Search PubMed⌕ Search

Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 217 records · Page 12Linked to original sources
PubMed1998

Phase I study of DMP 840 in pediatric patients with refractory solid tumors.

The bis-naphthalimide DMP 840 has demonstrated high level antitumor activity in a number of preclinical models and has been evaluated in several Phase I studies in adults. We enrolled 10 patients with refractory pediatric solid tumors to this Phase I study of DMP 840 given intravenously by short infusion daily for 5 days. The most frequent and dose-limiting toxicity was myelosuppression. The maximum tolerated dose on this schedule was 8.6 mg/m2 daily for 5 days. One patient had a complete response; there were no measurable tumor responses among the remaining 9 patients.

Adolescent↗
PubMed1998

Molecular, serological and population studies on a novel HLA-B allele--HLA-B*5002.

A novel HLA-B allele (B*5002), detected as a discrepancy between serological and PCR-SSP HLA-A and B phenotyping of bone marrow panel donors, was identified by nucleotide sequencing of exons 2 and 3. Titration studies on 39 HLA-B12/B21 cross-reactive antisera showed that the serological specificity of HLA-B*5002 was HLA-B45. PCR-SSP testing of 287 serologically defined HLA-B45-positive subjects from a panel of 12,411 donors, together with HLA-B*45 and B*5002 frequency data on 4,342 PCR-SSP typed subjects, indicated that 4.53% of serologically defined HLA-B45-positive subjects possess HLA-B*5002 and not HLA-B*4501. The phenotype frequency of HLA-B*5002 was 0.08954%; gene frequency was 0.00045 (n=16,753). In 73.3% of instances B*5002 appeared to be present on a haplotype with DRB1*0406 and DQB1*0402, 54.6% of which possessed A*2301. The B*5002, DRB1*0406, DQB1*0402 haplotype represents 52.4% of all haplotypes with DRB1*04 and DQB1*04 and 78.6% of haplotypes possessing DRB1*0406 and DQB1*0402.

Alleles↗
PubMed1998

Role of monocytes and bacteria in Staphylococcus epidermidis endocarditis.

The endocardial vegetation which is formed in the course of bacterial endocarditis (BE) contains tissue factor (TF)-dependent procoagulant activity. Earlier studies showed that monocytes are the main source of TF in the vegetations. The TF activity (TFA) of vegetations isolated from Streptococcus sanguis-infected rabbits depended on the numbers of bacteria as well as monocytes in the vegetation. In this study, we investigated whether for Staphylococcus epidermidis, a frequent pathogen in BE, an effect similar to that found for S. sanguis could be shown. In vitro, S. epidermidis was found to stimulate TFA of fibrin adherent monocytes significantly. This stimulation was maximal at a bacterium-to-monocyte ratio of 7. In vivo, TFA was found to be significantly higher in S. epidermidis-infected than in sterile catheter-induced vegetations. Reduction of vegetational bacterial numbers by teicoplanin treatment lead to a small but significant decrease of TFA. Reduction of monocyte numbers by etoposide did not affect vegetational TFA. Comparison of data for S. epidermidis and S. sanguis revealed that at equivalent bacterial numbers, vegetational TFAs were approximately the same for both microorganisms. Combining the results of the present study with those of a previous study using S. sanguis, we conclude that the main factor determining monocyte-dependent vegetational TFA is the number of vegetation-associated bacteria. The lower TFA found for S. epidermidis-infected than for S. sanguis-infected vegetations can be explained by the significantly lower bacterial numbers in the infected vegetations and consequently a lower stimulation of vegetation-associated monocytes.

Animals↗
PubMed1998

Pathogenesis and prevention of adhesion formation.

