scholarly journals Living in a Hostile World: Inflammation, New Drug Development, and Coronavirus

2021 ◽  
Vol 11 ◽  
Author(s):  
Geoffrey P. Dobson ◽  
Erik Biros ◽  
Hayley L. Letson ◽  
Jodie L. Morris
Keyword(s):  
Immune Response ◽  
Immune Dysfunction ◽  
Multiple Organ ◽  
Metabolic Dysfunction ◽  
Host Health ◽  
Secondary Tissue ◽  
History Of ◽  
Intersection Points ◽  
The Right ◽  
Recognition Receptor

We present a brief history of the immune response and show that Metchnikoff’s theory of inflammation and phagocytotic defense was largely ignored in the 20th century. For decades, the immune response was believed to be triggered centrally, until Lafferty and Cunningham proposed the initiating signal came from the tissues. This shift opened the way for Janeway’s pattern recognition receptor theory, and Matzinger’s danger model. All models failed to appreciate that without inflammation, there can be no immune response. The situation changed in the 1990s when cytokine biology was rapidly advancing, and the immune system’s role expanded from host defense, to the maintenance of host health. An inflammatory environment, produced by immune cells themselves, was now recognized as mandatory for their attack, removal and repair functions after an infection or injury. We explore the cellular programs of the immune response, and the role played by cytokines and other mediators to tailor the right response, at the right time. Normally, the immune response is robust, self-limiting and restorative. However, when the antigen load or trauma exceeds the body’s internal tolerances, as witnessed in some COVID-19 patients, excessive inflammation can lead to increased sympathetic outflows, cardiac dysfunction, coagulopathy, endothelial and metabolic dysfunction, multiple organ failure and death. Currently, there are few drug therapies to reduce excessive inflammation and immune dysfunction. We have been developing an intravenous (IV) fluid therapy comprising adenosine, lidocaine and Mg2+ (ALM) that confers a survival advantage by preventing excessive inflammation initiated by sepsis, endotoxemia and sterile trauma. The multi-pronged protection appears to be unique and may provide a tool to examine the intersection points in the immune response to infection or injury, and possible ways to prevent secondary tissue damage, such as that reported in patients with COVID-19.

scholarly journals Fulminant necrotizing streptococcal myositis with dramatic outcome – a rare case report

2021 ◽  
Author(s):  
Tudor Morar ◽  
Radu Pirlog ◽  
Sonia Vlaicu ◽  
Vasile Bintintan ◽  
Doinita Crisan
Keyword(s):  
Soft Tissue ◽  
Rapid Development ◽  
Multiple Organ ◽  
Penicillin G ◽  
High Dose ◽  
Streptococcal Toxic Shock Syndrome ◽  
Necrotizing Myositis ◽  
Rare Case Report ◽  
History Of ◽  
The Right

Necrotizing myositis represents a rare, aggressive form of bacterial-induced soft tissue necrotizing infection. We present a fulminant case of a 44-year-old patient with a necrotizing soft tissue infection  and a history of rheumatoid arthritis transferred to our service, Cluj-Napoca Emergency County Hospital, from a local hospital where he had been admitted two days before with chills and light-headedness after an accidental minor blunt trauma in the right thigh region. After admission to our hospital and first assessment, broad spectrum antibiotherapy was started with Meropenem, Vancomycin and Metronidazole along with surgical debridement. The evolution was fulminant with rapid development of multiple organ dysfunction syndrome, therefore he was transferred to the intensive care unit, intubated, and started the volemic resuscitation and vasopressor therapy. The blood culture was positive for group A beta-hemolytic streptococcus (GAS) and high dose Penicillin G was added to the therapeutic scheme. Despite all efforts, the patient developed disseminated intravascular coagulation syndrome and died in the next hours. The clinical picture together with the findings from the autopsy were suggestive for a streptococcal toxic shock syndrome developed as a complication of GAS induced necrotizing myositis.

