Financial implications of CT-guided lung biopsy in a tertiary centre: a radiologists' perspective.

AIM: To evaluate the financial costs of performing computed tomography (CT)-guided lung biopsies in a large tertiary centre to help guide service development. MATERIALS AND METHODS: Local financial data were collected to create a balance sheet, considering all expenses as well as revenue sources associated with the procedure. Data were based on accurate pricing and income data and evaluated on a per-procedure basis, with consideration of additional costs arising from post-procedural complications. Revenue data were estimated based on reimbursement information. A small coding quality audit was also performed to check if reimbursement claims were filed correctly. RESULTS: This study demonstrated a healthy income generated from CT-guided lung biopsy procedures with a profit margin of 50%. Notably different financial impact was observed when comparing the same procedure undertaken on an outpatient as opposed to inpatient basis with inpatient procedures generating a net loss of - £2,146.79 a year. Overall, the activity generated a profit of £157,015.25, after accounting for loss generated by inpatient activity. CONCLUSION: This analysis furthered understanding of the financial impact from performing CT-guided lung biopsy and will enable better planning and expansion of the service in the future, with emphasis around day-case and ambulatory service development, the positive intended consequence being an improved patient pathway.

Advantages and limitations of robotic endovacular catheters for carotid artery stenting.

Carotid artery stenting (CAS) is an important development in the treatment of carotid artery stenosis and prevention of stroke. However, despite advances in technology, including embolic protection devices (EDPs), there are concerns that the embolic stroke risk is still too high in many reports, including a number of randomized controlled trials. Robotic technology has the potential to reduce the embolic risk by facilitating accurate and safe navigation to place sheaths in the common carotid artery, reducing the embolic load during this phase of the procedure prior to EDP placement. This paper identifies the embolic risk associated with different phases of the CAS procedure and predisposing factors that are primarily implicated in increased embolic load from a literature review. The potential for robotic technology to reduce risk in CAS is discussed using preclinical and experimental studies.

Oral or intravenous iron as an adjuvant to autologous blood donation in elective surgery: a randomized, controlled study.

BACKGROUND: This study was performed to evaluate the capacity of oral and intravenous (i.v.) iron administration during autologous blood donation (ABD) to improve the efficacy of ABD and to prevent the need for allogeneic blood transfusion in patients without iron deficiency who are undergoing major elective surgery for which a minimum of 3 autologous units have been ordered. STUDY DESIGN AND METHODS: One hundred twenty-three patients were enrolled in an open-labeled, randomized, controlled trial and assigned to three treatment groups: patients in Group 1 received 3 x 100 mg of Fe2+ per day given orally for 5 weeks before operation; patients in Group 2 received 200 mg of Fe3+ given intravenously after each donation combined with initial i.v. iron supplementation in patients with hemoglobin under 15 g per dL; and patients in Group 3 were in the control group that received no iron medication. A modest ABD program involving weekly phlebotomy and threshold hemoglobin values for donation of 11.5 g per dL in women and 12.0 g per dL in men was performed. RESULTS: Ninety patients, 15 women and 15 men in each of the three groups, completed the study. The mean net red cell production during ABD was no higher (p>0.2) in the iron-treated groups (Group 1: 473 +/- 178 mL; Group 2: 436 +/- 170 mL; Group 3 (controls): 397 +/- 174 mL). The mean number of autologous units donated per patient did not differ (p>0.7) among the groups (Group 1: 3.1 +/- 0.6; Group 2: 2.9 +/- 0.7; Group 3: 3.0 +/- 0.7). The proportion of patients who needed allogeneic blood transfusion showed no significant (p>0.4) advantage for iron treatment, (Group 1: 7%; Group 2: 20%; Group 3: 10%). CONCLUSION: In non-iron-deficient patients undergoing modest ABD without erythropoietin therapy, neither oral nor i.v. application of iron during the preoperative period enhances the success of preoperative ABD.

Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase.

The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the homeostatic regulation of blood glucose. It is responsible for the formation of endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently, chlorogenic acid was identified as a specific inhibitor of the glucose-6-phosphate translocase component (Gl-6-P translocase) of this enzyme system in microsomes of rat liver. Glucose 6-phosphate hydrolysis was determined in the presence of chlorogenic acid or of new synthesized derivatives in intact rat liver microsomes in order to assess the inhibitory potency of the compounds on the translocase component. Variation in the 3-position of chlorogenic acid had only poor effects on inhibitory potency. Introduction of lipophilic side chain in the 1-position led to 100-fold more potent inhibitors. Functional assays on isolated perfused rat liver with compound 29i, a representative of the more potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of the compound for inhibition of hepatic glucose production also in the isolated organ model. Gl-6-P translocase inhibitors may be useful for the reduction of inappropriately high rates of hepatic glucose output often found in non-insulin-dependent diabetes.

2-[(2-pyridylmethyl)sulfinyl]-1H-thieno[3,4-d]imidazoles. A novel class of gastric H+/K(+)-ATPase inhibitors.

