Clinical manifestations of VX poisoning following percutaneous exposure in                 the domestic white pig

Nerve agents are a class of organophosphorus chemicals that inhibit certain cholinesterase enzymes (ChE). If untreated, percutaneous exposure to nerve agents, such as VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) can cause paralysis, apnoea and death. Much of the information concerning the percutaneous absorption and subsequent toxicity of nerve agents has been obtained using various rodent models. However, the most relevant ‘skin model’ is arguably the pig. Therefore, the purpose of this study was to examine the clinical manifestations of VX intoxication in the domestic white pig following a 2 LD50 (120 mg/kg) percutaneous challenge. There was a consistent onset of signs (where present) in each animal: mastication was followed by miosis, salivation, fasciculations and apnoea. Whilst ChE activity did not correlate with the onset of signs, there was a qualitative relationship in that mastication preceded substantial ChE inhibition, miosis lagged behind the linear decrease in acetylcholinesterase (AChE) activity and fasciculations and apnoea occurred after maximum ChE inhibition had been attained (5 / 10% of normal). These observations may be of use for the triage of patients exposed to VX. In comparison with similar studies with GD, VX did not affect glucose utilization. However, VX was similar to GD in that it caused a mild hyperkalaemia and hyperphosphataemia, although the significance of this observation was not clear. There was substantial lateral diffusion of the initial droplet of VX over the application site, indicating that, when decontaminating exposed skin, attention should also be directed to areas peripheral to the original site of exposure.

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Cardiovascular Calcification in Chronic Kidney Disease—Therapeutic Opportunities

Toxins ◽

10.3390/toxins12030181 ◽

2020 ◽

Vol 12 (3) ◽

pp. 181 ◽

Cited By ~ 1

Author(s):

Anika Himmelsbach ◽

Carina Ciliox ◽

Claudia Goettsch

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Imaging Techniques ◽

Management Strategies ◽

Clinical Manifestations ◽

Therapeutic Interventions ◽

Rodent Models ◽

Treatment And Prevention ◽

Resolution Imaging ◽

Meta Analyses

Patients with chronic kidney disease (CKD) are highly susceptible to cardiovascular (CV) complications, thus suffering from clinical manifestations such as heart failure and stroke. CV calcification greatly contributes to the increased CV risk in CKD patients. However, no clinically viable therapies towards treatment and prevention of CV calcification or early biomarkers have been approved to date, which is largely attributed to the asymptomatic progression of calcification and the dearth of high-resolution imaging techniques to detect early calcification prior to the ‘point of no return’. Clearly, new intervention and management strategies are essential to reduce CV risk factors in CKD patients. In experimental rodent models, novel promising therapeutic interventions demonstrate decreased CKD-induced calcification and prevent CV complications. Potential diagnostic markers such as the serum T50 assay, which demonstrates an association of serum calcification propensity with all-cause mortality and CV death in CKD patients, have been developed. This review provides an overview of the latest observations and evaluates the potential of these new interventions in relation to CV calcification in CKD patients. To this end, potential therapeutics have been analyzed, and their properties compared via experimental rodent models, human clinical trials, and meta-analyses.

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Skin and Soft Tissue Infections

Mayo Clinic Infectious Diseases Board Review ◽

10.1093/med/9780199827626.003.0033 ◽

2012 ◽

pp. 341-350

Author(s):

Imad M Tleyjeh ◽

Larry M Baddour

Keyword(s):

Soft Tissue ◽

Necrotizing Fasciitis ◽

Skin Infection ◽

Subcutaneous Tissue ◽

Clinical Manifestations ◽

Hair Follicles ◽

Soft Tissue Infections ◽

Exposed Skin ◽

Common Skin ◽

The Face

Common skin and soft tissue infections covered in this chapter include impetigo, folliculitis, furuncles, carbuncles, cellulitis, and necrotizing fasciitis. Impetigo is a superficial pustular skin infection. Multiple lesions occur on exposed skin of the face and extremities. Staphylococcus aureus causes most cases. Folliculitis is a superficial skin infection of hair follicles. A furuncle is a purulent, painful nodular skin infection involving the hair follicle that is usually a complication of folliculitis. A carbuncle is a cluster of abscesses in subcutaneous tissue that drain through hair follicles. The prevailing pathogen for both furuncles and carbuncles is S aureus. Skin abscesses involve the dermis and deeper skin tissues. Often a pustule is present on the skin. For most cases the pathogen is S aureus. Cellulitis involves skin and subcutaneous tissues. Clinical manifestations of cellulitis include swelling, erythema, tenderness, and warmth. Necrotizing forms of cellulitis are necrotizing fasciitis types I and II. Clinical features include fulminant destruction of tissue and systemic toxicity.

