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Biomedical subjects

T Reid

Publications and source records attributed to T Reid.

At least 19 recordsLinked to original sources

Colonic medication bezoar from extended-release nifedipine and procainamide.

We report an unusual case of a primary colonic bezoar composed of extended-release formulations of nifedipine and procainamide. Although these bezoars are rare, the increasingly frequent application of extended-release delivery systems to other commonly prescribed medications may increase the incidence of such bezoars in vulnerable patients. Clinicians should be aware of this potential problem when prescribing these medications, and have a high index of suspicion when painful or refractory constipation occurs.

Aged

Bilateral synchronous testicular germ cell cancer.

Bilateral synchronous testicular cancer is a rare occurrence usually associated with similar histologic findings in each testicle. We describe eight patients with bilateral synchronous testicular germ cell cancer, of whom four had dissimilar histologic findings. Contralateral disease in three patients was identified only by testicular ultrasonography or intraoperative exploration of the contralateral testicle, and in two cases by palpation 6 months after identification of the primary cancer. Treatment was determined by conventional staging and five of eight patients have remained free of recurrent disease.

Adult

Mechanisms of tumor necrosis factor cytotoxicity and the cytotoxic signals transduced by the p75-tumor necrosis factor receptor.

We have here provided evidence that TNF mediated cytotoxicity is genetically, pharmacologically, and temporally distinct from the cytotoxicity mediated by TNF/CHX. Most studies on TNF cytotoxicity have been done by the combined use of TNF/CHX. The relevance of this approach to the physiological mechanisms underlying cytotoxicity by TNF alone is at present unclear. We have described a system in which overexpression of the p75-TNFR causes TNF-resistant cells to become TNF-sensitive. These cells are killed by TNF alone in a very short period of time and they are a useful system to study the mechanism of TNF-cytotoxicity.

Animals

Impact of omeprazole on the plasma clearance of methotrexate.

Omeprazole inhibits the gastric hydrogen pump and is an effective treatment for peptic ulcers. Methotrexate is a chemotherapeutic agent that inhibits dihydrofolate reductase and is eliminated by a hydrogen-ion-dependent mechanism in the kidney. We present evidence that omeprazole inhibits methotrexate clearance and may result in potentially toxic methotrexate levels.

Adult

Hypersensitivity reactions to streptokinase in patients with high pre-treatment antistreptokinase antibody and neutralisation titres.

After streptokinase or antistreplase administration, raised antibody levels can persist for many years, but it is unclear if these antibodies can cause allergic reactions following streptokinase re-administration for myocardial re-infarction. Pretreatment antistreptokinase antibody (AB) and neutralisation titres (NT) were measured in 189 consecutive patients (57 received streptokinase or anistreplase). Seven patients had previous exposure to streptokinase or anistreplase; they had high mean (SEM) antibody titres of 1:801 (332) and neutralisation titres of 3.3 (1.7) million units. The 182 patients without previous thrombolysis had mean (SD) antibody titres of 1:25 (3) and neutralisation titres of 0.14 (0.08) million units; nine patients (4.95%), however, had raised antibody titres of > or = 1:160 and neutralisation titres of > or = 0.3 million units. Of the 15 patients with antibody titres of > or = 1:160, three received streptokinase or anistreplase. Hypersensitivity reactions occurred in all three patients--neutralisation titres 0.48, 1.5 and 1.1 million units respectively. Two became severely hypotensive with systolic pressures of 70 mmHg; one developed a serum sickness-like reaction. Importantly, none of the 54 patients with antibody titres of < 1:160 who received streptokinase or antistreplase reacted adversely to the thrombolytic agents (chi 2 with Yates's correction = 38.71, P < 0.01). High antibody titres are associated with hypersensitivity reactions to streptokinase. This has important implications in reinfarction thrombolysis. In patients whose antistreptokinase antibody titres are likely to be raised the avoidance of streptokinase-related thrombolytic agents should be considered.

