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Biomedical subjects

M Spies

Publications and source records attributed to M Spies.

15 recordsLinked to original sources

[Toxic epidermal necrolysis. A case for the burn intensive care unit].

Toxic epidermal necrolysis is a rare but life-threatening exfoliating disease of the skin and mucous membranes, commonly considered a drug sensitivity reaction. In this review of the literature we discuss the epidemiology, etiology, and pathology. We show diagnostic problems and current treatment strategies. Many of the problems associated with the disease, such as wound infection, sepsis, nutritional support, and pain management, are similar to problems in severely burned patients. Burn centers provide optimal logistics and knowledge to diagnose and treat this serious disease entity.

Biological Dressings↗

Skin toxicity induced by wet heat.

Pieces of human skin from the skin bank were heated in an autoclave for 1 or 5 min at temperatures 80, 90, 100, 110 and 135 degrees C. The pieces were then homogenized and the homogenates were injected intraperitoneally into groups of mice. The amount injected was either a quantity equivalent to 50 or 75% of the mouse body surface area. Fourteen separate experiments were carried out, each one with a variety of temperatures. Mortality in the groups of mice was recorded by the 8th day. Control mice received homogenates of skin heated to no more that 38 degrees C and out of a total of 104 control mice there were only 4 deaths. In contrast homogenates of skin heated to 135 degrees C killed from 80 to 100% of the mice in different groups, averaging 92%. Skin heated to 110 degrees C killed from 33 to 90% of the mice in different groups, averaging 63%. Skin heated to 100 degrees C killed from 0 to 80% of the mice in different groups, averaging 33%. Temperatures of 80 and 90 degrees C killed no more than 10% of the mice in any group, averaging less than 3%. One minute of heating seemed to be sufficient to induce the toxic effect in the skin. These findings indicated that wet heat application to skin was capable of inducing toxicity in a fashion similar to that demonstrated many years ago with hotter dry temperatures applied to skin for 15s. That application was shown to induce polymerization of skin cell membrane lipid proteins rendering them toxic. In this study, increasing toxicity appeared similarly to depend on the quantity of wet heat input as illustrated by the range of increasing temperatures. The relatively lower temperatures of scalding versus flame burns can accomplish similar dangerous effects; it is simply a quantitative matter of heat input.

Animals↗

Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound.

The use of systemic IGF-1 has been shown to attenuate the postburn hypermetabolic response and improve burn wound healing. Local IGF-1 gene therapy, however, promotes re-epithelialization in the burn wound without the side-effects associated with systemic delivery. We tested the hypothesis that these beneficial effects are due to changes in local cytokine production. Adult male Sprague-Dawley rats received a 40% total body surface area full-thickness scald burn and randomly received a subcutaneous injection at the burn wound margin of saline or cationic liposomes containing a IGF-1 cDNA construct. Animals were killed at 1, 4, 7 and 10 days after burn trauma. Skin biopsies at the wound border were harvested for total RNA extraction. Cytokine mRNA expression was determined using a multi-probe RNase protection assay. Data are presented as means +/- s.e.m. Statistical analysis used the unpaired t-test or Mann-Whitney test where appropriate. Significance was accepted at P < 0.05. Treatment of the burn wound with liposomal IGF-1-cDNA transfer decreased IL-1beta mRNA levels on day 10 after burn trauma from five-fold burn-induced increases compared with sham-treated rats, to near the control values present in unburned skin samples. Similarly, there was an eight-fold increase in TNF-alpha mRNA expression on postburn day 10 that was abrogated by IGF-1 gene therapy. Local IGF-1 gene transfer attenuates the mRNA expression of the inflammatory cytokines IL-1beta and TNF-alpha in the burn wound. This change may improve burn wound healing by decreasing prolonged local inflammation.

Animals↗

Modern burn care.

In the United States nearly 2 million people are burned every year; about 100,000 burns are moderate to severe and require hospitalization and about 5,000 deaths occur because of burns. The overall improvement in mortality and outcome of patients with severe burn trauma over the last decades can be attributed to the following: (1) emergency medical treatment with aggressive early resuscitation, (2) respiratory care and treatment of inhalation injury, (3) control of infection, (4) early burn wound excision and grafting, and (5) modulation of the hypermetabolic response to trauma. The authors present the major developments and changes in burn care regimens concerning emergency medical treatment, focusing on the requirement of early fluid resuscitation, criteria for hospital admission, and referral to burn centers. Also discussed are changes in respiratory management of burn patients and therapy of inhalation injury, infection control measurements, early burn wound excision and wound coverage, and the nutritional and pharmacological modulation of the hypermetabolic response to trauma. All these burn therapy regimens need to be continuously reassessed in clinical use and further improved to achieve still better outcome and quality of life for burn victims.

