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AT2 receptor stimulation may halt progression of pheochromocytoma.

Two patients with pheochromocytoma are described in whom treatment with a high dose of an angiotensin receptor blocker was associated with cessation of tumor growth as assessed by serial CT scanning and plasma norepinephrine estimation. If the association with drug treatment is causal, the mechanism may be through stimulation of the AT2 receptor consequent upon the elevation of plasma angiotensin II levels induced by AT1 receptor blockade. Similar observations in further patients should lead to a placebo-controlled study in patients with malignant or familial pheochromocytoma, or other tumors found to express the AT2 receptor.

Adrenal Gland Neoplasms↗

Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial.

PURPOSE: Recombinant human erythropoietin (rHuEPO) is the standard of care for patients with chemotherapy-related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response and decreases dosage requirements in patients with anemia of kidney disease, but its effect has not been studied in randomized trials in cancer patients. METHODS: This prospective, multicenter, open-label, randomized trial enrolled 157 patients with chemotherapy-related anemia (Hb <or= 105 g/L, serum ferritin <or= 450 pmol/L or <or= 675 pmol/L with transferrin saturation <or= 19%) receiving subcutaneously rHuEPO 40000 U once weekly to: (1). no-iron; (2). oral iron 325 mg twice daily; (3) iron dextran repeated 100mg IV bolus; or (4) iron dextran total dose infusion (TDI). Hb and quality of life (QOL) were measured at baseline and throughout. RESULTS: All groups showed Hb (P <.0001) increases from baseline. Mean Hb increases for both IV iron groups were greater (P <.02) than for no-iron and oral iron groups. The percentage of patients with hematopoietic responses was higher (P <.01) in both IV iron groups (each case 68%) compared with no-iron (25%) and oral iron (36%) groups. IV iron groups showed increases in energy, activity, and overall QOL from baseline, compared with a decrease in energy and activity for no-iron group and no change in activity or overall QOL for oral iron group. CONCLUSION: rHuEPO increases Hb levels and improves QOL in patients with chemotherapy-related anemia. Magnitude of Hb increase and QOL improvement is significantly greater if IV iron is added.

Abnormalities, Drug-Induced↗

Isoforms of mammalian cytochrome c oxidase: correlation with human cytochrome c oxidase deficiency.

We have reviewed the structure, function, and biogenesis of mammalian cytochrome c oxidase, examined the tissue-specific expression of isoforms of cytochrome c oxidase subunits in different mammals, and attempted to correlate the data with our knowledge of cytochrome c oxidase deficiency, illustrated by one particular patient. Cytochrome c oxidase was isolated from bovine tissues, and individual subunits examined by SDS-PAGE, N-terminal peptide sequencing, and antibody binding. Isoforms of subunits VIa, VIIa, and VIII were identified, manifesting one pattern of expression in heart and skeletal muscle, and another in liver, kidney, and brain. In rat heart and liver, only one form of subunit VIIa was identified. Northern analysis of bovine and rat tissues suggested that the tissue-specific expression of subunits VIa and VIII is regulated transcriptionally in liver, kidney, and brain, and posttranscriptionally in heart and skeletal muscle. In humans, antibody binding documented isoforms of subunits VIa and VIIa, with the pattern of expression in heart and skeletal muscle differing from that in liver, kidney, and brain; our data suggested that both isoforms of subunit VIa may be expressed in human heart. In a patient with cytochrome c oxidase deficiency, the clinical, morphologic, and biochemical manifestations were much more severe in heart than in skeletal muscle. Antibody binding suggested partial assembly of the enzyme in heart. These and other data suggest considerably more variability in the tissue-specific expression of isoforms of cytochrome c oxidase subunits than previously recognized.

Amino Acid Sequence↗

A renin-like activity in pineal gland and hypophysis.

The presence and distribution of renin-like activity in hypophysis, pineal gland and some neural tissues were studies in both normal and salt-loaded rats. The Boucher micromethod was used to detect enzymatic activity. In normal rats both the pituitary and pineal glands contained significantly higher values of renin-like activity than did the other tissues examined. In salt-loaded animals there was a significant decrease of the renin-like activity of the glandular tissue while in the other brain areas the activity increased. The results are discussed in terms of the possible physiological role of the central renin-angiotensin system in the regulation of fluid and electrolyte balance.

Animals↗

In-vitro in-vivo correlation models for glibenclamide after administration of metformin/glibenclamide tablets to healthy human volunteers.

