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A Phillips

Publications and source records attributed to A Phillips.

At least 19 recordsLinked to original sources
PubMed2001

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.

Adult↗
PubMed2001

Expression of inter-alpha-trypsin inhibitor and tumor necrosis factor-stimulated gene 6 in renal proximal tubular epithelial cells.

BACKGROUND: Our previous studies have demonstrated that renal proximal tubular epithelial cells (PTCs) may contribute to renal interstitial fibrosis by the generation of transforming growth factor-beta1 (TGF-beta1). In these in vitro experiments, TGF-beta1 was, however, secreted in its latent form. Plasmin has been implicated as a potential physiological activator of TGF-beta1. The inter-alpha-trypsin inhibitor (IalphaI) family of serum protease inhibitors together with tumor necrosis factor-stimulated gene 6 (TSG-6) recently have been implicated in the regulation of this protease pathway. The aim of the current study was to examine PTC synthesis of these proteins and to relate it to alterations of plasmin-protease activity. METHODS: PTCs were grown to confluence and stimulated under serum-free conditions with either interleukin-1beta (IL-1beta) or 25 mmol/L D-glucose. Alterations in IalphaI and TSG-6 generation were detected by Western analysis of both membrane extracts and supernatant samples. Alterations in gene expression were examined by reverse transcription-polymerase chain reaction. The effect of alteration in synthesis of TSG-6 on plasmin activity was determined by quantitating plasmin inhibitory activity of supernatant samples by in vitro calorimetric assay prior to and following TSG-6 immunoprecipitation. RESULTS: The data demonstrate that human PTCs constitutively express mRNA for bikunin and heavy chain 3 (H3) of IalphaI. Neither IL-1beta (1 ng/mL) nor 25 mmol/L D-glucose influenced their mRNA expression nor protein synthesis. In contrast, the addition of either IL-1beta or 25 mmol/L D-glucose increased TSG-6 mRNA expression. This was accompanied by an early up-regulation of TSG-6 protein expression following IL-1beta stimulation (24 h) and a late up-regulation after the addition of 25 mmol/L D-glucose (96 h) in the cell culture supernatant and associated with the cell membranes. Early induction of TSG-6 mRNA by IL-1beta was unaffected by the addition of the protein synthesis inhibitor cycloheximide. In contrast, the later glucose-stimulated induction of TSG-6 mRNA was abrogated by the addition of cycloheximide. Stimulation of TSG-6 by either IL-1beta or 25 mmol/L D-glucose was associated with an inhibition of total percentage plasmin activity. Immunoprecipitation of TSG-6 in these samples returned plasmin activity to control levels. CONCLUSIONS: : The data demonstrate that human PTCs constitutively express the bikunin and H3 components of the IalphaI family of serum protease inhibitors. Moreover, the addition of IL-1beta or 25 mmol/L D-glucose up-regulates the expression of TSG-6 in these cells, resulting in an inhibition of plasmin activity.

Alpha-Globulins↗
PubMed2000

Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure.

OBJECTIVE: To analyse the immunological and virological effects of treatment interruptions in HIV-1-infected patients with treatment failure and multidrug-resistant virus. METHODS: Drug susceptibility was assessed using Antivirogram and genotypic analysis was based on population and clonal sequencing for 48 patients who had interrupted treatment (> or = 2 months). RESULTS: Treatment interruption resulted in viral load increases (mean 0.7 log 10 copies/ ml; P = 0.0001) and CD4 cell count decreases (mean 89 x 10(6) cells/l; P = 0.0001). A complete shift to wild-type virus at the phenotypic, genotypic and clonal level was observed in 28/45 patients. These patients differed from those that did not show a shift to wild type in baseline CD4 cell counts (192 versus 59 x 10(6) cells/l; P= 0.007) and in the relationship between baseline viral load and CD4 cell count (no correlation versus a significant negative correlation; P= 0.008). Response to re-initiation of treatment fell with increasing viral load [relative hazard (RH) 0.33; P= 0.001] and with increasing total number of drugs with reduced susceptibility (RH 0.51; P = 0.0003); it improved with the number of new drugs received (RH 2.12; P = 0.0002) and a shift to wild type (RH 5.22, P = 0.006). CONCLUSIONS: Changes in surrogate markers suggest that treatment provided benefit in spite of virological failure and resistant virus. Although patients with a shift to wildtype virus responded better in the short term to treatment re-initiation, the long-term effects are not known and the risk of immune deterioration needs to be carefully considered.

