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Biodegradation of juvenoid diastereoisomers: radio-HPLC and MS analysis.

Microbial degradation of two diastereoisomeric forms 2 and 3 of a selected juvenoid (insect juvenile hormone bioanalog), ethyl N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl}carbamate was studied and the degradation products analyzed. Degradation experiments were performed using simple modeling under laboratory conditions. A Candida sp. strain T1, isolated from soil, was chosen as a biodegradation species. Radiolabeling of the studied compounds 2 and 3 was used in combination with radio-HPLC and MS analysis to increase the limits of detection, monitoring and isolation of trace quantities of the products of degradation and/or transformation. Resulting from the microbial processes using 2 or 3 as source compounds, three identical products (4-6) of their biodegradation were produced. Compound 2 also afforded two additional products (7, 8). Radio-HPLC analysis and separation, and subsequent MS analysis of the degradation mixtures resulted in identification of the degradation products. The degree and the rate of biodegradation of 2 and 3 were analyzed after 1, 3 and 7 days from the beginning of the experiment.

Animals↗

Open-label simultaneous radio-chemotherapy of glioblastoma multiforme with topotecan in adults.

BACKGROUND: Due to its radioresistance, the prognosis of glioblastoma multiforme (GBM) remains poor. Therefore, we investigated the impact of simultaneous radio-chemotherapy with topotecan (Hycamtin) on clinical outcome, tolerability and quality of life. PATIENTS AND METHODS: In this multicenter trial, 60 patients (19 females, 41 males) with histologically proven (5x biopsy, 31x subtotal resection, 24x total resection) GBM were included. Radio-Chemotherapy was performed with daily doses of 2.0 Gy (total, 60 Gy), and 0.5 mg (absolute dose) of topotecan intravenously 1 h prior to irradiation. Toxicity was assessed using common toxicity criteria (CTC). General condition and quality of life were assessed at baseline, at the end of therapy, and 6 weeks post-therapy. Local control and length of survival were compared with an historical control group of 67 patients only treated with postoperative radiotherapy following stereotactic biopsy (15x), subtotal resection (39x), or total resection (13x). RESULTS: 57 patients completed the therapy. Median radiation dose was 60 Gy (range 16-76 Gy). Median cumulative topotecan dose was 15 mg (range 7.5-18.5 mg). CTC toxicity grade 3 was observed in six patients and grade 4 toxicity in two patients (three events). Two patients died of septic disease. Mean Karnofsky index was 87% at baseline, 81% at the end of therapy, and 80% at 6 weeks post-therapy. Median survival time was 15 months, significantly longer than the 11 months seen in the control group (P < 0.002). Extent of tumour resection or patient age did not have a significant effect on survival. CONCLUSION: This multimodal approach is well tolerated, and quality of life remains preserved. The relatively long median survival time is promising but a further randomised double blind placebo controlled parallel designed clinical trial should be performed to confirm these results.

Adolescent↗

Radio-frequency catheter ablation of accessory pathway mediated tachycardia in a child after orthotopic heart transplantation.

Successful radio-frequency catheter ablation of accessory pathway mediated supraventricular tachycardia in the transplanted heart has been reported sporadically in adults, but has not been reported in children. This is the first report of a child having received a donor heart with manifest pre-excitation and who subsequently underwent successful radio-frequency ablation of the accessory pathway.

Adolescent↗

Dorso-medial ante-brachiocarpal luxation with radio-ulna luxation in a domestic shorthair.

An 8-year-old domestic shorthair was admitted with non-weight bearing left forelimb lameness. Examination and radiographs revealed dorso-medial ante-brachiocarpal luxation with palmar luxation of the distal radio-ulnar joint. Primary repair was performed and stabilised using an arthrodesis wire and type Ia Kirschner-Ehmer (K-E) external skeletal fixator (ESF). The cat regained excellent pain-free limb function by 14 weeks with only minor reduction in range of movement. This is the first case report of a cat with distal radio-ulnar joint luxation associated with ante-brachiocarpal luxation. Primary repair of carpal luxation in the cat should be considered before arthrodesis.

Animals↗

Contrast enhanced ultrasound for radio frequency ablation of canine prostates: initial results.

