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Biomedical subjects

R C Thompson

Publications and source records attributed to R C Thompson.

At least 127 records · Page 7Linked to original sources

Periprosthetic metastatic carcinoma. Pitfalls in the management of two cases initially diagnosed as osteolysis.

Periprosthetic osteolysis is a well-described phenomenon associated with total hip arthroplasty. Two cases are presented in which apparently healthy patients developed lytic lesions adjacent to cementless hip implants. Despite atypical features, the lesions were initially attributed to wear debris-induced osteolysis, and it was discovered during revision surgery that metastatic tumor was present. For one patient, if the initial diagnosis had been correct, subsequent surgery and related complications may have been avoided. It is important to consider the entire differential of radiolucent bone lesions whenever a patient presents with periprosthetic osteolysis. If revision surgery is not warranted on the basis of loosening, then a thorough medical examination, close follow-up evaluation, and/or biopsy should be performed to rule out metastatic disease.

Adenocarcinoma↗

Interleukin-1 beta-mediated regulation of mu-opioid receptor mRNA in primary astrocyte-enriched cultures.

Opioids have been found to modulate the immune system by regulating the function of immunocompetent cells. Several studies suggest that the interaction between immune and opioid systems is not unidirectional, but rather reciprocal, in nature. In the CNS, one cellular target of immune system activation is the astrocytes. These glial cells have been shown to produce the opioid peptide, proenkephalin, to express the mu-, delta-, and kappa-opioid receptors, and to respond to the immune factor interleukin-1 beta (IL1 beta) with an increased proenkephalin synthesis. To characterize more completely the astrocytic opioid response to immune factor stimulation, we examined the effect of IL1 beta (1 ng/ml) on the mu-receptor mRNA expression in primary astrocyte-enriched cultures derived from rat (postnatal day 1-2) cortex, striatum, cerebellum, hippocampus, and hypothalamus. A 24-h treatment with IL1 beta produced a 70-80% increase in the mu-receptor mRNA expression in the striatal, cerebellar, and hippocampal cultures but had no effect on this expression in the cortical and hypothalamic cultures. This observation represents one of the few demonstrated increases in levels of the mu-receptor mRNA in vitro or in vivo, since the cloning of the receptor. The enhanced mu-receptor mRNA expression, together with the previous observation that IL1 beta stimulates proenkephalin synthesis in astrocytes, supports the IL1 beta-mediated regulation of an astroglial opioid peptide and receptor in vitro, a phenomenon that may be significant in the modulation of the gliotic response to neuronal damage. Therefore, the astroglial opioid "system" may be important in the IL1 beta-initiated, coordinated response to CNS infection, trauma, or injury.

Animals↗

Clinical features of patients with beta-lactamase producing Haemophilus influenzae isolated from sputum.

Ampicillin resistance amongst isolates of Haemophilus influenzae is of increasing concern but its clinical impact is unclear. We performed a retrospective study of 34 hospital patients with lower respiratory tract infection (LRTI) caused by beta-lactamase positive (beta+) H. influenzae and compared these with 34 control patients with LRTI caused by beta-lactamase negative (beta-) strains. Chronic obstructive pulmonary disease was the most common underlying condition in both groups (beta+ 23/24, beta- 25/34). A recent course of antibiotics, especially ampicillin/amoxycillin, was significantly (P < 0.05) more common in the beta+ group (beta+ 17/34, beta- 3/34). Other pathogens were isolated more frequently in the beta+ group (beta+ 10/34, beta- 4/34). There was no difference in outcome between the two groups.

Adult↗

Systemic and local paracrine cytokine therapies using transduced tumor cells are synergistic in treating intracranial tumors.

Development of an effective immunotherapeutic approach for treatment of CNS tumors must take into account the unique anatomic and immunologic features of the brain. We explored the antitumor immune response in the brain elicited by nonreplicating melanoma cells genetically engineered to produce either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) in a paracrine fashion. Using a new model of intracranial melanoma in C57BL/6 mice, the cytokine-producing cells were given either as a subcutaneous vaccine to induce systemic antitumor immunity or as a direct injection into the brain as local immunotherapy. We found that GM-CSF-transduced cells, as a subcutaneous vaccine but not as an intracranial injection, afforded some protection from intracranial challenge with the wild-type tumor. In contrast, direct intracranial injection of tumor cells secreting IL-2 was protective whereas flank vaccination with IL-2 transductants was not. Combination therapy with both the subcutaneous GM-CSF-transductants as a vaccine and local administration of IL-2-transductants in the brain achieved a synergistic response. These findings provide a basis for the application of paracrine cytokine delivery to brain cancer therapy both as a systemic vaccine and via local administration. The demonstration of synergy between paracrine cytokine therapies holds promise as a novel therapy for brain tumors.