Adult↗
PubMed2000

Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology.

PURPOSE: Hepatoblastoma (HB) is a rare malignant liver tumor which occurs almost exclusively in childhood. In the 1970s, survival was approximately 20% to 30%. Since the introduction of cisplatin (PLA) and doxorubicin (DO) into the chemotherapy regimens used to treat these patients, the survival rate has improved dramatically. In most recent studies, primary surgery preceded chemotherapy. In this study by the liver group of the International Society of Pediatric Oncology the aim was to improve survival and reduce operative morbidity and mortality by using preoperative chemotherapy. PATIENTS AND METHODS: After biopsy and assessment of pretreatment extent of disease all patients were treated with continuous 24-hour intravenous infusion of PLA 80 mg/m(2) followed by DO 60 mg/m(2) over 48 hours (PLADO). After four courses of this chemotherapy, patients were reassessed. Where possible, the primary tumor was resected and treatment completed with two more courses of chemotherapy. RESULTS: One hundred fifty-four patients were registered in the study, and 138 received preoperative chemotherapy. One hundred thirteen (82%) showed a partial response with tumor shrinkage and serial decrease of serum alpha-fetoprotein levels. One hundred fifteen patients had delayed surgery, and 106 (including six with liver transplants) had complete resection of primary tumor. Five-year event-free survival was 66%, and overall survival was 75%. CONCLUSION: This study demonstrates that international collaboration on a large scale is feasible. The toxicity of chemotherapy and morbidity of surgery were acceptable and the overall survival gratifyingly high. We now regard PLADO chemotherapy and delayed surgery to be the best available treatment for children with HB. Other treatment programs should be measured against this standard.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Multiple sequence alignment in phylogenetic analysis.

Multiple sequence alignment is discussed in light of homology assessments in phylogenetic research. Pairwise and multiple alignment methods are reviewed as exact and heuristic procedures. Since the object of alignment is to create the most efficient statement of initial homology, methods that minimize nonhomology are to be favored. Therefore, among all possible alignments, the one that satisfies the phylogenetic optimality criterion the best should be considered the best alignment. Since all homology statements are subject to testing and explanation this way, consistency of optimality criteria is desirable. This consistency is based on the treatment of alignment gaps as character information and the consistent use of a cost function (e.g., insertion-deletion, transversion, and transition) through analysis from alignment to phylogeny reconstruction. Cost functions are not subject to testing via inspection; hence the assumptions they make should be examined by varying the assumed values in a sensitivity analysis context to test for the robustness of results. Agreement among data may be used to choose an optimal solution set from all of those examined through parameter variation. This idea of consistency between assumption and analysis through alignment and cladogram reconstruction is not limited to parsimony analysis and could and should be applied to other forms of analysis such as maximum likelihood.

Algorithms↗
PubMed2000

Assessment of patellar maltracking using combined static and dynamic MRI.

Between January 1995 and Jul 1997, 474 patients with anterior knee pain resistant to conservative treatment were referred for MR of the knee. The MR examination consisted of routine sequences with an additional patellofemoral dynamic examination using a technique that has been developed at this institution. The dynamic study examines both knees simultaneously, with the patient supine and the quadriceps loaded. No gating or restraint apparatus is needed. Patellar subluxation or tilt was present in 188(40%) of cases, bilateral in 104 and unilateral in 84 cases (right 39, left 45). It was classified as mild in 51%, moderate in 39% and severe in 10%. Subluxation was more prevalent in females than males (42% vs. 37%) and this was most obvious in the severe group where 68% were female. In 90 knees selected at random, four measurements of patellofemoral morphology were obtained using reconstructed images from a volume gradient echo sequence. These measurements were correlated with the degree of subluxation or tilt. A tibial tubercle distance greater than 20 mm, a femoral sulcus angle greater than 150 degrees, sulcus depth less than 4 mm were specific for subluxation but no measurement proved to be sufficiently sensitive to preclude a tracking study. MRI can be used to define more precisely the anatomy of the extensor mechanism and its relationship to the femur and tibia, in both a static and dynamic setting. In this way, patients with anterior knee pain can be classified more accurately and the outcomes of treatment more reliably assessed.

Adult↗
PubMed2000

Pretreatment prognostic factors for children with hepatoblastoma-- results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1.

The aim of this study was to investigate the prognostic significance of pretreatment patient and tumour characteristics for overall (OS) and event-free (EFS) survival in 154 children affected by hepatoblastoma (HB) in the first prospective liver tumour study run by the International Society of Paediatric Oncology. The pretreatment characteristics studied were age, alpha-fetoprotein, platelet count, histology; from radiology: intrahepatic tumour extension (PRETEXT), lung metastases, enlarged hilar lymph nodes, vena cava or extrahepatic vena porta tumour extension and tumour focality. Five-year OS was 75% (95% confidence interval (CI) 68-82%) and EFS 66% (95% CI 59-74%). Both were univariately associated with PRETEXT and the presence of metastases. Additionally tumour focality and enlargement of hilar lymph nodes at diagnosis were univariately associated with EFS. In multivariate analysis, PRETEXT was the only predictor of OS; PRETEXT and metastases were predictors of EFS. There is a need to investigate further these factors to confirm their validity.

Adolescent↗
PubMed2000

The in vitro life-span of human periodontal ligament fibroblasts.

The in vitro life-span of human periodontal ligament fibroblasts (PDLF) was studied on clones from periodontium of teeth extracted due to periodontitis and dental caries (69 clones/192 individuals, aged 20-80 years) and from periodontium of teeth extracted for orthodontic reasons (23 clones/26 individuals, aged 15-19 years). In the primary cultures the ratio of the number of cells expressing senescence-associated beta-galactosidase (SA-beta-Gal) to the total number of cells is significantly larger in PDLF (92 clones; 11.1+/-4.9%) than in human gingival fibroblasts (GF) (10 clones; 0.5+/-0.1 %). The finite population doubling numbers (PD) of PDLF are not age-matched and the mean PD of PDLF (7.1+/-2.9) is significantly smaller than GF (28.5+/-3.2), IMR-90 (human lung fibroblasts, 5 clones; 44.3 +/- 2.2), and human osteoblasts (5 clones; 19.7+/-1.4). Comparing the ratio of the number of SA-beta-Gal positive cells to the total number of cells in primary culture, and the finite PD in PDLF cultures: 1) the ratio of 15-19 years old donor group is significantly smaller than in the other donor groups (20-29, 30-39, 40-49, 50-59 and 60-80 years old), and 2) there were no statistically significant differences among the 20-29, 30-39, 40-49 and 50-59 year old donor groups, and the 30-39, 40-49, 50-59 and 60-80 year old donor groups. These findings suggest that the in vitro life-span of PDLF is shorter than other fibroblasts in the connective tissues and that PDLF may undergo senescence in adult clones without relation to donor's age. There may be more aged fibroblasts in periodontium than in other tissues, such as gingiva and lung.

Adult↗
PubMed2000

Impairment of osteocalcin production in senescent periodontal ligament fibroblasts.

Osteocalcin production of senescent periodontal ligament fibroblasts (PDLF) with the expression of senescence-associated beta-galactosidase (SA-beta-Gal) was investigated on clones from 50-80 years old donors (n=20) with teeth extracted due to periodontitis and dental caries, and from 15-19 year old donors (n=20) with normal teeth extracted for orthodontic reasons. Immunohistochemically, the nonsenescent PDLF in all cultures in passage 2 showed strong reactivity with anti-osteocalcin. The reactive intensity of PDLF (passage 2, PD 3.0) was significantly stronger in 50-80 year old donor group than in 15-19 year old donor group, suggesting that osteocalcin production of PDLF cultured in early passage is larger in cells from adult population than in cells from adolescent population. In PDLF cultures in passage 2 from 50-80 year old donor, two types of senescent cells were found: one with strong reactivity to anti-osteocalcin and the other with little detectable reactivity. The culture consisted of senescent PDLF (passage 8, PD 14.8) did not include cells which have a detectable reactivity with anti-osteocalcin immunohistochemically and the reactive intensity was significantly weaker in the senescent culture than in the culture in passage 2 by ELISA. This suggests that the production potential of osteocalcin is impaired in PDLF with aging in culture. Further, the reactive intensity with anti-osteocalcin of PDLF in passage 2 deprived of serum for 48 h was 6% of that of cells cultured with serum and the reaction increased after serum stimulation, suggesting that the osteocalcin production in PDLF in early passage is implicated in mitogenic stimulation.