Adult

An interview study of participants in the Tacoma, Washington, syringe exchange.

Although European and Australian studies of syringe exchange programs have reported safer injection among participants and no increase in drug use, the generalizability of these findings to the US is uncertain. We report on the operations and potential effectiveness of the longest-operating syringe exchange in the US and compare our results to studies of exchange programs outside the US. The sample of 204 study subjects reported no change in the frequency of injection, from 155 to 152 injections per month, and a decline in the frequency of unsafe injections, from 56 to 30 times per month, while participating in the program. In all studies, participants report reduction in unsafe injections, and no increase in illicit drug use. However, the comparison also suggests that a high proportion of Tacoma exchangers have higher initial rates of drug injection, unsafe injection and homelessness, all of which were associated with unsafe injection while using the exchange. These indicate a need for additional services but that the Tacoma program is no less effective than European and Australian programs.

Acquired Immunodeficiency Syndrome

Corneal storage medium preservation with defensins.

We used a synthetic defensin (rabbit neutrophil peptide-1; NP-1) as a microbicide in a corneal storage medium, Optisol without antimicrobial compounds. We established growth curves in Optisol for Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Each organism was evaluated separately at 4 degrees C, 23 degrees C, and 37 degrees C in Optisol with NP-1 at each of four different concentrations including 1, 10, 100, and 200 micrograms/ml. When the three organisms were evaluated in Optisol containing NP-1, we found that a concentration of 200 micrograms/ml of NP-1 successfully killed 99.9% (the limits of our assay) of all three organisms at all temperatures tested. We conclude that NP-1 exhibits promise as a nonantibiotic preservative agent in corneal storage media, since it was effective in killing organisms at all temperatures, including 4 degrees C.

Antifungal Agents

Resistance to killing by tumor necrosis factor in an adipocyte cell line caused by a defect in arachidonic acid biosynthesis.

We have found that TA1-R6, which are resistant to the cytotoxic effects of tumor necrosis factor (TNF) in the presence of cycloheximide (Reid, T. R., Torti, F., and Ringold, G. M. (1989) J. Biol. Chem. 264, 4583-4589), have reduced ability to release arachidonic acid (20:4) from membrane phospholipids in response to either TNF or the calcium ionophore A23187 treatment. However, no defect in the activity of phospholipase A2, the principal enzyme responsible for the release of 20:4 from phospholipids, was observed in these cells. Detailed biochemical characterization of these TNF-resistant cells has revealed that these cells are unable to synthesize 20:4 endogenously because of a defect in delta 6-desaturase, the rate-limiting enzyme of 20:4 biosynthesis. This deficiency leads to a marked decrease in the steady-state levels of 20:4 present in choline-containing phospholipid (PC) and ethanolamine-containing phospholipid (PE). The TA1-R6 cells, however, are capable of incorporating exogenous 20:4 into PC and PE, and when loaded in such manner they become significantly more sensitive to the cytotoxic effects of TNF in the presence of cycloheximide. Therefore, the release of arachidonic acid from phospholipids appears to be a critical element in the signaling pathway utilized by TNF and is essential to the rapid cytotoxic response elicited by TNF in the absence of protein synthesis in wild-type TA1 cells.

Adipose Tissue

The Tacoma Syringe Exchange.

For over a year, the Tacoma Syringe Exchange has been operating in spite of existing drug paraphernalia laws. One hundred fifty-four subjects have been interviewed regarding drug injection practices for the month prior to first use of the exchange and for the most recent month since using the exchange. Statistically significant reductions in mean frequency of obtaining used syringes, and in mean rate of passing on used syringes, have been reported. Mean number of times bleach was used to disinfect contaminated syringes has risen. The exchange continues to attract mainly men, median age 35, with a long history of injection. No differences have been observed in mean number of injections per month. In order to increase utilization, new sites are planned, but expansion has been hampered by a series of legal problems. Since the exchange draws many difficult to reach individuals, it is an important location for STD screening and drug treatment recruitment. Documentation of participation patterns and barriers to exchange use, and effects upon HIV serological status are recommended.

