In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs

Interleukin-6 (IL-6) administered as a single intravenous (IV) injection caused the following changes in the peripheral circulation of rats: (a) a biphasic neutrophilia with an initial peak at 1.5 hours and a second sustained wave of neutrophilia between four and 12 hours, (b) a mild lymphocytosis at 0.5 hours and a mild lymphopenia between 1.5 and four hours, and (c) a reticulocytosis between 12 and 24 hours. The bone marrow showed no significant changes at 1.5 hours, suggesting that the peripheral neutrophilia at that time is caused by demargination of intravascular neutrophils and not by release of marrow neutrophils. The bone marrow at 12 hours showed a mild left-shifted myeloid hyperplasia of myeloblasts and promyelocytes and a tremendous erythroid hyperplasia of intermediate and late normoblasts. The bone marrow at 24 hours showed a continued mild myeloid hyperplasia and striking erythroid hyperplasia. In conclusion, IL-6 in vivo acts as a stimulus for myelopoiesis and erythropoiesis and causes accompanying peripheral changes in the number of neutrophils, lymphocytes, and RBCs.     

Comparison of phaconit rollable IOL with acrylic foldable IOL

Background: Phaconit or ultra micro incision phacoemulsification cataract surgery involves phacoemulsification through a 0.9 millimetre sleeveless phaco tip and irrigating chopper followed by implantation of a rollable intraocular lens. The procedure leads to negligible astigmatism and faster visual recovery as compared to phacoemulsification with a foldable intraocular lens.     

Fluoroscopic‐guided balloon dilatation and stenting in tracheal stenosis with metallic self‐expandable stents and long‐term follow‐up results

The purpose of this study was to assess the safety and long‐term efficacy of self‐expandable stents in the treatment of benign tracheal stenosis. Nine patients (seven men) with tracheal stenosis (including one with fistula) of varied cause were treated by fluoroscopically guided balloon dilatation and stenting with self‐expandable metallic stents. The procedure was carried out under topical spray in eight patients and under general anaesthesia in one patient. The patients were followed up for a period ranging between 13 and 60 months. In eight of the nine patients, satisfactory positioning of the stent was achieved at the first instance, with immediate relief of dyspnoea. One patient with innominate artery aneurysm died 16 days after the procedure because of renal failure. At 1 month of follow up, six out of eight (75%) of our live patients were without any respiratory embarrassment. This dyspnoea‐free result reached almost 90% by the end of 1 year especially so in the fibrous strictures. Four out of the eight live patients (50%) had cough for 2 months and two (25%) had mild blood‐tinged sputum treated by inhalation and mucolytic agents. Secondary intervention was required in one patient at 1 month because of recurrent symptoms. The patient with tracheo‐oesophageal fistula required surgical intervention because of fracture of the stent. Fluoroscopically guided balloon dilatation and stenting of the tracheal stenosis is an effective non‐surgical therapy resulting in cure of fibrous strictures and palliation in cases of malignancy.     

Preoperative embolization of hypervascular head and neck tumours

The embolization of vascular tumours of the head and neck has become an important adjunct to the surgical treatment of these tumours. A vascular tumour in the head and neck region in a surgically treatable patient may be a candidate for embolization. Palliative embolization may be the sole treatment for high risk patients. Reducing intraoperative bleeding may shorten surgery time thus decreasing morbidity and mortality. The purpose of this study is to assess the efficacy of embolization as an adjunct to surgery or as a curative measure in the management of hypervascular head and neck tumours. We retrospectively reviewed the records of 46 consecutive patients (27 men and 16 women; mean age, 37.8 years) with 48 hypervascular head and neck tumours that had undergone preoperative transarterial, direct puncture or combined mode of embolization. Diagnosis of tumours was made on the basis of findings of imaging studies. The 46 patients underwent embolization either through transarterial route, by direct puncture technique or both direct puncture and arterial route. The devascularization reached 90–95% with the use of NBCA. The amount of devascularization reached by transarterial particle embolization is a little lesser. One patient (carotid body tumour) developed mild unilateral seventh, ninth and 10th cranial nerve palsy after transarterial embolization, transient hemiparesis was seen in another patient (nasopharyngeal angiofibroma). Both patients improved completely with steroids and had no deficit on follow up. One patient developed delayed glue migration into the middle cerebral artery territory 6 h after the procedure with no reported increase in size of the lesion in the following 5 years. Preoperative embolization of hypervascular tumour of head and neck region appears to be safe and improves the chance of complete removal during surgery with minimal blood loss.     

PGD15 Veterans'' Satisfaction with H2-Receptor Antagonist (H2RA) Drug Conversion

OBJECTIVES: To determine the relative cost-effectiveness of the inhaled corticosteroids beclomethasone dipropionate (BDP), budesonide (BUD), and fluticasone propionate (FP), for managing moderate to severe asthma in adults over a one-year time horizon from the perspective of the Ministry of Health (MOH) in Canada.
METHODS: A single-arm meta-analysis of randomized control trials containing at least one of FP, BUD, and BDP was performed in order to derive estimates of effectiveness and tolerance. A decision tree analysis was then used to model the cost-effectiveness analysis. Only direct medical costs were included in the analysis (i.e., inpatient care, emergency visits, physician services, nursing services, drugs, diagnostic tests). The time horizon of the study was 52 weeks, precluding discounting. All costs are presented in 1996 Canadian dollars (CDN$). The cost-effectiveness was the cost per additional symptom-free day ($/SFD).
RESULTS: 69 of 398 articles were included in the metaanalysis. The Monte Carlo base case analysis showed that FP and BUD resulted in an annual cost of $1,383 and $1,147 respectively (p > 0.01). FP produced 216 SFDs while BUD resulted in 214 SFDs, which were not significantly different at p = 0.01 (corrected for multiple comparisons). BDP cost $1,343/year and yielded 213 SFD/year (BDP was excluded from the final analysis, dominated by BUD). With no difference in effectiveness, a cost-minimization analysis showed that BUD was the cost-effective alternative, costing $236 CDN less than the FP strategy.
CONCLUSIONS: Of the inhaled corticosteroids available on the MOH Formulary in Canada, BUD is a costeffective alternative for the treatment of adults with moderate to severe asthma.     