Adolescent↗
PubMed2000

Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home.

OBJECTIVE: To describe the use of zanamivir during an influenza A outbreak. POPULATION: Residents of a 176-bed long-term-care facility for the elderly in Newmarket, Ontario, Canada, 90% of whom received influenza vaccine in the fall of 1998. OUTBREAK: When respiratory illness due to influenza A was confirmed, infection control measures and amantadine prophylaxis were initiated. Despite these measures, transmission of influenza A continued. INTERVENTION: Zanamivir inhalations, 10 mg daily for prophylaxis and 10 mg twice daily for treatment of influenza. RESULTS: There were 13 definite and 66 probable outbreak-associated cases of influenza A. Twelve (15%) cases developed pneumonia, 7 (9%) were hospitalized, and 2 (2.6%) died. All 12 culture-positive cases yielded influenza A/Sydney/H3N2/05/97-like virus, a 1998/99 vaccine component. The three isolates obtained prior to the initiation of amantadine were amantadine-susceptible; all nine obtained after prophylaxis was instituted were amantadine-resistant. One hundred twenty-nine (92%) of 140 residents who were offered zanamivir accepted it and were able to attempt inhalations. Of these 129, 78% (100) had no difficulty in complying with inhalations. Difficulty with inhalations was associated with decreased functional and mental status. Fifteen (58%) of 26 residents fully dependent in activities of daily living had difficulty compared to 14 (14%) of 100 others (P<.001). Twenty-two (45%) of 49 residents not oriented to person, place, or time had difficulty compared to 7 (10%) of 77 others (P<.001). In the 2 weeks after zanamivir prophylaxis, only 2 new cases of respiratory illness occurred, neither confirmed as influenza. No side effects were identified in 128 zanamivir-treated residents. CONCLUSION: A minority of nursing home residents have difficulty following instructions for zanamivir inhalations. Zanamivir was well tolerated, and its use was temporally associated with termination of an outbreak that amantadine had failed to control.

Activities of Daily Living↗
PubMed2000

Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.

OBJECTIVE: To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN: A multicentre randomised double blind placebo controlled trial. SUBJECTS: Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION: Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES: Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. RESULTS: 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). CONCLUSIONS: There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Acute Disease↗
PubMed2000

The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan.

To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug in the regimen to which the patient's virus was sensitive by genotyping methods, and by about two- to threefold for each additional drug that was sensitive by phenotyping.

Anti-HIV Agents↗
PubMed2000

HIV drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort.

OBJECTIVE: To assess the relationship between viral susceptibility at baseline and virological response in human immunodeficiency virus (HIV)-infected patients treated with multi-drug salvage regimens after multiple previous treatment failures. DESIGN: Retrospective analysis of 50 patients from the Frankfurt HIV cohort who had received treatment with a minimum of six drugs, and for whom a sample for baseline viral phenotyping was available. METHODS: Viral drug susceptibility was measured retrospectively from stored samples using the Antivirogram, a recombinant virus assay based method. Virological response was defined as a viral load of < 400 copies/ml at week 24. For analysis of treatment response, drop-outs were dealt with in two ways, either as failures (DAF) or censored (DAC). Several logistical regression models were applied to identify predictors of response, including baseline virus load, number of new drugs and phenotypic sensitivity scores. RESULTS: At baseline, drug resistance was extensive: 96% of patients had viruses resistant to at least one drug class and 32% had viruses resistant to all three drug classes. In the DAF analysis, 39 patients experienced virological failure. In the DAC analysis, eight were censored and 31 patients experienced virological failure. In multivariate models that adjust for baseline viral load, the number of new drugs and total phenotypic sensitivity scores, the baseline viral load and phenotypic sensitivity score remained significantly associated with virological outcome, whereas in those adjusted for baseline viral load, the number of new drugs, NRTI phenotypic sensitivity score and PI phenotypic sensitivity score, only the latter remained significantly associated with virological outcome. Both the DAF and DAC analyses produced similar results. In all models used, virological failure was shown to be significantly associated with baseline viral load and phenotypic sensitivity score. CONCLUSIONS: In this retrospective analysis based on a small number of patients, viral drug susceptibility at baseline was strongly associated with virological outcome at 24 weeks, independent of covariates such as baseline viral load and treatment history. Baseline viral load also maintained a significant, independent association with virological outcome in most models.

