Medical breakthroughs: chance and opportunity

QJM ◽  
2020 ◽  
Author(s):  
J M B Hughes

Abstract Medical advances of great importance in improving diagnosis, treatment or prevention of disease are often called ‘breakthroughs’. The processes by which breakthroughs are achieved are multiple, but may include necessity (a problem which must be solved), opportunity (the time must be right), chance (the unexpected), curiosity (a desire to understand mechanisms) and ingenuity (ability to find a solution). Discovery can be the start of a chain reaction, so that the breakthrough at the end of the chain becomes “inevitable”. Two examples are given in which these attributes played a part (i) the development of a vaccine against the poliomyelitis virus and (ii) the harnessing of penicillin as a therapeutic agent to treat serious bacterial infections.

1963 ◽  
Vol 10 (02) ◽  
pp. 400-405 ◽  
Author(s):  
B. A Amundson ◽  
L. O Pilgeram

SummaryEnovid (5 mg norethynodrel and 0.075 mg ethynylestradiol-3-methyl ether) therapy in young normal human subjects causes an increase in plasma fibrinogen of 32.4% (P >C 0.001). Consideration of this effect together with other effects of Enovid on the activity of specific blood coagulatory factors suggests that the steroids are exerting their effect at a specific site of the blood coagulation and/or fibrinolytic system. The broad spectrum of changes which are induced by the steroids may be attributed to a combination of a chain reaction and feed-back control.


2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S6-S6
Author(s):  
G Naidu ◽  
A Izu ◽  
R Wainwright ◽  
S Poyiadjis ◽  
D MacKinnon ◽  
...  

Abstract Background Infectious complications in children treated for cancer contribute to their morbidity and mortality. There is a paucity of studies on the incidence, microbiological etiology, risk factors, and outcome of serious bacterial infections in African children treated for cancer. Aim The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in South African children with cancer. Methods This prospective, single-center, longitudinal-cohort study enrolled children one-19 years old hospitalized for cancer treatment at the Paediatric Oncology Unit, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Children were investigated for infection as part of the standard of care. Results In total, 169 children were enrolled, 82 with hematological malignancy (HM), 87 with a solid tumor (ST), median age was 68.5 months and 10.7% were living with HIV. The incidence (per 100 child-years) of septic episodes (SE) and microbiologically confirmed SE (MSCE) was 101 (138 vs. 70, P < 0.001) and 70.9 (99.1 vs. 47.3; P < 0.001), respectively; higher in children with HM than ST. The incidence of MCSE in children with high-risk HM (137.7) was 4.32-fold greater compared with those with medium-risk HM (30.3; P < 0.001). Children with metastatic ST had a higher incidence (84.4) of MSCE than those with localized ST (33.6; aOR: 2.52; P < 0.001). The presence of an indwelling catheter was 3-fold (P < 0.001) more likely to be associated with MCSE compared with those without. There was no association for age group, nutritional status or HIV-status, and incidence of MCSE. The incidence of gram-positive (GPB) and gram-negative (GNB) SEs was 48.5 and 37.6, respectively, and higher in children with an HM. The most commonly identified GPB were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium; while the most common GNB were Escherichia coli, Acinetobacter baumannii, and Pseudomonas species. The median CRP was higher in children with MSCE compared with those with culture-negative SE (CNSE) (116.5 vs. 92; P < 0.001) in both HM (132.5 vs. 117; P < 0.001) and ST (87.5 vs. 46; P < 0.001). The procalcitonin was higher in those with MSCE compared with those with CNSE (2.30 vs. 1.40; P < 0.001) in both HM (2.95 vs. 1.60; P = 0.002) and ST (2.10 vs. 1.20; P < 0.001). The case fatality risk was 40.4%; 80% was attributed to sepsis. Of these, 35 (72.92%) had HM and 34 of the 35 (97.14%) had HR-HM. Children with HM had an overall sepsis CFR of 42.68%. Four (30.77%) of the 13 sepsis-related deaths in STs had metastatic disease and 8 (16.67%) of the total number of sepsis-related deaths were in children living with HIV. There was no association between malnutrition or HIV-positivity and death. The odds of dying from sepsis were higher in children with profound (aOR 3.96; P = 0.004) and prolonged (aOR 3.71; P = 0.011) neutropenia. Pneumonia (58.85% vs. 29.23%; aOR 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR 4.3; P = 0.005) were independently associated with a higher CFR. Conclusion The current study emphasizes the high burden of sepsis in African children treated for cancer, and especially HM, and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.


Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 78
Author(s):  
Melissa Bello-Perez ◽  
Mikolaj Adamek ◽  
Julio Coll ◽  
Antonio Figueras ◽  
Beatriz Novoa ◽  
...  

Recent studies suggest that short pentraxins in fish might serve as biomarkers for not only bacterial infections, as in higher vertebrates including humans, but also for viral ones. These fish orthologs of mammalian short pentraxins are currently attracting interest because of their newly discovered antiviral activity. In the present work, the modulation of the gene expression of all zebrafish short pentraxins (CRP-like proteins, CRP1-7) was extensively analyzed by quantitative polymerase chain reaction. Initially, the tissue distribution of crp1-7 transcripts and how the transcripts varied in response to a bath infection with the spring viremia of carp virus, were determined. The expression of crp1-7 was widely distributed and generally increased after infection (mostly at 5 days post infection), except for crp1 (downregulated). Interestingly, several crp transcription levels significantly increased in skin. Further assays in mutant zebrafish of recombinant activation gene 1 (rag1) showed that all crps (except for crp2, downregulated) were already constitutively highly expressed in skin from rag1 knockouts and only increased moderately after viral infection. Similar results were obtained for most mx isoforms (a reporter gene of the interferon response), suggesting a general overcompensation of the innate immunity in the absence of the adaptive one.


2021 ◽  
Vol 11 (2) ◽  
pp. 77-93
Author(s):  
Khalid O. Alfarouk ◽  
Sari T. S. AlHoufie ◽  
Samrein B. M. Ahmed ◽  
Mona Shabana ◽  
Ahmed Ahmed ◽  
...  

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.


2021 ◽  
Author(s):  
Ioannis Orfanos ◽  
Tobias Alfvén ◽  
Maria Mossberg ◽  
Mattias Tenland ◽  
Jorge Sotoca Fernandez ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Andre Mu ◽  
Daniel McDonald ◽  
Alan K. Jarmusch ◽  
Cameron Martino ◽  
Caitriona Brennan ◽  
...  

Abstract Background Infectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood. Results Our paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum. Conclusion Results from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections.


2021 ◽  
Vol 58 (1) ◽  
pp. 15-19
Author(s):  
Vikram Bhaskar ◽  
Prerna Batra ◽  
Prashant Mahajan

1980 ◽  
Vol 20 (18) ◽  
pp. 1197-1204 ◽  
Author(s):  
H. T. Chen ◽  
P. A. Chartier ◽  
S. Setthachayanon

Sign in / Sign up

Export Citation Format

Share Document