Animals↗

Bilateral central acetabular fracture dislocations secondary to sustained myoclonus.

This case report presents a patient with bilateral central acetabular fracture dislocations secondary to sustained myoclonus treated with delayed bilateral total hip arthroplasty. This is an unusual mechanism of injury, but is similar to other uncontrolled muscular contractions, such as electroconvulsive therapy and seizures. Because of ongoing myoclonus, the patient initially was treated nonoperatively. The patient then successfully had staged bilateral total hip arthroplasty 15 months after injury. This case exemplifies that forceful, uncontrolled muscular contraction can cause bilateral symmetric fracture dislocations. In patients with a history of seizure or myoclonic contracture with subsequent pain or loss of function, radiographs are indicated and skeletal fracture or joint dislocation must be ruled out. Secondary reconstruction can be recommended when the patient is medically stable.

Acetabulum↗

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci.

Certain derivatives of the glycopeptide antibiotic LY264826 with N-alkyl-linked substitutions on the epivancosamine sugar are active against glycopeptide-resistant enterococci. Six compounds representing our most active series were evaluated for activity against antibiotic-resistant, gram-positive pathogens. For Enterococcus faecium and E. faecalis resistant to both vancomycin and teicoplanin, the MICs of the six semisynthetic compounds for 90% of the strains tested were 1 to 4 micrograms/ml, compared with 2,048 micrograms/ml for vancomycin and 256 micrograms/ml for LY264826. For E. faecium and E. faecalis resistant to vancomycin but not teicoplanin, the MICs were 0.016 to 1 micrograms/ml, compared with 64 to 1,024 micrograms/ml for vancomycin. The compounds were highly active against vancomycin-susceptible enterococci and against E. gallinarum and E. casseliflavus and showed some activity against isolates of highly vancomycin-resistant leuconostocs and pediococci. The MICs for 90% of the strains of methicillin-resistant Staphylococcus aureus tested were typically 0.25 to 1 micrograms/ml, compared with 1 microgram/ml for vancomycin. Against methicillin-resistant S. epidermidis MICs ranged from 0.25 to 2 micrograms/ml, compared with 1 to 4 micrograms/ml for vancomycin and 4 to 16 micrograms/ml for teicoplanin. The spectrum of these new compounds included activity against teicoplanin-resistant, coagulase-negative staphylococci. The compounds exhibited exceptional potency against pathogenic streptococci, with MICs of < or = 0.008 microgram/ml against Streptococcus pneumoniae, including penicillin-resistant isolates. In in vivo studies with a mouse infection model, the median effective doses against a challenge by S. aureus, S. pneumoniae, or S. pyogenes were typically 4 to 20 times lower than those of vancomycin. Overall, these new glycopeptides, such as LY307599 and LY333328, show promise for use as agents against resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant pneumococci.

Animals↗

Primary bone tumors of the pelvis presenting as spinal disease.

Low back pain and sciatica are usually attributed to localized structural pathology; however, tumors of the pelvis may also cause these symptoms. Pelvic bone neoplasms are seldom immediately diagnosed and, therefore, may result in significant morbidity and mortality. Fourteen cases of malignant primary bone tumors of the pelvis that caused spinal symptoms were referred to our Musculoskeletal Tumor Service. Several recurring characteristics of these cases that may alert the clinician to the possibility of underlying pelvic bone malignancy in a patient with low back pain were identified: 1) age > or = 45 years; 2) insidious onset of symptoms without antecedent trauma; 3) prolonged symptoms for more than 1 month; 4) progressive pain that fails conservative therapy; and 5) presence of anorexia, malaise, or night pain. We suggest that in diagnosis of a patient presenting with these characteristics, the clinician instruct that the pelvis be included in initial radiographs. If plain radiograph is non-diagnostic and symptoms remain unresponsive, we recommend obtaining a bone scan, and then, if necessary, computerized tomography or magnetic resonance imaging.

Adult↗

Diagnosis of right atrial metastatic melanoma by transesophageal echocardiographic-guided transvenous biopsy.

