Beneficiary survey-based feedback on new Medicare informational materials

In response to the Balanced Budget Act (BBA) of 1997, the Center for Medicare & Medicaid Services (CMS) initiated a massive information and education campaign to promote effective health plan decision-making. Early results suggest that the pilot version of the Medicare & You handbook and other new Medicare informational materials were viewed favorably overall. Despite their limitations, most beneficiaries found the information useful. The longer, more comprehensive materials were not perceived to be more useful than the shorter, less complicated version. Additional research is needed to determine which subgroups of beneficiaries may need more and, possibly less, information.     

Relationship between the chest radiograph, regional lung function studies, exercise tolerance, and clinical condition in cystic fibrosis

This study evaluated the accuracy of the interpretation of the chest film in delineating localised abnormalities of ventilation and perfusion, as well as the overall severity of airways obstruction, exercise tolerance, and clinical condition in children with cystic fibrosis. Radiographic findings in various regions of the chest film were compared with the functional values obtained with regional lung function tests which evaluated the arrival and disappearance of boluses of radioactive nitrogen given by inhalation and infusion. While the more severely affected areas on the chest radiograph were found to correlate with similar regions on the lung function tests, as did overall scores, errors occurred in some cases if the x-ray film alone was used as a judge of regional physiological derangement. In addition the degree of airways obstruction, the exercise tolerance on a cycle ergometer, and clinical grading, each correlated significantly with the radiographic score. We conclude that the chest radiograph is a good indicator of the overall severity of the lung disease and that it correlates well with exercise tolerance and clinical condition in cystic fibrosis.     

A comparison of the acute effects of zotepine and other antipsychotics on rat cortical dopamine release, in vivo

The acute effects of systemic administration of the antipsychotic drug, zotepine, on extracellular dopamine (DA) in the frontal cortex of freely-moving rats were studied using in vivo microdialysis and compared with the actions of clozapine, olanzapine and haloperidol. Treatment with zotepine (1.0 mg/kg, i.p.) resulted in a prolonged elevation of cortical DA levels for up to 180 min post-drug. A maximal rise of +333% was observed at 120 min post-zotepine treatment. Clozapine (10.0 mg/kg, i.p.) also evoked a rise in extracellular DA which was similar in duration (200 min) to that resulting from treatment with zotepine. A maximal rise of +223% was observed at 100 min post-clozapine treatment. Olanzapine (1.0 mg/kg, i.p.) resulted in an immediate increase in DA levels which was maximal 40 min post-treatment (+280%) with levels returning to pre-injection values by 100 min after dosing. In contrast, haloperidol (0.1 mg/kg, i.p.) had no measurable influence on cortical DA levels. Local perfusion with the NA uptake inhibitor, nisoxetine (10 microM), resulted in an increase in cortical DA levels which was maximal at 100 min post-onset of perfusion (+257% above baseline). Administration of zotepine (1.0 mg/kg, i.p.) during nisoxetine perfusion elevated DA levels to a maximum of +301% above baseline, 60 min post-zotepine. These results show that acute administration of each of three drugs with an atypical antipsychotic profile causes an elevation of cortical DA in freely-moving rats at doses relevant to those derived from animal models which predict antipsychotic activity. As a dysfunction in cortical DA is thought to be involved in both the negative symptoms of schizophrenia and cognitive deficits in schizophrenic patients, it is possible that zotepine's ability to elevate cortical DA levels may underlie its effectiveness in successfully treating these components of schizophrenia. Furthermore, the ability of zotepine to elevate cortical DA is more likely to derive from its inhibition of the NA transporter rather than DA receptor blockade in this region.     

Variability of lipids in patients with Type 2 diabetes taking statin treatment: implications for target setting

Aims To determine the biological variability of lipids in patients with Type 2 diabetes (T2DM) who are on statin treatment and then to assess any implications for current lipid targets. Methods A cross‐over study of biological variation of lipids in 26 patients with T2DM taking either simvastatin 40 mg or atorvastatin 10 mg. After 3 months on one statin, fasting lipids were measured on 10 occasions over a 5‐week period. Following 3 months on the other statin, 10 further samples were taken over 5 weeks. The main outcome measures were biological variability of total cholesterol (TC), low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol and triglycerides. Results The coefficient of variation (CV) of TC, LDL, HDL and triglycerides on simvastatin was 8.17, 13.11, 7.95 and 12.06%, respectively, whereas the CV on atorvastatin was 6.92, 10.30, 5.13 and 19.71%, respectively, with no statistically significant differences between statins. Treating to sustain a target TC < 5.0 mmol/l or LDL < 3.0 mmol/l means needing to maintain a mean TC of 4.3–4.4 mmol/l or LDL of 2.4–2.5 mmol/l. Treating to consistently achieve an LDL < 2.0 mmol/l means aiming for a mean of only 1.5–1.6 mmol/l. Conclusion In patients with T2DM taking either simvastatin or atorvastatin, the mean TC and LDL concentrations needed to consistently remain below a target are much lower than the target value itself. This means that guideline target limits extrapolated from the mean values of patients participating in clinical studies may overestimate the lipid reductions required.     

Surgical oncology in university departments of surgery in the United States

Data on surgical oncology and multidisciplinary cancer program activity were obtained from 124 of 126 university surgery departments in the United States. Most of these institutions have American College of Surgeons-approved cancer programs (84%) as well as divisions of medical (95%), radiation (94%), pediatric (76%), and gynecologic (79%) oncology. Only 47 departments (38%) have formal divisions of surgical oncology. There are no major staffing or activity differences in surgical departments with or without such divisions, but multidisciplinary cancer program activity is greater in those institutions with a surgical oncology focus. Peer-reviewed cancer research grants are more frequent in departments of surgery with a surgical oncology division (68% vs 47%). The activities of the existing 47 divisions of surgical oncology are mainly operative, with breast cancer, melanoma, and soft-tissue sarcomas being the major clinical responsibilities. Chemotherapy is also frequent (81%). Cancer education for undergraduate and postgraduate surgical trainees is a major responsibility of most divisions, but only a small proportion (28%) have postresidency surgical oncology training programs. In contrast to the growth of some oncologic specialties, the establishment of surgical oncology within university departments has been slow, and the manpower needs appear modest.     

