Assessing cost effects of nursing-home-based geriatric nurse practitioners

Employment of geriatric nurse practitioners (GNPs) is one strategy to improve nursing home care. The effects of GNPs on costs and profitability of nursing homes and on costs of patient medical service use outside the nursing home are examined. Employment of GNPs does not adversely affect nursing home costs or significantly affect profits. There is some evidence of cost savings in medical service use for newly admitted patients but no evidence of savings for continuing residents. GNPs reduce the use of hospital services for both groups, and the reduction is statistically significant for newly admitted patients.     

Sertindole (Serdolect): preclinical and clinical findings of a new atypical antipsychotic

This review first describes the preclinical findings with sertindole, a novel phenyl indole derivative antipsychotic agent. Second, a summary is provided of the major clinical trials conducted to date. Based on these findings, sertindole appears to be an effective antipsychotic agent for the treatment of positive and negative symptoms of schizophrenia, with efficacy that is clearly superior to placebo. Sertindole is as effective as haloperidol, however, is much better tolerated with significantly fewer adverse neurologic effects across a wide dosage range of both drugs. Sertindole is associated with a significant mean prolongation of the QT and QTc intervals of 3 - 6% from baseline in placebo-controlled studies. This potential adverse effect should be taken into account when treating specific patients with known risk factors for ventricular arrhythmias. Sertindole should prove to be a very useful addition to the therapeutic options available for the treatment of psychotic disorders.     

Does a mid-lumbar block level provide adequate anaesthesia for transurethral prostatectomy?

In this prospective, randomized study, 23 patients having spinal anaesthesia for transurethral prostatectomy (TURP) were evaluated for the adequacy of their block using a visual analog pain score (V4 PS). Each patient with a “standard”(≥T₁₀) block level (n = 5) or “intermediate” (L₁ or T₁₂) block level (n = 5) found the block adequate. Sixty-two percent (8/13) of patients with a “low”-L₃) block level found their block adequate. The VAPS was assessed every five minutes or whenever pain abruptly increased during TURP; an “inadequate block” was defined as a V4 PS ≥ 5 /10 during prostatic resection. Intravesical pressure was monitored and kept <15 mmHg to distinguish between pain from bladder distension and from prostatic resection. “Low” block patients (LBP) who found their block inadequate (n = 5) received supplemental intrathecal local anaesthetic given through a spinal catheter. The subsequent L₁ block level was adequate for TURP. In LBP, who found their block adequate (n = 8), a higher (P < 0.01) VAPS was observed than in patients with a “standard” block level. However, a smaller (P < 0.05) maximum percent decrease in diastolic blood pressure was found in LBPs, than in “intermediate” or “standard” block patients. It is concluded that a spinal block ≥L₁) is adequate during TURP when bladder pressure is monitored and kept low. Mid-lumbar block levels should be reserved for patients in whom the benefit of minimizing haemodynamic changes outweighs the risk of a “less complete” anaesthetic.     

The precision of practice analysis results in the professions

A practice analysis, in which an appropriate sample of professionals is asked to describe what they do in their practices, is considered an essential part of the content-related validity evidence for licensure and certification tests. This article examines the precision of estimates of the mean frequencies for categories of activities in an activity inventory administered on two occasions about 6 weeks apart. In particular, it explores the variability in estimates of the mean frequencies for categories due to the sampling of respondents, activity statements, and occasions. The results suggest that samples of 200 respondents, about 10 to 20 activity statements per category, and one occasion are adequate for estimating the mean frequency for each category.     

Activation of K-p21ras and N-p21ras, but not H-p21ras, is necessary for mitogen-induced human airway smooth-muscle proliferation

