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Biomedical subjects

J Harnett

Publications and source records attributed to J Harnett.

11 recordsLinked to original sources
PubMed2000

TNF-alpha increases tracheal epithelial asbestos and fiberglass binding via a NF-kappaB-dependent mechanism.

Tumor necrosis factor (TNF)-alpha is released from alveolar macrophages after phagocytosis of mineral fibers. To determine whether TNF-alpha affects the binding of fibers to epithelial cells, we exposed rat tracheal explants to TNF-alpha or to culture medium alone, followed by a suspension of amosite asbestos or fiberglass (MMVF10). Loosely adherent fibers were removed from the surface with a standardized washing technique, and the number of bound fibers was determined by scanning electron microscopy. Increasing doses of TNF-alpha produced increases in fiber binding. This effect was abolished by an anti-TNF-alpha antibody, the proteasome inhibitor MG-132, and the nuclear factor (NF)-kappaB inhibitor pyrrolidine dithiocarbamate. Gel shift and Western blot analyses confirmed that TNF-alpha activated NF-kappaB and depleted IkappaB in this system and that these effects were prevented by MG-132 and pyrrolidine dithiocarbamate. These observations indicate that TNF-alpha increases epithelial fiber binding by a NF-kappaB-dependent mechanism. They also suggest that mineral particles may cause pathological lesions via an autocrine-like process in which the response evoked by particles, for example, macrophage TNF-alpha production, acts to enhance subsequent interactions of particles with tissue.

Animals↗
PubMed2000

A randomized, controlled trial of child psychiatric assessments conducted using videoconferencing.

We used a PC-based videoconferencing system to conduct child psychiatry assessments. The telecommunications link was six digital lines, giving a total bandwidth of 336 kbit/s. Twenty-three patients (aged 4-16 years), accompanied by their parents, completed two psychiatric assessments, one via videoconferencing and another face to face (FTF). The order of assessments was randomized. Questionnaires were used to record the diagnosis, treatment recommendations and the psychiatrists', patients' and their parents' satisfaction with each assessment. An independent evaluator concluded that in 22 cases (96%) the diagnosis and treatment recommendations made via the videoconferencing system were the same as those made FTF. The psychiatrists stated that videoconferencing assessments were an adequate alternative to FTF assessments and did not interfere with diagnosis. However, the responses from the psychiatrist satisfaction questionnaire showed that they preferred FTF assessments. No significant difference was found in the patients' or parents' satisfaction responses after the two types of assessment. The majority of children (82%) 'liked' using the telepsychiatry system and six (26%) preferred it to a FTF assessment. Most parents (91%) indicated that they would prefer to use the videoconferencing system than to travel a long distance to see a psychiatrist in person.

Adolescent↗
PubMed1998

Homocamptothecins: synthesis and antitumor activity of novel E-ring-modified camptothecin analogues.

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Comparison of Lp(a) concentrations and some potential effects in hemodialysis, CAPD, transplantation, and control groups, and review of the literature.

Apolipoprotein (a)-Lp(a)-is reported to be an independent risk factor for coronary artery disease and for hemodialysis (HD) access occlusion. Homology with plasminogen may predispose to thrombosis. High concentrations usually have been reported in patients on HD and on continuous ambulatory peritoneal dialysis (CAPD), but near-normal values in many kidney transplants (TP). We used Pharmacia immunoradiometric assay in 52 patients on HD, 58 on CAPD, 94 after TP, and 56 controls. The Lp(a) mean levels for CAPD, HD, TP, and control groups were 738, 647, 348, and 368 U/l and the medians were 542, 537, 96 and 143 U/l, respectively. The means and medians for CAPD and HD were significantly greater than those for TP and controls (p < 0.003 for means and < 0.005 for medians). We found no significant difference between: (1) Lp(a) means or medians comparing HD and CAPD or TP and controls; (2) Lp(a) means for the 33 patients with insulin-dependent diabetes mellitus and the 171 without; (3) number of occlusions of HD fistulae or grafts in patients with high Lp(a) values and without; (4) mean Lp(a) for CAPD patients on gemfibrozil and also for TP patients on 3-hydroxy-methylglutaryl coenzyme 1 reductase inhibitors, or diet alone, before and after treatment, and (5) mean Lp(a) values for HD and CAPD patients with and without myocardial infarction. Lp(a) did not correlate significantly with fractional shortening or left ventricular end systolic or diastolic diameter by echocardiogram or with ejection fraction. For TP patients, Lp(a) and serum creatinine correlated (p = 0.004), and mean Lp(a) for 71 TP on ciclosporin A exceeded that for the other 23 patients (p < 0.03). Lp(a) fell in 13 of 14 patients after TP (mean fall 77%). The dominant Apo(a) isoform in 10 of 13 patients on CAPD or HD with high Lp(a) values was the equivalent of S2 (Utermann). Lp(a) in HD or CAPD is often elevated and regulated by both genetic and renal failure factors, but falls after TP with return of renal function and mainly genetic regulation. Lp(a) was not a risk factor for coronary artery disease in HD or CAPD patients and did not fall significantly with two drugs or diet.