Abdominal and pelvic adhesions are a major cause of morbidity. Appendicitis and appendicectomy are the commonest cause of intra-abdominal adhesion formation. Peritoneal injury, from a variety of causes, leads to peritoneal inflammation and with it the production of plasminogen activator inhibitors. These inhibitors result in the loss of normal mesothelial fibrinolytic activity, and if prolonged, this allows the organisation of fibrinous adhesions into permanent fibrous adhesions. Adhesions may be prevented by minimising injury and there is increasing evidence that laparoscopic surgery is an important method of adhesion prevention. A wide variety of products have been used experimentally to prevent adhesion formation but clinical interest at present is focused on the use of bioresorbable membranes which allow localised adhesion prevention. These products have been proven effective by randomised clinical trials and their use as a routine method of preventing intra-abdominal adhesion formation is likely to increase.

Fibrinolysis↗
PubMed1998

HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales.

Accurate estimates of HLA-A, B, DR and DQ phenotype, gene and haplotype frequencies (HF) in the normal population are of importance in, for example, disease susceptibility studies, platelet transfusion support and transplantation. HLA population genetics studies have been performed on numerous groups, however, no major studies have been carried out on the population of Wales. As part of the validation process for our routine HLA-A and B typing by PCR using sequence-specific primers (PCR-SSP) we examined 1,798 normal, unrelated Caucasoid blood donors living in Wales and recruited onto the Welsh Bone Marrow Donor Registry (WBMDR). Typing was performed by serology (HLA-A, B) and PCR-SSP at low resolution (HLA-A, B, DR, DQ) resulting in a particularly rigorous level of HLA specificity assignment. Four discrepancies were found between the HLA-A and B serological and PCR-SSP specificity assignments: (1) two instances of HLA-A2 by serology were undetected by PCR-SSP and were a new HLA-A2 allele - A*0224; (2) one example of HLA-B*15 by PCR-SSP failed to react by serology, and remained undetectable by serology in subsequent samples, and (3) one example of HLA-B45 by serology was identified as HLA-B*5002 by PCR-SSP. Hardy-Weinberg and homozygosity analysis showed that the goodness-of-fit was excellent (p > 0.05), for both phenotype distribution and the number of homozygotes identified, for all four loci. The phenotype and gene frequencies for the 18 HLA-A, 34 -B, 15 -DR and 8 -DQ specificities identified and two- and three-locus HF, linkage disequilibrium and related values for HLA-A/B, B/DR, DR/DQ and HLA-A/B/DR and B/DR/DQ were essentially typical of a northern European population. HLA-A2, B44, DR4 and DQ2 were the highest frequency phenotypes and HLA-A2403, A34, A74, B42, B75, B2708, B48, B67 and B703 occurred once only. There were no examples of: A36, A43, A69, A80, B46, B54, B59, B73, B76, B77, B7801, B8101 or DR18 specificities. DR17, DQ2 and A1, B8, DR17 were the highest frequency two- and three-locus haplotypes identified. Diverse HLA-A, B, DR phenotypes were identified in 87.0% (1,564) of subjects. When HLA-DQ was also considered, different four locus phenotypes were identified in 89.1% (1,602) of subjects. This frequency information will be beneficial as a high-quality reference control for disease susceptibility studies and in calculating the chances of identifying a bone marrow donor in a patient's extended family. This process was successful for the validation of our HLA-A and -B PCR-SSP typing procedure and the findings suggest an accurate level of specificity assignment of WBMDR panel donors who had previously been typed by serology alone.

Adolescent↗
PubMed1998

Use of ECT for the inpatient treatment of recurrent major depression.

OBJECTIVE: The authors' goals were to determine the frequency and distribution of ECT for general hospital inpatients with recurrent major depression and to estimate the effects of prompt ECT on the length and cost of inpatient care. METHOD: Data from the 1993 Healthcare Cost and Utilization Project were analyzed to determine the rate of ECT use for adult inpatients with a principal discharge diagnosis of major depression, recurrent. Associations between prompt initial use of ECT (in the first 5 hospital days) and length and cost of inpatient care were examined before and after control for sociodemographic, diagnostic, and hospital organizational characteristics. RESULTS: An estimated 9.4% of general hospital adult inpatients with a principal diagnosis of recurrent major depression received ECT in the survey year. A majority (59.2%) of these received their initial ECT session within the first 5 days after hospital admission. In univariate analyses, the likelihood of receiving ECT was greater for older patients, whites, privately insured individuals, and patients who lived in more affluent areas. Patients who received ECT tended to have relatively long and costly admissions. After control for several demographic, diagnostic, and hospital organizational characteristics, prompt ECT (as compared with delayed ECT or none) was associated with significantly shorter and less costly inpatient care. CONCLUSIONS: The longer stays and higher treatment costs associated with ECT may be a consequence of patient selection. When patient selection is taken into account, prompt administration of ECT is associated with shorter and less costly hospital stays. Nonetheless, economically disadvantaged patients are relatively unlikely to receive this treatment.

