Lacking the 'protective label' of diabetes: Phenytoin-induced distal symmetrical peripheral neuropathy. A clinical case report.

This report documents an unusual case of distal symmetrical peripheral neuropathy (DSPN) in an otherwise healthy patient without diabetes mellitus (DM) presenting to a podiatric wound care clinic. The development of gas gangrene coupled with Charcot neuroarthropathic changes ultimately resulted in a potentially life-saving transmetatarsal (TMT) amputation. Causation of, or at least a contributor to, the DSPN was likely phenytoin usage for epileptic seizures. Long-term use of phenytoin can lead to axonal shrinkage and random clusters of nerve demyelination [1]. Clinical standards for DM-induced DSPN indicate that annual comprehensive neurological assessment to detect nerve function deterioration is warranted [2]. This can aid in identifying patients at high risk of diabetic foot ulceration. However, oftentimes, patients exhibiting medication-induced neuropathy are not assessed to determine severity of the neuropathy nor are they educated about ulcer prevention in the same manner as patients with DM. This report advocates for a standardized threshold of diagnostic and preventative investigation for neuropathy of all aetiologies; diabetic, traumatic, viral, medication-induced and idiopathic.

[Toxins of Clostridium perfringens as a natural and bioterroristic threats]. / Toksyny Clostridium perfringens jako zagrozenie naturalne i bioterrorystyczne.

Clostridium perfringens is absolutely anaerobic rod-shaped, sporeforming bacterium. The morbidity is connected with producing toxins. Depending on the type of toxin produced Clostridium perfringens can be divided into five serotypes:A-E. Under natural conditions, this bacterium is responsible for local outbreaks of food poisoning associated with eating contaminated food which which was improperly heat treated. Some countries with lower economic level are endemic foci of necrotizing enteritis caused by Clostridium perfringens. The bacterium is also a major cause of gas gangrene. It is a disease, associated with wound infection, with potentially fatal prognosis in the case of treatment's delays. In the absence of early radical surgery, antibiotic therapy and (if available) hyperbaric treatment leads to the spread of toxins in the body causing shock, coma and death. Due to the force of produced toxins is a pathogen that poses a substrate for the production of biological weapons. It could potentially be used to induce outbreaks of food poisoning and by missiles contamination by spore lead to increased morbidity of gas gangrene in injured soldiers. C. perfringens types B and D produce epsilon toxin considered to be the third most powerful bacterial toxin. Because of the ability to disperse the toxin as an aerosol and a lack of methods of treatment and prevention of poisoning possible factors it is a potential tool for bioterrorism It is advisable to continue research into vaccines and treatments for poisoning toxins of C. perfringens.

The oncopathic potency of Clostridium perfringens is independent of its alpha-toxin gene.

Hypoxia in solid tumors is a major obstacle in conventional treatment because of inefficient delivery of therapeutic agents to the lesions, but offers the potential for anaerobic bacterial colonization that can lead to tumor destruction. We have previously reported a recombinant Clostridium perfringens (Cp) strain constructed by deletion of the superoxide dismutase (sod) gene and insertion of the Panton-Valentine leukocidin (PVL) gene, Cp/sod(-)/PVL, which showed elevated oxygen sensitivity, tumor selectivity, and oncopathic potency in an orthotopic model of pancreatic cancer in immune-competent and syngeneic mice, and that led to substantial prolongation of animal survival. A major limitation to Cp/sod(-)/PVL in clinical applications is that it expresses phospholipase C (plc), the alpha-toxin and the major virulence determinant in Cp that is causative in the development of gas gangrene. In this study, the plc gene in Cp/sod(-)/PVL was knocked out to create Cp/plc(-)/sod(-)/PVL, which was shown to be incapable of inducing gas gangrene in mice. Intravenous injection of Cp/plc(-)/sod(-)/PVL spores led to a significant survival advantage in tumor-bearing mice with the same efficacy as Cp/sod(-)/PVL, indicating that the oncopathic potency of Cp is independent of a functional plc gene. The treatment also did not lead to an attenuated immune response to a subsequent pathogen challenge, indicating that a systemic immune-suppressive effect in the host is absent. Consequently, Cp/plc(-)/sod(-)/PVL is a novel oncopathic bacterial agent for the effective treatment of pancreatic cancer and other poorly vascularized tumors, with a substantially enhanced safety profile, which is essential for the development of translational studies in the future.

Role of Clostridium perfringens phospholipase C in the pathogenesis of gas gangrene.

Gas gangrene is an acute and devastating infection most frequently caused by Clostridium perfringens and characterized by severe myonecrosis, intravascular leukocyte accumulation, and significant thrombosis. Several lines of evidence indicate that C. perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in this disease. This toxin is a Zn2+ metalloenzyme with lecithinase and sphingomyelinase activities. Its three dimensional structure shows two domains, an N-terminal domain which contains the active site, and a C-terminal domain required for the Ca2+dependent interaction with membranes. Cp-PLC displays several biological activities: it increases capillary permeability, induces platelet aggregation, hemolysis, myonecrosis, decreases cardiac contractility, and is lethal. Experiments with genetically engineered Cp-PLC variants have revealed that the sphingomyelinase activity and the C-terminal domain are required for toxicity. The myotoxicity of Cp-PLC is largely dependent on its membrane damaging effect. In addition, it has been suggested that the alterations in the blood flow induced by this toxin also contribute to muscle damage. In gas gangrene, Cp-PLC dysregulates transduction pathways in endothelial cells, platelets and neutrophils leading to the uncontrolled production of several intercellular mediators and adhesion molecules. Thus, Cp-PLC alters the traffic of neutrophils to the infected tissue and promotes thrombotic events, enhancing the conditions for anaerobic growth.

Gas gangrene following intra-arterial injection of oral medication in a drug abuser.

We report a patient in whom intra-arterial injection of oral medication led to the development of fulminating gas gangrene and death, despite the initial clinical symptoms being minor. We believe that prophylactic antibiotics should be administered to patients following intra-arterial injection of oral medication especially if immunocompetence, such as from human immunodeficiency virus (HIV) infection, is likely.

[Gas and oedema producing infections--today still a challenge (author's transl)]. / Gas- und ödembildende Infektionen--auch heute noch ein Problem

Clostridial infections, putrid infections with aerobic and anerobic growing germs, air forced into the tissue during the primary trauma and the formation of gas by contact of the wound with aluminium, H2O2 and gasoline may be causes for the formation of gas and oedema in the tissues. Only infections with Clostridia are gas gangrene. We must differentiate the clostridial cellulitis from the clostridial myositis. Bacterioscopy allows a rapid differentiation to be made between putrid and clostridial infection. Beside intensive care and antibiotics, putrid infections demand an early extensive incision, for gas gangrene the radical excision of the damaged tissue is required. The effect of hyperbaric oxygenation is still under discussion. It can never replace surgical treatment.