Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.     

Additional antiischemic effects of long-term L-propionylcarnitine in anginal patients treated with conventional antianginal therapy

Cardiac L-carnitine content, essential for mitochondrial fatty acid transport and ATP-ADP exchange, decreases during ischemia. In animal models, administration of the natural derivative, L-propionylcarnitine, may reduce ischemia and improve cardiac function. To evaluate possible antiischemic effects of L-propionylcarnitine was compared with placebo in a randomized, double-blind, parallel design, in addition to preexisting therapy. Patients with > or = 2 anginal attacks per week and objective signs of ischemia with angina during bicycle exercise testing were included. After an initial 2-week, single-blind placebo phase, 37 patients received 500 mg L-propionylcarnitine tid, and 37 patients received placebo for 6 weeks. Both groups were comparable at baseline. Three patients discontinued the study while on placebo (two because of noncompliance, one because of palpitations) and one while on L-propionylcarnitine (noncompliance). Although heart rate, blood pressure at rest, and maximal exercise were not affected, L-propionylcarnitine increased the time to 0.1 mV ST-segment depression [44 +/- 3 vs. 8 +/- 2 seconds (mean +/- SEM) in the placebo group; p = 0.05], and exercise duration improved by 5% compared with placebo. Anginal attacks and the consumption of nitroglycerin were not affected in either group. Thus, following a 6 week treatment period, L-propionylcarnitine induced additional, albeit marginal, antiischemic effects in anginal patients who were still symptomatic despite maximal conventional antianginal therapy. It is questionable whether in these patients this form of metabolic treatment will achieve great benefit, although in some improvement can be expected.     

Trazodone and valproate in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal symptoms and taper outcome

Dithiocarbamate compounds are widely used agricultural fungicides that display low acute toxicity in mammals and that may become neurotoxic after prolonged exposure. Mancozeb, among other dithiocarbamates tested, proved to be the most potent (Ki= 0.27 microM) at noncompetitively inhibiting the in vitro ATP-dependent uptake of [3H]glutamate in rat cortical vesicles. Furthermore, mancozeb partially (20%) inhibited the ATP-dependent uptake of [14C]methylamine, used as an index for the vesicular transmembrane proton gradient (DeltapH), and evoked its efflux from organelles previously incubated with the 3H-labeled marker. Meanwhile, the vesicular uptake of 36chloride- anions whose concentrations regulate the transmembrane potential gradient (DeltapsiSV) was not impaired. The dithiocarbamate effects on the vesicular transport of [3H]glutamate thus appeared to involve mainly the DeltapH gradient rather than the potential gradient. Dithiocarbamate metabolites, the potent neurotoxin carbon disulfide included, did not affect the uptake process, thus implying the relevance for inhibition of the persistence, if any, of parent compounds in the brain. The present novel and potent in vitro interferences of selected dithiocarbamate pesticides with the vesicular transport of glutamate, if representative of in vivo alterations, may play some role in the probably complex origin of dithiocarbamate neurotoxicity.     

Bone mineral density in patients on long-term therapy with levothyroxine

The aim of the study was to determine the influence of replacement and suppressive thyroxine therapy on bone mineral density (BMD). 30 postmenopausal women; 19 on replacement therapy (dose 1.22 +/- 0.35 micrograms/kg; duration 11.4 +/- 7.2 years) and 11 on suppressive therapy (dose 1.45 +/- 0.71 micrograms/kg; duration 9.5 +/- 7.2 years). Controls were 60 healthy women matched for age and menopausal status. BMD at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter was measured by dual-energy absorptiometry. Forearm BMD at distal site was measured by single-photon absorptiometry. Mean thyroid hormone values and TSH were within normal limits, although the patients on suppressive therapy had significantly higher T3 (p < 0.05) than the patients on replacement therapy. BMD on each site was significantly lower in the replacement treated group than in controls. BMD in patients on suppressive therapy was lower, but not significantly, compared to controls. Thyroxine therapy could have an adverse effect on BMD. The magnitude of bone loss depends on the serum level of thyroid hormones and on the functional state of thyroid hormone receptor in bone tissue, as well.     