Adolescent↗

Finding and evaluating clinical practice guidelines.

Clinical practice guidelines are valuable, clinical decision-making aids for preventive, diagnostic, therapeutic, and palliative patient care. This article identifies ways to access clinical practice guidelines and discusses evaluative criteria for identifying gold-standard evidence-based practice guidelines. Finally, clinicians are reminded of crucial questions to ask before applying any guidelines to patient care.

Databases, Factual↗

Cell proliferation, apoptosis, NF-kappaB expression, enzyme, protein, and weight changes in livers of burned rats.

Thermal injury has been shown to alter gut epithelium and heart myocyte homeostasis by inducing programmed cell death. The effect of thermal injury on hepatocyte apoptosis and proliferation, however, has not been established. The purpose of this study was to determine whether a large thermal injury increases liver cell apoptosis and proliferation and whether these changes were associated with alterations in hepatic nuclear factor kappaB (NF-kappaB) expression and changes in liver enzymes and amount of protein. Sprague-Dawley rats received a 40% total body surface area scald burn or sham burn. Rats were killed and livers were harvested at 1, 2, 5, and 7 days after burn. Liver cell apoptosis was determined by terminal deoxyuridine nick end labeling (TUNEL) assay and cell proliferation by immunohistochemistry for proliferating cell nuclear antigen. Hepatic NF-kappaB expression was determined by Western blot, and total hepatic protein content was determined by protein assay. Protein concentration decreased after burn compared with sham controls (P < 0.05). Liver cell apoptosis, proliferation, and NF-kappaB expression in hepatocytes increased in burned rats compared with controls (P < 0.05). It was concluded that thermal injury induces hepatic cell apoptosis and proliferation associated with an increase in hepatic NF-kappaB expression and a decrease in hepatic protein concentration.

Alkaline Phosphatase↗

Treatment of extensive toxic epidermal necrolysis in children.

OBJECTIVE: Toxic epidermal necrolysis (TEN) is a rare but life-threatening disease of the skin and mucous membranes. We report our experience in the treatment of pediatric TEN patients with early debridement of necrotic skin and coverage with human allograft skin. METHODS: From 1984 to 2000, 15 children (6 girls, 9 boys, 7.2 +/- 1.5 years) with a histologic diagnosis of TEN and involvement of >30% total body surface area were treated at the Shriners Hospitals for Children in Galveston. All were treated in a specialized pediatric burn intensive care unit after our standard treatment protocol, including operative debridement of sloughing skin and allografting within 24 hours of admission. Outcome parameters were mortality, length of hospital stay, wound healing, clinical complications, causative drugs, corticosteroid use, and delay in referral to a burn center. RESULTS: Taking a new medication (antibiotics, anticonvulsive drugs) was associated with all cases of TEN. Patients who were treated with early debridement and coverage with allograft skin showed no wound infection, and overall mortality was 7%. Total length of hospital stay was 26 +/- 3 days. Long-term sequelae were changes in skin pigmentation (100%), ophthalmologic problems (40%), and diffuse itching early after wound healing (53%). CONCLUSION: Although a rare disease in children, TEN was managed successfully in a burn center environment, using early debridement and wound coverage with allograft skin as a biological dressing. The use of corticosteroids and referral patterns seems unchanged during the past 2 decades, indicating an additional need for information and education about the disease.

Child↗

The RadA protein from a hyperthermophilic archaeon Pyrobaculum islandicum is a DNA-dependent ATPase that exhibits two disparate catalytic modes, with a transition temperature at 75 degrees C.

The radA gene is an archaeal homolog of bacterial recA and eukaryotic RAD51 genes, which are critical components in homologous recombination and recombinational DNA repair. We cloned the radA gene from a hyperthermophilic archaeon, Pyrobaculum islandicum, overproduced the radA gene product in Escherichia coli and purified it to homogeneity. The purified P. islandicum RadA protein maintained its secondary structure and activities in vitro at high temperatures, up to 87 degrees C. It also showed high stability of 18.3 kcal.mol-1 (76.5 kJ.mol-1) at 25 degrees C and neutral pH. P. islandicum RadA exhibited activities typical of the family of RecA-like proteins, such as the ability to bind ssDNA, to hydrolyze ATP in a DNA-dependent manner and to catalyze DNA strand exchange. At 75 degrees C, all DNAs tested stimulated ATPase activity of the RadA. The protein exhibited a break in the Arrhenius plot of ATP hydrolysis at 75 degrees C. The cooperativity of ATP hydrolysis and ssDNA-binding ability of the protein above 75 degrees C were higher than at lower temperatures, and the activation energy of ATP hydrolysis was lower above this break point temperature. These results suggest that the ssDNA-dependent ATPase activity of P. islandicum RadA displays a temperature-dependent capacity to exist in two different catalytic modes, with 75 degrees C being the critical threshold temperature.

