Testolactone-associated high androgen levels, a pharmacologic effect or a laboratory artifact?

Testolactone, an aromatase inhibitor, blocks conversion of androgens to estrogens. In familial male precocious puberty, slowing of pubertal progression and growth velocity occurs with testolactone and spironolactone. Girls with McCune-Albright syndrome, given testolactone, respond similarly. A 2-yr-old female (case 1) on testolactone for non-McCune-Albright gonadotropin independent precocious puberty had marked elevations of androstenedione (18 ng/mL, normal: 0.2-3.1) and testosterone (3.6 ng/mL, normal < 0.2) but no virilization. Investigations were undertaken to determine whether elevations in testosterone and androstenedione were caused by interference in these RIAs. After a single oral dose of testolactone (5 mg/kg in case 1; 4 mg/kg in case 2, a 3-yr-old boy with familial male precocious puberty; 10 mg/kg in a healthy postmenopausal control), serum testosterone and androstenedione were measured serially by RIA for 24 h. Androstenedione went from normal to a mean peak of 45.4 ng/mL at 1-2 h and returned to baseline by 24 h. Testosterone, undetectable at baseline (case 1 and control) or 1.8 ng/mL (case 2) rose to a mean peak of 6.9 ng/mL and returned to baseline by 24 h. Testolactone, in serial dilutions, cross-reacted in the testosterone assay. Testolactone significantly interferes in these serum RIAs, making their use unreliable in follow-up of patients treated with testolactone.     

Dietary xylitol protects against weakening of bone biomechanical properties in ovariectomized rats

The effects of dietary xylitol (xyl) on bone biomechanical properties in ovariectomized rats (ovx) were studied. Forty-two 3-mo-old female Wistar rats were divided into three groups of 14. Rats in two groups were ovariectomized, while those in the control group underwent a sham operation. All rats received a basal diet, and half of the ovx were given an additional 10 g/100 g dietary xyl supplementation. Three months later the rats were killed and their tibias, femurs and humeri were prepared. The tibias were used for analyses of bone density and trabecular bone volume (BV/TV) and for the three-point bending test. The femurs were used for the torsion test and for the loading test of the femoral neck. The humeri were used for analyses of bone ash weight and bone concentrations of calcium and phosphorus. Dietary xyl gave a significant protection against ovariectomy-caused decline of tibial stress in the three-point bending test, of femoral shear stress in the torsion test, and of stress of the femoral neck, without affecting bone elasticity values. Xyl restricted the ovariectomy-caused reduction in bone density, in bone ash weight and in concentrations of bone calcium and phosphorus. Furthermore, trabecular bone loss in ovx was significantly suppressed by dietary xyl. These results indicate that a 10% dietary supplementation of xyl in ovx has a protective effect against the weakening of bone biomechanical properties. This is related to greater BV/TV and maintained bone mineral content.     

The early effect of pelvic floor muscle exercise after transurethral prostatectomy

PURPOSE: We evaluate the early effect of pelvic floor muscle exercise on the frequency of urination, terminal dribbling, urinary incontinence and satisfaction with life in patients after transurethral prostatectomy. MATERIALS AND METHODS: From February to October 1996, 50 patients who had undergone transurethral prostatectomy were selected for study. The first 25 men served as a control group and the next 25 were the experimental group. Pelvic floor muscle exercise was started after removal of the Foley catheter postoperatively in the experimental group. The patients were evaluated before pelvic floor muscle exercise and weekly at our outpatient department after discharge from the hospital. Results for the later 25 patients treated with the pelvic floor muscle exercise program were compared to those of the prior 25 patients. RESULTS: There was a statistically significant difference (p <0.05) in the strength of pelvic floor muscle contractions at 4 weeks, length of between void interval (p <0.01), terminal dribbling at week 4 (p <0.05) and urinary incontinence at weeks 3 and 4 between the 2 groups after pelvic floor muscle exercise. During this study no complication or mortality occurred and there were no cases of hospitalization for either group. After pelvic floor muscle exercise patients in the experimental group had better satisfaction with life than the control group (p <0.01). CONCLUSIONS: We conclude that pelvic floor muscle exercise seems to help reduce symptoms within the first 4 weeks after transurethral prostatectomy, and provides better psychological and social quality of life.     