Adolescent↗
PubMed1998

What role for antibiotics in otitis media and sinusitis?

In patients with otitis media or sinusitis, antibiotics must be used judiciously. First-line treatment for both uncomplicated acute otitis media and acute sinusitis is amoxicillin. Erythromycin ethylsuccinate and sulfisoxazole or TMP-SMZ may be used in patients who are allergic to penicillin. Beta-lactamase-stable agents should be given when no response occurs within 48 to 72 hours. In cases in which penicillin-resistant pneumococcus is suspected, high-dose amoxicillin, with or without clavulanate, or clindamycin should be considered. Antibiotics are not indicated for initial treatment of otitis media with effusion but may be considered for effusions lasting longer than 3 months. Prophylactic antibiotics should be considered only for recurrent acute infections occurring three or more times within 6 months or four or more times within a year. The common cold should not be treated with antibiotics, and antimicrobial therapy should be initiated only when there is reasonable clinical certainty about the presence of acute sinusitis.

Acute Disease↗
PubMed1998

Breast-milk sodium as a predictor of breastfeeding patterns.

This study partially replicates and extends a study reporting that elevated breast-milk sodium BM [Na+] during early lactogenesis was predictive of poor breastfeeding outcomes. The present study used 6-day postpartum breast milk. Consistent with the findings of the earlier study, 80% of those with a BM [Na+] of 16 mmol/L or lower at day 6 sustained a high level of breastfeeding at week 4, compared to only 50% of those with an elevated BM [Na+] (chi 2 = 4.05, df = 1, p = .04). This difference was even greater in a subgroup of mothers predicted to be at high risk for insufficient milk supply on the basis of support density and self-perception variables. Of the latter group, 75% with low BM [Na+] sustained a high level of breastfeeding at 4 weeks postpartum, compared to only 22% with an elevated BM [Na+] (chi 2 = .65, df = 1, p = .01). In contrast, among the low-risk mothers BM [Na+] levels were not associated with any difference in breast-milk sustainment (89% and 82% sustainment for low- and high-sodium groups, respectively). Thus a normal drop in BM [Na+] is predictive of higher sustainment of breastfeeding. However, the predictive validity of this marker appears to be enhanced by combining it with the psychosocial variables of support density and self-perception of breastfeeding by the mother.

Adult↗
PubMed1998

Adenovirus enterocolitis in human small bowel transplants.

This report describes two cases of pediatric small bowel transplant patients who developed diffuse adenovirus enterocolitis of their allografts. Based upon the presenting symptoms for this complication, in both patients a differential diagnosis of allograft rejection versus viral infection was clinically entertained. The clinical condition in both instances rapidly deteriorated and both patients died shortly after the development of the symptoms of fulminant septicemia. Autopsies were performed and histologic examination revealed extensive denudation of the gastrointestinal mucosa with edema and a marked acute and chronic inflammatory infiltrate involving the entire wall of the grafts. Numerous viral intranuclear and intracytoplasmic inclusions were evident and an immunohistochemical stain specific for adenovirus was strongly positive in the infected cells. In addition, while in the first case the adenovirus appeared confined to the GI tract, the second patient displayed numerous viral inclusions in the lung as well as within multiple liver abscesses. At this point, the incidence of adenovirus as a cause of gastroenteritis in small bowel transplant patients remains to be determined. We believe that the importance of recognizing this particular type of viral infection in this group of patients lies primarily in differentiating it from other viral organisms (e.g., CMV) that require a specific antiviral therapy. Moreover, an identification of this entity could help avoid a misdiagnosis of rejection which could lead to an unnecessary increase in immunosuppressive therapy and a possible exacerbation of the underlying condition.

