral alpha-(4-chloro-phenoxy)alkanoic acids.

One or two methyl groups have been introduced on the aromatic ring of two chiral clofibric acid analogs, 2-(4-chloro-phenoxy)propanoic and 2-(4-chloro-phenoxy)butanoic acids. The biological activity of the derivatives obtained (3-6) has been evaluated on the skeletal muscle chloride conductance (gCl). The results confirm the hypothesis of two different sites modulating chloride channel function, an excitatory site that increases channel activity and an inhibitory site that produces a channel block. In fact, this chemical modification strongly reduces the blocking activity of the (R)- and (S)-enantiomers in comparison with the parent compounds, but does not markedly affect the ability of the (R)-enantiomers to increase chloride channel conductance.

[The identification of the criteria of malignancy and the tissue characterization of expansive processes in periskeletal soft tissues. The current role of magnetic resonance]. / Identificazione dei criteri di malignità e caratterizzazione tissutale dei processi espansivi dei tessuti molli peri-scheletrici. Ruolo attuale della Risonanza Magnetica.

INTRODUCTION: Expansive masses arising from periskeletal soft tissues are a frequent challenge for the imaging specialist. Lesion diagnosis and characterization, and the assessment of benign/malignant nature are very important factors for treatment planning. We investigated MR capabilities in distinguishing benign from malignant masses and for histopathologic lesion characterization, also in the light of the latest most authoritative literature reports. MATERIAL AND METHODS: February 1995 to November 1997, we examined 237 patients with known space-occupying lesions arising from periskeletal soft tissues. T1- and PD/T2-weighted SE images were acquired on the most suitable planes. The findings were independently evaluated by two groups of radiologists who were asked a benignity/malignancy judgment based on specific morphological criteria and then a presumptive histopathologic characterization. The results were then compared with pathologic findings. RESULTS: We had high agreement rates for benignity/malignancy judgements, with only < or = 3.8% error rates. In contrast, rates were quite variable for histopathologic characterization and differed greatly by lesion type. The lesions, defined as malignant, could not be characterized histologically in approximately 18% of cases by both groups. DISCUSSION AND CONCLUSIONS: Our results, which are in substantial agreement with the recent authoritative literature, confirm MRI as an extremely reliable tool for distinguishing benign from malignant expansive masses arising from periskeletal soft tissues. On the contrary, MRI exhibits good specificity in histopathologic characterization only for the masses with such development as to permit identification of the anatomical compartment of origin, which are usually benign, as well as the masses with typical or pathognomonic tissue signal.

Influence of chronic Naltrexone treatment on growth hormone and insulin secretion in obese subjects.

OBJECTIVE: Recent studies have demonstrated the restoration of a normal 24 h GH profile induced by a reduction of insulinaemia after weight loss, suggesting a reciprocal relationship between plasma insulin and GH concentrations. We aimed to clarify if an opiate-induced reduction in plasma insulin could affect GH secretion in obesity. DESIGN: We have studied the insulin response to an oral glucose tolerance test (OGTT) and the GH response to GHRH before and after prolonged treatment with Naltrexone (NTX). C-peptide, IGF-I, IGFBP-3 plasma levels and the IGF-I/IGFBP-3 molar ratio were also determined. SUBJECTS: Twelve obese women (aged 25-41 y; Body mass index (BMI): 31-39 kg/m2) and six lean normal women (aged 25-38; BMI: 19.8-23.1 kg/m2). MEASUREMENT: GH was determined by the IRMA method; insulin, C-peptide, IGF-I and IGFBP-3 were assayed by the RIA method. For molar comparison between IGF-I and IGFBP-3 we have considered 30.5 kDa the molar weight of IGFBP-3. Results are expressed as mean +/- s.e.m. RESULTS: We observed a significant decrease in basal concentration of both insulin (230.1 +/- 34.9 vs 133.2 +/- 16.9 pmol/L; P < 0.005) and C-peptide (3.7 +/- 0.3 vs 2.4 +/- 0.1 micrograms/L; P < 0.02). No modifications in the insulin secretory response to the OGTT were observed. A significant increase of the GHRH-induced GH peak response (7.7 +/- 1.4 vs 19.7 +/- 3.1 micrograms/L; P < 0.01) and GH-AUC (533 +/- 151 vs 1415 +/- 339 micrograms/L/120 min; P < 0.01) was found after NTX treatment. A negative correlation was found between basal insulin and GH peak values, both before (r = -0.641, P = 0.027) and after NTX (r = -0.714, P = 0.013). No modifications were found in IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio. Moreover, NTX affected neither the insulin response to OGTT or IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio in a group of six lean controls. Conversely, NTX significantly reduced the GH response to GHRH, when expressed as both peak and AUC values. CONCLUSIONS: The opiate antagonist significantly reduced basal insulin concentrations and augmented the GH response to GHRH in obese subjects. In the absence of modifications in IGF-I and IGFBP-3 plasma levels and their molar ratio, we propose that insulin may exert a negative feedback on GH secretion.