In this study, level C and A in-vitro in-vivo correlation (IVIVC) models were developed for glibenclamide. In-vitro dissolution data were collected for the glibenclamide component of three metformin/glibenclamide tablets using a USP Type II apparatus. In-vivo plasma concentration data were obtained after administration of the prototype formulations to 24 healthy volunteers and subject to deconvolution analysis to obtain percentage in-vivo absorbed profiles. Multiple linear level C models were developed for CMAX and AUC(0-48) using percentage in-vitro dissolved data at 10, 45 and 120 min. Initially, the level A model was constructed for the first 2 h only, based on availability of in-vitro data. Another level A model was attempted using a time-scaled approach, with percentage in-vivo absorbed at time t and percentage in-vitro dissolved at time t/I as the correlating data. Internal predictability was evaluated for the level C and time-scaled level A models. For all level C approaches, linear regression models with r2 > 0.99 were determined. The prediction errors (% PE) for Cmax and AUC(0-48) were less than 1% for all formulations at all three chosen time points. The deconvolution analysis indicated biphasic absorption for glibenclamide, with one phase occurring at 2-3h and another at 6-12h after dose administration. The level A model using 2-h data was not unique for all formulations and was therefore not developed. The time-scaling factor I correlated highly (r2 = 0.99) with in vitro mean dissolution time (MDT). A linear regression time scaled model (r2 = 0.97) was successfully developed using in-vitro and in-vivo data from all 3 formulations. However, the internal predictability of the time-scaled model was poor, with % PE values for Cmax and AUC(0-48) being as much as 30.5% and 18.7%, respectively. The results indicate that level C models have good internal predictability. Though a time-scaled level A IVIVC model was successfully developed, the model was found to have poor internal predictability.

Adult↗

Preventing the withdrawal response associated with rocuronium injection: a comparison of fentanyl with lidocaine.

We compared the efficacy of IV fentanyl with IV lidocaine as pretreatment for the prevention of withdrawal response after rocuronium injection. For this prospective, randomized, placebo-controlled, double-blind study we recruited 90 patients aged between 18 and 65 yr, ASA physical status I or II, who had undergone elective surgery requiring general anesthesia and positive pressure ventilation. Patients were randomly allocated to 1 of 3 groups: group F received 2 mL IV fentanyl 50 microg/mL (100 microg), group L received 2 mL of preservative-free lidocaine 2% (40 mg), and group P (placebo) received 2 mL of normal saline. The incidence of withdrawal response after rocuronium was 57%, 30%, and 7% in the placebo, lidocaine, and fentanyl groups, respectively. We found a significant reduction in incidence of withdrawal response in both the fentanyl and lidocaine groups when compared with the placebo group (P < 0.05), with the fentanyl group being most effective (P < 0.05). In conclusion, both fentanyl and lidocaine are effective clinical treatments to alleviate the withdrawal response associated with rocuronium injection, with fentanyl being more effective.

Adolescent↗

The dysfunctional foreskin.

Although important, the foreskin is not absolutely essential to penile function. Dysfunction is common and a cause of considerable morbidity, and is sometimes associated with mortality from squamous cell carcinoma (SCC). Penile dermatoses herald, complicate or cause preputial dysfunction. Their effective diagnosis and management reduces morbidity and possibly mortality. Medical treatment has its limitations and circumcision is often required.

Balanitis↗

Outcome of 249 patients attending a nuclear medicine department with well differentiated thyroid cancer; a 23 year review.

249 patients with well differentiated thyroid cancer attended the Nuclear Medicine Department of the Royal Liverpool Hospital (formerly housed at the Liverpool Clinic) from 1967 to 1990. Papillary carcinoma was histologically evident in 68% of patients and follicular carcinoma in 32%. Fifteen percent of all patients died of their cancer. The extent of initial surgery did not appear to influence the recurrence of disease, nor the patient survival. Univariate analysis showed that males had a worse survival rate than females during the 5 years after diagnosis but thereafter survival rates were similar. Multivariate analysis indicated that unfavourable survival factors were "age over 45 years at diagnosis" and "presence of distal metastases". Survival was not significantly different with or without 131I ablation where there were no distal metastases. Outcome of pregnancy after 131I ablation gave no cause for concern. No serious complications were observed following 131I therapy. Serum thyroglobulin tests were introduced only half way through the review period and were helpful in predicting the presence of tumour recurrence but these data are to be discussed in another communication.

Adenocarcinoma, Follicular↗

The value of ventilation-perfusion imaging in pregnancy.

Pulmonary embolism (PE) is a major cause of maternal death during pregnancy. The aims of this retrospective study were to review 5 years experience of ventilation-perfusion (V/Q) imaging in pregnancy, to evaluate the effect of the V/Q scan report on the referring clinician's use of anticoagulants and to monitor the course and outcome of pregnancy. 82 patients (aged 17-44 years, gestation 6-40 weeks) underwent V/Q imaging for suspected PE, over a 5 year period. Modified PIOPED criteria were used to assess the probability of PE. 31 patients were shown to have normal scans (38%); 19 (23%) had low probability (LP) scans; 14 (17%) had intermediate probability (IP) scans and 18 (22%) had high probability (HP) scans for PE. Referring clinicians saw the reports and took action within 12 h. Anticoagulation was continued or started in 31 patients (all HP, 12 IP and 1 LP). Anticoagulation was considered unnecessary in 52 patients (all normal, 19 LP and 2 IP). None of the patients with normal or LP scans had documented PE during the follow-up period (median 25 months, range 3-60 months). No complications of anticoagulation were observed and no adverse outcome of pregnancy were reported. V/Q imaging is a valuable technique in the management of pregnant women suspected of having PE.

