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Biomedical subjects

R C Thompson

Publications and source records attributed to R C Thompson.

At least 235 records · Page 13Linked to original sources
PubMed1991

In vitro and in vivo efficacy of epsiprantel against Echinococcus granulosus.

In vitro, epsiprantel at a concentration of 10 micrograms ml-1 caused tegumental damage and death of protoscoleces, juveniles (seven-day-old) and adult (37-day-old) Echinococcus granulosus. Degenerative changes and death occurred more rapidly in the older parasites. Similarly, epsiprantel was more effective against adult (28-day-old) than seven-day-old experimental infections of E granulosus in dogs. Oral doses of 2.5, 5 and 7.5 mg kg-1 were greater than 96 per cent, 99.9 per cent and 99.99 per cent active, respectively, against mature worms, whereas in seven-day-old infections doses of 5, 7.5 and 10 mg kg-1 produced greater than 94 per cent, 90 per cent and 99.8 per cent reduction in worm burdens, respectively. No side effects from treatment were seen.

Administration, Oral↗
PubMed1991

Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro.

Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1). Inhibition of this cytokine has been a strategy for studying disease and for new drug development. A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms. IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.

Animals↗
PubMed1991

Serial magnetic resonance imaging in patients following acute myocardial infarction.

The detection of serial changes in magnetic resonance (MR) signal intensity of the heart following acute myocardial infarction may provide a useful method of characterizing tissue healing. Fourteen patients with acute Q-wave infarction underwent T2-weighted, spin-echo cardiac imaging during hospitalization, followed by one or more additional MR studies (total 31) over a 6- to 27-wk period (mean: 3 mo). Visual assessment of the images demonstrated a gradual reduction in signal intensity and localization of the bright signal to the subendocardium of the infarction region over the three-mo study period. A quantitative measurement of signal intensity (infarction/normal myocardium) fell from 1.81 +/- 0.42 on the initial study to 1.34 +/- 0.37 (p less than 0.05) at a mean of 14 wk. Two patients had an increase in signal intensity on the follow-up study and both patients had been readmitted with acute coronary syndromes. In summary, characterization of changes in signal intensity may provide a useful method of assessing myocardial healing following acute myocardial infarction. Further studies are indicated to determine the prognostic significance of these parameters.

Female↗
PubMed1991

Inhibition of interleukin-1-induced synovitis and articular cartilage proteoglycan loss in the rabbit knee by recombinant human interleukin-1 receptor antagonist.

Intra-articular injection of interleukin-1 (IL-1) into the knee joints of rabbits produces a synovitis associated with the loss of proteoglycan from the matrix of articular cartilage. This experimental finding supports the hypothesis that IL-1 is a possible mediator of the pathology of inflammatory joint diseases and suggests that antagonism of IL-1 could offer a therapeutic approach to these diseases. It has recently been reported that culture of human monocytes on adherent IgG stimulates these cells to synthesize a specific inhibitor of IL-1 bioactivity (IL-1ra) that acts as a receptor antagonist with lymphocytes and mesenchymal cells. We have now shown that intravenous injection of IL-1ra into rabbits given an intra-articular injection of recombinant IL-1 beta not only inhibits the entry of leukocytes into the synovial lining and joint cavity but blocks the ability of IL-1 to cause loss of proteoglycan from articular cartilage. This ability of IL-1ra to inhibit IL-1-induced arthritis in the rabbit reveals that this protein has appropriate pharmacokinetic and pharmacodynamic properties and further strengthens the belief that it may be a useful therapeutic agent.

Animals↗
PubMed1991

Right-to-left shunt across a patent foramen ovale caused by cardiac tamponade: diagnosis by transesophageal echocardiography.

Cardiac tamponade can manifest as profound hypoxemia from intracardiac shunting across a patent foramen ovale. As a consequence, pulmonary embolus can be erroneously diagnosed. As demonstrated in the case described herein, transesophageal echocardiography can be useful in determining the correct diagnosis, especially if transthoracic echocardiography is technically limited. In our patient, the findings on transesophageal echocardiography also helped determine the appropriate treatment. The relative inaccessibility of the pericardial effusion to needle drainage prompted open surgical drainage.

Aged↗
PubMed1991

Percutaneous transluminal coronary angioplasty in the elderly: early and long-term results.