Naloxone effects on post-prandial glucose, insulin and C-peptide levels in obese subjects.

In order to investigate the relationships between glucose metabolism, insulin secretion and endogenous opioids in obese patients, we have studied the effects of a naloxone infusion on insulin and C-peptide release after a normal meal (800 kcal) eaten at 12.00 hr in 16 obese women, aged 20-61 yr, with a BMI ranging from 25 to 37.2 kg/m2, with normal glucose tolerance (Group 1) and with NIDDM (Group 2). Naloxone was administered in a bolus of 1.6 mg i.v., followed by a continuous infusion of 4 mg in 2 hr starting immediately after feeding. In Group 1 naloxone infusion significantly increased the glucose levels, but insulin secretion was unaffected. In Group 2, naloxone infusion failed to modify significantly the postprandial levels of glucose, insulin and C-peptide. Therefore, in our study naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese subjects by increasing their glycemic levels, with no evidence of expected insulin decrease. In diabetic obese patients we observed a trend towards decrease in glycemic values during naloxone infusion, as expected, due to insulin plasma levels increase. By these data we can hypothesise a complex regulatory role of opioids in metabolic balance in obesity. In diabetic patients, naloxone can improve the surviving insulin secretion with better glucose tolerance. In non-diabetic subjects naloxone exerts its effects, probably, on peripheral organs.

Adult acute lymphoblastic leukemia: description and analysis of long-term survivors. A retrospective study.

This retrospective study, including 118 patients with acute lymphoblastic leukemia (ALL) aged greater than 15 years, with a minimum follow-up of 6 years, was aimed at defining potentially "cured" adults with ALL. At present, 21 out of 92 patients who achieved complete remission (CR) are long survivors: 16 in first CR, off-therapy; 4 in 2nd CR (3 off-therapy); 1 in 3rd CR, on treatment. On the basis of available data, we tried to identify factors at diagnosis which might predict long-term survival: white blood cell (WBC) count on admission was the only significant prognostic factor for overall survival (p = 0.0002) and first CR duration (p = 0.0005). The survival hazard rate (risk of death from acute leukemia per day) reaches 0 between 8 and 9 years from diagnosis. From our data we can identify two groups of ALL long-term survivors: the first includes 16 patients in 1st continuous CR (CCR), 12 of whom in CCR for over 8 years may be considered "cured"; the second group comprises 5 patients, relapsing once or twice, alive in 2nd or 3rd CR.

Protection of mouse lung by WR-2721 after fractionated doses of irradiation.

The radioprotective effect of WR-2721 on mouse lung has been studied after single doses, 4 or 7 equal fractions of X rays. Using breathing rate and lethality to measure lung injury up to 1 year after radiation, significant protection against both pneumonitis at 7 months and fibrosis at 12 months was observed using 300 mg/kg of WR-2721. The degree of radioprotection was similar for pneumonitis and fibrosis and was not less after doses per fraction of 4.0 Gy. These data indicate that protection of mouse lung by WR-2721 will not be less in a multifractionated schedule of radiation, at least for doses per fraction greater than 4.0 Gy.

The effect of breathing 100% oxygen on lung response to radiation in mice.