Adenosine Triphosphatases↗

[Emotional disorders. Stable mental health and chronic illnesses over a 10-year course in the general population].

In a comparison of extreme groups 124 german inhabitants of the city of Mannheim were investigated. They descended from a representative sample with 600 persons out of 3 years of birth (1935, 1945, 1955) in the general population (psychotic disorders were excluded). They were within a period of 10 years either in stable mental health or in chronic illness. The comparison between this two groups concerned demographic variables, development during childhood, personality, stressful life events, social network and clinical data. The ascertained prevalence is 12.7% (from n = 600) for stable mental health and 3.5% for chronic illness. The group with the highest risk of chronic diseases is those of women and men with bad achievement and small social competence.

Achievement↗

Regulation of acetate metabolism in Corynebacterium glutamicum: transcriptional control of the isocitrate lyase and malate synthase genes.

In the amino-acid-producing microorganism Corynebacterium glutamicum, the specific activities of the acetate-activating enzymes acetate kinase and phosphotransacetylase and those of the glyoxylate cycle enzymes isocitrate lyase and malate synthase were found to be high when the cells were grown on acetate (0.8, 2.9, 2.1, and 1.8 U/mg protein, respectively). When the cells were grown on glucose or on other carbon sources such as lactate, succinate, or glutamate, the specific activities were two- to fourfold (acetate kinase and phosphotransacetylase) and 45- to 100-fold (isocitrate lyase and malate synthase) lower, indicating that the synthesis of the four enzymes is regulated by acetate in the growth medium. A comparative Northern (RNA) analysis of the C. glutamicum isocitrate lyase and malate synthase genes (aceA and aceB) and transcriptional cat fusion experiments revealed that aceA and aceB are transcribed as 1.6- and 2.7-kb monocistronic messages, respectively, and that the regulation of isocitrate lyase and malate synthase synthesis is exerted at the level of transcription from the respective promoters. Surprisingly, C. glutamicum mutants defective in either acetate kinase or phosphotransacetylase showed low specific activities of the other three enzymes (phosphotransacetylase, isocitrate lyase, and malate synthase or acetate kinase, isocitrate lyase, and malate synthase, respectively) irrespective of the presence or absence of acetate in the medium. This result and a correlation of a high intracellular acetyl coenzyme A concentration with high specific activities of isocitrate lyase, malate synthase, acetate kinase, and phosphotransacetylase suggest that acetyl coenzyme A or a derivative thereof may be a physiological trigger for the genetic regulation of enzymes involved in acetate metabolism of C. glutamicum.

Acetate Kinase↗

Identification of a gene fragment which codes for the 364 amino-terminal amino acid residues of a SecA homologue from Bacillus subtilis: further evidence for the conservation of the protein export apparatus in gram-positive and gram-negative bacteria.

A DNA fragment that codes for the 364 amino-terminal amino acid residues of a putative Bacillus subtilis SecA homologue has been cloned using the Escherichia coli secA gene as a probe. The deduced amino acid sequence showed 58% identity to the amino-terminus of the E. coli SecA protein. A DNA fragment which codes for 275 amino-terminal amino acid residues of the B. subtilis SecA homologue was expressed in E. coli and the corresponding gene product was shown to be recognized by anti-E. coli SecA antibodies. This polypeptide, although only about 30% the size of the E. coli SecA protein, also restored growth of E. coli MM52 (secAts) at the non-permissive temperature and the translocation defect of proOmpA in this mutant was relieved to a substantial extent.

Adenosine Triphosphatases↗

Frequency of nasoenteral tube displacement and associated risk factors.

A pilot study was conducted to describe the frequency with which spontaneous tube displacement occurred in 105 tube-fed patients followed on a prospective basis. In addition, risk factors thought to be associated with tube displacement were studied. Since only about one-third of the tubes were monitored by followup radiographs, the actual occurrence of tube displacement is unknown. On those days when tube position was documented, a comparison of risk factors for spontaneous tube displacement was made with chi-square statistics. Two risk factors, coughing and decreased level of consciousness, were found to occur with significantly greater frequency in patients with displaced weighted nasogastric tubes, while coughing, tracheal suctioning, and upper airway intubation were significant in the dislodgement of unweighted nasointestinal tubes. None of the risk factors were significant in patients with weighted nasointestinal tubes.

Consciousness↗