Ras proteins (H-, K-, and N-p21ras) play critical roles in the control of normal and neoplastic cell growth. To date, however, little is known about the role of p21ras in regulating mitogen-induced smooth muscle and, specifically, human airway smooth-muscle (HASM) cell growth. We postulate that p21ras is a critical signaling event regulating mitogen-induced HASM cell proliferation. Growth-arrested, confluent HASM cells were treated for 1 h with 10 ng/ml epidermal growth factor (EGF), 1 U/ml thrombin, or 5 microM bradykinin, then cell lysates were immunoprecipitated using anti-p21ras antibody. Immunoblot analysis using a pan p21ras antibody, which recognizes H-, K-, and N-p21ras, found no significant difference in p21ras expression in HASM after stimulation with either agent, as compared with control. In parallel experiments, we characterized that HASM cells express K- and N-p21ras, but not H-p21ras. Further, there was no difference between the levels of each p21ras isoform after stimulation with any of the agonists. The time course of p21ras activation, however, was markedly different among agonists. EGF rapidly activated p21ras within 30 s and was sustained for up to 30 min. Although thrombin also induced a rapid rise in p21ras activity after 2.5 min, the activation was transient. In contrast, bradykinin, which is nonmitogenic for HASM cells, did not activate p21ras. Using single-cell microinjection, the role of p21ras activation in modulating mitogen-induced HASM DNA synthesis was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and anti-BrdU immunofluorescent staining. Thrombin- and EGF-induced DNA synthesis in cells microinjected with Y13-259, a neutralizing p21ras antibody, was significantly inhibited as compared with those microinjected with isotype-matched rat immunoglobulin G(1) or a vehicle control. These data suggest that activation of p21ras appears to be necessary for EGF and thrombin-induced HASM cell proliferation and that activation of K- and N-p21ras, but not H-p21ras, mediates smooth-muscle cell growth.     

Spinal intradural tumours: Part I--Extramedullary

Sixty-six patients had surgery for an intramedullary nerve sheath tumour under the care of one surgical team in a 16-year period. Surgery concentrated on radical intra- and extradural excision combined if necessary with vertebral column reconstruction. Ninety procedures were used in 35 males and 30 females with an age range 12-81 years. Forty-five per cent were located in the cervical, 26% in the thoracic and 29% in the lumbosacral region. Eighteen patients had NF1 and two patients NF2. Sixty-five per cent were schwannomas, 27% were mixed histology and 6% malignant. In terms of functional outcome, 37 patients improved by one or more Frankel grades, three deteriorated by one Frankel grade and no one who presented with symptoms alone deteriorated. There were no operative deaths; no instrumentation failures and five patients developed a CSF leak.     

Facilitation of spontaneous defibrillation by moxonidine during regional ischaemia in an isolated working rabbit heart model

Moxonidine has been shown to be antiarrhythmic during ischaemia in vivo. This study aimed to investigate its electrophysiological effects in isolated working rabbit hearts in vitro. Monophasic action potential duration, effective refractory period and conduction delay were measured at three ventricular sites. The hearts were treated before and during ischaemia and reperfusion with vehicle, moxonidine (0.01, 0.1 and 1 microM) or labetalol (1 microM). In all groups, ventricular fibrillation was always induced during ischaemia. Only 0.1 microM moxonidine decreased the incidence of sustained ventricular fibrillation from 86 to 17%, although it did not affect any electrophysiological parameters measured. Similarly, labetolol, an adrenoceptor blocker, facilitated spontaneous defibrillation without any electrophysiological effects. In conclusion, moxonidine directly facilitates spontaneous defibrillation of ventricular fibrillation during ischaemia. Since the same effect is observed with labetalol, it is possible that the defibrillatory action of moxonidine is related to its peripheral antiadrenergic activity, although other mechanisms cannot be excluded.     

Evaluation of phosphoramidon and three synthetic phosphonates for inhibition of botulinum neurotoxin B catalytic activity

Three putative metalloprotease inhibitors were synthesized and tested for their ability to inhibit the catalytic activity of botulinum neurotoxin B light chain (BoNT/B LC). The compounds were designed to emulate the naturally occurring metalloprotease inhibitor phosphoramidon, which has been reported to be a weak antagonist of BoNT/B action. All three analogs contained the dipeptide Phe-Glu in place of Leu-Trp of phosphoramidon and possessed a phenyl, ethyl or methyl group in place of the rhamnose sugar of the parent compound. The inhibitors were evaluated in a cell-free assay based on the detection of a fluorescent product following cleavage of a 50-mer synaptobrevin peptide ([Pya(88)] S 39-88) by BoNT/B LC. This peptide corresponds to the hydrophilic core of synaptobrevin-2 and contains a fluorescent analog L-pyrenylalanine (Pya) in place of Tyr(88). Cleavage of [Pya(88)] S 39-88 by BoNT/B LC gives rise to fragments of 38 and 12 amino acid residues. Quantification of BoNT/B-mediated substrate cleavage was achieved by separating the 12-mer fragment (FETSAAKLKRK-Pya) that contains the C-terminal fluorophore and measuring fluorescence at 377 nm. The results indicate that the phenyl-substituted synthetic compound ICD 2821 was slightly more active than phosphoramidon, but analogs with methyl or ethyl substitutions were relatively inactive. These findings suggest that phosphonate monoesters may be useful for providing insights into the structural requirement of BoNT/B protease inhibitors.