2-[(2-Pyridylmethyl)sulfinyl]thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The [3,4-d] isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo. Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thieno[3,4-d]imidazole lead to highly active compounds with a favorable chemical stability. Various substitution patterns in the thieno[3,4-d]imidazole moiety result in lower biological activity. The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation. Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K(+)-ATPase blocker introduced on the market.

Gastric acid inhibitory profile of saviprazole (HOE 731) compared to omeprazole.

Saviprazole (HOE 731), a substituted thienoimidazole, caused a dose-dependent inhibition of gastric acid secretion in dogs and rats with ID50 values which were not significantly different from that of omeprazole indicating that both compounds are equally effective. The duration of action in dogs lasted for more than 24 h and was dependent on the state of stimulation. Measurement of serum concentrations of 1 mg/kg saviprazole after intravenous or intraduodenal administration revealed a bioavailability of about 60% in dogs. The elimination half-life was about 30 min following both routes of administration. In rats basal acid secretion was inhibited by saviprazole. In addition stimulation of acid secretion by histamine, desglugastrin, carbachol and isobutylmethylxanthine-forskolin was equally inhibited. This was in agreement with the known mechanism of action, inhibition of the gastric proton pump which is the last step of acid secretion within the parietal cell. Surprisingly, at high dose levels, saviprazole differed from omeprazole. After saviprazole, 1 mg/kg i.v. to dogs, acid output dropped to zero but recovered within 30 min to a level of 90%, whereas omeprazole depressed acid output completely over the whole observation period (4.5 h). Similar results were obtained in pylorus-ligated rats.

The inhibitory effect of HOE 731 in isolated rabbit gastric glands.

HOE 731, a substituted thienoimidazole derivative, was studied on [14C] aminopyrine uptake and oxygen consumption in isolated rabbit gastric glands. HOE 731 caused a concentration-dependent inhibition of [14C]aminopyrine uptake during histamine and dbcAMP stimulation. The inhibition during dbcAMP stimulation was in accordance with its proton-pump inhibiting properties, which has already been reported. (Herling et al., Gastroenterology 96: A206, 1989). IC50 values were during histamine stimulation 0.8 +/- 0.3 microM and during dbcAMP stimulation 1.3 +/- 0.4 microM. The inhibition was reversible after addition of dithioerythritol and was of a non-competitive type. Omeprazole caused similar inhibitory effects in the same concentration-range. During time-course studies in glands, the inhibitory effect on [14C]aminopyrine uptake of 0.1 microM HOE 731 already appeared after 10 min of incubation but decreased with increasing incubation time, while 0.1 microM omeprazole caused an unchanged inhibition which started after 30 min of incubation. The concentration of 3 microM of HOE 731 and omeprazole caused a comparable constant inhibition. After pre-incubation for 135 min under basal conditions with subsequent stimulation of the glands with dbcAMP, the inhibitory effect of 10 microM HOE 731 also decreased in contrast to omeprazole. During stimulation for 4 hr, the inhibition of both compounds remained constant. In oxygen consumption studies HOE 731, at 100 microM, caused a strong inhibition down to basal values. This inhibitory effect could be prevented totally when 10 mM imidazole was added to neutralize the acidic compartment of the parietal cell during stimulation. It is concluded that HOE 731 needs acid-activation like omeprazole to inhibit the proton pump, but probably due to its chemical differences (stability, pH for conversion of HOE 731 to its active form) it shows a different inhibitory profile (faster transformation into its active moiety with faster onset of a partially reversible inhibition) as compared to omeprazole.

Evaluation of an automated tabletop blood biochemical analyzer for the veterinary clinical pathology laboratory.

The importance of accurate quantitative blood biochemical analysis for the diagnosis and management of disease is recognized by most veterinarians. In recent years, several biochemical analyzers have become available for the veterinary market. One of these analyzers was evaluated for its suitability in measuring several biochemical variables--alkaline phosphatase, urea nitrogen, creatinine, glucose, alanine transaminase (dog and cat only), and aspartate transaminase (horse only)--in dogs, cats, and horses. Instrument within-day precision ranged from 1.0 to 7.1%, and between-day precision ranged from 1.6 to 7.4%. During the 6-month period of the study, the analyzer required recalibration for only 1 analyte (creatinine). Concentrations of individual analytes were similar when blood (collected in anticoagulant), plasma, and serum were assayed in parallel. The accuracy of the analyzer, as measured by correlation to a reference method, ranged from 0.861 for creatinine in horses to greater than 0.950 for each of the other analytes in the 3 species. Mean values for each analyte were similar, except for alkaline phosphatase, which had consistently lower values by use of the analyzer method. A data base was established for reference values in each species.

A substituted thieno[3.4-d]imidazole versus substituted benzimidazoles as H+, K+-ATPase inhibitors.