The response of the lung after single doses of radiation was measured in mice breathing air, or 100% oxygen, or in air-breathing mice given the hypoxic cell sensitizer misonidazole 30 min before irradiation. There was a clear enhancement of only the pneumonitis response in the mice breathing oxygen when breathing rate or lethality was used to assess injury. Less enhancement of the late fibrotic reaction was observed in these animals. No enhancement of either phase of lung response was observed in the misonidazole-treated mice. Dose reduction factors (DRF) were estimated from these data and used to calculate oxygen concentration in the lung, giving values ranging between 187 and 250 micron oxygen.

A new desk-top artificial pancreas (Betalike) utilizing extracorporeal hemofiltration: realization and clinical trials.

We present in this work a new artificial endocrine pancreas (BETALIKE), smaller than the available ones, transportable and fully automated. In the clinical trials performed this device showed good blood glucose controls and glycemic measurements were highly correlated with other automatic analyzer assays. No side effect was reported.

Bone marrow involvement at onset of Hodgkin's disease.

Bilateral trephine bone marrow biopsies of 370 patients with Hodgkin's disease first seen at the Institute of Hematology, University of Rome, between 1970 and 1981, revealed tumor involvement of the bone marrow in 18 cases. The histologic type was mixed cellularity in 7 cases, lymphocytic depletion in 4 cases, nodular sclerosis in 4 cases, and lymphocytic prevalence in 1 case. Anemia with less than 10 g/dl of hemoglobin was observed in 5 patients; white blood cells were less than 4.0 X 10(9)/liter in 2 patients; platelets were less than 12.0 X 10(9)/liter in 1 case; a pancytopenic condition was observed in only 1 case. B symptoms were present in 14 of the 18 patients. All patients who underwent laparosplenectomy presented spleen involvement, 4 also had liver involvement. All patients were treated with chemotherapy; MOPP regimen was employed in 11 cases, ABVD in 5 patients, and PROVECIP in 1 case. Of the 13 patients evaluable for therapeutic response, 11 achieved complete remission, with a median actuarial relapse-free survival of 15 months. The actuarial survival curve showed that 50% of all patients are projected alive at 47 months with a follow-up ranging from 1 to 109 months.

The time course of radioprotection by WR 2721 in mouse skin.

The radioprotective effect of 400 mg/kg of WR 2721 on mouse skin has been investigated over a series of times from 5 to 60 minutes after intravenous or intraperitoneal injection of the drug. The acute desquamation reaction on the hind leg of white mice was studied. Dose response curves were obtained for the average reaction over 15 to 25 days after single-dose irradiation. A high dose-rate electron beam (13--17 Gy/min) was used to minimize the irradiation time. Single doses of 20 to 60 grays were given. Dose modifying factors (DMFs) of 1.7--2.1 were obtained at 30 to 60 minutes, but only 1.1 to 1.3 at 5 minutes and intermediate values at 10 and 15 minutes. DMFs rose slightly faster and to slightly higher values after i.v. than after i.p. injection of WR 2721. We conclude that 30 minutes is the shortest interval which should be used between injection of Wr 2721 and irradiation with this normal tissue.

Acute non lymphoid leukaemia following Hodgkin's disease. Clinical, biological and cytogenetic aspects of 3 cases.

In a groups of 254 patients treated for Hodgkin's disease with a follow up period of minimum 2 years, 3 cases of acute non lymphoid leukaemia (ANLL) were observed: erythroleukaemia, myelomonocytic and myeloblastic leukaemia, respectively. The crude incidence of leukaemia in all patients was 0.0128 and patient year risk was estimated to be 0.003652. All 3 patients had received radiation therapy and chemotherapy. In all cases of haemopoietic dysplasia preceded ANLL. Bone marrow chromosome investigations showed an abnormal karyotype in all patients: chromosomal changes were present in 100% of cells and revealed a non-random distribution, the most frequent involvement being clustered to chromosomes nos 11, 17 and 21. Hypodiploidy was prevalent and multiple structural rearrangements, such as markers, rings and minutes, were present in a high percentage of cells. Other changes involved chromosomes nos 5, 7 and 14. Our results are compared with other previously reported cases and possible pathogenetic implications are discussed.