The immediate and long-term efficacy of coronary angioplasty in the elderly was determined by studying 752 patients greater than or equal to 65 years old and comparing patients greater than or equal to 75 years old with those 65 to 74 years old. The oldest patients were more highly symptomatic, were more likely to be in heart failure, had more multivessel disease and were more likely to undergo multivessel dilation. The immediate success rate of angioplasty was higher in the oldest patients (92.8% versus 82%) (p = 0.0003). The hospital mortality rate was also higher (6.2% versus 1.6%) (p less than 0.001). Long-term overall survival was high. However, long-term event-free survival was lowest in the oldest patients, and recurrent severe angina was particularly common. Thus, in very elderly patients, coronary angioplasty is usually successful, but extra caution is warranted; also, long-term relief from angina is less common than in younger patients.

Aged↗
PubMed1991

Pro- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats.

A specific interleukin-1 (IL-1) receptor antagonist (IL-1ra) was used to examine the roles of IL-1 in an experimental model designed to analyze the reactivation phase of erosive arthritis, induced in rats with peptidoglycan-polysaccharide polymers (PG-APS) isolated from cell walls of group A streptococci. Monoarticular arthritis was initiated by injection of a small dose of PG-APS into an ankle joint, and reactivation was induced by intravenous injection of PG-APS 20 days later. Human recombinant IL-1ra given at a dose of 2 to 3 mg/kg at the time of reactivation of arthritis and at 6-h intervals inhibits the increase in joint swelling by at least 60%. Joint swelling is suppressed 30 to 50% when the initial treatment with IL-1ra is delayed until 6 h after reactivation. IL-1ra is not effective when the initial injection is delayed 12 or 24 h. With an injection schedule of IL-1ra given at the time of reactivation and every 6 h, treatment can be stopped at 24 h and the suppression of swelling is no different from that in rats for which injections are continued for 4 days. The results indicate that IL-1 has a prominent, although not exclusive, role in initiating inflammation in this model and is involved in the amplifying processes in progressive inflammation and chronic erosive disease. An anti-inflammatory function of IL-1 is also indicated from data showing that IL-1ra treatment limited to 6 h or less after the induction of reactivation enhances joint swelling, whereas intravenous injection of human recombinant IL-1 beta 24 h before reactivation suppresses the reactivation of arthritis.

Animals↗
PubMed1991

Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates.

Interleukin (IL)-1 is an early mediator of host response to inflammation, although its contribution to individual components of the acute phase reaction is still unclear. To evaluate how the hemodynamic, metabolic, and hormonal responses to sublethal endotoxemia compare with IL-1 administration, baboons received intravenously either lipopolysaccharide (LPS) or 0.1, 10, or 100 micrograms/kg IL-1 alpha. LPS induced an early tachycardia and a fall in mean arterial pressure, as well as lacticacidemia and hypoaminoacidemia. Similar hemodynamic and metabolic changes were seen with 10 or 100 micrograms/kg of IL-1 alpha. An increase in adrenocorticotropic hormone and fall in serum iron were induced by IL-1 alpha but not by LPS. Plasma tumor necrosis factor-alpha (TNF-alpha) was not measurable after IL-1 alpha administration, whereas LPS induced a monophasic TNF-alpha response. IL-6 levels were significantly greater after LPS than IL-1 alpha administration. Histopathological lesions, similar in LPS- and 100 micrograms/kg IL-1 alpha-treated groups, were present only in the adrenal cortex. We conclude that many, but not all, of the effects of sublethal endotoxemia can be replicated by IL-1 alpha administration, and these responses are dose dependent.

Amino Acids↗
PubMed1991

Anti-neutrophil elastase defense of the normal human respiratory epithelial surface provided by the secretory leukoprotease inhibitor.

Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease with a high capacity for inhibiting neutrophil elastase (NE), is produced by cells of mucosal surfaces including the human lung. The molar concentrations of SLPI in total respiratory tract epithelial lining fluid (ELF) were 56 +/- 10% that of alpha 1-antitrypsin, suggesting SLPI may be more important for the anti-NE protection of the pulmonary epithelial surface than previously thought. However, evaluation demonstrated that SLPI in respiratory ELF was only one-third functional. Studies aerosolizing recombinant SLPI (rSLPI) to sheep demonstrated that in the short term, neither aerosolization and alveolar deposition nor the lavage procedure inactivated the SLPI molecule. In vitro studies with rSLPI demonstrated that exposure to oxidants did not modify the form of the molecule, while exposure to oxidants and NE caused the molecule to be cleaved from 12 to 8 kD. Consistent with this, evaluation of SLPI in lavage fluid of individuals with cystic fibrosis (a condition with oxidants and NE on the respiratory epithelium) showed that the SLPI was degraded. However, evaluation of SLPI in normal ELF by molecular sieve analysis and Western analysis demonstrated an intact 12-kD molecule, suggesting that the partial inactivation of SLPI in normals in vivo is not because it is complexed to NE or exposed to oxidants + NE. Together, these observations demonstrate that SLPI is present in large amounts in respiratory ELF, but since the majority of the SLPI is inactive, it likely does not play a significant role in protecting the normal respiratory epithelium, except perhaps in the upper airways where the levels of SLPI are the highest.

