The air strikes on “Zastava” complex in Kragujevac, in the spring of 1999, caused extensive environmental pollution with damage to soil, water and air. Since the main problem was the leakage of several tones of polychlorinated biphenyls (PCBs) as well as heavy metals Cr and Ni into the environment and groundwater, we decided to evaluate influence of the environmental contamination on eventual changes of genetic constitution of human body cells. The subjects analyzed were 36 phenotypically healthy newborn babies, who were born 12 months (n = 22) and 18 months (n = 14) after environmental contamination, and 25 newborns in 1998 as a control group. For the assessment of mutagenic effects of environmental pollutants in vivo, the cytokinesis-block micronucleus test was employed. The results show significant increase of micronuclei (MN) in lymphocytes from newborns born 12 months after contamination (9.36 ± 5.60), in comparison to controls (5.53 ± 3.02) and newborns born 18 months after contamination (6.14 ± 3.57). Only 3 newborns (12%) out of 25 controls showed more than 1 MN/1000 binucleated cells in respect to 8/22 after 12 months (36%) and 2/14 after 18 months from contamination (14%). The mean number of binucleated cells with MN significantly varied in function of sex and environmental changes in newborns born 12 months after contamination (as demonstrated by the analysis of covariance F = 9.61, p < 0.003). After 18 months of contamination, environmental components had no noticeable effects on MN frequency (F = 0.5, p > 0.48). These results suggest that the exposure to environmental pollutants in utero affects genetic constitution of fetus and increases MN values in their body cells, which is detectable right after birth in peripheral blood lymphocytes.
Carbohydrate antigen-125 (CA-125) is a tumor marker that has been used for differential diagnosis of peritoneal malignancies. The aim of the present study was to evaluate the diagnostic usefulness of simultaneous quantification of CA-125 in peritoneal fluid and serum for abdominal cancer cases and noncancer diseases. Noncancer disease group included cirrhotic patients (n = 28) and spontaneous bacterial peritonitis (SBP) patients (n = 11). Abdominal cancer group was composed of histologically diagnosed various malignancies (n = 10), such as gastric cancer. CA-125 levels were quantified by chemiluminescent enzyme immuno-assay. Diagnostic usefulness tests and receiver operating characteristics (ROC) curve analysis were performed for the levels of peritoneal fluid CA-125 (pCA-125) and serum CA-125 (sCA-125), and the ratio of pCA-125 to sCA-125 (p/sCA-125). The sCA-125 levels were significantly higher in noncancer patients than those in the cancer patients, while the pCA-125 levels showed no significant difference between the two groups. Notably, the p/sCA-125 ratio was significantly lower in the noncancer patients than that in the cancer patients. Area under the ROC curve was 0.267 for sCA-125, 0.542 for pCA-125 and 0.831 for p/sCA-125. The accepted cutoff values were the combination of values that gave the greatest diagnostic sensitivity plus specificity. Either sCA-125 or pCA-125 value gave lower diagnostic accuracy, whereas p/sCA-125 value demonstrated a significantly higher diagnostic accuracy (sensitivity-specificity pairs: 0.40-0.33 for sCA-125, 0.60-0.54 for pCA-125, and 0.80-0.72 for p/sCA-125, respectively). Hence, determination of p/sCA-125 improves the biochemical discrimination of abdominal cancerous cases from noncancerous diseases.
Shoulder pain is a common complaint in elder population and may cause an important functional disability. The aim of this study was to compare the effects of suprascapular nerve block with those of steroid injection in patients with non-specific shoulder pain. A total of 60 patients with shoulder pain lasting for more than four weeks were included in this study. After 1:1 randomization, patients were included in the steroid group (n = 30) or the suprascapular nerve block group (n = 30). Single injection was performed in both groups. All patients were evaluated before treatment, within one week after treatment, and one month later, in terms of pain, range of motion (ROM) (flexion, abduction, internal and external rotations, and total constant shoulder ROM score), satisfaction, and disability (Pennsylvania shoulder scale function score). Steroid injection was applied at two points in order of lateral and anterior routes. Suprascapular nerve block with lidocaine was applied at the suprascapular notch. No difference was noted in the indicated parameters before the treatment between the groups (p > 0.05). The difference in all follow-up parameters was statistically significant in the assessment periods in both groups (p < 0.05). No method was found to be superior to each other (p > 0.05). No complications occurred in suprascapular nerve block in contrary to steroid injection. We suggest that suprascapular nerve block can be considered the preferred treatment for non-specific shoulder pain because of being as effective as steroid injection with rare side effects.
