Pre-hospital ECPR in an Australian metropolitan setting: a single-arm feasibility assessment-The CPR, pre-hospital ECPR and early reperfusion (CHEER3) study.

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.

A single point mutation in Drosophila dihydrofolate reductase confers methotrexate resistance to a transgenic CHO cell line.

Sequence analysis of a cDNA encoding dihydrofolate reductase (DHFR) from a selected methotrexate-resistant Drosophila melanogaster cell line (S3MTX) revealed a substitution of Gln for Leu at position 30. Although the S3MTX cells were approximately 1000 fold more resistant to methotrexate (MTX), the karyotype was similar to the parental line and did not show elongated chromosomes. Furthermore, kinetic analysis of the recombinant enzyme showed a decreased affinity for MTX by the mutant DHFR. To determine if the resistance phenotype could be attributed to the mutant allele, Drosophila Dhfr cDNAs isolated from wild type and S3MTX cells were expressed in Chinese hamster ovary (CHO) cells lacking endogenous DHFR. The heterologous insect DHFRs were functional in transgenic clonal cell lines, showing approximately 400-fold greater MTX resistance in the cell line transfected with the mutant Dhfr than the wild type Dhfr. Resistance to other antifolates in the CHO cells was consistent with the drug sensitivities seen in the respective Drosophila cell lines. ELevated Levels of Dhfr transcript and DHFR in transgenic CHO cells bearing the mutant cDNA were not seen. Taken together, these results demonstrate that a single substitution in Drosophila DHFR alone can confer Levels of MTX resistance comparable with that observed after considerable gene amplification in mammalian cells.

A clinical study of tinnitus maskers.

This report describes a three-centre study of the effectiveness of tinnitus maskers, combination instruments (masker plus hearing aid), and hearing aids in the management of tinnitus. Some 472 patients entered the study with 382 reaching the first evaluation session after a minimum period of 6 months from fitting, and 206 reaching the second evaluation not less than 6 months after the first. The study included two control groups, by which to assess the comparative benefit to be derived solely from the investigation and counselling of such patients. The principal results were as follows: thorough investigation and careful counselling do much to help the patient; much further benefit is given by tinnitus masking instruments of various kinds; maskers are more often effective than hearing aids, although the latter are frequently the most appropriate first treatment of those patients who have substantial (but not yet treated or insufficiently treated) hearing difficulties as well; there is no evidence of masking having any harmful effect on hearing. None of the audiometric or tinnitus tests currently employed can be regarded as predictive, either of tinnitus severity, or of the eventual outcome of masking therapy, however certain measurements may help as a guide to patient management.

Measurement and management of tinnitus. Part I. Measurement.

This paper comprises mainly a description of the clinical practice and experience of the Tinnitus Clinic at the General Hospital, Nottingham, which has evolved as a result of and during the course of a 3-year DHSS-sponsored study of the efficacy of tinnitus maskers. The paper is supported by some experimental data from laboratory, epidemiological and clinical studies, and by information on the number of patients who can be seen, the staff required and the methods used in the clinic.

Differences in brainstem response latency with age and sex.

Brainstem evoked potentials in response to clicks at 60dB, 70dB and 80dB were recorded from a group of 70 normally hearing subjects. There were 10 subjects (5 male, 5 female) for each of the decades from the second to the eighth. The youngest subject was 14 years, the oldest 79 years. The possibility of there being increased latencies as a function of age was examined. The results indicated that there was, for practical purposes, no such increase. On the other hand there was very strong evidence that in females latenceis are shorter than in males. In addition, amplitudes were reduced in the case of older subjects. Condifidence limits for latency were calculated. These may be helpful in deciding whether or not a particular latency is outside the normal range.