Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males

GH is being used by elite athletes to enhance sporting performance. To examine the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) administration could be detected through suppression of non-22-kDa isoforms of GH, we studied seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) randomized to rhGH or placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20 min). Serum was assayed for total GH (Pharmacia IRMA and pituitary GH), 22-kDa GH (2 different 2-site monoclonal immunoassays), non-22-kDa GH (22-kDa GH-exclusion assay), 20-kDa GH, and immunofunctional GH. In the study, 3 h after the last dose of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous 22-kDa GH. Non-22-kDa and 20-kDa GH levels were suppressed. Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups. In identical exercise studies repeated between 24 and 96 h after cessation of treatment, the magnitude of the responses of all GH isoforms was suppressed (P < 0.01), but the relative proportions were similar to those before treatment. We conclude: 1) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days; 2) the dearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH abuse in athletes.

Intravenous cisplatin administration in sulphur-crested cockatoos (Cacatua galerita): Clinical and pathologic observations

The prevalence of neoplasia in birds is generally low; however, in some species of companion and aviary birds, the incidence is high and neoplasia is a common cause of death. Surgical excision or limb amputation has been performed as the therapeutic plan. Chemotherapy in the treatment of avian neoplasia is largely empirical and poorly documented. For example, cisplatin has been used intralesionally in macaws (Ara species) with limited clinical success. Eight sulphur-crested cockatoos (Cacatua galerita), under general isoflurane anesthesia, were infused intravenously with cisplatin at 6.4 or 1.0 mg/kg over 1 hour and hydrated with lactated Ringer's solution for 1 hour before and 2 hours after cisplatin infusion. Birds were euthanatized 96 hours after infusion, except for 2 birds given the low cisplatin dose, which were euthanatized on day 35 after dosing. All birds tolerated the study procedure while under anesthesia. Blood pressure, heart rate, and respiratory rate did not change significantly. In the low-dose group, the mean cloacal temperature decreased significantly during the infusion period (P < .001) and then rose progressively to preinfusion values by 24 hours. Also in this group, the mean body weight tended to increase during the infusion period before significantly decreasing (P < .05) by 5% at 96 hours after dosing. At 24 hours after dosing, all birds were bright and eating. However, intermittent regurgitation and fecal changes (moist, dark green feces and yellow urates) occurred in 3 of 8 birds, especially those given the high dose. By 72 hours after dosing, droppings in the low-dose group were normal in appearance. One bird in the high-dose group died by 94 hours after dosing. Myelosuppression was not observed in any bird and at necropsy, no evidence of cisplatin toxicity was found except in 1 bird given the high cisplatin dose. On histology, this bird showed nephrotoxicity, and its serum uric acid levels and mean estimated white blood cell count increased significantly by 24 hours after dosing. This paper reports for the first time the effect of systemic cisplatin administration in birds and provides veterinarians data for formulating efficacious and safe protocols for platinum-containing compounds when treating neoplasia in parrots and other companion birds.

Drug use evaluation of ipratropium bromide at two tertiary referral hospitals in Brisbane.

Objective: To assess the appropriateness of ipratropium bromide prescribing in two tertiary referral hospitals. Method: Criteria for optimal use were developed based on current literature and modified after consultation with respiratory physicians and clinical pharmacists. A prospective review of prescribing was performed over a 2-month period to assess conformity to these criteria. Results: Information was collected from 84 patients; 5% were receiving inhalers and 96% nebuliser therapy (one patient used both). 77% of patients (n = 65) had a principal diagnosis of chronic obstructive pulmonary disease, 14% (n = 12) asthma and 8% (n = 7) had neither diagnosis. 75% of patients were using ipratropium outside the guidelines. The major areas where the guidelines were not met were a lack of therapeutic justification, use of inappropriate doses, and use of an inappropriate delivery device. Feedback and educational interventions were designed and delivered based on the data obtained. Conclusions: There was widespread use of ipratropium outside the developed guidelines. Interventions in specific areas could lead to significant improvements in the use of this high cost drug

Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol

Aims Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect charges in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers. to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption. Methods Healthy male subjects (n = 12) received intravenously infused 2500 mg sinistrin (glomerular filtration) and 440 mg p-aminohippuric acid (PAH; anion secretion), and orally administered 100 mg fluconazole (reabsorption) and 15 mg rac-pindolol (cation secretion). The potential interaction between these markers was investigated in a pharmacokinetic study where markers (M) or fluconazole (F) were administered alone or together (M + F). Validated analytical methods were used to measure plasma and urine concentrations in order to quantify the renal handling of each marker. Plasma protein binding of fluconazole was measured by ultrafiltration. All subjects had an estimated creatinine clearance within the normal range. The renal clearance of each marker (Mean +/- s.d.) was calculated as the ratio of the amount excreted in urine and thearea-under-the-concentration-time curve. Statistical comparisons were made using a paired t-test and 95% confidence intervals were reported. Results The renal clearances of sinistrin (M: 119 +/- 31 ml min(-1); M + F: 130 +/- 40 ml min(-1); P = 0.32), PAH (M: 469 +/- 145 ml min(-1); M + F: 467 +/- 146 ml min(-1); P = 0.95), R-pindolol (M: 204 +/- 41 ml min(-1); M + F: 190 +/- 41 ml min(-1); P = 0.39; n = 11), S-pindolol (M: 225 +/- 55 ml min(-1); M + F: 209 +/- 60 ml min(-1); P = 0.27; n = 11) and fluconazole (F: 14.9 +/-3.8 ml min(-1); M + F: 13.6 +/- 3.4 ml min(-1); P = 0.16) were similar when the markers or fluconazole were administered alone (M or F) or as a cocktail (M + F). Conclusions This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes call be used to simultaneously investigate pathways of renal drug elimination.

Early rise in blood pressure following administration of adrenocorticotropic hormone-[1-24] in humans

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mug ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.

Cohesion among nurses: a comparison of bedside vs. charge nurses' perceptions in Australian hospitals

Aim. This study examines the extent to which hospital nurses view their working environment in a positive sense, working as a cohesive group. Background. Despite the fact that nursing in Australia is now considered a profession, it has been claimed that nurses are an oppressed group who use horizontal violence, bullying and aggression in their interactions with one and other. Methods. After ethical approval, a random sample of 666 nurses working directly with patients and all 333 critical care nurses employed in three large tertiary Australian hospitals were invited to participate in the study in the late 1990s. A mailed survey examined the perceptions of interaction nurses had with each other. The hypothesis, that level of employment (either Level I bedside nurses or Level II/III clinical leaders) and area of work (either critical care or noncritical care) would influence perceptions of cohesion, as measured by the cohesion amongst nurses scale (CANS) was tested. Results. In total 555 (56%) surveys were returned. Of these, 413 were returned by Level I and 142 by Level II/III nurses. Of this sample, 189 were critical care and 355 noncritical care nurses. There was no difference between Level I and II/III nurses in mean CANS scores. It is interesting to note that the item rated most positively was, 'nurses on the units worked well together', however, the item rated least positive was 'staff can be really bitchy towards each other' for both Level I and II/III nurses. There was no difference in CANS scores between critical care and noncritical care nurses. Conclusions. Nurses working in Australian hospitals perceived themselves to be moderately cohesive but, as would be expected in other work settings, some negative perceptions existed.

Route of administration of chimeric BPV1VLP determines the character of the induced immune responses

To examine the mucosal immune response to papillomavirus virus-like particles (PV-VLP), mice were immunized with VLP intrarectally (i.r.), intravaginally (i.va.) or intramuscularly (i.m.) without adjuvant. PV-VLP were assembled with chimeric BPV-1 L1 proteins incorporating sequence from HIV-1 gp 120, either the V3 loop or a shorter peptide incorporating a known CTL epitope (HIVP18I10). Antibody specific for BPV-1 VLP and P18 peptide was detected in serum following i.m., but not i.r. or i.va. immunization. Denatured VLP induced a much reduced immune response when compared with native VLP, Immune responses following mucosal administration of VLP were generally weaker than following systemic administration. VLP specific IgA was higher in intestine washes following i.r. than i.va. immunization, and higher in vaginal washes following i.m. than i.r. or i.va. immunization. No differences in specific antibody responses were seen between animals immunized with BPV-1 P18 VLP or with BPV-1 V3 VLP. Cytotoxic T lymphocyte precursors specific for the P18 CTL epitope were recovered from the spleen following i.m., i.va. or i.r. immunization with P18 VLP, and were similarly detected in Peyer's patches following i.m. or i.r. immunization. Thus, mucosal or systemic immunization with PV VLP induces mucosal CTL responses and this may be important for vaccines for mucosal infection with human papillomaviruses and for other viruses.

Quality of care of patients hospitalized with acute coronary syndromes

Background: Measurement and improvement of quality of care is a priority issue in health care. Patients hospitalized with acute coronary syndromes (ACS) constitute a high-risk population whose care, if shown to be suboptimal on the basis of available research evidence, may benefit from quality improvement interventions. Aim: To evaluate the quality of in-hospital care for patients with ACS, using explicit quality indicators. Methods: Retrospective case note review was undertaken of 397 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between 1 October 2000 and 17 April 2001. The main out-come measures were 12 process-of-care quality indicators, calculated as either: (i) the proportion of all patients who received specific interventions or (ii) the proportion of ideal patients who received -specific interventions (i.e. patients with clear indi-cations and lacking contraindications). Results: Quality indicators with values above 80% included: (i) patient selection for thrombolysis (100%) and discharge prescription of beta-blockers (84%), (ii) antiplatelet agents (94%) and (iii) lipid-lowering agents (82%). Indicators with values between 50% and 80% included: (i) timely per-formance of electrocardiogram (ECG) on admission (61%), (ii) early coronary angiography (75%), (iii) measurement of serum lipids (71%) and (iv) discharge prescription of angiotensin-converting-enzyme (ACE) inhibitors (73%). Indicators with values <50% included: (i) timely administration of thrombolysis (35%), (ii) non-invasive risk assessment (23%) and (ii) formal in-hospital and post-hospital cardiac rehabilitation (47% and 7%, respectively). Conclusion: There were delays in performing ECG and administering thrombolysis to patients who presented to emergency departments with ACS. Improvement is warranted in use of non-invasive procedures for identifying high-risk patients who may benefit from coronary revascularization as well as use of serum lipid measurements, ACE inhibitors and cardiac rehabilitation.