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Nasal cell micronuclei, cytology and clinical symptoms in stainless steel production workers exposed to chromium.

The objective of the present study was to determine whether workers in stainless steel production with low exposure to various forms of chromium show an increase in micronucleated nasal cells or an excess of nasal symptoms or disease. Altogether, 48 workers employed in a stainless steel production chain were studied, 29 of them in the steel melting shop with exposure to hexavalent chromium (Cr(6+)), 14 in the sintering and crushing departments of the ferrochromium plant with exposure to trivalent chromium (Cr(3+)) and five in the mine with exposure to chromite ore (Cr(3+)). Thirty-nine workers from the cold rolling mill, with very low exposure to chromium, served as referents. All the subjects were never smokers with a minimum of 14 years employment in the same department. There were no significant differences between the exposure groups and the referents regarding the mean frequency of centromere-negative or centromere-positive micronuclei (studied by pancentromeric fluorescence in situ hybridization), nasal diseases and symptoms or mucociliary clearance of the nasal cavity. No statistically significant differences in the incidence of cell atypia or inflammatory cells were detected between the exposed workers and the reference group, except for an increase in lymphocytes among the chromite ore workers. Anterior rhinoscopy indicated slight inflammatory changes in nasal mucosa and secretion more often in the Cr(6+) and Cr(3+) groups than in the referents, the Cr(6+)-exposed workers showing more livid or oedemic epithelium. In conclusion, the stainless steel production workers, with low exposure to dusts or fumes containing hexavalent or trivalent chromium, did not show clinical changes in the nasal mucosa or an increase in nasal cell micronuclei or symptoms of nasal diseases, except for slight changes in the nasal epithelium and secretion.

Adult↗

Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica.

BACKGROUND: From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients. METHODS: Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. RESULTS: With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. CONCLUSION: Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.

Adult↗

Isolation and characterization of major gangliosides from frog liver.

Four major gangliosides isolated from frog liver were characterized by compositional analysis involving GLC and GC-MS, methylation analysis, chromium trioxide oxidation, and enzymatic hydrolysis. The results revealed that the most major ganglioside in the tissue was GM4 containing N-acetylneuraminic acid and the others were GM4 containing N-glycolylneuraminic acid, GD1a, and a fucosyl ganglioside which was tentatively assigned to be alpha-galactosyl alpha-fucosyl GM1. This is the first report describing the presence of GM4 containing N-glycolylneuraminic acid. The fatty acids in both GM4 were mainly alpha-hydroxylated, and those in the fucosyl ganglioside were exclusively nonhydroxy fatty acids. The GD1a contained both nonhydroxy and alpha-hydroxy fatty acids in a ratio of about 3:2. The predominant species were 22:0, 23:0, 24:0, and 24:1 in both species of the fatty acids. The long-chain bases of these four gangliosides consisted of C18-sphingosine and C18-phytosphingosine together with significant amounts of C16 to C19 dihydroxy and trihydroxy bases with iso and anteiso structures.

Animals↗

Comparison of inert markers [chromic oxide or insoluble ash (Celite)] for determining apparent metabolizable energy of wheat- or barley-based broiler diets with or without enzymes.

A broiler chick bioassay was used to measure the effect of two inert digestibility markers on the determination of dietary AME. Diets contained 80% of either wheat or barley (with or without enzyme) and either chromic oxide at 0.5% or one of three levels of insoluble ash (0.5, 1.0, or 1.5%) as markers. The various cereal and marker diet combinations were consumed ad libitum (0 to 21 d) by two groups of 10 male broilers in each of two trials. The AME of each diet was determined by measuring the respective marker ratios between diet and excreta (collected for 24 h at 7 or 21 d) or ileal digesta collected at 21 d. Growth and feed conversion were measured on each group of birds between 0 and 21 d. There was no effect of marker on growth or feed efficiency. However, determination of AME of wheat- or barley-based diets with or without enzymes were affected by choice of marker and whether markers were measured in excreta (7 or 21 d) or ileal digesta. Chromic oxide was viewed as the least accurate method for determining AME, based on chronic oxide's inability to define AME differences between barley-based diets with and without enzymes, whereas insoluble ash clearly demonstrated improved AME of wheat- and barley-based diets with an enzyme. The optimum levels of insoluble ash for accuracy and repeatability were between 0.5 and 1.0%. The AME of the diets were, on average, 5% lower when determined with 7 vs 21 d excreta and 2.5% lower for ileal digesta than excreta collected at 21 d. It was concluded that identification of components that result in variability in AME levels of diets will be improved if a bioassay uses insoluble ash as a marker.

