1/12. Correction of ureagenesis after gene transfer in an animal model and after liver transplantation in humans with ornithine transcarbamylase deficiency.We report effects of gene transfer and liver transplantation on urea synthesis in ornithine transcarbamylase deficiency (OTCD). We measured the formation of [15N] urea after oral administration of 15NH4Cl in two girls with partial OTCD before and after liver transplantation. Ureagenesis was less than 20% of that observed in controls before transplantation, and was normalized afterward. Studies performed on the OTCD sparse fur (spf/Y) mouse showed discordance between OTC enzyme activity and ureagenesis with modest increases in OTC enzyme activity after gene transfer resulting in significant improvement in ureagenesis. This study suggests that both liver transplantation and gene therapy may be effective in improving ureagenesis in OTCD.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
2/12. Iron-mobilizing properties of the gadolinium-DTPA complex: clinical and experimental observations.BACKGROUND: gadolinium (Gd) magnetic resonance imaging (MRI) contrast agents are considered to be safe in patients with impaired renal function. Our study investigates a mechanism of severe iron intoxication with life-threatening serum iron levels in a haemodialysis patient following MRI with Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. His previous history was remarkable for multiple blood transfusions and biochemical evidence of iron overload. We hypothesized that Gd-DTPA may have an iron-mobilizing effect in specific conditions of iron overload combined with prolonged exposure to the agent. methods: For the in vitro study, Gd-DTPA was added to mice liver homogenate and iron metabolism parameters were measured after incubation in comparison with the same samples incubated with saline only. For the in vivo study, an experimental model of acute renal failure in iron-overloaded rats was designed. Previously iron-overloaded and normally fed rats underwent bilateral nephrectomy by renal pedicle ligation, followed by Gd-DTPA or saline injection. Iron and iron saturation levels were checked before and 24 h after Gd-DTPA or vehicle administration. RESULTS: Significant mobilization of iron from mice liver tissue homogenate in mixtures with Gd in vitro was seen in the control (saline) and in the experimental (Gd) groups (513 /-99.1 vs 1117.8 /-360.8 microg/dl, respectively; P<0.05). Administration of Gd-DTPA to iron-overloaded rats after renal pedicle ligation caused marked elevation of serum iron from baseline 143 /-3.4 to 570 /-8 microg/dl (P<0.0001). There were no changes of the named parameter, either in iron-overloaded anuric rats after saline injection or in normal diet uraemic animals, following Gd-DTPA administration. CONCLUSIONS: The combination of iron overload and lack of adequate clearance of Gd chelates may cause massive liberation of iron with dangerous elevation of free serum iron. It is highly recommended that after Gd contrast study, end-stage renal disease patients with probable iron overload should undergo prompt and intensive haemodialysis for prevention of this serious complication.- - - - - - - - - - ranking = 3keywords = administration (Clic here for more details about this article) |
3/12. Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections.BACKGROUND: Necrotising soft-tissue infections due to group A streptococcus (GAS) are rare (about 0.2 cases per 100000 people). The disease progresses rapidly, causing severe necrosis and hydrolysis of soft tissues. Histopathological analysis of necrotic tissue debrided from two patients (one with necrotising fasciitis and one with myonecrosis) showed large quantities of bacteria but no infiltrating neutrophils. We aimed to investigate whether the poor neutrophil chemotaxis was linked with the ability of group A streptococcus (GAS) to degrade host chemokines. methods: We did RT-PCR, ELISA, and dot-blot assays to establish whether GAS induces synthesis of interleukin 8 mRNA, but subsequently degrades the released chemokine protein. Class-specific protease inhibitors were used to characterise the protease that degraded the chemokine. We used a mouse model of human soft-tissue infections to investigate the pathogenic relevance of GAS chemokine degradation, and to test the therapeutic effect of a GAS pheromone peptide (SilCR) that downregulates activity of chemokine protease. FINDINGS: The only isolates from the necrotic tissue were two beta-haemolytic GAS strains of an M14 serotype. A trypsin-like protease released by these strains degraded human interleukin 8 and its mouse homologue MIP2. When innoculated subcutaneously in mice, these strains produced a fatal necrotic soft-tissue infection that had reduced neutrophil recruitment to the site of injection. The M14 GAS strains have a missense mutation in the start codon of silCR, which encodes a predicted 17 aminoacid pheromone peptide, SilCR. growth of the M14 strain in the presence of SilCR abrogated chemokine proteolysis. When SilCR was injected together with the bacteria, abundant neutrophils were recruited to the site of infection, bacteria were cleared without systemic spread, and the mice survived. The therapeutic effect of SilCR was also obtained in mice challenged with M1 and M3 GAS strains, a leading cause of invasive infections. INTERPRETATION: The unusual reduction in neutrophils in necrotic tissue of people with GAS soft-tissue infections is partly caused by a GAS protease that degrades interleukin 8. In mice, degradation can be controlled by administration of SilCR, which downregulates GAS chemokine protease activity. This downregulation increases neutrophil migration to the site of infection, preventing bacterial spread and development of a fulminant lethal systemic infection.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
4/12. octreotide in intestinal lymphangiectasia: lack of a clinical response and failure to alter lymphatic function in a guinea pig model.Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing lymphatic pumping.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