PURPOSE: We determined the feasibility of contrast enhanced ultrasound for radio frequency ablation of the entire prostate as a method of minimally invasive treatment for prostate cancer in a canine model. MATERIALS AND METHODS: Approval of the Institutional Animal Use and Care committee was obtained. Initially 5 dogs (group 1) were tested using variable power (5 to 30 W), time (4 to 12 minutes), bolus (0.01 to 0.04 ml/kg) and infusion (3 to 11 ml per minute at 0.015 microl/kg) injections of an ultrasound contrast agent with conventional grayscale power Doppler and pulse inversion harmonic imaging to establish optimal parameters. Subsequently 4 dogs (group 2) underwent entire prostate ablation using parameters based on group 1. The size of the thermal lesions and residual viable tissue was measured with ImageJ software (National Institutes of Health, Bethesda, Maryland) on ultrasound and pathological study. Linear regression and Student's t test were used for statistical analysis. RESULTS: A bolus of 0.04 ml/kg, an infusion of 11 ml per minute at 0.015 microl/kg and the contrast enhanced pulse inversion harmonic imaging mode were ranked best for guiding ablation. Thermal lesion volume was proportional to ablation power and time. There was no significant difference in measured thermal lesion size in group 1 between ultrasound and pathological findings (mean +/- SD 1.51 +/- 0.74 and 1.46 +/- 0.74 cm3, p = 0.56) or in residual viable tissue in group 2 (0.43 +/- 0.043 and 0.41 +/- 0.291 cm3, p = 0.21). The average volume of prostate ablation achieved in group 2 was 96.3%. CONCLUSIONS: Contrast enhanced pulse inversion harmonic imaging is able to guide, monitor and control radio frequency ablation of the entire prostate.

Animals↗

Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS.

The cross-bridged tetraamine ligand 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H2CB-TE2A) allows formation of a radio-copper complex with higher in vivo stability than that of the corresponding non-cross-bridged analog 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA). The structure of the natCu(II) complex of CB-TE2A has been previously determined by X-ray crystallography; however, direct high-pressure liquid chromatography (HPLC) characterization of the corresponding 64Cu complex was inaccessible due to the inability to detect the complex by ultraviolet absorbance at the radiotracer level. A reverse-phase HPLC separation of a series of natCu(II)-tetraazamacrocyclic complexes, both traditional and cross-bridged, was developed and applied toward characterization and assessment of the purity of the corresponding no-carrier-added 64Cu-labeled complexes. Verification of the identity of copper-64-labeled compounds was also achieved by coupling this HPLC method with mass spectrometry. The radio-liquid chromatography/mass spectrometry methodology was further extended to study the in vivo metabolic fates of 64Cu-azamacrocyclic complexes.

Animals↗

Concomitant chemo-radio-immunotherapy has a lethal therapeutic effect on tongue carcinomas independent of the clinical stage and histological characteristics of the tumor.

We examined the effect of concomitant chemo-radio-immunotherapy on 80 patients with tongue carcinoma. Disappearance of the tumor without recurrence was observed in 21 patients (38.9%) in intravenous infusion chemotherapy group (A) and in 20 patients (76.9%) in intra-arterial infusion chemotherapy group (B) (P<0.005). A total of 41 patients (51.3%) were free from the tumor after the combined therapy. Along with the good therapeutic effect, oral function was preserved with minimal impairment of speech and mastication. Tumor stage, the mode of tumor cell invasion and tumor cell differentiation were not correlated with the therapeutic effect. In addition, the expression of p53, p21(Cip1/WAF1) and proliferating cell nuclear antigen did not differ between the patients with lethal and non-lethal effects. The 5-year-survival rate was 56.8% in Group A, 76.9% in Group B and 59.6% overall. Thus, combined chemo-radio-immunotherapy, especially intra-arterial infusion, may bring a universal therapeutic effect in tongue carcinoma regardless of the tumor stage and the expression of cell phase-regulating proteins.

Aged↗

Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials.

BACKGROUND AND PURPOSE: According to common conviction rectal tumour shrinkage after preoperative radio(chemo)therapy increases the likelihood of anterior resection (AR). In order to verify this belief, we performed a systematic review of randomised trials. PATIENTS AND METHODS: We identified 10 randomised trials encompassing altogether 4596 patients in whom preoperative radio(chemo)therapy resulted in tumour shrinkage in the experimental arm as compared to the control arm. RESULTS: Tumour shrinkage observed in the experimental groups did not result in a statistically significant higher ARs rate in any study when we performed an analysis of all the randomised cases. Subgroups of patients considered to be candidates for abdominoperineal resection before randomisation were identified in three trials. A statistically significantly higher rate of ARs was demonstrated in the experimental arm of the CAO/ARO/AIO 94 study. However, in that study, sphincter preservation was a secondary endpoint and some features of the trial may bias the estimation of the effect. The benefit of sphincter preservation was not confirmed by subgroup analyses performed in the Lyon R90-01 study and in the Polish study, which were originally designed to evaluate the sphincter preservation issue. CONCLUSION: The body of evidence gathered from randomised trials does not support the concept of a beneficial effect of preoperative radiotherapy on the ARs rate.