Adult↗
PubMed1991

Expression of the secretory leukoprotease inhibitor gene in epithelial cells.

The secretory leukoprotease inhibitor (SLPI) gene codes for a 12-kD protein that within the lung protects the airway epithelium from neutrophil elastase. Screening of 228 alleles in 114 individuals for sequence differences by RNase protection of genomic DNA revealed no detectable polymorphisms in SLPI gene exons II-IV. SLPI gene expression in the lung was demonstrated by identifying SLPI mRNA transcripts in bronchial epithelial cells freshly isolated from normals. Cell lines derived from mucosal surfaces (HS-24 bronchial squamous cell carcinoma, HeLa cervical carcinoma) actively transcribe the SLPI gene and contain SLPI mRNA transcripts, while lung fibroblasts demonstrate no evidence of SLPI gene expression. SLPI mRNA transcripts appear to be relatively stable, with mRNA levels only mildly affected by inhibition of RNA synthesis. Chromatin DNA of HS-24 cells demonstrates two DNase I hypersensitivity sites within the 5' flanking region of exon I of the SLPI gene, whereas fibroblast chromatin has no DNase I accessible sites in the same region. Further analysis of the 5' flanking region demonstrated two contiguous transcription start sites, CAAT and TATA boxes, and several potential regions of known DNA binding proteins. Overall, the SLPI gene appears to be a relatively nonpolymorphic, stable gene that is constitutively expressed at specific tissue sites, but has the potential to be modulated at both the transcriptional and posttranscriptional levels.

Base Sequence↗
PubMed1991

Osteoarthrotic changes after acute transarticular load. An animal model.

The canine patellofemoral joint was subjected to a standardized transarticular load of 2170 newtons for two milliseconds, and the gross and histological changes were examined at two, twelve, and twenty-four weeks after injury. Initially, the load creates fractures in the zone of calcified cartilage, with minimum damage to the articular cartilage surface. Surface fissures were visible in all patellae only after staining with India ink. Histologically, these surface clefts extended into the transitional or superficial radial zone, and they did not communicate with the subchondral bone except in two patellae. However, there were reproducible clefts in the region of the subchondral bone and the zone of calcified cartilage in all patellae. Six months after loading, there was a loss of safranin-O staining above the deep clefts, and there was new-bone formation in the subchondral region and fibrillation of the cartilaginous surface. Thus, the initial changes had progressed to osteoarthrotic-like conditions at six months. In this animal model, the joint is not invaded and the changes that result from loading are reproducible. The injury to the joint creates superficial disruption of the cartilage and subchondral changes that lead to arthritic-like degeneration of the cartilage within six months.

Animals↗
PubMed1991

The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.

Endotoxin, a lipopolysaccharide (LPS) component of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1). Lipopolysaccharide and IL-1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection, suggesting that LPS-induced IL-1 expression contributes to the pathogenesis of LPS-induced acute inflammation. In the present study, the role of IL-1 in LPS-induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of LPS as compared to the same timepoint after the intratracheal coinjection of LPS and IL-1 receptor antagonist (IL-1ra). The IL-1ra was found to inhibit LPS-induced acute inflammation (P greater than 0.0001) as measured by the number of neutrophils recovered in bronchoalveolar lavage. The LPS-induced emigration of neutrophils was inhibited by as much as 45%. Recombinant IL-1 beta-induced neutrophil emigration into the lung was inhibited by 95% when IL-1ra was coinjected intratracheally with IL-1 beta. Coinjection of recombinant IL-1 beta and LPS increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone. Intratracheal injection of LPS induces a progressive increase in IL-1ra mRNA expression in whole-lung RNA preparations, suggesting that endogenous IL-1ra may play an important role as a negative feedback mechanism to downregulate LPS initiated IL-1-mediated acute inflammation. In conclusion IL-1ra inhibits both LPS- and IL-1-induced neutrophilic inflammation and may therefore prove clinically useful as an anti-inflammatory agent for the therapy of either septic or aseptic IL-1-mediated acute inflammation.

Animals↗
PubMed1991

A simple method for cloning Giardia duodenalis from cultures and fecal samples.

