Follow-up assessment of vestibular schwannomas: volume quantification versus two-dimensional measurements

Introduction  A conservative treatment strategy is often proposed as a primary treatment option in the management of vestibular schwannomas (VS). In this “wait and scan” policy, audiovestibular symptoms are monitored regularly, and VS growth is measured on consecutive magnetic resonance images (MRI). The aim of this study is validation of two-dimensional versus volume MRI assessment in the longitudinal follow-up of VS and to define tumor growth beyond measurement error. Methods  MRI scans of 68 consecutive patients with VS were analyzed retrospectively. Two-dimensional and volume measurements on contrast enhanced (CE) T1- and T2-weighted images were performed independently by two readers. Smallest detectable differences (SDD) were calculated, and intraclass correlation coefficients (ICCs) were determined for both assessment methods. Results  Two-dimensional and volume measurements both showed best reproducibility on CE T1-weighted images. SDD for differences relative to baseline MRI [SDD (%)] for two-dimensional measurements had a higher interobserver error compared to volume measurements (40% versus 19.7%), which decreases when tumor size increases. The ICC for two-dimensional measurements in three directions was 0.947, 0.974, and 0.978 and for volume measurements 0.999. Conclusion  Volume measurements are more accurate compared to two-dimensional measurements for the evaluation of VS growth. These measurements are assessed preferably on CE T1-weighted images. SDD (%) strongly depends on VS size. SDD between consecutive scans exceeds the common clinical applied criterion of 1 or 2 mm growth to define growth.     

A controlled multicentre therapeutic trial to determine the efficacy of a novel antacid (AI-Mg-hydroxy-carbonate) in duodenal ulcer

Tisacid (a new, modern Hungarian AI-containing antacid) with a high acid-neutralizing capacity (greater than 26.8 mmol/g) also enhances gastric mucosal defense mechanisms (prostaglandin-dependent gastroprotection). A simple-blind, prospective, randomized, parallel multicentre clinical trial has been performed on both the clinical efficacy and possible side-effects of Tisacid monotherapy (AI-Mg-hydroxy-carbonate) on informed patients suffering from active duodenal ulcers. The four study groups were as follows: Group A: 3 g/day of Tisacid (acid-neutralizing capacity = 78 mmol, n = 85), Group B: 6 g/day of Tisacid (acid-neutralizing capacity = 156 mmol, n = 88), Group C: 12 g/day of Tisacid (acid-neutralizing capacity = 312 mmol, n = 68), Group D (as control): 1.0 g/day cimetidine (n = 91). The total number of patients was 332. It was found that the new Hungarian antacid compound (both tablet and suspension) can essentially accelerate the healing rate of duodenal ulcers; the cumulative healing rate of ulcers and the decrease of complaints can be achieved equally by relatively low doses of Tisacid monotherapy and cimetidine alone; and there were no essential differences between the clinical potency and side-effects of Tisacid tablets or the suspension.     

Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis

Fibrosis and apoptosis are juxtaposed in pulmonary disorders such as asthma and the interstitial diseases, and transforming growth factor (TGF)-beta(1) has been implicated in the pathogenesis of these responses. However, the in vivo effector functions of TGF-beta(1) in the lung and its roles in the pathogenesis of these responses are not completely understood. In addition, the relationships between apoptosis and other TGF-beta(1)-induced responses have not been defined. To address these issues, we targeted bioactive TGF-beta(1) to the murine lung using a novel externally regulatable, triple transgenic system. TGF-beta(1) produced a transient wave of epithelial apoptosis that was followed by mononuclear-rich inflammation, tissue fibrosis, myofibroblast and myocyte hyperplasia, and septal rupture with honeycombing. Studies of these mice highlighted the reversibility of this fibrotic response. They also demonstrated that a null mutation of early growth response gene (Egr)-1 or caspase inhibition blocked TGF-beta(1)-induced apoptosis. Interestingly, both interventions markedly ameliorated TGF-beta(1)-induced fibrosis and alveolar remodeling. These studies illustrate the complex effects of TGF-beta(1) in vivo and define the critical role of Egr-1 in the TGF-beta(1) phenotype. They also demonstrate that Egr-1-mediated apoptosis is a prerequisite for TGF-beta(1)-induced fibrosis and remodeling.     

Mucopolysaccharidosis I cats mount a cytotoxic T lymphocyte response after neonatal gene therapy that can be blocked with CTLA4-Ig.

Although gene therapy has reduced manifestations of genetic diseases, immune responses can abrogate the effect. One approach to inducing tolerance is to perform gene transfer in newborns when the immune system is immature. We demonstrate here that the dose of retroviral vector (RV) is important in mice, as mucopolysaccharidosis I (MPS I) mice that received neonatal intravenous gene therapy with a high dose of a canine alpha-L-iduronidase (cIDUA)-expressing RV had stable expression, while those that received a low dose did not. It was unclear, however, if neonatal transfer with any dose could induce tolerance in large animals. Therefore, newborn MPS I cats were injected intravenously with the RV expressing cIDUA. Although this resulted in high serum IDUA activity due to secretion by transduced cells, expression fell due to a CTL response. Cats that transiently received the immunosuppressive agent CTLA4-Ig did not develop a CTL response. In contrast, MPS I dogs, which can respond immunologically to canine IDUA, had stable serum IDUA activity after neonatal gene therapy. We conclude that cats, but not dogs, mount a potent CTL response to canine IDUA after neonatal gene therapy, which can be prevented with transient CTLA4-Ig.     

Approach to decreasing emergency department ambulance diversion hours

Analysis between two local Emergency Departments (EDs) suggested an oscillatory phenomenon for ambulance diversion: When one hospital went on diversion it led to a disproportionate flow of ambulance traffic to a neighboring facility that subsequently was forced to go on divert. We hypothesized if one hospital could avoid diversion status, the need for diversion could be averted in the neighboring facility. ED A secured additional resources and made a commitment to no diversion for 1 week. No changes in operations occurred in hospital B. We found no differences in ambulance runs or ED census at either facility comparing the week before, during, and after the trial. There was a dramatic decline in diversion hours from 19.7 to 1.4 and 27.7 to 0 at hospitals A and B, respectively, during the trial period (p < 0.05) compared to the weeks before and after. We conclude that reciprocating effects can be decreased with one institution's commitment to avoid diversion, thus decreasing the need for diversion at a neighboring facility.     

Haematological toxicity of clozapine and some other drugs used in psychiatry

OBJECTIVE: To review recent work on the haematological toxicity of clozapine and some other drugs used in psychiatry concerning especially (i) the mechanism of antipsychotic-induced neutropenia/agranulocytosis, (ii) criteria for clozapine prescribing in benign ethnic neutropenia, (iii) options in the event of worrying falls in white cell count (WCC), including measures to boost WCC with or without continued clozapine administration, (iv) criteria for clozapine rechallenge in the event that treatment was suspended because of a fall in WCC and (v) safety concerns regarding clozapine in children/adolescents. CONCLUSIONS: There remain several difficult areas, including the criteria for clozapine rechallenge. Experience has emphasised (i) the role of appropriate timing of WCC sample collection to ensure that clozapine is not withdrawn unnecessarily and (ii) the success of agents such as filgrastim in promoting rapid production of granulocytes if the situation so demands. On the other hand, the use of lithium to promote a leucocytosis has taken hold without a clear risk: benefit analysis. Be this as it may, should patients decide that they no longer wish to undergo WCC monitoring after 12 months on clozapine, cessation of monitoring is probably preferable to stopping the drug since overall mortality is decreased in patients treated with clozapine.