Anti-HIV Agents↗
PubMed1999

Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy.

OBJECTIVE: HIV-induced CD4 lymphocyte depletion is partially reversed by antiretroviral therapy but it is unclear if the degree to which the CD4 count rises depends on viral suppression (if so, the extent of viral suppression required to achieve a maximal CD4 count rise), whether the rise is sustainable and whether it occurs in patients with CD4 count <10 x 10(6) cells/l. We aimed to address these issues. METHODS: We studied CD4 count and plasma HIV RNA values every 4 weeks for 72 weeks in 154 patients starting indinavir-containing regimens. RESULTS: Mean baseline HIV RNA and CD4 count were 4.8 log10 copies/ml and 180 x 10(6) cells/l, respectively. Overall, there was a mean increase in CD4 count of 143 x 10(6) cells/l by 72 weeks. The adjusted mean increase (adjusted for initial viral load, CD4 count and age) was strongly related to the mean viral suppression over the follow-up period (P < 0.0001). Importantly, there was a highly significant difference (P = 0.0004) in the rise in CD4 count between those with 2-3 log suppression (161 x 10(6) cells/l) and those with > 3 log suppression (314 x 10(6) cells/l; mean 3.6 log suppression in this group), suggesting that with even greater suppression the rise in CD4 lymphocytes may be still larger. We also studied whether CD4 counts were still rising after 72 weeks in patients with sustained suppression of at least 3 log in viral load. There was a significant (P = 0.004; paired t-test) rise in count of 43 x 10(6) cells/l between weeks 64 and 72 in these patients, suggesting that regeneration continues at least up to 72 weeks after therapy, provided virus replication continues to be suppressed. Patients with initial CD4 counts < 10 x 10(6) cells/l experienced no smaller rises than those at higher levels, even after adjustment for other factors. CONCLUSION: These results strongly support a direct causal relationship between HIV replication and CD4 lymphocyte count depletion. The rise in those with > 3 log suppression provides the best available indicator of the potential for natural CD4 regeneration in HIV-infected patients. However, since still greater CD4 count rises may be seen with more suppressive regimens, it may not be possible to study the intrinsic CD4 regenerative capacity until such regimens are available.

Adult↗
PubMed1999

Fair game.

Explore the source record for details and available documents.

Clinical Competence↗
PubMed1999

Screening urine for exogenous testosterone by isotope ratio mass spectrometric analysis of one pregnanediol and two androstanediols.

We propose a new screening method for testosterone (T) doping in sport. The current method for detecting T administration is based on finding a T to epitestosterone ratio (T/E) in urine that exceeds six. The difficulties with T/E are that T administration does not always result in a T/E>6 and that a rare individual will have T/E>6 in the absence of T administration. Our previous studies reveal that carbon isotope ratio helps to determine the origin of the urinary T because the values for T and its metabolites decrease after the administration of exogenous T. In this study, we present a rapid and efficient screening sample preparation method based on three successive liquid-solid extractions, deconjugation with E. coli beta-glucuronidase after the first extraction, acetylation after the second extraction, and a final extraction of the acetates. The 13C/12C of two T metabolites (5beta-androstane-3alpha,17beta-diol and 5alpha-androstane-3alpha,17beta-diol) and one pregnanediol as endogenous reference (5beta-pregnane-3alpha,20alpha-diol) was measured by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) on 10 ml of urine collected from 10 healthy men before and after T administration. Following T administration, the 13 C/12C of 5beta-androstane-3alpha,17beta-diol diacetate and 5alpha-androstane-3alpha,17beta-diol diacetate declined significantly from -26.2 per thousand to -30.8 per thousand and from -25.2 per thousand to -29.9 per thousand, respectively and the 13C/12C of 5beta-pregnane-3alpha,20alpha-diol diacetate was unchanged. In addition, the ratio of androstanediols to pregnanediol increased in the post-T urines.

Adult↗