Is the limulus amebocyte lysate the sole predictor of septic episodes in major thermal injuries?

Septic episodes in thermal injuries are usually hallmarked by a series of physiologic parameters that include tachypnea, prolonged paralytic ileus, hyperthermia or hypothermia, altered mental status, thrombocytopenia, leukocytosis or unexplained leukopenia, acidosis, and hyperglycemia. Recent studies with polycystic kidney disease have clearly indicated that the limulus amebocyte lysate (LAL) assays were predictive of fungal infections in this patient population. Because both bacteria and fungi produce lipopolysaccharide that can be identified with the LAL assay, we randomly assayed sequential sera of 45 patients with major thermal injuries for positivity in the LAL assay, with use of the QCL-1000 kit (BioWhittaker, Walkersville, Md). The average burn size of this patient population was 63.43% total body surface area. The average age of the patient was 6.2 years. The sex distribution included 30 males and 15 females. The infectious agents included gram-positive cocci and gram-negative rods, and 14 patients had concomitant fungal infections. Eighty-five percent of the patients tested were positive for endotoxin, with levels ranging from < 0.1 EU/mL to > 1.0 EU/mL. The predominant organism isolated before or on the date the serum was drawn was Pseudomonas aeruginosa (51%), followed by Klebsiella pneumoniae (15%). The remaining 34% were a variety of Enterobacteriaceae. Of the 14 patients who yielded a fungus, 3 had negative LAL assays. Two patients with an elevated LAL grew only Staphylococcus epidermidis in the bloodstream and the wounds. These data clearly indicate that the LAL assay cannot be relied on as the sole predictor of septic episodes; however, it can be an adjunctive test to confirm sepsis when the other parameters have been considered.

Generation of neutralizing antipeptide antibodies to the enzymatic domain of Pseudomonas aeruginosa exotoxin A.

Burn patients suffer a break in the physical barrier (skin), which, when combined with their generalized state of immunodeficiency, creates an open window for opportunistic infections, mainly with Pseudomonas aeruginosa. Infection of the burn wound has always been a major factor in retardation of wound healing, and sepsis remains the leading cause of death in burn patients. Because studies have shown that topical treatment with antiexotoxin A (ETA) antibodies significantly increases survival in rats infected with toxin-producing strains of P. aeruginosa, we examined 11 synthetic peptides encompassing 12 to 45 amino acid (aa) residues, representing what were predicted by computer analysis to be the most hydrophilic and antigenic regions of ETA. These synthetic peptides were injected into rabbits for antibody production. Different groups of rabbits were immunized with a combination of peptides, with each combination representing one of the three distinct domains of ETA. Animals immunized with various peptide combinations produced peptide-specific antibodies that exhibited cross-reactivity to ETA. Two major epitopes were identified on the ETA molecule by experiments with peptide-specific antibodies in enzyme-linked immunosorbent assay and immunoprecipitation. One of these epitopes was located in the translocation domain (II) (aa 297 to 310), while the other was mapped to the last 13 aa residues at the carboxy-terminal end of the enzymatic domain (III) (aa 626 to 638). Of these two regions, the epitope in the enzymatic domain induced a much higher level of neutralizing antibodies that abrogated the cytotoxic activity of ETA in vitro. Antibodies to this epitope blocked the ADP-ribosyltransferase activity of ETA and appeared to interfere with binding of the substrate elongation factor 2 to the enzymatic active site of the ETA molecule. We conclude that polyclonal, as well as monoclonal, antibodies to short peptides, representing small regions of ETA, may have therapeutic potential in passive immunization or topical treatment of burn patients infected with toxin-producing strains of P. aeruginosa.

Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model.

PURPOSE: Many systemic and topical therapeutic agents such as growth hormone, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth factor (IGF) have been used as vulnerary agents. However, the role of nitric oxide (NO) as a wound-healing stimulant has been received with mixed reviews. NO is a potent vasodilator that is thought to be an endothelium-dependent relaxing factor, and a regulator of blood pressure and regional blood flow. It affects vascular smooth muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Therefore we compared the effects of several topical substances that have similar or reverse properties. METHODS: Using the excisional rat wound model, we evaluated the topical effects of Dermaide Aloe (D-Aloe, Dermaide Research Corp, Palos Heights, IL), nitroglycerin, Aquaphor (Beuersdorf, Inc., Norwalk, CT) alone, with D-Aloe with nitroglycerin, 2%, and L-NAME (NO inhibitor) with Aquaphor, and L-NAME with Aquaphor and D-Aloe for a 21-day period. All wounds were measured by planimetry at 1, 7, 10, 13, 16, 18, and 21 days. RESULTS: At day 1, all wounds had an average wound size of 2.27 cm2 (SD +/- 0.372) with no significant difference in wound size among the groups. Topically applied D-Aloe appeared to promote wound healing faster than the remaining other topicals (p < .05, Student-Newman-Keuls and Dunn's Method) over the study period. However, topicals combined with D-Aloe, the vehicle Aquaphor, and L-NAME improved the wound healing process when compared with nitroglycerin alone (p < .05). CONCLUSIONS: D-Aloe appears to have a wound-healing advancement factor that can reverse the effects of petrolatum- and nitroglycerin-based products as observed in the remaining groups when compared with nitroglycerin alone. It appears that D-Aloe's effect of preventing dermal ischemia by reversing the effects of thromboxane synthetase (TxA2) may act synergistically with NO or could be an oxygen radical scavenger.

Petrol sniffer's encephalopathy. A study of 25 patients.

OBJECTIVES: To determine the clinical features, response to treatment and outcome of petrol sniffers presenting to Perth's teaching hospitals. DESIGN: Retrospective study of all admissions to Perth's tertiary referral hospitals that were related to petrol sniffing from 1 January 1984 to 31 December 1991. RESULTS: Twenty-five patients (22 male and 3 female) were admitted with a diagnosis of intentional petrol sniffing. Five presented with acute petrol intoxication as the result of an isolated action. The remaining 20 patients were "chronic petrol sniffers". The mean age was 17.7 years (range, 5-27 years). Twenty patients were Australian Aborigines, including 18 of 20 chronic petrol sniffers and the three females. In the chronic petrol sniffers, a high prevalence of seizures and an alarmingly high case fatality ratio (8 of 20), usually by sudden death, were found. An altered mental state was universal, manifesting as drowsiness, delirium or stupor. Generalised tonic-clonic seizures occurred in 14, three with status epilepticus. Myoclonus (9), chorea (8) and cerebellar ataxia (appendicular and truncal) (13) were common. High blood lead levels on presentation were associated with a poor prognosis (survivors v. deaths, P = 0.002). Eighteen of the 20 patients were treated with specific agents to reduce the lead load, but the results were extremely disappointing. CONCLUSION: Petrol sniffing is an important cause of sickness and death in young people from some rural Aboriginal communities. It can cause sudden death or irreversible encephalopathy. Those severely affected have a poor prognosis, despite treatment. Effective strategies for prevention are needed.

Phenelzine associated peripheral neuropathy--clinical and electrophysiologic findings.

Phenelzine associated sensorimotor peripheral neuropathy is reported in two patients. Symptoms were predominantly sensory, and improvement occurred after withdrawal of phenelzine. Electrophysiologic findings were consistent with an axonal process.

Sister Mary Joseph's nodule.

A case of ovarian carcinoma that spread to the umbilicus and resulted in Sister Mary Joseph's nodule is described in which the mode of metastasis can be demonstrated. To our knowledge, this is the first report of confirmed contiguous extension from the peritoneal surface.