Traditionally, tissue diagnosis of malignant melanoma metastatic to the heart necessitated thoracotomy or was done at autopsy. More recently, right or left ventricular endomyocardial biopsy under fluoroscopic guidance has been used to confirm metastatic involvement of the heart by various neoplasms including malignant melanoma; results have been excellent, and morbidity has been low. High-quality images of intracardiac masses with excellent anatomic details can be obtained by transesophageal echocardiography. Herein we describe a 73-year-old man with a history of malignant melanoma in whom cardiac metastatic involvement was documented by percutaneous transesophageal echocardiographic-guided transvenous biopsy of a right atrial mass; thus, the need for a more invasive approach to tissue documentation was avoided.

Aged↗

Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity.

Reductive alkylation of the A82846 family of glycopeptide antibiotics has the potential of producing seven products. N-Alkylation of the disaccharide amino function can be accomplished selectively, and offers the greatest increase in antibacterial activity. Products resulting from N-alkylation of LY264826 (A82846B) provide the most potent derivatives as compared to other members of this class of antibiotics. Two of these derivatives, LY307599 and LY333328 are approximately 500 times more active than vancomycin against vancomycin-resistant enterococci.

Alkylation↗

Percutaneous transluminal coronary angioplasty in the elderly.

Selected elderly patients, even the very elderly, can undergo percutaneous transluminal coronary angioplasty (PTCA) with a high expected rate of procedural success; however, procedural mortality is higher than in younger patients and, although long-term survival is very good, long-term relief of angina is less reliable. Patient selection is the key to optimal outcome.

Aged↗

Genetic variability in parasites and host-parasite interactions.

We have examined genetic variability in parasites in the context of ecological interactions with the host. Recent research on Echinococcus, Giardia and Cryptosporidium has been used to illustrate: (i) the problems that parasite variability and species recognition pose for understanding the complex and often controversial relationship between parasite and host occurrence; (ii) the need for accurate parasite characterization and the application of appropriate molecular techniques to studies on parasite transmission if fundamental questions about zoonotic relationships and risk factors are to be answered; (iii) our lack of understanding about within-host interactions between genetically heterogeneous parasites at the inter- and intraspecific levels, and the significance of such interactions with respect to evolutionary considerations and the clinical outcome of parasite infections. If advances in molecular biology and mathematical ecology are to be realized, we need to give serious consideration to the development of appropriate species concepts and in vivo systems for testing the predictions and assumptions of theoretical models.

Animals↗

A comparison of two methods for assessing drug sensitivity in Giardia duodenalis.

This study compared two published methods for assessing the in-vitro drug sensitivity of Giardia duodenalis: the 3H-thymidine incorporation assay (BOREHAM et al. 1984) which radiometrically measures nucleic acid synthesis; and inhibition of adherence (MELONI et al. 1990). Giardia trophozoites were exposed to a range of concentrations of metronidazole or albendazole for 24 hours and their viability measured by both assays in order to determine the degree of correlation between the two methods of measuring viability. Due to the different modes of action of metronidazole and albendazole on Giardia, measuring the inhibition of adherence appears to be a more accurate indicator of trophozoite viability than measuring 3H-thymidine incorporation.

Albendazole↗

Giardia duodenalis: exposure to metronidazole inhibits competitive interactions between isolates of the parasite in vitro.

The competitive interactions of genetically distinct isolates of Giardia duodenalis with different growth rates were studied in vitro. Electrophoretic analysis of mixed cultures showed that competition between 2 cloned isolates occurs under normal in vitro culture conditions, with faster-growing isolates outcompeting those with slower growth rates. The addition of sublethal concentrations of metronidazole to clonal mixtures in vitro prevented the competitive exclusion, which was seen in normal culture. This apparently occurred because the drug reduced the growth rate of the faster-growing but not the slower-growing clone.

Animals↗

Morphological and molecular characterization of Giardia isolated from the straw-necked ibis (Threskiornis spinicollis) in Western Australia.