Clinical Trials as Topic↗

Variation of urinary enzymes N-acetyl-beta-glucosaminidase, alanine-aminopeptidase, and lysozyme in patients receiving radio-contrast agents.

A urinary enzyme pattern consisting of two lysosomal enzymes, N-acetyl-beta-glucosaminidase and lysozyme, and one enzyme originating from kidney tubular brush border membrane, alanine-aminopeptidase, were studied in 30 patients undergoing intravenous urography and arteriography. N-acetyl-beta-glucosaminidase and lysozyme showed the greatest diagnostic sensitivity and were still abnormal on the fifth day after the administration of radio contrast agent. The results, which are statistically significant (Student's t test), suggest that radio-contrast agents are potentially nephotoxic.

Acetylglucosaminidase↗

The need for radio-opaque side markers on CT of the paranasal sinuses.

AIM: To audit the presence of a radio-opaque "side marker" routinely placed on the right side of the face of all patients undergoing computed tomography (CT) of the paranasal sinuses in our hospital and to audit awareness levels amongst ear, nose and throat (ENT) clinical and theatre staff regarding the "marker". MATERIALS AND METHODS: An audit of 100 CT studies of the paranasal sinuses was carried out with regard to the presence or absence of the marker. A further audit was conducted relating to the awareness amongst ENT clinical staff and theatre nurses regarding the marker. Re-audit of a second cohort of 100 sinus CT studies was carried out after implementing changes indicated by the first audit cycle. Awareness amongst staff concerned was similarly re-audited. RESULTS: In audit cycle I the side marker was positively identified in 85% of the CT examinations and were deemed absent in 15%. Of the clinical staff interviewed, only 30% were aware of the presence of the "marker" and it's significance. In audit cycle II the "side marker" was positively identified in 100% of the scans reviewed. Awareness of the presence of the "marker" amongst clinical staff was found to be 90%. CONCLUSIONS: The routine placement of a radio-opaque side marker on the right zygoma of all patients undergoing CT of paranasal sinuses is a simple yet effective additional means of denoting the correct side whilst interpreting such images. This has important implications regarding surgery. The audit has shown an improvement in both the placement of the side marker as well as in awareness levels amongst staff involved to ensure best practice.

Awareness↗

The radio-opacity of fishbones--species variation.

Plain radiographs are often taken to localize fishbones which lodge in the oropharynx and hypopharynx, but which are not seen on clinical examination. Fishbones which are thus revealed can then be removed by endoscopy. For a lateral neck radiograph to be useful in excluding a fishbone when mirror examination is difficult or fails to reveal a foreign body, it is important to know which types of fishbone are radio-opaque. We used a pig's neck preparation to simulate a human neck to determine the radio-opacity of the bones of 14 different species of fish eaten in the British Isles. We conclude that only the bones from cod, haddock, cole fish, gurnard, lemon sole, monk fish, grey mullet and red snapper are well seen by soft tissue radiographic techniques.

Animals↗

Identification of receptor subtypes in the rabbit and human urinary bladder by selective radio-ligand binding.