Acquired Immunodeficiency Syndrome

Chromosomal abnormalities in human retinoblastoma. A review.

In part because of an association between the tumor and the constitutional chromosome 13q deletion syndrome and the finding of 13q deletions or monosomy 13 in retinoblastoma cells from individuals with normal constitutional karyotypes, chromosome 13q is postulated to contain a gene responsible for tumorigenesis in retinoblastoma. A review of the cytogenetics of retinoblastoma (incorporating an analysis of five previously unpublished cases and 77 cases from the literature) revealed recurrent abnormalities (in addition to those involving number 13, 21% of cases) that included: additional copies of 1q material (44%), isochromosome (6p) (45%), monosomy 16 (18%), marker 1p+ (13%), and homogeneously staining regions and double minutes (9%). Possible roles for these chromosome abnormalities in tumor development are discussed.

Alleles

Isolation and characterization of fibronectin from bovine aqueous humor.

Aqueous humor collected from freshly enucleated bovine eyes was passed over a gelatin affinity column, and bound material was eluted with 4M urea. When fractionated by sodium dodecyl sulfate electrophoresis, the eluted material co-migrated with human plasma fibronectin and protein standards of approximately 220,000 daltons. Amino acid analyses demonstrated a composition similar to that of human plasma fibronectin and fibronectin synthesized by cultured cells. The concentration of fibronectin in aqueous humor is approximately 100 times less than in human plasma.

Amino Acids

Homogeneously staining region in a retinoblastoma cell line: relevance to tumor initiation and progression.

A human retinoblastoma cell line was found to contain a homogeneously staining region (HSR) on chromosome 1 (at 1p34). An HSR had previously been identified at the same site in a human neuroblastoma cell line. Of the original retinoblastoma line, a subpopulation was found which did not contain the 1pHSR but did contain a 3p+ chromosome in which the additional segment resembled a small HSR. The 3p+ was most likely the result of the translocation between the 1pHSR and the short arm of a chromosome 3. Preliminary results also indicate that the retinoblastoma cells with the 1pHSR produced tumors in athymic nu/nu mice in an average of 28 days, while identical numbers of the retinoblastoma cells with the 3p+ (probable HSR) produced tumors in an average of 75 days.

Cell Line

Plasma levels of 8-methoxypsoralen determined by high-pressure liquid chromatography in psoriatic patients ingesting drug from two manufacturers.

We have adapted a rapid and sensitive high-pressure liquid chromatographic technique (HPLC) to measure plasma levels of 8-methoxypsoralen (8-MOP) in 22 psoriatic patients receiving photochemotherapy with 8-MOP and long-wave ultraviolet light (PUVA). In this procedure, 1 ml plasma samples containing ammidin as an internal standard are extracted with benzene. After evaporation under nitrogen the residue is redissolved in methylenechloride:acetonitrile, 95:5, and chromatographed using a normal phase HPLC system with a 10 mu silica particle column and a UV detector at 254 nm. The sensitivity of the method is 10 ng/ml plasma. Plasma concentrations of 8-MOP were measured between 2 and 4 hr after ingestion of therapeutic doses of 8-MOP provided by 2 manufacturers. Mean 8-MOP plasma levels were 27 +/- 35 ng/ml plasma 2 hr after ingestion of the only drug presently available on the U.S. market, 8-MOP (Elder). These values were significantly below (p less than 0.001) those obtained with 8-MOP (Roche) which were 104 +/- 79 ng/ml plasma. A number of patients on 8-MOP (Elder) did not have detectable levels of 8-MOP 2 hr after ingestion. The time course patterns also differed, possibly indicating a slower and less complete absorption for 8-MOP (Elder). Repeated time course studies in the same patient were reproducible although the absolute concentrations showed some variation. Preliminary evidence indicates that the plasma levels of 8-MOP have therapeutic relevance.

Adolescent