Aging↗

Five and ten year estimated survival and disease-free rates after intraperitoneal chromic phosphate; stage I ovarian adenocarcinoma.

From 1975 to 1982, 25 evaluable patients with FIGO Stage I ovarian cancer were treated with intraperitoneal chromic phosphate (32P). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy with (28%) or without (72%) omentectomy, with no other surgical staging procedures prior to referral. Patients were restaged by laparoscopy (inspection of diaphragms, abdomen, and pelvis), biopsy of suspicious lesions, and peritoneal cytologic washings prior to intraperitoneal chromic phosphate therapy. For the 25 patients, the estimated 5- and 10-year recurrence-free rates and the 5- and 10-year survival rates are 84% and 75%, respectively. Excellent 10-year recurrence-free rates were achieved for Stages IA and IC, nonruptured cysts, and Grade I and II tumors. In contrast, very low 10-year survival rates were achieved for patients with Stage IB, ruptured cysts, or Grade III tumors.

Adenocarcinoma↗

Peritoneoscintigraphy in detection of improper placement of peritoneal catheter into bowel lumen prior to chromic phosphate P-32 therapy. A case report.

Radionuclide peritoneoscintigraphy has been used prior to chromic phosphate P-32 (P-32CP) intraperitoneal therapy to assure proper placement of the catheter in the peritoneal cavity, to exclude loculation, and to predict inadequate distribution of P-32CP. This is a case report of the detection of a peritoneal catheter improperly placed into the bowel lumen by pretherapy radionuclide peritoneoscintigraphy, and this case demonstrates the distinguishing characteristics of the radiocolloid distribution secondary to an intraluminal injection relative to an intraperitoneal injection.

Adenocarcinoma↗

Intraperitoneal distribution imaging prior to chromic phosphate (P-32) therapy in ovarian cancer patients.

This study addressed the technique of intraperitoneal distribution imaging (IDI). A literature search (MEDLINE database) revealed wide variations in IDI techniques without a basis for comparison. From April 1990 to September 1992, the authors studied 8 patients (age 43-65 years) with ovarian cancer. A total of 1000 ml of normal saline and 1 mCi of Tc-99m SC was infused intraperitoneally for IDI. In one patient loculation was observed, but only 250 ml of normal saline was infused with Tc-99m SC. A repeat study using our standard technique rendered free intraperitoneal distribution in this patient, as well as in the other seven cases. Some investigators recommend low volumes, but in our experience this produced the finding of pseudoloculation, which could change treatment inappropriately. Although the number of patients studied at our institution was small, administration of 1 liter intraperitoneally provided consistent IDI results.

Chromium Compounds↗

Adjuvant intraperitoneal chromic phosphate therapy in a woman with early ovarian carcinoma and pelvic infection with resulting catastrophic complications.

Women diagnosed with early stage ovarian cancer may be considered for adjuvant therapy. Intraperitoneal chromic phosphate (P-32) is commonly used in these patients with few complications. A woman found to have early stage ovarian cancer was given intraperitoneal P-32 in the presence of a lingering pelvic infection, which is usually not mentioned as a contraindication to its use. Radiation damage to the small bowel and cecum developed as did damage to the ureter and bladder, which then required surgery.

Adult↗

Repetitive phosphorus-32 peritoneal instillations in a patient with malignant ascites.

During the last decade, intraperitoneal injection of phosphorus-32 chromic phosphate (P-32 CP) has been used principally for its initial intended purpose, the palliative management of malignant ascites. The authors describe a patient with a stage IIIB well-differentiated extraovarian peritoneal serous papillary adenocarcinoma. As a palliative treatment for malignant ascites, P-32 CP was instilled intraabdominally eight times. Adverse effects were limited to the third instillation, when abdominal pain occurred as a result of leakage of the P-32 CP in the subcutaneous tissue. The P-32 CP instillations reduced the frequency of paracentesis for almost 1 year, until disease progression prevented palliation. Considering the few palliative options, there could be more widespread use of P-32 CP as a palliative treatment for patients with malignant ascites caused by ovarian cancer or extraovarian peritoneal adenocarcinoma. However, intraperitoneal P-32 CP is not without potential intestinal complications, which must be considered before it is recommended.

Adenocarcinoma, Papillary↗

Drug inhibition of the macrophage response to metal wear particles in vitro.

The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.

Ammonium Chloride↗

Phosphate-32 colloid radiosynovectomy in hemophilia: outcome of 125 procedures.