P1123HEMOPERFUSION COMBINED WITH CRRT IN SEPTIC SHOCK AKI PATIENTS CAUSED BY OSTEOFASCIAL COMPARTMENT SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Xiaohua Sheng ◽  
Niansong Wang ◽  
Weifeng Huang ◽  
Gang Yu ◽  
Hongda Bao ◽  
...  
Keyword(s):  
Septic Shock ◽  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Compartment Syndrome ◽  
Blood Circulation ◽  
Kidney Injury ◽  
Lower Leg ◽  
Multiple Organ ◽  
History Of ◽  
The Right

Abstract Background and Aims Although Osteofascial compartment syndrome is rare, it can cause severe complications, including septic shock and acute kidney injury. Most commonly found on the palmar side of the forearm and lower leg. This article reported two cases of septic shock with acute kidney injury caused by osteofascial compartment syndrome, and explored the application of hemoperfusion combined with continuous renal replacement therapy in these two severe patients. Method Two young men, patient A was 38 years old and patient B was 44 years old. Hospitalized in June 2016 and February 2018, respectively. Previous healthy, after questioning, patient A had a history of type 1 diabetes and patient B had a history of gout. Patient A had a history of being beaten by his wife, patient B has no clear history of injury. Patient A showed swelling and pain in the right forearm and patient B showed swelling and pain in the right lower leg. After admission, they quickly developed shock, oliguria, acute kidney injury, multiple organ dysfunction. They were received fluid resuscitation, vasopressors, anti-infectives, respiratory support, nutritional support, and vital signs monitoring. Blood culture of patient A showed a case of group A hemolytic streptococcus, patient B showed streptococcus pyogenes and staphylococcus hemolytic. Patient A was performed CRRT for 3 days, combined with two hours hemoperfusion (HA-330, Jafron, Zhuhai City, China) on the first day of CRRT, once every 24 hours for two days. Patient B was performed CRRT for 16 days. combined with two hours hemoperfusion (HA-330, Jafron, Zhuhai City, China) on the first day of CRRT, once every 24 hours for two days. Both patients underwent multiple orthopaedic surgeries. Patient A underwent right upper limb amputation and patient B underwent right thigh amputation. Results After hemoperfusion, the amount of norepinephrine was significantly reduced, and the circulation became stable. Finally, two patients improved and were discharged from the hospital, and their renal function returned to normal. Conclusion Once the osteofascial compartment syndrome is diagnosed, the fascia should be decompressed immediately. After local incision and decompression, blood circulation is improved, and a large number of toxins from necrotic tissue enter the blood circulation, which can lead to serious complications such as sepsis, shock, acute kidney injury, and multiple organ failure. Renal replacement therapy and amputation surgery may save lives. Hemoperfusion can reduce the amount of norepinephrine, improve circulation and win surgical opportunities.

scholarly journals 349 COVID Induced Acute Ischaemic Limb

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
B Shah ◽  
M Kedrzycki
Keyword(s):  
Multiple Organ ◽  
Hypercoagulable State ◽  
Organ Support ◽  
Therapeutic Anticoagulation ◽  
Life Threatening ◽  
History Of ◽  
Sliding Scale ◽  
The Right ◽  
Diabetes And Obesity

Abstract The coronavirus pandemic has overwhelmed healthcare systems worldwide, with more than 40 million affected and 1 million deaths. In addition to the typical symptoms, less clinically obvious was the underlying hypercoagulable state, termed COVID-19 associated coagulopathy (CAC). The exact mechanism of CAC is unknown, but it is suspected to involve all three aspects of Virchow’s Triad: endothelial injury, stasis, and a hypercoagulable state. Here we report the case of a woman in her 60’s who was admitted with COVID-19 and developed CAC with subsequent complications. She presented with a 3-day history of fevers, severe shortness of breath, and cough. Past medical history was significant for hypertension, poorly controlled insulin dependant diabetes, and obesity. She was admitted with COVID induced type 2 respiratory failure (pO2 of 5.5 on 15L), DKA (ketones 2.1), AKI (Cr 163), and a hypercoagulable state (D-dimer >20 000). She was intubated and commenced on an insulin sliding scale, therapeutic anticoagulation, and antibiotics. On day 2 she became anuric, with CT-angio demonstrating thrombus extending from renal arteries down to the right popliteal artery. She underwent an embolectomy and 4 compartment fasciotomy and was started on renal replacement therapy. Unfortunately, her leg was not deemed viable, and due to persistent hyperkalaemia required amputation 2 days later. She continued to deteriorate despite maximal multiple organ support and was palliated 15 days later. CAC can have life-threatening sequelae, and patients with COVID-19 infection should be commenced on anticoagulation upon diagnosis.