Craniofacial malformations are among the most common congenital deformities. Meckel's cartilage plays a major role in the development of the mandible and is highly susceptible to maternal teratogenic drug use. We therefore investigated possible protective effects of prenatal administration of folic acid on a retinoic-acid induced maxillofacial defect model. Sprague-Dawley pregnant female rats (n = 36) were used in this study. Retinoic acid was administered orally at the dose of 40, 60, or 80 mg/kg respectively on gestational day 8. Folic acid of 4.0 mg/kg was injected intraperitoneally on 7th, 8th and 9th days of pregnancy. Animals were sacrificed on the day 17th. Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused severe ultrastructural damages in Meckel's cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg. In addition, there was a marked decrease in the number of degenerated chondrocytes and an improvement in the structure of granular endoplasmic reticulum along with intact nuclei. We conclude that folic acid has protective effects on retinoic acid-induced intracellular damages in Meckel's cartilage
A novel and simple procedure for the controlled-rate cryopreservation of peripheral blood progenitor cells (PBPCs) was introduced. A freezing bag housed in a protective aluminum canister was placed on top of a styrene foam box in the −85°C electric freezer. A second set of samples was kept in cryotubes placed in a double styrene foam box in the same electric freezer. Measurement of the freezing rate in the PB bags and cryotubes demonstrated that this simple method for PBPC cryopreservation provided optimal conditions for both large-scale and small-scale cryopreservation. Within several days after autologous peripheral blood stem cell transplantation, we thawed the cells in the small sample tubes and evaluated the cell viability, the cell recovery, and the recovery rates of hematopoietic progenitor cells (HPCs), such as CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) colonies. The median duration of cryopreservation was 59 days (range, 14 - 365 days). According to our analysis, infusions of more than 2 × 106 CD34+ cells/kg body weight and 0.5 × 106 CFU-GM colonies/kg body weight after thawing had favorable influences on the neutrophil engraftment. We have therefore established a simple freezing method for cryopreservation of human PBPCs, which ensures the transplantability of hematopoietic progenitors even after thawing. In vitro HPC assay after thawing is important to evaluate the quality of cryopreservation procedures.
Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral endothelium-dependent vasodilatation. Aerobic exercise has the potential to improve local endothelial function. We sought to analyze the effects of regular aerobic training on brachial artery endothelial function in endurance athletes. We studied diameter and blood flow of the brachial artery in 32 endurance male athletes and 30 healthy male subjects. In the same subjects flow-mediated dilatation of the brachial artery was recorded by inducing an ischemia through a forearm arterial occluding cuff. Maximal oxygen consumption was significantly higher in the athletes group than in the controls (61.24 ± 5.43 vs 44.49 ± 2.68 ml/kg/min, p < 0.001). Flow-mediated dilatation of the brachial artery induced by forearm arterial occlusion in athletes was also higher than that of the control subjects (17.1 ± 2.3 vs 11.2 ± 1.7, p = 0.002). Furthermore, there was an association between flow-mediated dilatation and VO2max (r = 0.69, p < 0.001). Baseline measurements of the diameter and the blood flow volume of the brachial artery were similar in both groups. During reactive hyperemia period, the percent of the changes of endothelial diameters and flow were significantly higher in athletes than in controls. Higher flow-mediated dilatation levels in athletes reflect better vascular adaptation to habitual aerobic exercise.
Minamata disease (MD) was caused by ingestion of seafood from the methylmercury-contaminated areas. Although 50 years have passed since the discovery of MD, there have been only a few studies on the temporal profile of neurological findings in certified MD patients. Thus, we evaluated changes in neurological symptoms and signs of MD using discriminants by multiple logistic regression analysis. The severity of predictive index declined in 25 years in most of the patients. Only a few patients showed aggravation of neurological findings, which was due to complications such as spino-cerebellar degeneration. Patients with chronic MD aged over 45 years had several concomitant diseases so that their clinical pictures were complicated. It was difficult to differentiate chronic MD using statistically established discriminants based on sensory disturabance alone. In conclusion, the severity of MD declined in 25 years along with the modification by age-related concomitant disorders.
The aim of this study is to evaluate the results of treatment for hypopharyngeal cancer and indicate the future prospect of the treatment. Seventy-four patients with squamous cell carcinoma of the hypopharynx admitted to Miyagi Cancer Center from 1993 through 2000 are reviewed. Sixty-four patients received radical treatment, and 10 patients received palliative treatment or no treatment. The cancer was advanced (stages III and IV) in 82% of all the patients. The overall 5-year survival rate of all the patients was 38%. The overall 5-year survival rate of 64 patients received radical treatment was 43%. The ten patients who received palliative treatment or no treatment died of cancer within 16 months. Fifty-two out of the 74 patients underwent neck dissection for the neck lymph node involvement; forty of the 52 patients underwent ipsilateral neck dissection and 12 underwent bilateral neck dissection. Four out of the 40 patients, who underwent ipsilateral neck dissection alone, developed late contralateral regional recurrence but were successfully treated by contralateral neck dissection at the time of recurrence. Twenty-three out of 74 patients had multiple primary cancers synchronously or metachronously (31%). Cause of the death of six patients out of 74 patients was confirmed to be primary cancers other than hypopharyngeal cancer, as judged by physicians in other department or other hospitals. Most of the patients died due to distant metastasis from hypopharyngeal cancer or other primary cancers. We therefore conclude that contralateral elective neck dissection which is frequently chosen for the treatment of hypopharyngeal cancer surgery is unnecessary. Even if locoregional control is accomplished, distant metastasis or multiple primary cancers emerge and make prognosis poor. To improve the prognosis, we should develop some strategy against hypopharyngeal cancer for each patient. New strategies including chemoprevention and surgery against distant metasistasis are necessary.
Oxidized low-density lipoproteins (oxLDL) are involved in initiation of atherosclerosis. Paraoxonase 1 (PON1), the isoenzyme of PON, is located on high-density lipoprotein (HDL) and protects against the oxidative modification of both HDL and LDL by hydrolysing lipid peroxides. Postmenopausal women have a higher risk of cardiovascular events compared with premenopausal women. The aim of this clinical study was to evaluate the effects of hormone replacement therapy (HRT) on oxLDL and PON1 activity in menopausal status. The subjects included 45 healthy postmenopausal women, aged 43 to 57 years, and 30 premenopausal women with regular cycles, aged 31 to 40 years. None of the participating women had a history of hypertension, diabetes mellitus or medications known to affect the cardiovascular system. Twenty five of the postmenopausal women received conjugated estrogens at dose of 0.625 mg/day per oral (P.O.) and medroxyprogesterone acetate (MPA) (1 mg/d P.O.) for 10 days. Twenty of the postmenopausal women received 17-beta estradiol (2 mg/day) and norethysterone acetate (NETA) (5 mg/day P.O.) for 10 days. Fasting blood samples were taken from premenopausal women (baseline) and postmenopausal women after HRT of 6 months to determine serum malondialdehyde (MDA), oxLDL, and PON1 activity. After 6-month therapy, MDA and oxLDL levels showed a statistically significant reduction in the treated groups versus baseline (p < 0.05), whereas PON1 activities were increased (p < 0.05). Increase in oxidative status may be one of the factors leading to reduction in PON1 activity and increased oxLDL in menapouse. HRT may be effective on oxidative stress and lipoprotein metabolism in apparrently healthy postmenopausal women.
A 12-year-old Japanese boy was referred to our hospital with a 2-month history of persistent proteinuria. Despite urinary protein excretion in the nephrotic range, associated with hypoproteinemia, the patient did not complain of any disability. A percutaneous renal biopsy revealed minor glomerular abnormalities, without any evidence of immune complex deposition. Therapy with prednisolone (60 mg/day) was initiated, and while the proteinuria decreased after 4-week therapy, elevated urinary protein excretion persisted thereafter, at 1-2 g/day. Because of the steroid-resistant proteinuria, mizoribine (MZR), was started at 150 mg/day (3 mg/kg), administered as a single daily dose an immunosuppressive agent, in combination with prednisolone. Although there was some fluctuation in the urinary protein excretion, heavy proteinuria persisted for the next 4 weeks. The peak blood level of MZR was 0.9 μg/ml. Since we have previously reported the efficacy and safety of oral MZR pulse therapy, which is associated with higher peak serum MZR levels than conventional MZR therapy in selected patients with lupus nephritis, we adopted MZR pulse therapy for this patient, after obtaining informed consent. MZR was started at the daily dose of 300 mg (6 mg/kg), administered as a single dose before breakfast, twice a week (on Monday and Thursday). The peak blood level of MZR then increased to 1.29 μg/ml. Thereafter, despite a gradual reduction of the concomitantly administered prednisolone dose, the urinary protein excretion decreased rapidly to around 0.3 g/day and remained at this level thereafter. No adverse effects of MZR were observed. Based on these clinical observations, we suggest that oral MZR pulse therapy may be the treatment of choice in selected patients of steroid-resistant nephrotic syndrome, in addition to those of lupus nephritis.