Recent advances in receptor technology have demonstrated that subtypes of each autonomic receptor exist. Using both direct radio-ligand studies and the inhibition of receptor binding by subtype-selective pharmacological antagonists, we have studied the distribution of subtypes of alpha and beta adrenergic receptors and muscarinic cholinergic receptors in the urinary bladder of the rabbit and man. Alpha adrenergic receptors were quantified by direct binding of tritiated prazosin (alpha-1), yohimbine (alpha-2), and the non-selective alpha adrenergic ligand dihydroergocriptine (DHE). These studies demonstrated that the distribution of alpha receptor subtypes in the bladder base (for both rabbit and human) is approximately 80% alpha-1 and 20% alpha-2. Beta receptor subtypes were identified by the inhibition of the non-selective ligand 3H-dihydroalprenalol (DHA) by the beta-1 selective inhibitor ICI-89 and the beta-2 selective inhibitor ICI-118. Initial studies demonstrated that the beta adrenergic density of the bladder body was 92 fmol per mg. protein for the rabbit and 32 fmol per mg. protein for human bladder body. Inhibition of DHA binding by ICI-118 demonstrated a single class of receptor with an IC50 of approximately 0.013 microM for both rabbit and human. Inhibition of DHA binding by ICI-89 also demonstrated one class of receptors with an IC50 of approximately 9.0 microM for both species. These results indicate that there are primarily beta-2 receptors in the rabbit and human bladder body. Although the number of muscarinic subtypes in existence is currently being re-evaluated, there are at least two which can be identified by the selective muscarinic agent pirenzepine (PZP). The brain has been shown to contain both high and low affinity PZP sites. Using both direct PZP binding to the bladder body, and the inhibition by PZP of the non-selective radio-ligand quinuclidinyl benzylate (QNB), we have demonstrated that both the rabbit and human bladder body have no observable high affinity PZP-selective binding and the inhibition of 3H-QNB by PZP demonstrated that there was only the low-affinity PZP binding site. Although receptor subtypes in the bladder have been the subject of numerous investigations, this is the first study describing the distribution of both adrenergic and cholinergic receptor subtypes in both the rabbit and human.

Animals↗

[Contribution of quantitative radio-scintigraphy to diagnosis of wrist injuries undetected on plain films: a prospective study of 154 cases].

PURPOSE OF THE STUDY: Fractures of the scaphoid must be diagnosed quickly to avoid persistent nonunion and the risk of osteoarthritis. Despite meticulous physical examination and adequate x-ray detection, numerous occult fractures still go unrecognized. The aim of this prospective study was to analyze the pertinence of quantitative radio-scintigraphy (QRS) presently used for the diagnosis of occult wrist fractures. MATERIAL AND METHODS: Quantitative radio-scintigraphy (QRS) is a new imaging technique associating quantitative bone scan and numerical fusion between bone scan images and x-ray images. We conducted a prospective study between November 1994 and March 1999 to evaluate the pertinence of this examination technique for the diagnosis of occult wrist fractures in patients presenting clinical symptoms suggestive of wrist fracture but whose plain x-rays were initially considered normal. Further some patients had several series of plain x-rays performed at several week intervals in order to search for fractures becoming progressively visible on plain x-rays. After the QRS data was acquired, these patients' x-rays were reviewed again. We also compared the cost of QRS, repeated x-rays, bone scan and MRI at the Besançon University Hospital. RESULTS: QRS was performed in all 154 patients and revealed 61 fractures (56 single-line and 5 multiple-line fractures). Thus 43.5% of these patients had occult wrist fractures (41% of which involved the carpal scaphoid). DISCUSSION: Occult fracture of the wrist, particularly the carpal scaphoid, is frequent. Repeated x-ray examination does not increase the rate of detection of these fractures. Bone scans may also fail to reveal occult fractures. MRI is a key examination in the assessment of wrist fracture symptoms, but is presently not available in all institutions. Bone scan is classically insufficiently precise. QRS is a rapidly available low-cost examination which we have found to be indispensable for the diagnosis of occult wrist fractures. With early QRS diagnosis, the risk of neglected carpal scaphoid fracture and subsequent nonunion and osteoarthritis together with the personal, social, and medicolegal consequences can be avoided.

Adolescent↗

A radio-gas chromatographic method for the determination of 11-oxotestosterone in fish plasma: its use in confirming estimations by radioimmunoassay.

A radio-gas chromatographic method has been devised for the estimation of 11-oxotestosterone (17beta-hydroxyandrost-4-ene-3, 11-dione) in fish plasma samples which provides an independent means of validating the radioimmunoassay described earlier. Estimates of the concentration of 11-oxotestosterone in a sample of male rainbow trout plasma by radio-gas chromatography using peak height and peak weight measurements were 6.9 microgram/100 ml and 7.4 microgram/100 ml respectively, in good agreement with that of 7.1 microgram/100 ml determined by radioimmunoassay.

Animals↗

Predictors for maximal outcome in patients undergoing salvage surgery for radio-recurrent prostate cancer.