Ig heavy chain of the sturgeon Acipenser baeri: cDNA sequence and diversity

To investigate the gene organization of the IGH locus, and the VH diversity of the Siberian sturgeon, a cDNA library was constructed and screened with VH-specific probes from two holostean fish. Isolated clones were analyzed and domain-specific probes used in rescreening of the library, Southern blot analysis, and northern blots. It was concluded that the Siberian sturgeon has one IGH locus with a translocon type of organization. Two allelic variants of the mu gene were found, with identities ranging from 80 to 100% for the different domains (highest for CH4 and lowest for CH2). Sturgeon CH sequences are most closely related to those of holostean fish. There are three distinct VH families, VHI grouping with mammalian clan III, VHII grouping with the teleost clan, and VHIII grouping with the archaic clan. The variability of the CDR 3 region is substantial, and we identified a number of conserved motifs in the D segment. Further, we deduced that there are at least nine different JH segments in the locus, contributing to the antibody repertoire of the sturgeon. The variable segments of the three families can be associated with any of the D or JH segments in the rearrangement. Sturgeon, in addition to the random rearrangement of VH, D, and JH segments, have exonuclease activity, and an introduction of N and probably P nucleotides at the site of rearrangement.     

Braking electric-powered wheelchairs: effect of braking method, seatbelt, and legrests

PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer. METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody. RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases. CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.     

Compliance, tolerance and effectiveness of a short chemoprophylaxis regimen for the treatment of tuberculosis

OBJECTIVE: To evaluate compliance, side effects and the efficacy of a short course of chemoprophylaxis for tuberculosis with isoniazid plus rifampin during 3 months, compared with the classic course of isoniazid for 9 months. PATIENTS AND METHODS: Prospective, comparative, randomized and open study of patients with the suitable criteria for chemoprophylaxis, in accordance with the guidelines of the Centers for Disease Control of 1990. Patients were divided into 2 groups: the group of isoniazid plus rifampin, received isoniazid (300 mg per day) plus rifampin (600 mg per day) for 3 months, and the group of isoniazid, that received isoniazid at a dose of 300 mg per day for 9 months. RESULTS: 238 patients were included, of which 42 refused chemoprophylaxis. Of the remaining 196 patients, 98 were included in each group. Both groups were comparable at base level. The side effects, neither light nor severe showed significant differences. The appearance of adverse effects obliged the suspension of treatment in 7 patients in group isoniazid and of 9 patients in group isoniazid plus rifampin. Three patients in group isoniazid plus rifampin and 11 in group isoniazid stopped treatment (OR 4.14, 95% CI 1.02-19.45; p = 0.04). Efficacy was comparable in the two groups; only one case of tuberculosis was detected in a patient who gave up chemoprophylaxis at day 30. CONCLUSIONS: Tolerance in group isoniazid plus rifampin compared with group I was similar. Compliance was better in the short-term group with a lower percentage of abandonment. On comparing, both groups have shown similar efficacy in preventing the appearance of tuberculosis.     

Structural, functional, and genetic characterization of Gastrophilus hemoglobin

Hemoglobin of Gastrophilus intestinalis (Insecta, Diptera), was purified and characterized. At least two isoforms have been identified by isoelectrofocusing, mass spectrometry, and genomic Southern blotting. Functional studies show a high oxygen affinity due to a low ligand dissociation rate (koff = 2.4 s-1) and a relatively high autoxidation rate (t1/2 = 1.6/h). The globins were separated under denaturing conditions, and the sequence of Hb1 (Mr = 17,965 +/- 2) was determined at the protein and DNA level. The open reading frame codes for a polypeptide of 150 amino acids. Although the globin is distantly related to globins from other species, it has a low penalty score against globin templates. Freshly isolated hemoglobin was crystallized from polyethylene glycol. Crystals contain two hemoglobin molecules per asymmetric unit. Solution of the three-dimensional structure by molecular replacement could not be achieved, possibly due to the presence of three protein isoforms in the crystals. In order to determine its three-dimensional structure, G. intestinalis Hb1 was overexpressed in Escherichia coli, resulting in a fully functional molecule as confirmed by ligand binding affinity. The globin gene contains two introns at positions D7.0 and G7.0. The D7.0 intron is unprecedented, suggesting that globin gene evolution is much more complex than originally thought.     

Variant clinical course of mucopolysaccharidosis type VII in two groups of mice carrying the same mutation

It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-gamma) production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC) mAb (W6/32) suppressed lymphocyte proliferation by 90% in cultures stimulated with alpha CD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-gamma production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-gamma levels were suppressed by more than 60%, while in the other 2 cultures IFN-gamma levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs) or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.