Adolescent↗

Outcome of 259 patients with primary proliferative polycythaemia (PPP) and idiopathic thrombocythaemia (IT) treated in a regional nuclear medicine department with phosphorus-32--a 15 year review.

259 patients with primary proliferative polycythaemia (PPP) and idiopathic thrombocythaemia (IT) have been treated with 32P over the last 15 years. Complete follow-up data were obtained in 238 patients. PPP was the diagnosis in 183 patients and 76 patients had IT. The sex ratio in PPP was male/female 1.1:1 and in IT 1:1.4. Patients' ages ranged from 28 to 95 years (median 72 years). The number of 32P administrations per patient ranged from 1 to 13 (median 2) and the total administered activity per patient ranged from 81.4 to 4162 MBq (median 496 MBq). The outcome showed a normalization of the full blood count in 50% of patients after a single administration of 32P and in 73% after two treatments. 13 patients (5.5%) developed myelofibrosis; 18 (7.6%) developed leukaemia while other cancers arose in 19 patients (8%). 32P therapy proved to be of particular value in the elderly. 32P is easy to administer and is cost effective, compared with the alternative of chemotherapy where good compliance and frequent hospital visits are required.

Adult↗

The fog clears.

Explore the source record for details and available documents.

Adult↗

16 detector multislice CT versus skeletal scintigraphy in the diagnosis of wrist fractures: value of quantification of 99Tcm-MDP uptake.

To compare the measured uptake of 99Tcm-methylene diphosphonate (99Tcm-MDP) in those scaphoid fractures seen on both 16 detector multislice CT and scintigraphy, with those seen only on scintigraphy. Over a 12 month period a total of 51 patients with suspected fracture underwent both conventional 99Tcm-MDP scintigraphy and 16 detector multislice CT on the same day. The 99Tcm-MDP uptake was then quantified in patients with identified fracture. This was measured by placing a region of interest (ROI) over the fracture site and the mean and maximum number of counts were compared with those in a similar size ROI placed over background bone activity. A total of 23 fractures were identified on scintigraphy of which 16 were also detected on CT (concordant). In seven cases the fracture was not seen on CT, even in retrospect (discordant). In the discordant cases, follow-up radiographs and MRI (where available) also failed to demonstrate a fracture. The mean fracture count to background bone activity ratio averaged 7.7 (range 3.2-18.5) for concordant fractures and 3.8 (range 1.7-5.3) for discordant fractures (t-test p=0.04). The maximum fracture count to background bone activity ratio averaged 12.7 (range 4.3-27.7) for concordant fractures and 6.3 (range 2.6-9.5) for discordant fractures (t-test p=0.03). It is speculated whether these discordant fractures with less 99Tcm-MDP uptake may represent a less severe injury such as bone bruise.

Adolescent↗

Hepatocellular carcinoma tumour thrombus in a re-canalised para-umbilical vein: detection by 18-fluoro-2-deoxyglucose positron emission tomography imaging.

This case report describes an unusual site of tumour thrombus in a re-canalised para-umbilical vein, in a patient with hepatocellular carcinoma (HCC) and cirrhosis. The tumour thrombus was suspected on conventional radiography and confirmed using PET imaging, illustrating the complimentary value of structural and functional imaging in achieving the correct diagnosis.

Carcinoma, Hepatocellular↗

Case report: False negative 16 detector multislice CT for scaphoid fracture.

We discuss a case of a 19-year-old man with scaphoid trauma. We describe the imaging findings on three sets of radiographs, bone scintigraphy, CT and MRI. CT failed to identify a scaphoid fracture, which was present on 6 week radiographs, MRI and scintigraphy. The case illustrates that despite multidetector technology, CT still relies upon cortical and or trabecular displacement to demonstrate fractures.

Adult↗

GroEL chaperone binding to beetle luciferases and the implications for refolding when co-expressed.

The folding of many proteins including luciferase in vivo requires the assistance of molecular chaperone proteins. To understand how a chaperone targets luciferase, we took three luciferases that give different bioluminescence with the same luciferin substrate and with differences in homology. The three luciferase genes, firefly luciferase (FF-Luc) (from Pyrocoelia miyako), and red (RE-Luc) and green (GR-Luc) bioluminescence-emitting luciferases (from Phrixothrix railroad-worms), were expressed in Escherichia coli to produce fusion proteins with predicted molecular masses. Subsequently, we observed that DnaK and GroEL were co-purified along with recombinant luciferase. Although the amount of co-purified DnaK was almost the same compared to FF-Luc, GroEL was 25 and 32 times higher in GR-Luc and RE-Luc respectively. Furthermore, co-expression of GroEL/GroES along with luciferase substantially refolded RE-Luc and GR-Luc compared to FF-Luc.

Animals↗