OBJECTIVES: To determine preradiation and preoperative clinical staging and postoperative pathologic factors that can predict disease-free survival in patients undergoing salvage surgery for radio-recurrent prostate cancer. METHODS: A retrospective review was performed on 40 patients who underwent salvage surgery for radio-recurrent prostate cancer. Preradiation and preoperative clinical staging factors, as well as pathologic stage were analyzed as predictors of disease-free survival. Biochemical failure was defined as a persistent serum prostate-specific antigen (PSA) elevation greater than 0.4 ng/mL. RESULTS: As a group, salvage surgery provided excellent clinical disease control in 35 of 40 patients (87.5%). Overall, 18 of 38 (47.4%) patients analyzed had no evidence of biochemical progression. Preradiation clinical stage and pathologically organ-confined disease were statistically significant predictors of disease-free survival (P = 0.03 and P = 0.02, respectively). Seminal vesicle invasion and positive lymph nodes were the worst pathologic prognostic factors. Preoperative clinical T1c disease approached statistical significance in predicting pathologically organ-confined disease and disease-free survival (P = 0.08 and P = 0.07, respectively). CONCLUSIONS: Ideal candidates for salvage surgery should have preradiation and preoperative clinically organ-confined disease. All patients with pathologically organ-confined disease following salvage prostatectomy were disease free at a mean follow-up of 36.1 months. Salvage surgery, although technically feasible, should not be widely advocated as an effective curative treatment in patients with locally advanced disease at the time of diagnosis.

Adenocarcinoma↗

Radio-iodination of neurotrophins and their delivery in vivo: advantages of membrane filtration and the use of disposable syringes.

This paper reports two simple improvements for the radio-iodination of neurotrophins and their delivery in vivo. (1) Neurotrophins can be effectively separated from free iodide by using membrane filtration devices. Seven methods for the separation of free iodide are compared, including dialysis, gel filtration, and membrane filtration. Membrane filtration of the iodinated protein has several important advantages over dialysis or gel filtration. These include the precise control over the final concentration; excellent recovery of the neurotrophin; easy and inexpensive procedure; performance of the entire procedure in a fume hood; and reduced volume of radioactive waste. (2) Disposable, inexpensive syringes are suitable for the delivery of small volumes of radio-iodinated or non-radioactive neurotrophins. Plastic disposable insulin syringes are compared with Hamilton syringes. The ejection volume of the disposable syringes is surprisingly reliable in the dose range 2-15 microl. Their in vivo performance was tested by injections in the eyes of chick embryos in ovo. The amounts remaining in the eye varied significantly less with the disposable syringes. Leakage into the surrounding eye-muscles after intraocular injection was significantly more frequent with Hamilton syringes than with the disposable syringes. Thus, disposable syringes can be a reliable and cost-effective alternative for drug delivery of 2-15 microl volumes.

Animals↗

Lipid composition in jaundiced rat liver by radio-thin-layer chromatography and photodensitometry.

In vitro hepatic synthesis of lipids starting from (1-14C)acetate was investigated for 14 days in rats with biliary obstruction by ligation of the common bile duct using radio-thin-layer chromatography (radio-TLC). This study was correlated with a quantitative assay of the various hepatic lipids using TLC correlated with photodensitometry. Hepatic total lipid synthesis increased progressively with time. With concern to the single fractions, the major modifications were verified on the 3rd day with a decreased incorporation of the labelled acetate into the triglycerides. On the other hand, using photodensitometry, they demonstrated a percentage increase. These variations can be justified by the presence of a feedback mechanism. The syntheses of cholesterol and the other fractions were maximum during this period. Histologic examination revealed, especially on the 3rd day, a neoformation of biliary ductules and on the 14th day, a regression of these histological changes.

Acetates↗

Radiological evolution of the rheumatoid wrist after radio-lunate arthrodesis.

Radio-lunate arthrodesis of the rheumatoid wrist is an established technique which has been in use for more than 12 years. The evolution of 26 operated wrists and 20 non-operated wrists has been studied with a mean follow-up of 5 years. The results show that although radio-lunate arthrodesis can prevent dislocation of an unstable wrist, it cannot prevent deterioration. Collapse, ulnar translation, tilt of the lunate, and the inter-carpal instability continued with time, whether the wrists were operated on or not. The speed of deterioration was dependent on the type of rheumatoid arthritis and is faster in the disintegration type than in the osteoarthritis or the ankylosis type. The technique is applicable to the osteoarthritis type of rheumatoid arthritis, in the middle stage (2 to 4a according to the Larsen-Alnot classification). At that stage, the ankylosis type and the disintegration type, and the osteoarthritis type at an advanced stage, are better treated by total arthrodesis or total prosthetic arthroplasty.

Adult↗