Rocastine (AHR-11325), a rapid acting, nonsedating antihistamine

Rocastine [AHR-11325, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido-[3,2-f]-1,4- oxazepine-5(4H)-thione (E)-2-butenedioate)] is a rapid-acting, potent, nonsedating antihistamine. In guinea pigs challenged with a lethal dose of histamine, rocastine is as effective [based on 1 hr. oral, protective dose (PD50S)] as brompheniramine, chlorpheniramine, pyrilamine, and promethazine and superior to astemizole, diphenhydramine, terfenadine, and oxatomide. Rocastine has a faster onset of action than does terfenadine; rocastine being as effective with a 15 min pretreatment time (PD50 = 0.13 mg/kg) as it is with a 1 hr pretreatment time (PD50 = 0.12 mg/kg), while the 15 min PD50 of terfenadine (PD50 = 44.0 mg/kg) is 22 times greater than the 1 hr PD50 (PD50 = 1.93 mg/kg). Against aerosolized histamine, rocastine was 7.12 x, 2.63 x, and equipotent to pyrilamine in preventing histamine-induced prostration at pretreatment times of 1,3, and 6 hr, respectively. Rocastine protected guinea pigs from collapse induced by aerosolized antigen; rocastine was approximately 36 x more potent (based on 1 hr PD50) than diphenhydramine and as potent as oxatomide and terfenadine. Rocastine did not alter the EEG of cats at doses in vast excess (150x) of its antihistaminic dose nor did it potentiate yohimbine toxicity in mice. Further, rocastine possesses no anticholinergic, antiadrenergic, or antiserotonergic properties in vitro. Rocastine is a selective, nonsedating, H1-antagonist with a rapid onset of action.     

Selection of Rabbit Single-chain Fv Fragments against the Herbicide Atrazine using a New Phage Display System

A convenient new bacteriophage display vector, pSD3, has been constructed and used to generate rabbit monoclonal anti-pesticide antibody fragments. Following amplification of immunoglobulin light chain, and heavy chain variable region gene libraries, restriction enzymes Sfi I and PflM I are used to assemble scFv libraries in pSD3. This allows the number of stages involving the polymerase chain reaction and restriction enzyme digestion to be minimized to optimize maintenance of the original diversity of the variable region genes in the libraries. The vector also incorporates an amber codon, a 6xHis tag and a c-myc epitope to facilitate soluble single-chain Fv production detection and purification. Using the pSD3 system two anti-atrazine single-chain Fvs were isolated from a library derived from the spleen cells of a rabbit immunized with bovine serum albumin-atrazine conjugate. Characterization of single-chain Fvs by competition and equilibrium ELISA indicated good specificity and affinity to atrazine.     

Characterisation of sodium-dependent uptake of 5-hydroxytryptamine into guinea-pig brain

The uptake of 5-hydroxytryptamine (5-HT) was studied using isolated nerve endings (synaptosomes) prepared from the corpus striatum of the guinea pig. Analysis of temperature-dependent uptake revealed that two processes were involved, a sodium-dependent and sodium-independent mechanism. Kinetic studies indicated that the affinity of 5-HT (Ku) and the transport capacity (Vu) of the uptake process were dependent upon the external concentration of sodium. The transport capacity increased linearly with increasing concentrations of sodium up to 140 mmol/l, whereas the affinity for 5-HT was enhanced at concentrations of sodium up to 100 mmol/l, but reduced at 130 mmol/l sodium. The findings of this study suggest that uptake of 5-HT occurs as a result of a mobile carrier transport system which, depending upon the external concentration of sodium proceeds by a single or double displacement mechanism.     

Solitary fibrous tumor of the skin.

Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor that typically arises in the pleural cavity. Comprised of spindled cells characteristically arranged in diverse architectural patterns, SFT histologically simulates a variety of benign and malignant mesenchymal tumors. The diagnosis of SFT has been refined by the availability of newer immunohistochemical markers such as CD-34 and factor XIIIa, facilitating the identification of SFTs arising in multiple extrapleural sites, including the skin. We describe three cases of primary cutaneous SFT, review the literature, and discuss the histologic and immunohistochemical differential of other cutaneous tumors that SFT can mimic.     

Effect of tolcapone, a catechol-O-methyltransferase inhibitor, on striatal dopaminergic transmission during blockade of dopamine uptake.

To examine the mechanisms of tolcapone in the central nervous system (CNS), we analyzed alterations in parameters of striatal dopamine transmission induced by this drug (30 mg/kg) co-administered with the selective dopamine uptake inhibitor, GBR 12909 (10 mg/kg). Using microdialysis in freely moving rats, it was determined that combined administration of tolcapone with GBR 12909 resulted in a further increase of dopamine levels over that obtained without the catechol-O-methyltransferase inhibitor, while tolcapone alone failed to change dopamine levels. Fast-scan cyclic voltammetric monitoring of electrically evoked dopamine did not show any changes in dopamine release after the combination of the drugs, but there was a pronounced decrease in the rate of dopamine clearance after GBR 12909 alone and when co-administered with tolcapone. These data indicate that in rat striatum, a tolcapone-induced increase in extracellular dopamine is not observed because of the presence of uptake. These results also support the hypothesis that under normal conditions, uptake, rather than metabolism, control extracellular levels of dopamine.