Respiratory arrest in near-fatal asthma

BACKGROUND AND METHODS. The majority of asthma-related deaths occur outside the hospital, and therefore the exact factors leading to the terminal event are difficult to ascertain. To examine the mechanisms by which patients might die during acute exacerbations of asthma, we studied 10 such patients who arrived at the hospital in respiratory arrest or in whom it developed soon (within 20 minutes) after admission. RESULTS. The characteristics of the group were similar to those associated in the literature with a high risk of death from asthma, including a long history of the disease in young to middle-aged patients, previous life-threatening attacks or hospitalizations, delay in obtaining medical aid, and sudden onset of a rapidly progressive crisis. Extreme hypercapnia (mean [+/- SD] partial pressure of arterial carbon dioxide, 97.1 +/- 31.1 mm Hg) and acidosis (mean [+/- SD] pH, 7.01 +/- 0.11) were found before mechanical ventilation was begun, and four patients had hypokalemia on admission. Despite the severe respiratory acidosis, no patient had a serious cardiac arrhythmia during the resuscitation maneuvers or during hospitalization. We observed systemic hypertension and sinus tachycardia in eight patients, atrial fibrillation in one, and sinus bradycardia in another. In both patients with arrhythmia the heart reverted to sinus rhythm immediately after manual ventilation with 100 percent oxygen was begun. The median duration of mechanical ventilation was 12 hours, and all patients had normocapnia on discharge from the hospital. CONCLUSIONS. We conclude that at least in this group of patients, the near-fatal nature of the exacerbations was the result of severe asphyxia rather than cardiac arrhythmias. These results suggest that undertreatment rather than overtreatment may contribute to an increase in mortality from asthma.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

Disability-Adjusted Life Years Averted Versus Quality-Adjusted Life Years Gained: A Model Analysis for Breast Cancer Screening

ObjectivesTo quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies.MethodsUsing the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs.ResultsBreast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs.ConclusionsUsing DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold.     

Properties of a filamentous virus isolated from grapevines affected by corky bark

Summary A virus with highly flexuous filamentous particles c. 800 nm long, showing distinct transverse striations was isolated with high frequency (60%) by inoculation ofNicotiana occidentalis with sap from grapevine accessions indexing positive for corky bark. The virus, for which the name grapevine virus B (GVB) is proposed, has an ssRNA genome with mol. wt. of c. 2.5×10⁶ Da (c. 7600 nt) and coat protein subunits with mol. wt. of c 23,000 Da. GVB has a very restricted herbaceous host range and was experimentally transmitted by the mealybugPseudococcus ficus. The physicochemical and ultrastructural properties of GVB resemble those of closteroviruses. However, it is serologically unrelated to other grapevine closteroviruses including grapevine virus A, with which it shares some biological and physicochemical properties.     

Trichovirus,a new genus of plant viruses

Summary The genusTrichovirus embraces five viral species (two definitive and three tentative) with similar biological, morphological, physicochemical, and ultrastructural properties. Viral replication is likely to occur in the cytoplasm, where virions accumulate in more or less loose bundles or paracrystalline aggregates. The genome is a 3 polyadenylated, positive-sense, single stranded RNA of 7.5–8.7 kb in size. In definitive species (apple chlorotic leaf spot and potato T viruses), the genome is constructed of three slightly overlapping open reading frames coding for replication-related proteins (ORF 1), a putative movement protein (ORF 2), and the coat protein (ORF 3), respectively. ORFs 2 and 3 are probably expressed through subgenomic RNAs. Grapevine virus A (GVA) and grapevine virus B (GVB), two tentative species, may express an extra small open reading frame at the 3 terminus, encoding, in the case of GVB, a polypeptide with homologies with the small RNA-binding protein of carlaviruses. The taxonomic relevance of this difference in genome organization remains to be ascertained.     

Pyrimido[4,5,6-kl]acridines. Synthesis, in vitro cytotoxicity and structure-activity relationships

In a previous report we described the synthesis and biological properties of a group of pyrimido[4,5,6-kl]acridines 2, related to the pyrazolo[4,5,6-kl]acridines 1, promising antitumor agents possessing a broad spectrum of activity. Since the substitution of the pyrazole ring of the pyrazoloacridine chromophore with a pyrimidinone leads to derivatives that retain in vitro cytotoxic activity, we decided to further investigate the pyrimido[4,5 6-kl]acridines. Modifications at the ring system level, leading to chromophores with different characteristics, changes of substituent groups in position 6, simultaneous alteration of the chromophore and the introduction of a second cationic side chain in position 1 afforded 29 new pyrimido[4,5,6-kl]acridines, which were tested in vitro against the human colon adenocarcinoma HT29 cell line. Interesting structure-activity relationships could be drawn. Some selected derivatives were screened for their cytotoxic activity on the National Cancer Institute cell panel (60 human tumor lines).     

Ipriflavone inhibits osteoclast differentiation in parathyroid transplanted parietal bone of rats

Summary Ipriflavone, a synthetic isoflavone-derived flavonoid, was shown to have inhibitory effect on bone resorption. In order to study its mechanism of action directly on bone, 46 female Wistar rats were divided into six groups and medicated orally for 25 days as follows: groups 1 and 2 were given 1% carboxymethylcellulose solution (vehicle), groups 3, 4, 5, and 6 were administered ipriflavone at doses of 0.178, 0.356, 0.712, and 1.424 mmol/kg/day (suspended in vehicle), respectively. On the 22nd day, parathyroid glands, taken from donor rats, were transplanted in contact with the outer surface of the periosteum of both the right and the left parietal bones of rats from groups 2, 3, 4, 5, and 6. The group 1 rats underwent sham operation. Bone histomorphometry, performed on the ectocranial periosteum of parietal bones, showed that absolute erosion boundary, absolute eroded area, absolute erosion depth, number of tartrate-resistant acid phosphatase (TRAP)-positive polinucleated osteoclasts, and number of TRAP-positive mononucleated cells decreased in ipriflavone-treated rats compared with group 2 rats. The reduction was roughly proportional to the increase of drug dosage and reached statistical significance in rats of groups 5 and 6. The same parameters were extremely low in group 1 rats. Mineral apposition rate did not differ in any of the groups. Significant increase of serum calcium and significant decrease of serum phosphate were found in group 2 rats compared with group 1 rats, whereas no differences from controls were detected in ipriflavone-treated animals.The results demonstrate that ipriflavone has a direct inhibitory effect upon bone resorption, probably by reducing recruitment or differentiation of osteoclasts, rather than by inhibiting the resorption activity of differentiated osteoclasts. Ipriflavone also seems to exert a protective action against parathyroid hormone (PTH) diffusion from the site of parathyroid gland transplantation.     

POSSIBLE INVOLVEMENT OF INOSITOL-LIPID METABOLISM IN MALIGNANT HYPERTHERMIA

-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [³H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP₃)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP₃ content. As 1,4,5-IP₃,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH. ^*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany. Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn.