Toluene in blood as a marker of choice for low-level exposure to toluene

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

Effects of methanol on styrene metabolism among workers occupationally exposed at low concentrations

A survey was conducted in the second half of a work week on 39 male workers who were occupationally exposed to styrene in combination with methanol and methyl acetate during the production of plastic buttons. Time-weighted average exposure during an 8-h shift to styrene (Sty-A) and methyl acetate was monitored by carbon cloth-equipped personal samplers and to methanol by water-equipped ones. Urine samples were collected near the end of the shift and analyzed for mandelic (MA-U) and phenylglyoxylic acids (PhGA-U) by HPLC. Geometric mean styrene concentration was 12.4 ppm (g/g) with the maximum of 46 ppm, whereas the values for methanol and methyl acetate in combination were 23.5 ppm and 229 ppm, respectively. The relationship of MA-U and PhGA-U with Sty-A was examined by linear regression analysis. The equations for the regression lines were compared with the results from a previous survey (Ikeda et al. 1983) in which workers were exposed only to styrene, and the methods employed were identical with that in the present study. The comparison showed no evidence to suggest that styrene metabolism is suppressed by coexposure to methanol and methyl acetate at low concentrations below the current occupational exposure limit of 200 ppm.     

Redo cardiac surgery for active prosthetic valve endocarditis associated with hereditary hemorrhagic telangiectasia: report of a case

Hereditary hemorrhagic telangiectasia (HHT) is caused by an autosomal dominant gene and characterized by multiple arteriovenous malformations in several organs, leading to bleeding or shunting. These patients often suffer severe infections and heart failure, which should be managed in the perioperative period, when open heart surgery is indicated. We report a case of successful aortic root replacement for active prosthetic valve endocarditis and ventricular septal perforation in a patient with HHT, who had severe heart failure.     

Small polydisperse low density lipoproteins in familial hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity

Lipoprotein abnormalities were analyzed in 3 cases of marked hyperalphalipoproteinemia caused by complete deficiency of cholesteryl ester transfer activity. The probands were all men, aged 34, 43 and 48 years, respectively. The serum high density lipoprotein (HDL)-cholesterol levels of these patients were higher than 150 mg/dl (157-254 mg/dl), while serum total cholesterol levels ranged from 227 to 360 mg/dl. Sequential flotation-ultracentrifugation analysis disclosed that low density lipoprotein (LDL)-cholesterol was slightly decreased and that cholesteryl ester accumulated solely in the HDL2 fraction, which was also enriched with apolipoprotein E. Cholesteryl ester transfer activity was completely absent in all of these cases. High-performance liquid chromatography showed a decrease of LDL particle size in combination with a marked enlargement of HDL particle size. Analytical ultracentrifugation disclosed heterogeneity of LDL with the presence of small LDL subpopulations. We conclude that hyperalphalipoproteinemia due to complete deficiency of cholesteryl ester transfer activity is characterized by the presence of both small polydisperse LDL and markedly large HDL enriched with cholesteryl ester and apolipoprotein E.     

Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma: a case report

Low-grade endometrial stromal sarcoma (ESS) is a rare neoplasm and is generally an indolent tumor with estrogen and progesterone receptors. Objective responses by hormonal treatment with progestin or aromatase inhibitor have been reported, however, long-term management of this disease could be difficult if it becomes refractory to one of these hormonal therapies. A 34-year-old woman was diagnosed with stage I low-grade ESS at the time of hysterectomy for presumed uterine fibroma. Five years later, she recurred with multiple tumors in the lower abdomen. After an optimal surgery, she was free from progression for 6 years with progestin treatment (medroxyprogesterone acetate: MPA, 200–600 mg daily). Thereafter, she recurred twice during the MPA treatment and received debulking surgery each time. MPA was discontinued at age of 53, because another recurrent tumor grew up to 13 cm in diameter. Aromatase inhibitor anastrozole was then given at a daily dose of 1 mg with partial response (the tumor size decreased to 7 cm in diameter) for a duration of 9 months. After complete resection of the recurrent tumor, she remains progression-free for 16 months. Anastrozole was effective to recurrent low-grade ESS even after being refractory to progestin therapy. Aromatase inhibitor treatment may be a useful option as a second-line hormonal treatment to low-grade ESS.     

Enhanced oncogenicity of human papillomavirus type 16 (HPV16) variants in Japanese population

To investigate whether HPV16 E6 variants carry an elevated risk for cervical cancer in Japanese population, we investigated the E6 sequence variation in 40 cervical intraepithelial neoplasias (CINs) I-III and 43 invasive cervical cancers (ICCs), all positive for HPV16. HPV16 E6 variants were frequently found in ICCs than in CINs (88 vs. 65%, P=0.01). The E6 D25E, a rare variant in Western countries, was most frequently observed in ICC (44%). CIN I/II lesions with HPV16 variants were less likely to regress than those with HPV16 prototype (P=0.048). The finding that HPV16 E6 variants represent a significant risk factor is common between Western and Japanese women despite the different distribution of each variant.