GH replacement in patients with non-functioning pituitary adenoma (NFA) treated solely by surgery is not associated with increased risk of tumour recurrence.

BACKGROUND: Subjects with non-functioning pituitary adenomas (NFAs) frequently develop GH deficiency due to tumour expansion or as a consequence of tumour therapy. The safety of GH replacement (GHR) in these individuals remains unclear. OBJECTIVE: To assess the effect of GHR on tumour recurrence in patients with NFAs solely treated by surgical removal. PATIENTS AND METHODS: The study involved all patients with NFA who presented to the Department of Endocrinology in Oxford between January 1989 and July 2005 and were treated solely by surgical removal of the tumour. Patients with follow up < 1 year were excluded. Recurrence was diagnosed on the basis of radiological appearances (detectable tumour after gross total removal or regrowth of pre-existing residue) on regular imaging surveillance. RESULTS: One hundred and thirty patients were included in the study, and were followed up for a mean period of 6.8 +/- 4.2 years (median 5.7, range 1.2-17.6). Twenty-three patients received GHR [16 male, 7 female, mean age at tumour diagnosis 53.7 +/- 14.6 years (range 20-80)]. The mean duration of GHR was 4.6 +/- 2.5 years (median 5.3, range 0.4-8.7). One hundred and seven subjects did not receive GH therapy [61 male, 46 female, mean age at tumour diagnosis 56.2 +/- 14.0 years (range 20-87)]. Tumour regrowth occurred in 38 non-GH treated subjects (36%) and 8 GHR subjects (35%). Regrowth was detected at a mean of 4.8 +/- 2.8 years (range 1-11 years) in the non-GH treated group, and at 6.5 +/- 2.3 years in the GHR group. In the GHR group, recurrence occurred after a mean of 2.9 +/- 2.2 years (range 0.4-5.9 years) following commencement of GH treatment. The Cox regression analysis showed that after adjusting for sex, age at tumour diagnosis, cavernous sinus invasion at diagnosis and type of tumour removal (partial or complete based on postoperative scan), GH treatment was not a significant independent predictor of recurrence (P = 0.09; hazard ratio = 0.51; 95% CI, 0.24-1.12). CONCLUSION: GH replacement in patients with NFA treated by surgery alone is not associated with an increased risk of tumour recurrence.

The elimination profiles of tenoxicam and hydroxytenoxicam in equine urine and serum after a 200-mg oral dose.

Tenoxicam (Mobiflex) was administered orally to four standardbred mares at a dose of 200 mg. Elimination profiles of tenoxicam and hydroxytenoxicam were generated based on quantitation of these analytes in urine and serum by liquid chromatography (LC) with ultraviolet detection. Tenoxicam was confirmed by LC-tandem mass spectrometry daughter ion mass spectra in the last postadministration sample in which tenoxicam was detected. The tenoxicam and hydroxytenoxicam urinary elimination profiles had the same shape for the same horse; however, each horse was significantly different from the others. One horse (Horse 15) showed a much broader and flatter elimination profile than the other horses. Each horse had a peak in analyte concentration at different collection times. The latest detection for both tenoxicam and hydroxytenoxicam was 29-31 h for all horses. The urinary tenoxicam limit of detection (LOD) and limit of quantitation (LOQ) were 0.3 and 0.4 microg/mL, respectively. The urinary hydroxytenoxicam LOD and LOQ were 0.6 and 0.8 microg/mL, respectively. Hydroxytenoxicam was found to be completely conjugated and tenoxicam completely unconjugated in equine urine. Serum elimination profiles of tenoxicam were measured to 120 h postadministration. Hydroxytenoxicam was not detected in postadministration serum. The last serum tenoxicam detection was at the 24-h collection time for all horses. The peak average concentration was 434.5 ng/mL at 3 h. The serum tenoxicam LOD and LOQ were 5.7 and 7.3 ng/mL.

The elimination profiles of oxaprozin in equine urine and serum after a 4.8-g dose.