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Strongyloidiasis, hookworm, and other gut strongyloid nematodes

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.070904_update_001 ◽

2010 ◽

pp. 1163-1167

Author(s):

Michael Brown

Keyword(s):

Clinical Manifestation ◽

Chest Radiography ◽

Epigastric Pain ◽

Clinical Manifestations ◽

Strongyloides Stercoralis ◽

Significant Morbidity ◽

Exposed Skin ◽

Larva Currens

Strongyloides stercoralis and hookworms are common soil-transmitted nematodes in tropical and subtropical regions. After the organisms penetrate exposed skin, most infections are asymptomatic, but heavy infections can result in significant morbidity. The roundworm S. stercoralis infects an estimated 30 million to 100 million people. Clinical manifestations include: (1) skin—often the only clinical manifestation, commonly in the form of larva currens, a serpiginous, pruritic, erythematous eruption at the site of migrating larvae; (2) lungs—cough and tracheal irritation; less commonly wheeze; patchy infiltrates on chest radiography with eosinophilia; (3) intestinal—epigastric pain and diarrhoea; (4) ...

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Metabolic and Histological Reversibility of Thiamine Deficiency

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1983.73 ◽

1983 ◽

Vol 3 (4) ◽

pp. 468-477 ◽

Cited By ~ 25

Author(s):

Antoine M. Hakim ◽

Stirling Carpenter ◽

Hanna M. Pappius

Keyword(s):

Short Duration ◽

Thiamine Deficiency ◽

Glucose Utilization ◽

Metabolic Response ◽

Clinical Manifestations ◽

Local Cerebral Glucose Utilization ◽

Rapid Improvement ◽

Cerebral Glucose Utilization

The rapid improvement in the clinical manifestations of thiamine deficiency with thiamine supplementation is well known. To study this process in more detail, we rendered rats thiamine deficient either by dietary deprivation alone (DD) or, in addition, by daily pyrithiamine administration (DD + PT). We observed the cerebral metabolic and histological responses of these rats after 1 or 7 days of thiamine supplementation both prior to and at the onset of clinical sequelae. The cerebral metabolic response to thiamine deficiency and replenishment was determined with the [14C]deoxyglucose technique for measurement of local cerebral glucose utilization (LCGU). Our results indicate that thiamine replenishment reverses the LCGU changes resulting from thiamine deprivation of short duration. However, prolonged thiamine deprivation may result in LCGU changes that are not completely reversible by thiamine replenishment, before the appearance of the clinical or histological consequences of thiamine deficiency.

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Morphologic alteration in the muscles of patients with hypokalemic periodic paralysis or myopathy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158650 ◽

1990 ◽

Vol 48 (3) ◽

pp. 222-223

Author(s):

T. Shimizu ◽

Y. Muranaka ◽

I. Ohta ◽

N. Honda

Keyword(s):

Clinical Manifestations ◽

Quadriceps Muscle ◽

Honeycomb Structure ◽

Periodic Paralysis ◽

Ultrastructural Changes ◽

Hypokalemic Periodic Paralysis ◽

Electron Microscopic ◽

Tubular Aggregates ◽

Hypokalemic Myopathy ◽

Transmission Electron

There have been many reports on ultrastructural alterations in muscles of hypokalemic periodic paralysis (hpp) and hypokalemic myopathy(hm). It is stressed in those reports that tubular structures such as tubular aggregates are usually to be found in hpp as a characteristic feature, but not in hm. We analyzed the histological differences between hpp and hm, comparing their clinical manifestations and morphologic changes in muscles. Materials analyzed were biopsied muscles from 18 patients which showed muscular symptoms due to hypokalemia. The muscle specimens were obtained by means of biopsy from quadriceps muscle and fixed with 2% glutaraldehyde (pH 7.4) and analyzed by ordinary method and modified Golgimethod. The ultrathin section were examined in JEOL 200CX transmission electron microscopy.Electron microscopic examinations disclosed dilated t-system and terminal cistern of sarcoplasmic reticulum (SR)(Fig 1), and an unique structure like “sixad” was occasionally observed in some specimens (Fig 2). Tubular aggregates (Fig 3) and honeycomb structure (Fig 4) were also common characteristic structures in all cases. These ultrastructural changes were common in both the hypokalemic periodic paralysis and the hypokalemic myopathy, regardless of the time of biopsy or the duration of hypokalemia suffered.

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The organization of cell surface membrane domains

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100155992 ◽

1989 ◽

Vol 47 ◽

pp. 804-805

Author(s):

Michael Edidin

Keyword(s):

Cell Surface ◽

Membrane Lipids ◽

Surface Membrane ◽

Lateral Diffusion ◽

Cell Types ◽

Membrane Domains ◽

Membrane Biology ◽

Morphological Polarity ◽

Discrete Domains ◽

Membrane Components

Cell surface membranes are based on a fluid lipid bilayer and models of the membranes' organization have emphasised the possibilities for lateral motion of membrane lipids and proteins within the bilayer. Two recent trends in cell and membrane biology make us consider ways in which membrane organization works against its inherent fluidity, localizing both lipids and proteins into discrete domains. There is evidence for such domains, even in cells without obvious morphological polarity and organization [Table 1]. Cells that are morphologically polarised, for example epithelial cells, raise the issue of membrane domains in an accute form.The technique of fluorescence photobleaching and recovery, FPR, was developed to measure lateral diffusion of membrane components. It has also proven to be a powerful tool for the analysis of constraints to lateral mobility. FPR resolves several sorts of membrane domains, all on the micrometer scale, in several different cell types.

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