Update in systemic fluoride therapy

From January 1990 to August 1994, more than 6000 patients with silicone-gel breast implants were clinically assessed regarding their implant status. Of these, 82 patients requested removal of their implants (150 implants). Of the 150 implants that were removed, 24 (16%) demonstrated calcified capsules. All 12 patients with calcification demonstrated this finding bilaterally. All calcified capsules demonstrated discrete calcified plaques on their inner surface. All 12 patients presented with Baker class IV contractures, with pain as their chief complaint. One patient demonstrated calcification on a routine chest radiograph. One patient demonstrated a stippled appearance on xeromammogram. Capsular calcification was related to the duration of implantation. All 6 implants that had been in place for 23 to 26 years were associated with calcification. These implants were all of the thick-walled Dacron-backed type. All thick-walled Dacron-backed implants that were removed in this study were associated with calcification. Of the 69 implants that had been inserted for 11 to 20 years, 18 (26.1%) were associated with calcification. Fifteen of these 16 implants were ruptured. None of the implants that had been in place for 10 years or less demonstrated calcification.     

Immediate and long-term results of combined therapy of patients with endometrial neoplasms depending on the effect of counter-suppression of blood lymphocytes

The short-term (wound healing) and end-results (relapse and metastasis frequency, duration of relapse-free survival and 2-, 3- and 5-year survival) of combined treatment (surgery + gamma therapy) of 97 patients with endometrial carcinoma (stage I-II and stage III-IV) (FIGO, 1988) versus the effect of preoperative counter-suppression of blood lymphocytes were investigated. Both short-term and end-results appeared to be much better in patients showing the counter-suppression effect; they were much worse in patients who revealed the effect prior to combined therapy, and still worse--in cases of inverse effect involving enhanced suppression. It is suggested that the effect of blood lymphocyte counter-suppression before combined treatment is a factor of favorable prognosis in patients with endometrial carcinoma.     

Decreased prevalence of symptomatic atherosclerosis in arthritis patients on long-term aspirin therapy

To determine the effect of long-term aspirin therapy on the prevalence of symptomatic atherosclerosis, autopsy results from 44 arthritis patients taking aspirin were compared with a cohort from the general autopsy population. No decrease in the prevalence of symptomatic atherosclerosis was noted in patients with less than 8 years of arthritis, compared with controls. In contrast, the prevalence of symptomatic atherosclerosis was significantly decreased in arthritis patients with 8 or more years of arthritis and aspirin use. In these subjects, the prevalence of symptomatic atherosclerosis was inversely related to duration of arthritis. The inverse relationship between prevalence of symptomatic atherosclerosis and duration of aspirin therapy, as well as the decrease in all forms of symptomatic atherosclerosis, raise the possibility that this decrease is due to primary prevention of atherosclerosis.     

Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.     

Value of fluoride therapy in osteoporosis

Fluoride salts are the currently most effective stimulators of the osteoblasts. Since the therapeutic effect depends on the concentration of fluoride ions achieved in the plasma, differences in fluoride content and bioavailability must be taken into account when using sodium fluoride or sodium monofluorophosphate. The optimal therapeutic range is assumed to be 10 to 20 mg bioavailable fluoride ions daily. The classical indication for fluoride is manifest osteoporosis in the elderly woman with fractures of the vertebrae. Available data, however, suggest that its early use in both men and women, as also in corticoid-induced osteoporosis, is justified. Under long-term treatment with fluoride, the bone mass of the vertebrae increases dose-dependently and linearly. At very high doses of fluoride, the quality of the newly formed bone-which is often excessive is presumably initially inadequate. A moderate increase in bony substance of about 4 to 6% a year is the therapeutic objective. Regular physical exercise and gymnastics, together with requirement-related supplementation with calcium and vitamin D ensures an improvement in the mechanical stability of the bone, and thus the desired reduction in the fracture risk.     

Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes

Atmospheric pollution represents a relevant environmental hazard which has been associated with considerable excess mortality, morbidity, and increased rates of respiratory diseases in humans. To date, more than 3,000 environmental chemical compounds have been identified in the ambient atmosphere, including a variety of mutagenic and/or carcinogenic agents, such as polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and heterocyclic compounds. Positive associations between cytogenetic markers and airborne levels of PAHs have been reported by experimental and human studies. Traffic has been implicated as the major determinant for the concentration of PAHs and, therefore, for the genotoxic activity of urban air. A biomonitoring study has been conducted in 82 italian traffic police workers exposed to air pollutants and 34 control subjects (matched by age, gender, and smoking habits) not exposed to traffic pollutants. The aim of this study was to assess the cytogenetic effects, such as micronucleus frequency in peripheral blood lymphocytes, and to estimate the association with individual exposure to PAH. Statistical analysis of the frequency of micronuclei in binucleated cells showed higher mean levels in referent subjects (4.03%) than in traffic police officers (3.73%). Smoking showed no effect on the frequency of micronuclei. The study failed to detect any association between micronucleus frequency and individual level of benzo(a)pyrene, considered a marker of exposure to PAHs. These findings indicate that exposure to urban air pollutants does not result in increased levels of micronuclei in peripheral white blood cells.     