Using a novel method for cloning Giardia duodenalis from cultures and fecal samples, 47 clones from 7 isolates were established in vitro. Average colony-forming efficiency in established cultures was 43.2% compared to 11.2% when cloning directly from excystation. The highest success rate of cloning was found with the Portland (P1, ATCC No. 30888) isolate, with a colony-forming efficiency of 92.7%. Cloned and parent populations were compared over a range of 13 enzymes using starch gel electrophoresis. No genetic difference was found between any of the clones and the parent isolates.

Animals↗
PubMed1991

A new approach to the resection of pulmonary osteosarcoma metastases. Results of aggressive metastasectomy.

Pulmonary metastases are the primary cause of death from bone and soft-tissue sarcoma. Recognition that even multiple resections of metastases can improve survival has led to a more aggressive surgical approach to these patients. The authors instituted an aggressive approach and a new technique and retrospectively analyzed the results of multiple, pulmonary metastasectomies for pulmonary metastases in 34 patients, 21 of whom had osteogenic sarcoma (OGS). A number of cases were referred from other institutions, where they had been considered inoperable because of extensive or recurrent disease. Using lateral thoracotomies, laser technique with minimal parenchymal excision, and thin gloves for palpation, aggressive metastectomy was carried out. A mean of 3.1 thoracotomies were performed, with an average of 10.6 nodules resected per thoracotomy. Operative morbidity and mortality were minimal. Evaluation of potential prognostic factors revealed no statistically significant survival difference on the basis of disease-free interval (DFI), number of nodules resected, number of thoracotomies, or size of largest nodule resected. There was a clear trend toward decreased survival of patients with larger nodules (greater than 2 cm), but because of the small number of patients in this group, no firm conclusions can be drawn. Five-year survival was 49% for the study group as a whole, and 39% for the OGS patients. Aggressive surgical resection of pulmonary metastases from bone and soft-tissue sarcoma should be considered when there is control of local disease, no evidence of extrapulmonary metastasis, and adequate postresection pulmonary reserve. The presence of bilateral, extensive, or recurrent disease is not a contraindication to thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Tumefactive fibroinflammatory lesion of the extremity. Report of a case and review of the literature.

Tumefactive fibroinflammatory lesion is an idiopathic fibroinflammatory process of the head and neck region. Although benign histopathologically, it is invasive, destructive, and locally recurrent, leading to uncertainty regarding its proper management; as the disease is rare, determining optimal treatment is difficult, given the anecdotal nature of reports. We report the first case of a tumefactive fibroinflammatory lesion occurring outside the head and neck region. Our patient was treated with corticosteroids and had a favorable response, supporting this approach as initial treatment. Immunohistochemical studies performed on a pretreatment specimen were consistent with a secondary inflammatory component because no monoclonal nor aberrant phenotypes were detected. The tumefactive fibroinflammatory lesion appears to be indistinguishable from the other known idiopathic fibroinflammatory processes; patients presenting with any one of these should be evaluated for the others.

Adrenal Cortex Hormones↗
PubMed1990

Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production.

Inhibitory factors towards IL-1 have been identified in the urine and in the supernatants of human monocyte cultures and have been shown to act as receptor antagonists. We have investigated whether a natural inhibitor purified from human urine (uIL-1ra) and a recombinant molecule expressed using the gene for an IL-1 antagonist isolated from monocytes (rIL-1ra) can alter responses to human rIL-1 alpha in organ cultures of fetal rat long bones and neonatal mouse calvariae. The two preparations probably contained similar or identical molecules, because an antibody to rIL-1ra reacted with uIL-1ra by Western blot analysis. uIL-1ra and rIL-1ra specifically blocked stimulation of bone resorption by rIL-1 in both culture systems, as well as the increase in PGE2 production in cultured calvariae. Resorptive effects of parathyroid hormone and TNF-alpha were not blocked. The uIL-1ra preparation had some intrinsic resorbing activity, but on gel chromatography this appeared in fractions that eluted earlier than uIL-1ra. Concentration ratios of rIL-1ra to rIL-1 as low as 10 could block the resorptive response of fetal rat long bones, whereas concentration ratios of 100 to 1000 were required to block IL-1 action on neonatal mouse calvariae. The inhibitory effects appeared to be competitive, because increasing concentrations of IL-1 overcame the block of bone resorption in both systems and the inhibition of PGE2 production in calvariae.

Animals↗
PubMed1990

Interleukin-1 receptor antagonist reduces mortality from endotoxin shock.

About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.

Animals↗