Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.     

In vitro and in vivo metabolism of the progestagen Org 30659 in several species

The metabolism of Org 30659 [(17alpha)-17-hydroxy-11-methylene-19-norpregna-4, 15-dien-20-yn-3-one], a new potent progestagen currently under clinical development by NV Organon for use in oral contraceptive and hormone replacement therapy, was studied in vivo after oral administration to rats and monkeys and in vitro using rat, rabbit, monkey, and human liver microsomes and rat and human hepatocytes. After oral administration of [7-3H]Org 30659 to rats and monkeys, Org 30659 was extensively metabolized in both species. Fecal excretion appeared to be the main route of elimination. In rats, opening of the A-ring, resulting in a 2-OH,4-carboxylic acid, 5alpha-H metabolite of Org 30659, was the major metabolic route in vivo. Other metabolic routes involved the introduction of an OH group at C15beta, followed by a shift of the Delta15-double bond to a 16/17-double bond with subsequent removal of the OH group at C17 and reduction of the 3-keto,Delta4 moiety followed by sulfate conjugation of the 3-OH substituent. These metabolic routes observed in vivo were also major routes in incubations with rat hepatocytes. In rat liver microsomes, Org 30659 was metabolized by reduction of the 3-keto,Delta4 moiety. Rat hepatocyte incubations with Org 30659 were more representative of the in vivo metabolism of Org 30659, compared with rat microsomal incubations. Both in vitro and in vivo, the majority of the metabolites were 3alpha-OH,4,5alpha-dihydro derivatives. In monkeys, Org 30659 was mainly metabolized at the C3- and C17-positions in vivo. The 3-keto moiety was reduced to both 3beta-OH and 3alpha-OH substituents. In addition to phase I metabolites, glucuronic acid conjugates were observed in vivo. In monkey liver microsomes, the 6beta-OH metabolite of Org 30659 was the major metabolite present. Similar to the monkey liver microsomes, rabbit and human liver microsomes converted Org 30659 to the 6beta-OH metabolite. This metabolite was also the major metabolite in incubations with human hepatocytes.     

Food Cent$--implementing and evaluating a nutrition education project focusing on value for money

The photophysics and polarization of the phosphorescence and delayed fluorescence of erythrosin in conditions compatible with the current biological applications of the dye (aqueous buffers at pH 7.4 at ambient temperatures) and in ethanol have been studied as a function of dye concentration (10(-7)-10(-5) M) and temperature (245-333 K). The emission decay is strictly single exponential and the detailed kinetic analysis of all the rate processes connected with the emitting T1 state showed that (1) the lowering of the emission lifetime at the higher temperatures is due to a very efficient self-quenching process, (2) the back intersystem crossing rate T1-->S1 is temperature dependent (delta ETS approximately 7 kcal mol-1) but the T1-->S0 is not (Ea < 0.1 kcal mol-1) and (3) both intersystem crossing processes are very sensitive to solvent polarity, which accounts for the solvent dependence of the phosphorescence yield and lifetime. The high value of the phosphorescence anisotropy (r0 = 0.25 +/- 0.006) is independent of the excitation and emission wavelengths, and its evolution in time accurately reflects the rotational restrictions in solid solutions. The relevance of these findings to studies with protein-dye conjugates is also outlined to facilitate the design and interpretation of phosphorescence depolarization experiments that probe the microsecond-ms dynamics of biomolecules and supramolecular systems.     

Activators of the nuclear receptor PPARgamma enhance colon polyp formation

A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene expression in response to fatty acids, lipid-derived metabolites and antidiabetic drugs. To explore the role of the PPARs in diet-induced carcinogenesis, we treated mice predisposed to intestinal neoplasia with a synthetic PPARgamma ligand. Reflecting the pattern of expression of PPARgamma in the gastrointestinal tract, treated mice developed a considerably greater number of polyps in the colon but not in the small intestine, indicating that PPARgamma activation may provide a molecular link between a high-fat diet and increased risk of colorectal cancer.     

Comparison of tamoxifen effects on the actions of triiodothyronine or growth hormone in the ovariectomized-hypothyroid rat

Recent studies have suggested that a subset of estrogen responses arise via modulation of triiodothyronine (T3) actions, and depend on T3 for expression: other estrogen responses are not T3-dependent. Moreover, tamoxifen acts as a full estrogen agonist in T3-dependent responses but behaves as an antiestrogen in T3-independent responses. T3 directly induces a variety of metabolic enzymes and proteins, and also induces rat growth hormone (GH). Thus, some T3-dependent tamoxifen effects might reflect modulation of GH rather than T3 actions. To address this issue, tamoxifen effects on somatotropic and metabolic actions of T3 and GH were compared in ovariectomized rats with methimazole-induced hypothyroidism. Rats were given T3 (10 micrograms/kg/day) or ovine GH (2 mg/kg/day) with or without tamoxifen (0.5 mg/kg/day) for 30 days. GH was poorly effective in producing a sustained increase in somatic growth in hypothyroid rats compared to T3; nonetheless, GH effects to increase body weight, tibia length and serum insulin-like growth factor I while decreasing fat mass and evoking small increases in body temperature were not inhibited by tamoxifen. Tamoxifen also did not inhibit GH trends to increase tibia bone mineral density. T3 increased body temperature, insulin-like growth factor I levels and all measures of somatic growth and, unlike GH, increased food intake and tended to decrease tibia bone mineral density. Tamoxifen inhibited the somatotropic actions of T3 (including increases in insulin-like growth factor I levels), and produced significant increases in tibia bone mineral density only in T3-treated rats. Tamoxifen had no effect on T3 actions to increase food intake or body temperature. T3 alone increased fat mass and exhibited a tendency to decrease serum triglycerides: tamoxifen had no effect on these parameters in the absence of T3. However, coadministration of tamoxifen with T3 produced a marked decrease in fat mass and increased serum triglycerides. GH had no effect on serum triglycerides in either the presence or absence of tamoxifen. Serum glucose levels appeared normal in all groups. The data indicate that multiple tamoxifen effects on growth and metabolism may reflect modulation of T3 rather than GH actions.     

An Arabic language version of the health promotion lifestyle profile

BACKGROUND: Characteristic features of cholesteatoma of the middle ear are destruction of the bone and a high tendency for recurrent disease. The choice of surgical procedure is determined by audiological results and the rate of recurrent cholesteatoma. PATIENTS: One hundred fifty patients who underwent primary cholesteatoma surgery were investigated 3-5 years postoperatively. Preoperative and postoperative audiological results and rate of revision surgery were compared for the respective surgical procedures. All cholesteatomas were treated with an open surgical technique. The lateral attic walls and cholesteatomas were removed. RESULTS: Cholesteotoma recurred in 15 patients (10%). Primary reconstruction of the ossicular chain with a tympanoplasty (type III) was performed in 98 patients in the first operation. Approximately 80% of patients treated with a type III tympanoplasty had a maximum postoperative air-bone gap of 20 dB in the main speech range, depending on the frequency. In about 50% of patients, this value was 10 dB or less. Comparison of preoperative and postoperative conductive hearing loss between 250 Hz and 8000 Hz revealed an improvement (p < 0.05) of 10 dB (500 Hz, 3000 Hz, 4000 Hz) and 15 dB (250 Hz, 1500 Hz, 2000 Hz, 8000 Hz). CONCLUSIONS: In our opinion, a second look operation should be performed in cases where a large cholesteatoma cannot be removed with sufficient reliability. This applies especially to a cholesteatoma in the oval window. Here, we suggest second-look surgery after one year.