Adenovirus Infections, Human↗
PubMed1998

Safety of completion thyroidectomy for multicentric carcinoma.

The role of completion thyroidectomy after lobectomy for well-differentiated thyroid carcinoma remains controversial. The purpose of the present study is to compare the relative safety of a one-stage versus a two-stage approach in the management of thyroid cancer. Thirty consecutive patients with thyroid carcinoma were studied. In 14 patients, frozen-section diagnosis of carcinoma allowed total thyroidectomy at the initial operation. In 16 patients, carcinoma was found only on permanent section; thus, completion thyroidectomy was undertaken as a second stage. Transient hypocalcemia occurred in one patient in each group (one-stage, 7%; two-stage, 6%). There was one unilateral recurrent nerve paresis in the one-stage group and none in the two-stage group. We conclude that a two-stage procedure is a safe and effective approach for the treatment of thyroid cancer and can be employed in those instances in which the diagnosis of malignancy is insecure at the initial operation.

Adenocarcinoma, Follicular↗
PubMed1998

Altered irinotecan and SN-38 disposition after intravenous and oral administration of irinotecan in mice bearing human neuroblastoma xenografts.

The antitumor activity of irinotecan in vitro primarily results from its hydrolysis by carboxylesterase to the active metabolite SN-38. The present study was conducted to evaluate the effect of human neuroblastoma xenografts on irinotecan and SN-38 disposition after i.v. and oral irinotecan administration. Non-tumor-bearing mice and mice bearing three different human neuroblastoma xenograft lines (NB1691, NB1643, and NBEB) were given irinotecan (10 mg/kg) by short i.v. injection into the tail vein or by oral gavage. Serial plasma samples were obtained, processed to isolate irinotecan and SN-38 lactone, and assayed with a sensitive and specific high-performance liquid chromatography assay. Noncompartmental and compartmental pharmacokinetic analyses were performed. A four-compartment model was used for analysis of irinotecan and SN-38 concentration-time data after i.v. administration. The presence of tumor increased irinotecan systemic exposure (1.2-3.8-fold; P < 0.05) after i.v. and oral administration in mice bearing neuroblastoma xenografts compared to non-tumor-bearing mice. Moreover, SN-38 systemic exposures were higher (1.3-3.8-fold; P < 0.05) in mice bearing human neuroblastoma xenografts as compared to non-tumor-bearing mice, with the greatest effect observed after oral administration of irinotecan. A schematic model is presented to provide a mechanistic basis for our observations. These results emphasize the need to perform preclinical pharmacokinetic studies to evaluate the influence of tumor on drug disposition.

Administration, Oral↗
PubMed1998

Urinary catheters for intermittent use.

Intermittent catheterisation is suitable for a range of patients and has a high level of patient satisfaction. Careful education is required to minimise the risk of complications and nurses should be aware of the various types of catheter available.

Female↗
PubMed1998

Extending principles learned in model systems to clinical trials design.

Clinical results with irinotecan (CPT-11 [Camptosar]) and other camptothecin derivatives in various cancers, although encouraging, have fallen short of the expectations predicted by preclinical models. One proposed explanation for this is that preclinical xenograft models do not predict for the sensitivity of human cancer. In this article, we describe the results of several studies suggesting that this explanation is incorrect. Instead, our results indicate that the discrepancy between clinical response rates and findings in preclinical models may be due to a failure to incorporate the principles learned from preclinical studies into the design of clinical trials. Our analysis suggests that if differences in host tolerance are taken into account, the xenograft models are quite accurate predictors of clinical response. Moreover, application of the principles derived from preclinical models to the design of clinical trials may significantly enhance clinical response rates. Thus, the camptothecin analogs provide a paradigm for better integrated, pharmacokinetically driven, preclinical and clinical development of new drugs.

Animals↗