Cytogenetic investigations on patients with oral submucous fibrosis

Lymphocyte cultures were set up from venous blood samples collected from 23 patients of submucous fibrosis (SMF) and 10 normal controls. Slides, thus prepared, were processed and screened for G-, C-banding and sister chromatid exchange (SCE) frequency analysis. No gross chromosomal anomalies except that a few breaks and gaps were observed to be randomly distributed throughout the genome. However, a proportionate increase in SCE frequency in SMF patients as compared to the normal control individuals was observed. An attempt has been made to correlate the period of betel leaves, nuts, quid and tobacco chewing with the incidence of chromosomal anomalies and increase in SCE frequency and its sexwise distribution in these patients.     

Cardiovascular effects of long-term L-thyroxine therapy for Hashimoto's thyroiditis in children and adolescents

Morphology and function of the left ventricle were evaluated by echo and Doppler examination in 16 females affected by Hashimoto's thyroiditis, aged 13.3 (4.5) years (range 7.9-24.6). They were on L-thyroxine (L-T4) treatment for a period of 2.8 (2.8) years (range 0.8-7.6) with a mean daily dose of 77 (18) micrograms/m2. Left ventricular mass, systolic and diastolic function, cardiac output and systemic vascular resistance did not differ from a control group matched for age, sex and body size. A further analysis of the patients according to thyrotrophin serum levels (less or more than 0.1 mU/l) gave similar results. Moreover, no relationship was found between echocardiographic findings and age, L-T4 daily doses, duration of treatment and serum level of thyroid hormones. We can therefore conclude that chronic L-T4 treatment for Hashimoto's thyroiditis at the given doses did not affect cardiac function and morphology in children and adolescents; however, a longer follow-up is needed before confirming the safety of this therapy in the long term.     

Cytogenetic abnormalities in patients with severe aplastic anemia

BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.     

Short and long-term cardiovascular effects of growth hormone therapy in growth hormone deficient adults

OBJECTIVE: Since GH substitution therapy is now available for adult GH deficient patients, information on the cardiovascular effects of GH substitution has assumed major clinical interest. We have therefore assessed cardiovascular effects of short and long-term growth hormone substitution therapy in these patients. PATIENTS AND MEASUREMENTS: Doppler echocardiography was performed in 21 GH deficient patients after 4 months placebo and 4 months GH therapy, in a double blind cross-over study. In an open design study, 13 patients were reinvestigated following 16 months and 9 patients following 38 months of GH therapy. Twenty-one age and sex-matched normal control subjects were also investigated. RESULTS: Heart rate was increased in placebo treated patients as compared to controls. After 4 months of GH treatment, heart rate showed a further increase (10%, P < 0.01) and seemed to remain elevated after 16 months of GH therapy. Systolic and diastolic blood pressures were significantly lower in placebo treated patients than in controls, and did not change significantly after GH treatment. The left ventricular diastolic diameter was reduced in patients as compared to controls, but increased after 4 months GH therapy (P > 0.05) and seemed to increase further during prolonged GH treatment. Cardiac index was at the same level in controls and in placebo-treated patients, but increased by 20% following GH therapy and remained elevated after 16 and 38 months (P < 0.05) of GH substitution. CONCLUSION: Following GH substitution in GH deficient adult patients, left ventricular diastolic dimensions increased and seemed to normalize, while heart rate and cardiac output were found to be increased to supranormal levels.     

Adjuvant effects of fluoride on oral immunization of chickens

The present study was conducted to examine the antibody responses of chickens after oral immunization and the influence of sodium fluoride (NaF) on their immunological states. Bovine serum albumin (BSA) was used as an antigen, and the response was measured by enzyme-linked immunosorbent assays of serum samples, bile samples, and lachrymal fluids. Oral immunization of chickens with antigen alone hardly induced antibody responses in sera, bile samples or lachrymal fluids. Moreover, compared to control chickens, these orally immunized chickens exhibited a lower serum IgG response to subsequent parenteral immunization, suggesting that oral immunization induced immunological tolerance in chickens. A mucosal adjuvant, NaF, could abrogate oral tolerance and elicit an increase in antibody responses. Chickens, which received oral administration of antigen and NaF simultaneously, showed a significant rise in serum IgG antibody. Although there were variations among individual chickens and the titers were low, IgA antibodies were detected in bile samples and lachrymal fluids.