“It ain't over … till it's over!” Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health-care needs of COVID-19 patients. During the adaptation phase, GI services are calibrated towards a “new normal,” and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long-term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence-based decision-making during the adaptation and consolidation phases.     

Chromosomal changes in an ovarian granulosa cell tumor: similarity with carcinoma

The chromosomal changes in an ovarian granulosa cell tumor were studied after short-term culture in defined medium. The abnormalities found included X monosomy, structural rearrangements of chromosome #1, and an interstitial deletion of the long arm of chromosome #6. This pattern is closely related to that found in ovarian carcinoma and argues for the malignant nature of such tumors at the cellular level.     

Identification of Heterozygous and Homozygous Individuals with the Novel RYR1 Mutation Cys35Arg in a Large Kindred

Background: Malignant hyperthermia (MH) is a potentially fatal, often autosomal dominant, disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalational anesthetics. In this article, the authors describe a malignant hyperthermia susceptible (MHS) kindred in which both parents of the proband are MHS and are first-degree cousins. Haplotype analysis in this kindred with chromosome 19 linked markers revealed that the proband and another sibling were homozygous for the affected RYR1 allele.

Methods: Eighteen members of this large pedigree were investigated, with a clinical examination for signs of a myopathy, a caffeine halothane contracture test, a histo-enzymologic study on the muscle biopsies, and linkage analysis on genomic DNA isolated from family blood samples. RYR1 cDNA was amplified by polymerase chain reaction and was cloned and sequenced, facilitating mutation detection.

Results: Linkage analysis demonstrated linkage between RYR1-linked markers and MH susceptibility in this family. DNA sequencing identified a T to C transition at nucleotide position 103, resulting in the substitution of an arginine for cysteine 35, representing the most N-terminal mutation reported to date in the RYR1 gene. This mutation segregates fully with the MHS trait, generating a lod score of 4.65 in favor of linkage to MHS at a recombination frequency of 0.0.     

Screening tests for malignant hyperthermia susceptibility

The ideal screening test for malignant hyperthermia susceptibility (MHS) has yet to be discovered. It should be simple noninvasive, yet totally specific and sensitive. Until such an ideal test becomes available, allowing simple routine preoperative screening, tests should only be used in certain specific situations. These include: patients in whom a clinical crisis was suspected; the members of the family of a subject labeled MHS because of a fatal, or otherwise, crisis, or in whom tests were positive; patients with other pathological conditions which could be linked to malignant hyperthermia (MH) (some myopathies, effort or stress MH, neuroleptic malignant syndrome). The various tests proposed in the literature aim at revealing MHN subjects, using or not a triggering agent, halothane most often. However, detecting these abnormalities sometimes gives greater insight into the physiopathology of MH than in the detection of an individual patient's susceptibility. The tests have been classified as in vivo, electrophysiological, blood, and in vitro muscle biochemical, morphological, and pharmacological tests. The discovery of new tests gives renewed hope: CPK levels, platelet tests, calcium sarcoplasmic reticular reuptake, lymphocyte Quin 2 test, nuclear magnetic resonance spectroscopy. However, experts worldwide agree that the only reference test to this day remains the in vitro halothane caffeine contracture tests. These tests have shown their reliability; they must be performed on muscle strips obtained from surgically removed muscle biopsies, by laboratories used to this technique and who have at their disposal a sufficiently large group of MHS subjects with a clear-cut clinical crisis, as well as controls. The patients must therefore travel to these laboratories. The design of common protocols for European laboratories on one hand, and the North American laboratories on the other, is a good guarantee of the reliability of these tests.     

新疆藁本有效成分coniselin的全合成研究

新疆藁本有效成分ｃｏｎｉｓｅｌｉｎ的全合成研究丁平羽，于德泉（中国医学科学院，中国协和医科大学药物研究所北京１０００５０）新疆藁本（ＣｏｎｉｓｅｌｉｎｕｍｖａｇｉｎａｔｕｍＴｈｅｌｌ）是新疆地区常用中药藁本的代用品，应用广泛，主要功能是祛风散寒。本研...     

Basic Cardiac Life Support Providers Checking the Carotid Pulse: Performance, Degree of Conviction, and Influencing Factors

The American Heart Association recently abolished the carotid pulse check during cardiopulmonary resuscitation for lay rescuers, but not for health care providers. OBJECTIVES: The aim of the study was to evaluate health care providers' performance, degree of conviction, and influencing factors in checking the carotid pulse. METHODS:Sixty-four health care providers were asked to check the carotid pulse for 10 or 30 seconds on a computerized mannequin simulating three levels of pulse strength (normal, weak, and absent). Health care providers were asked whether they felt a pulse and how certain were they that they felt a pulse. Performance was evaluated, as well as degree of conviction about the answer, using a visual analog scale. Data were compared by using a general linear model procedure. RESULTS: In the pulseless situations, the answers were correct in 58% and 50% when checking the pulse for 10 and 30 seconds, respectively. In the situation with a weak pulse, the answer was correct in 83% when checking the pulse for 10 seconds. In situations with a normal pulse, the answers were correct in 92%, 84%, and 84%, respectively, when checking the pulse for 10 (twice) and 30 seconds. The exactitude of the answer was correlated with the pulse strength (p < 0.05). The degree of conviction about the answer was correlated with the exactitude of the answer (p < 0.01) and the pulse strength (p < 0.0001). CONCLUSIONS: These results question the routine use of the carotid pulse check during cardiopulmonary resuscitation, including for health care providers.     

Basement membranes and tumor pathology

The distribution of four basement membrane components, type IV collagen (C IV), laminin (LM), heparan sulfate proteoglycan (HSP) and fibronection (FN) has been studied by indirect immunofluorescence using specific antibodies, in benign and malignant proliferations of the mammary gland and in soft tissue tumors. In breast carcinomas, specially intraductal cancers, there is a progressive and concomitant loss of these macromolecules around tumoral cells, preceding an overt tumoral invasion. In sarcomas, FN is frequently seen between malignant cells but the regular pericellular labeling observed around normal muscular cells, Schwann cells and adipocytes is absent. Nevertheless, the persistance of some pericellular staining with anti-C IV, anti-LM, anti-HSP and anti-FN antisera, in most differentiated territories of liposarcomas, leiomyosarcomas and neurifibrosarcomas can help to the diagnosis of such lesions.     

Effects of veratridine on mechanical responses of human malignant hyperthermic muscle fibers

Background : To determine if alteration in the function of the sodium channel may in turn modify halothane-induced changes in mechanical responses of muscle bundles from patients susceptible to malignant hyperthermia (MH).
Methods : Mechanical responses of muscle bundles from 12 MH-susceptible and 20 MH non-susceptible patients were measured prior to and during administration of halothane alone and in the presence of 10μM veratridine, an inhibitor of sodium channel inactivation. Peak tension (PT), time to peak tension (TPT), positive peak of isometric tension derivative (+dP/dtmax) were used to characterize the inotropic state. Analysis of relaxation process was performed using half relaxation time (RT1/2) and the negative peak of isometric tension derivative (-dP/dtmax). The ratio (R)=(+dP/dtmax)/(-dP/dtmax) was used to measure the coupling between contraction and relaxation under isometric condition.
Results : Veratridine significantly enhanced the 0.5, 1, 2 and 3 vol% halothane-induced contracture and induced a negative inotropic effect in MH-susceptible muscle bundles. R increased by nearly 90% indicating that the combined effects were more pronounced in the relaxation phase. In MH non-susceptible muscle, veratridine did not significantly enhance the effects of halothane.
Conclusions : These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of an inhibitor of sodium channel inactivation.