Radiosynovectomy offers a potentially effective, minimally invasive option for patients with chronic hemarthrosis and synovitis. The long-term outcome of patients with hemophilia who were treated with phosphate-32 chromic phosphate radiosynovectomy was evaluated. One hundred twenty-five procedures in 81 patients were done. Two- to 10-year followup by age and joint included joint bleeding and quality-of-life assessment. In addition, a relative cost comparison, scintigraphic imaging, and evaluation of biodistribution of the radionuclide were done. Of 125 procedures, 54% resulted in complete cessation of bleeding into the treated joint after the procedure, and 73% of patients reported improved mobility of the treated joint. Of patients 18 years old and younger, 79% had a greater than 75% reduction in bleeding incidence, and of patients older than 40 years, only 56% had a similar reduction. Seventy-nine percent of patients surveyed had a significant improvement in quality of life attributable to the treated joint. No evidence of significant leakage was observed. Billing records analysis indicated that radiosynovectomy costs less than 5% of surgical synovectomy. Phosphate-32 chromic phosphate radiosynovectomy is a clinically useful, safe, and cost-effective outpatient procedure in the treatment of patients with chronic hemarthrosis and synovitis.

Adolescent↗

Intraperitoneal radioactive chromic phosphate P 32 in the treatment of ovarian cancer.

The use of intraperitoneal radioisotopes in the management of women with ovarian cancer is controversial. We analyzed the experience with intraperitoneal chromic phosphate P 32 at our institution, from October 1979 to February 1983, in 22 patients with various stages and grades of ovarian malignancy. Survival in stage I is 87.5% and in stage II, 50%. Survival is 88.9% among patients with grade 1 tumors and 33.3% for those with grade 3 lesions. Morbidity related to chromic phosphate P 32 was minimal; small bowel obstruction occurred in only one patient who had also received external pelvic irradiation. Our results suggest that chromic phosphate P 32 is a safe, well tolerated, inexpensive, and effective adjuvant to surgery in the management of selected patients with ovarian malignancy.

Adenocarcinoma↗

Kidney dysfunction, inflammation, and coronary events: a prospective study.

Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl <60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl > or =90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl <60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl < or =74 ml/min but not in women with an estimated CrCl > or =75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl < or =74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and > or =90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations.

Adult↗

Chromium allergy: significance of both Cr(III) and Cr(VI).

Most studies investigating chromium allergy have been performed with Cr(VI). However, real exposure to chromium from leather products includes both Cr(III) and Cr(VI). We have determined and compared the minimum elicitation threshold (MET) concentration for Cr(III) and Cr(VI) in Cr(VI)-sensitive patients. In addition, reactions to combinations of Cr(III) and Cr(VI) were compared to reactions elicited by Cr(III) and Cr(VI) alone. Dilution series of Cr(III) and Cr(VI) were applied in Finn Chambers on the back of 18 patients. The patches were left for 2 days and readings were done on days 2, 3 and 7. The MET10% for Cr(III) and Cr(VI) was calculated from the dose-response curves to be 0.18 microg/cm2/48 h (6 p.p.m.) and 0.03 microg/cm2/48 h (1 p.p.m.), respectively. No significant differences in the response to combined Cr(III) and Cr(VI) solutions versus single solutions were found. Cr(III) was concluded to play an important role in chromium allergy, because Cr(III) and Cr(VI) were both capable of eliciting eczema at low concentrations. Rather than regarding chromium dermatitis as a result of Cr(VI) allergy alone, it may be more correct to consider it as a result of a combined Cr(III) and Cr(VI) allergy.

Carcinogens, Environmental↗

Cr(III) reactivity and foot dermatitis in Cr(VI) positive patients.

Chromium allergy has become synonymous with Cr(VI) allergy. However, real exposure to chromium from leather products may include both Cr(III) and Cr(VI). In this study, we investigate the reactivity to both Cr(VI) and Cr(III) in consecutive patients to analyse the relation between foot eczema/leather exposure and reactivity to Cr(III). From March 2002 to December 2004, 2211 consecutive patients with suspected allergic contact dermatitis were patch tested with 0.5% potassium dichromate (Cr(VI)) and 13% chromium trichloride (Cr(III)). A total of 71 (3.2%) patients had a positive reaction to Cr(VI), of which 31 also had a positive Cr(III) reaction. No Cr(VI) negative patients had a positive reaction to Cr(III). An increased risk of foot dermatitis was found in Cr(VI) positive patients with a concomitant positive or doubtful reaction to Cr(III) compared with Cr(VI) positive patients with no reactions to Cr(III). The increased risk was not due to a higher degree of sensitivity to Cr(VI). Leather was reported most frequently as the suspected cause of chromium dermatitis (54%). However, Cr(VI) allergics having foot eczema and positive or doubtful Cr(III) reactions often had positive reactions to other shoe allergens. Thus, Cr(III) allergy is part of a multiple shoe allergy pattern.

Allergens↗