Following the first report of avian Giardia infection in Australia, isolates of the parasite recovered from naturally infected straw-necked ibis (Theskiornis spinicollis) were characterized using median body morphology, scanning electron microscopy, multilocus enzyme electrophoresis, random amplified polymorphic DNA (RAPD), and small subunit ribosomal RNA (SSU-rRNA) analyses. Results were compared with Giardia from other birds and mammals, and the extent of genetic diversity between a range of ibis isolates collected in Western Australia was determined. The ibis isolates of Giardia were genetically relatively homogeneous, which is in contrast to the extensive genetic heterogeneity often displayed by mammalian Giardia isolates. Morphologically, Giardia from ibis were similar to Giardia ardeae although they differed genetically and by the fact that the ibis isolates could not be established in in vitro culture. Sequence data of the DNA coding for the SSU-rRNA found a 96% homology between the ibis isolates from Western Australia and G. ardeae, suggesting that they represent distinct strains of the same species. In contrast, the ibis isolates were genetically and morphologically very different than Giardia duodenalis and Giardia muris from mammals.

Animals↗

Simplified methods for obtaining purified oocysts from mice and for growing Cryptosporidium parvum in vitro.

Seven- to 8-day-old Arc/Swiss mice were infected with 100,000-120,000 Cryptosporidium parvum oocysts. At 8 days postinfection (PI) the jejunum, ileum, cecum, colon, and rectum were removed. Using a simple extraction procedure and purification by Ficoll gradient centrifugation, we rountinely obtained between 3-6 million and up to 15 million purified oocysts per mouse. For in vitro cultivation, purified oocysts were pretreated in a low pH (2.5-3) 0.5% trypsin solution for 20 min, resuspended in supplemented RPMI-1640 containing glucose 0.1 g (5.55 mM), sodium bicarbonate 0.3 g, bovine bile 0.02 g, folic acid 25 micrograms, 4-aminobenzoic acid 100 micrograms, calcium pantothenate 50 micrograms, ascorbic acid 875 micrograms, penicillin G 10,000 U and streptomycin 0.01 g per 100 ml, and 1% fetal bovine serum (pH 7.4 before filtration), and used to inoculate confluent monolayers of the human adenocarcinoma cell line HCT-8. Incubation was in a candle jar at 37 C. We tested numerous supplements to RPMI-1640, different pHs, and atmospheric conditions and found the parameters described above produced the greatest parasite numbers in vitro. We obtained significantly superior growth of C. parvum grown in HCT-8 cells using the conditions described above than in culture conditions described previously.

Adenocarcinoma↗

Primary astroglial cultures derived from several rat brain regions differentially express mu, delta and kappa opioid receptor mRNA.

The existence of opioid receptors within glial cell membranes has been proposed by several laboratories based on biochemical and radioligand binding data. The recent cloning of the mu, delta and kappa receptors has enabled us to directly examine the issue of opioid receptor expression in rat brain astroglia by using solution hybridization/ribonuclease protection assays to analyze the total RNA obtained from primary cultures of cortical, striatal, cerebellar, hippocampal and hypothalamic astrocytes. The results indicate that all five glial cultures expressed mu, delta and kappa receptor mRNA. The rank order of receptor mRNA abundance, expressed collectively across all five cultures, was determined to be delta > or = kappa >> mu. An analysis of the glial distribution profile for each receptor type revealed that mu receptor mRNA levels were the most abundantly expressed in cortical cultures, while the greatest levels of delta receptor mRNA were found in the cortical and hypothalamic cultures, and significant kappa receptor mRNA levels were produced by the cortical, hypothalamic and cerebellar cultures. Furthermore, the five glial cultures each expressed different levels of total opioid receptor (mu + delta + kappa) mRNA. The rank order of total opioid receptor mRNA expression across different astroglial cultures was found to be cortex > hypothalamus > cerebellum = hippocampus > striatum. An analysis of the relative expression profiles for mu, delta and kappa receptor mRNA within each culture revealed that all cultures manifested relatively high levels of delta and kappa receptor mRNA, but relatively low levels of mu receptor mRNA. Generally, cortical, hippocampal and hypothalamic cultures were characterized by comparable levels of delta and kappa receptor mRNA, and little, if any, mu receptor mRNA. However, striatal cultures were characterized by a high level of delta receptor mRNA which was approximately twice and four times that of the kappa and mu receptor mRNA, respectively. In contrast, cerebellar cultures expressed predominantly kappa receptor mRNA at a level which was almost twice that of the delta receptor mRNA, and expressed very little mu receptor mRNA. These data show that primary astroglial cultures not only express mu, delta and kappa receptor mRNAs, but they do so in a manner dependent upon receptor type and brain region. This suggests a regional heterogeneity of astrocytes with respect to opioid receptor expression, a characteristic previously described only for neurons. Furthermore, it suggests the existence of an additional anatomical component in CNS opioid systems.

Animals↗