5/12. Current trends in managing oral mucositis.Oral mucositis is an inflammatory and ulcerative process of the oral cavity that results from an assault on the epithelial mucous membrane tissue and most commonly is associated with the administration of radiotherapy and chemotherapy. The incidence of oral mucositis ranges from 15%-40% in patients receiving stomatotoxic chemotherapy or radiotherapy and 70%-90% in bone marrow recipients. knowledge regarding the pathophysiology of oral mucositis has evolved and now guides practice. Assessment tools to measure the level of mucositis provide valuable data concerning the status of the oral cavity. No single oral assessment tool has been found to be appropriate in all clinical settings. mucositis has a significant impact on patients' quality of life and treatment plan. Management of oral mucositis is aimed at minimizing this side effect and its subsequent sequelae. The strategies of care are geared toward early intervention and supportive care for patients at risk for developing mucositis and include specific targeted therapies for the management of debilitating side effects. This article provides an overview of the risk factors, pathophysiology, incidence, impact, clinical presentation, oral assessment tools, management strategies, and nursing implications related to oral mucositis.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
6/12. Intraocular inflammation of denatured viscoelastic substance in cases of cataract extraction and lens implantation.I present three successive pseudophakic cases that had intraocular inflammation (iritis) and bullous keratopathy presumably caused by denatured sodium hyaluronate (Healon). The denatured Healon was injected into the anterior chamber mixed with fresh Healon during routine planned extracapsular cataract extraction and intraocular lens implantation, when the cannula was reused after sterilization by disinfectants and autoclaving. A residuum of the viscoelastic substance remained inside the cannula and its nature was changed to a toxic chemical by the action of disinfectants and the sterilization procedures. The first two cases developed pseudophakic bullous keratopathy and had successful penetrating keratoplasties performed. The third case had minimal intraocular inflammation. The hypothesis that this intraocular reaction was due to denatured Healon was confirmed by use of a rabbit eye model. I recommend using a single-use disposable cannula for intracameral administration of Healon.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
7/12. Clinical and experimental studies of phenytoin-induced hyperkinesias.phenytoin administration occasionally leads to the induction of hyperkinetic movement disorders. The pathophysiologic basis of this phenomena is unknown, but thought to be a toxic effect of phenytoin. Study of two cases of this disorder and a review of the literature suggest that antecedant pathologic changes in the basal ganglia are prerequisites for the development of phenytoin-induced hyperkinesias. In an animal model of tardive dyskinesia, phenytoin was found to enhance neuroleptic-induced behavioral supersensitivity but have no effect in control animals. We conclude that phenytoin induced hyperkinesias reflect a specific effect of phenytoin on an abnormal neural substrate and suggest the presence of an otherwise silent pathological alteration of the corpus striatum. The diagnostic value of an episode of phenytoin-induced hyperkinesia is discussed.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
8/12. ketoconazole, an oral antifungal: laboratory and clinical assessment of imidazole drugs.miconazole, a parenterally administered imidazole antifungal agent has been shown to produce responses in systemic fungal infections in man. ketoconazole, an analogue, can be given by mouth. It is inhibitory in vitro at low concentrations to most fungi. blood levels after oral administration to animals and man greatly exceed these inhibitory concentrations for several hours. The efficacy of this drug has been demonstrated in animal models. Initial clinical evaluation has produced responses to therapy with 200-400 mg/day in 13 of 16 evaluable patients with systemic and superficial fungal infections, involving 10 fungal pathogens. No toxicity has been noted to date in these human studies. ketoconazole is a promising agent needing further extensive evaluation.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
9/12. Experimental model for combination chemotherapy with metronidazole using human uterine cervical carcinomas transplanted into nude mice.Human uterine cervical carcinomas (Yumoto strain) and HeLa cell tumors were transplanted into nude mice, and their transplantable strains were established. The fundamental histological features of these tumors were analyzed according to their histological construction and cytological maturation. The effect of administered drugs was examined morphologically. The Yumoto strain is a well-differentiated epidermoid-type carcinoma consisting of regularly arranged basal-type, parabasal-type, and keratinizing-type cells. The HeLa cell tumor is made up of solid medullary carcinoma cell nests in which trabecular arrangements begin to appear around the medullary areas after the third passage. This feature is maintained up to the 17th generation. The basal layer-type cancer cells of the Yumoto strain as well as trabecularly arranged cancer cells in the HeLa cell tumor were selectively influenced by administration of bleomycin and/or mitomycin and showed considerable degeneration or complete disappearance. On the contrary, metronidazole (a drug for vaginal trichomoniasis; Flagyl) displayed a cytotoxic effect on the parabasal-type and/or more mature cancer cells of the Yumoto strain as well as on the solid medullary area of the HeLa cell tumor. This result may indicate a selective affinity of drugs for malignant cells according to their histological construction, and it is conceivable that these types of carcinoma can be affected by combination administration of metronidazole and oncostatic chemicals such as bleomycin and mitomycin. This speculation was realized in this experimental animal research.- - - - - - - - - - ranking = 2keywords = administration (Clic here for more details about this article) |
10/12. Hazards of calcium gluconate therapy in the newborn infant: intra-arterial injection producing intestinal necrosis in rabbit ileum.Five infants received 10% calcium gluconate via umbilical artery catheters, which resulted in intestinal bleeding and lesions of the buttock, anus, groin, and thigh. The effects of intra-arterial calcium gluconate in two animal models were investigated. Injection of calcium into the aorta in the region of the posterior mesenteric artery resulted in immediate hyperperfusion of the descending colon; this may be an early hemodynamic response to injury in the area of colon supplied by this vessel. injections into the arterial arcade of the rabbit ileum resulted in intestinal necrosis and villous atrophy. The use of umbilical artery catheters for administration of calcium gluconate is potentially hazardous.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
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