S 3337, 2-(2-ethylaminobenzylsulfinyl)-5,6-dimethoxybenzimidazole, and S 1924, 2-(5-methyl-2-picolylsulfinyl)-1H-thieno[3.4-d]imidazole, are members of new classes of H+, K+-ATPase inhibitors. Their effects on H+, K+-ATPase and 14C-aminopyrine uptake in gastric glands were studied as well as in vivo in pylorus-ligated rats, stomach-lumen-perfused rats and Heidenhain pouch dogs. Their inhibitory effects were compared with the effect of omeprazole. In pylorus-ligated rats the two compounds showed a similar effectiveness as omeprazole. In stomach-lumen-perfused rats and in particular in Heidenhain pouch dogs, S 3337 was clearly less effective than omeprazole, while S 1924 was similarly effective in all in vivo models and in the H+, K+-ATPase assay as omeprazole. The difference in potency between S 1924 and omeprazole on 14C-aminopyrine uptake in gastric glands can be explained by the lower pKa value of S 1924 (3.4) than that of omeprazole (4.0). Additionally, this study shows that there was no correlation between the effects in rats, particularly in pylorus-ligated rats, and in dogs for the H+, K+-ATPase inhibitors tested. It is concluded from this study that substituted thieno[3.4-d]imidazoles represent a new class of potent gastric acid inhibitors.

Inhibition of HCG-induced ovarian and uterine weight augmentation in the immature rat by analogs of GnRH.

PIP: Results of studies of the inhibition of human chorionic gonadotropin (HCG)-induced ovarian and uterine weight augmentation in the immature rat by analogs of GnRH are presented. HCG augmented weight gain has been used as a bioassay for measurement of follicle stimulating hormone (FSH). 21-day-old HCG-primed (50 IU twice daily) animals, either intact or hypophysectomized, were injected with GnRH analogs (D-Leu(6), des-GlyNH(2), Pro-ethylamide(9))-GnRH (I). Both the intact and hypophysectomized rat displayed reduced ovarian weight after injection with .2-5 mcg I from Days 22 to 24 (p less than .01). This inhibitory effect was present even when exogenous luteinizing hormone was given in addition to HCG or when FSH was augmented by HCG. Both HCG and HCG + I injected on Days 22-24, significantly advanced the day of vaginal opening (p less than .01). However, when treatment was continued into puberty, vaginal opening was delayed.^ieng

Regression of corpora lutea in the rabbit after injection of a gonadotropin-releasing peptide.

We have shown that a potent agonist of the luteinizing hormone injected on either Day 11 of pseudopregnancy of Day 15 of pregnancy causes luteinization of ovarian follicles and a rapid regression of functional corpora lutea. Serum levels of progesterone declined markedly within 3 days of peptide injection in pregnant animals. In the presence of regressing corpora lutea, fetal resorption occurs which can be prevented by estradiol (500 ng, twice a day) or progesterone. Daily levels of estradiol below 4 mug did not maintain either corpora lutea weight or fetal survival, whereas 4 mug of the steroid maintained corpora lutea weight, but not pregnancy.

Ovulation and gonadotropin-releasing activity of [p-LEU-6, DES-GLY NH2-10, pro-ethylamide-9] -GNRH.

The ovulation-inducing and gonadotropin-releasing activities of [d-Leu-6, des-Gly NH2-10, Pro-ethylamide-9]-GnRH (II), were evaluated in rats, rabbits, and sheep. A sc dose of 3.4 ng/100 g body wt of the analog was equal to 160 ng/100 g body wt of GnRH in causing ovulation in the diestrous rat. At these dose levels, the integrated LH release was 1.9 times greater for the analog. Both the time of increase and maximum serum concentrations of LH were delayed after injection of the analog. Oral administration of II and GnRH to the proestrous rat resulted in an ED50 for ovulation of 0.92 and 54 mug/100 g body wt,respectively. Serum levels of LH and FSH were highly variable for the various treatment groups when both releasing substances were administered orally. The intense ovulating activity of II was also evident in the estrous rabbit as indicated by an activity 31 times greater than that of GnRH. Additionally, the analog was at least 50 times more active than GnRH in releasing LH in both the mid-luteal and anestrous ewe. From our experiments with the cycling rat it appears that the intense ovulation-inducing activity of II can be accounted for by the intrinsic LH-releasing activity of the nonapeptide, rather than by a prolonged release stimulus.

PIP: Ovulation and gonadotropin-releasing activity of D-Leu6, des-Gly NH2 10, Pro-ethylamide 9 -GnRH (38715) (2) were investigated in rats, rabbits and sheep. When given to the diestrous or proestrous rat, 2 was 47 and 59 times, respectively, more effective than pGlu-His-Trp-Ser-Tyr-Gly -Leu-Arg-Pro-Gly-NG2 (GnRH) in causing ovulation. The analog increased the number of ova shed at the higher dose levels in the diestrous rat (p less than .05) but neither peptide affected the number of ova recovered from proestrus rats. Generally, serum luteinizing hormone and follicle stimulating levels were related to the dose of the peptide. The integrated luteinizing hormone (LH) release was 1.9 times greater for the analog and the time of increase and maximum serum concentrations of LH were delayed after injection of the analog. The analog was at least 50 times more active than GnRH in releasing LH in both the midluteal and anestrous ewe. It appears that the intense ovulation-inducing activity of 2 can be accounted for by the intrinsic LH-releasing activity of the nonapeptide rather than by a prolonged release stimulus.