Biodisposition and metabolism of [18F]fluorocholine in 9L glioma cells and 9L glioma-bearing fisher rats

PURPOSE: [(18)F]Fluorocholine ([(18)F]FCH) was developed as an analog of [(11)C]choline for tumor imaging; however, its metabolic handling remains ill defined. In this study, the metabolism of [(18)F]FCH is evaluated in cultured 9L glioma cells and Fisher 344 rats bearing 9L glioma tumors. METHODS: 9L glioma cells were incubated with [(18)F]FCH and [(14)C]choline under normoxic and hypoxic (1% O(2)) conditions and analyzed for metabolic fate. [(18)F]FCH and [(14)C]choline kinetics and metabolism were studied in Fisher 344 rats bearing subcutaneous 9L tumors. RESULTS: [(18)F]FCH and [(14)C]choline were similarly metabolized in 9L cells in both normoxic and hypoxic conditions over a 2-h incubation period. In normoxia, radioactivity was predominantly in phosphorylated form for both tracers after 5-min incubation. In hypoxia, the tracers remained mainly in nonmetabolized form at early timepoints (<20 min). Slow dephosphorylation of intracellular [(18)F]phosphofluorocholine (0.043-0.060 min(-1)) and [(14)C]phosphocholine (0.072-0.088 min(-1)) was evidenced via efflux measurements. In rat, both [(18)F]FCH and [(14)C]choline showed high renal and hepatic uptake. Blood clearance of both tracers was rapid with oxidative metabolites, [(18)F]fluorobetaine and [(14)C]betaine, representing the majority of radiolabel in plasma after 5 min postinjection. Oxidation (in liver) and lipid incorporation (in lung) were somewhat slower for [(18)F]FCH relative to [(14)C]choline. The majority of radiolabel in hypoxic subcutaneous tumor, as in hypoxic cultured 9L cells, was found as nonmetabolized [(18)F]FCH and [(14)C]choline. CONCLUSIONS: [(18)F]FCH mimics choline uptake and metabolism by 9L glioma cells and tumors. However, subtle changes in biodistribution, oxidative metabolism, dephosphorylation, lipid incorporation, and renal excretion show moderate effects of the presence of the radiofluorine atom in [(18)F]FCH. The decrease in phosphorylation of exogenous choline by cancer cells should be considered in interpretation of positron emission tomography images in characteristically hypoxic tumors.     

Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers.

Elevated levels of choline (trimethyl-2-hydroxyethylammonium) and choline kinase (CK) activity in neoplasms have motivated the development of positron-labeled choline analogs for noninvasive detection of cancer using PET. The aim of this study was to further evaluate [(18)F]fluorocholine (fluoromethyl-dimethyl-2-hydroxyethylammonium [FCH]) as an oncologic probe in comparison with several other closely related molecules. METHODS: FCH, [(18)F]fluoromethyl-methylethyl-2-hydroxyethylammonium (FMEC), [(18)F]fluoroethyl-dimethyl-2-hydroxyethylammonium (FEC), and [(18)F]fluoropropyl-dimethyl-2-hydroxyethylammonium (FPC) were synthesized through [(18)F]fluoroalkylation reactions. In vitro phosphorylation rates of the (18)F-labeled choline analogs and [methyl-(14)C]choline (CH) were studied using yeast CK. Several choline radiotracers were also evaluated in cultured PC-3 human prostate cancer cells. Data on chemical stability, radiation dosimetry, and toxicity of FCH were obtained. PET studies with FCH were performed on a patient with prostate cancer and a patient with a brain tumor. RESULTS: FCH and FMEC revealed in vitro phosphorylation by CK that was similar to that of choline, whereas rates of phosphorylation of FEC and FPC were 30% (P < 0.01) and 60% (P < 0.01) lower, respectively. Accumulations of FCH, CH, and FPC in cultured PC-3 cancer cells were comparable, whereas uptake of FEC was approximately one fifth that of FCH. Dosimetry estimates using FCH biodistribution data in mice indicated that the kidneys are radiation-dose-critical organs for FCH. PET images of a patient with recurrent prostate cancer showed uptake of FCH in the prostatic bed and in metastases to lymph nodes. FCH PET showed uptake in malignancies in a patient with metastatic breast cancer. PET revealed FCH uptake in biopsy-proven recurrent brain tumor with little confounding uptake by normal brain tissues. CONCLUSION: The fluoromethyl choline analog FCH may serve as a probe of choline uptake and phosphorylation in cancer cells, whereas fluoroethyl (FEC) and fluoropropyl (FPC) analogs appear to have relatively poorer biologic compatibility. Preliminary PET studies on patients with prostate cancer and with breast cancer and brain tumor support further studies to evaluate the usefulness of FCH as an oncologic probe.