Z-line degradation and phagocytosis of sarcomeric fragments in myonecrosis

1983 ◽  
Vol 41 ◽  
pp. 790-791
Author(s):  
Melinda L. Estes ◽  
Samuel M. Chou
Keyword(s):  
Vastus Lateralis ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
White Female ◽  
Inflammatory Cell Infiltrate ◽  
Limb Weakness ◽  
Muscle Diseases ◽  
History Of ◽  
The Right ◽  
Mononuclear Inflammatory Cell

Many muscle diseases show common pathological features although their etiology is different. In primary muscle diseases a characteristic finding is myofiber necrosis. The mechanism of myonecrosis is unknown. Polymyositis is a primary muscle disease characterized by acute and subacute degeneration as well as regeneration of muscle fibers coupled with an inflammatory infiltrate. We present a case of polymyositis with unusual ultrastructural features indicative of the basic pathogenetic process involved in myonecrosis.The patient is a 63-year-old white female with a one history of proximal limb weakness, weight loss and fatigue. Examination revealed mild proximal weakness and diminished deep tendon reflexes. Her creatine kinase was 1800 mU/ml (normal < 140 mU/ml) and electromyography was consistent with an inflammatory myopathy which was verified by light microscopy on biopsy muscle. Ultrastructural study of necrotizing myofiber, from the right vastus lateralis, showed: (1) degradation of the Z-lines with preservation of the adjacent Abands including M-lines and H-bands, (Fig. 1), (2) fracture of the sarcomeres at the I-bands with disappearance of the Z-lines, (Fig. 2), (3) fragmented sarcomeres without I-bands, engulfed by invading phagocytes, (Fig. 3, a & b ), and (4) mononuclear inflammatory cell infiltrate in the endomysium.

Popliteal artery thrombosis secondary to a tibial osteochondroma

VASA ◽  
2011 ◽  
Vol 40 (3) ◽  
pp. 251-255 ◽  
Author(s):  
Gruber-Szydlo ◽  
Poreba ◽  
Belowska-Bien ◽  
Derkacz ◽  
Badowski ◽  
...  
Keyword(s):  
Case Report ◽  
Magnetic Resonance Angiography ◽  
Popliteal Artery ◽  
Doppler Ultrasonography ◽  
Histopathological Examination ◽  
Previous History ◽  
Plain Radiography ◽  
Artery Thrombosis ◽  
History Of ◽  
The Right

Popliteal artery thrombosis may present as a complication of an osteochondroma located in the vicinity of the knee joint. This is a case report of a 26-year-old man with symptoms of the right lower extremity ischaemia without a previous history of vascular disease or trauma. Plain radiography, magnetic resonance angiography and Doppler ultrasonography documented the presence of an osteochondrous structure of the proximal tibial metaphysis, which displaced and compressed the popliteal artery, causing its occlusion due to intraluminal thrombosis..The patient was operated and histopathological examination confirmed the diagnosis of osteochondroma.

COMMONWEALTH Forum: The Politics of Science or the Science of Politics

Commonwealth ◽  
2017 ◽  
Vol 19 (1) ◽  
Author(s):  
John Arway
Keyword(s):  
Public Policy ◽  
Natural Resource ◽  
Factual Information ◽  
The Past ◽  
Difference Of Opinion ◽  
History Of ◽  
The Right ◽  
Scientific Facts ◽  
Environmental Agency ◽  
Laws And Regulations

The challenges of including factual information in public policy and political discussions are many. The difficulties of including scientific facts in these debates can often be frustrating for scientists, politicians and policymakers alike. At times it seems that discussions involve different languages or dialects such that it becomes a challenge to even understand one another’s position. Oftentimes difference of opinion leads to laws and regulations that are tilted to the left or the right. The collaborative balancing to insure public and natural resource interests are protected ends up being accomplished through extensive litigation in the courts. In this article, the author discusses the history of environmental balancing during the past three decades from the perspective of a field biologist who has used the strength of our policies, laws and regulations to fight for the protection of our Commonwealth’s aquatic resources. For the past 7 years, the author has taken over the reins of “the most powerful environmental agency in Pennsylvania” and charted a course using science to properly represent natural resource interests in public policy and political deliberations.