A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented. Confirmation of oxaprozin in postadministration extracts was accomplished by gas chromatographic- mass spectrometric analysis of methylated extracts or liquid chromatography with tandem mass spectrometry daughter ion mass spectra of underivatized extracts. Daypro, a formulation of oxaprozin, was administered orally at a dose of 4.8 g to four standardbred mares. Urine and serum samples were collected to 120 h postadministration. Base hydrolysis of equine urine before extraction resulted in an increase in the amount of oxaprozin measured, an indication of conjugation by ester formation. The urinary elimination profiles of each horse were significantly different from each other with more than one peak in oxaprozin concentration before the 29-31-h collection time. After this collection time, the differences between the oxaprozin urinary concentrations of each horse follow each other more closely. The peak average urinary concentrations of oxaprozin were 25.1 and 17.0 microg/mL at collection times of 8-10 and 18-22 h, respectively. The latest detection of oxaprozin in urine was at the last collection time of 119-121 h postadministration at a concentration close to the detection limit of approximately 0.1 microg/mL. The serum elimination profiles do not vary between horses as much as the urinary elimination profiles. The peak average serum concentration was 49.0 microg/mL at a collection time of 6 h postadministration. The latest detection was at the last collection time of 120 h. Oxaprozin is metabolized in the horse by hydroxylation. Two major urinary metabolites were isolated and identified as hydroxylated oxaprozin. The two urinary metabolites were isolated from equine postadministration urine and analyzed by mass spectrometry and proton nuclear magnetic resonance spectroscopy, which showed that the hydroxylation had occurred at the para positions of the two aromatic rings.

The urinary elimination profiles of diazepam and its metabolites, nordiazepam, temazepam, and oxazepam, in the equine after a 10-mg intramuscular dose.

A method for the extraction of diazepam and its metabolites (nordiazepam, temazepam, and oxazepam) from equine urine and serum and their quantitation and confirmation by liquid chromatography-tandem mass spectrometry is presented. Valium, a formulation of diazepam, was administered at a dose of 10 mg intramuscularly to four standard-bred mares. Diazepam is extensively metabolized in the horse to nordiazepam, temazepam, and oxazepam. Diazepam urinary concentrations were found to be less than 6 ng/mL. Nordiazepam was found to be mainly in its glucuronide-conjugated form and was measured out to a collection time of 53-55 h. Oxazepam and temazepam were entirely conjugated, and their urinary concentrations were measured out to collection times of 121 h and 77-79 h, respectively. Diazepam and nordiazepam were measured in equine postadministration serum out to collection times of 6 and 54 h, respectively. Oxazepam and temazepam were not detected in postadministration serum.

Significance of the pulmonary artery diastolic-pulmonary wedge pressure gradient in sepsis.

An initially widened pulmonary artery diastolic-pulmonary wedge pressure (PAD-PWP) gradient greater than 5 mm Hg has been reported to be associated with an 83% mortality rate in septic patients. To confirm and extend these observations, we retrospectively reviewed the charts of 47 septic patients. The patients were divided into 2 groups: group 1-12 patients who never had an abnormal gradient during their hospital course, and group 2-35 patients who had an abnormal gradient sometimes during their course. There were no hemodynamic differences. However, the mortality rate in group 2 patients was significantly higher than in group 1 patients (60% vs 25%, p less than 0.01). In patients with an initial gradient, the mortality rate was 61% which is not significantly different than the 83% previously reported. In patients with a persistent or increasing gradient before death or the resolution of sepsis, the mortality rate was 91%. We conclude that although an initial PAD-PWP gradient in patients with sepsis is associated with a high mortality, a much more sensitive indicator is whether the gradient increases or persists over time. There is a 91% mortality in patients with persisting or increasing gradients.

Verrucous ulcerative skin lesions in sarcoidosis. An unusual clinical presentation.

A twenty-seven year old man with a two year history of sarcoidosis and systemic manifestations of this disease along with verrucous ulcerative skin lesions is presented. Biopsy specimens of the cutaneous lesions showed typical noncaseating granulomas as well as necrotizing granulomatous inflammation. After other possible etiologies were excluded, prednisone therapy was instituted with prompt resolution of the skin lesions, leaving atrophic scars.