Multiple subluxations and comminuted fracture of the cervical spine in a sheep

2015 ◽  
Vol 43 (01) ◽  
pp. 44-38
Author(s):  
C.-C. Lin ◽  
K.-S. Chen ◽  
Y.-L. Lin ◽  
J. P.-W. Chan
Keyword(s):  
Cervical Spine ◽  
Pain Perception ◽  
Cervical Vertebrae ◽  
Traumatic Injury ◽  
Spinal Reflexes ◽  
Spine Trauma ◽  
Blunt Force Trauma ◽  
Comminuted Fracture ◽  
History Of ◽  
The Right

SummaryA 5-month-old, 13.5 kg, female Corriedale sheep was referred to the Veterinary Medicine Teaching Hospital, with a history of traumatic injury of the cervical spine followed by non-ambulatoric tetraparesis that occurred 2 weeks before being admitted to the hospital. At admission, malalignment of the cervical spine with the cranial part of the neck deviating to the right was noted. Neurological examinations identified the absence of postural reactions in both forelimbs, mildly decreased spinal reflexes, and normal reaction to pain perception tests. Radiography revealed malalignment of the cervical vertebrae with subluxations at C1–C2 and C2–C3, and a comminuted fracture of the caudal aspect of C2. The sheep was euthanized due to a presumed poor prognosis. Necropsy and histopathological findings confirmed injuries of the cervical spine from C1 to C3, which were consistent with the clinical finding of tetraparesis in this case. This paper presents a rare case of multiple subluxations of the cervical spine caused by blunt force trauma in a young sheep. These results highlight the importance of an astute clinical diagnosis for such an acute cervical spine trauma and the need for prompt surgical correction for similar cases in the future.

Accelerating Agricultural Growth—Is Irrigation Institutional Reform Necessary? (Distinguishedl Lecture)

1996 ◽  
Vol 35 (4I) ◽  
pp. 399-417 ◽  
Author(s):  
John W. Mellor
Keyword(s):  
Growth Rates ◽  
Irrigation System ◽  
Institutional Reform ◽  
Residual Effect ◽  
Agricultural Growth ◽  
The Past ◽  
Major Reform ◽  
History Of ◽  
The Right ◽  
Economic Growth Rates

The right to the flow of income from water is vigorously pursued, protected, and fought over in any arid part of the world. Pakistan is of course no exception. Reform of irrigation institutions necessarily changes the rights to water, whether it be those of farmers, government, or government functionaries. Those perceived rights may be explicit and broadly accepted, or simply takings that are not even considered legitimate. Nevertheless they will be fought over. Pakistan has a long history of proposals for irrigation reform, little or none being implemented, except as isolated pilot projects. Thus, to propose major changes in irrigation institutions must be clearly shown to have major benefits to justify the hard battles that must be fought and the goodwill of those who might win those battles for reform. Proponents of irrigation institution reform have always argued the necessity of the reforms and the large gains to be achieved. Perhaps, however, those arguments have not been convincing. This paper will briefly outline the failed attempts at irrigation reform to provide an element of reality to the discussion. It will then proceed to make the case of the urgency of reform in a somewhat different manner to the past. Finally, current major reform proposals will be presented. This paper approaches justification of irrigation reform by focusing on the agricultural growth rate. It does so because that is the critical variable influencing poverty rates and is a significant determinant of over-all economic growth rates. The paper decomposes growth rates and suggests a residual effect of deterioration of the irrigation system that is large and calls for policy and institutional reform. The data are notional, suggesting the usefulness of the approach and paves the way for more detailed empirical analysis and enquiry for the future.

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