Adolescent↗
PubMed1988

Sonographic and urographic correlation in Bardet-Biedl syndrome (formerly Laurence-Moon-Biedl syndrome).

To determine the spectrum of urologic disease and the value of ultrasound as a screening mechanism, renal imaging was performed on 23 patients with Bardet-Biedl syndrome. On intravenous urography (IVU), abnormal calices were present in 22 patients, with communicating cortical cysts/diverticula in 17. Ultrasound detected caliceal or cystic changes in 70%. On IVU, 21 patients had fetal-type lobular outlines that were detected on sonography in 95%. Renal structural abnormalities are characteristic of the Bardet-Biedl syndrome, and are still best imaged by urography.

Adolescent↗
PubMed1977

A hyperimmunoglobulin E syndrome with normal chemotaxis in vitro and defective leukotaxis in vivo.

A 26-yr-old male with a lifelong history of atopic dermatitis and recurrent severe staphylococcal abscesses was found to have hyperimmunoglobulinemia E. Evaluation of both the humoral and cellular aspects of chemotaxis in vitro showed both neutrophils and monocytes to be normal. However, quantitative neutrophil migration in vivo was significantly suppressed using the patient's own serum as the attractant. This defective migration in vivo was partially corrected by serum from normal donors as the attractant and also partially corrected following plasma infusion in this patient. Evaluation of quantitative leukocyte migration in vivo may be most useful in patients suspected of defects of leukocyte mobility.

Abscess↗
PubMedDate not supplied

Factors related to success and failure rates at 3-year follow-up in a multicenter study of overdentures supported by Brånemark implants.

An international prospective study of Brånemark implants retaining overdentures was conducted at nine clinical centers. One hundred thirty-three subjects were recruited in a 12-month period and provided with 510 implants, 117 of which were in maxillae and 393 were in mandibles. This study reports the 3-year follow-up status of 120 overdentures and 444 implants. There were 11 overdenture failures (9.2%). Maxillary overdenture failure rates (27.6%) were nearly nine times greater than mandibular overdenture failure rates (3.3%). Maxillary overdenture treatment was less successful than previously reported fixed implant-supported restorations. However, their mandibular counterparts had success rates slightly higher than those reported for fixed implant-supported restorations. At 3 years, 150 implants remained submerged and 66 implants had been withdrawn because the subjects discontinued study participation. Eleven mandibular and 29 maxillary implants had failed and had been removed from 21 subjects. Logistic regression with forward model selection indicated that one two-way interaction was significantly related to implant failure. At highest risk were the subjects who possessed dental arches with bone quantity E and bone quality 4. Subjects with one implant failure were likely to have more than one failure. The Generalized Estimating Equation was used to adjust for the cluster effect in this population because multiple implants (2 to 6) were placed and evaluated in each of the 133 subjects.

Adult↗
PubMedDate not supplied

A 5-year prospective multicenter follow-up report on overdentures supported by osseointegrated implants.

This report presents the results of a 5-year prospective multicenter study including nine centers worldwide. A total of 30 patients received 117 Brånemark implants in the maxillae, and 103 patients received 393 implants in the mandibles. According to the protocol, all integrated maxillary implants were to be loaded; however, only two of four mandibular implants were planned for support of the overdentures, leaving the remaining implants covered by mucosa as backup for possible implant failures. Thirty-five patients (26.3%) who were provided with 127 implants (24.9%) were withdrawn from the study. Six patients treated in the maxilla lost all their implants and resumed wearing complete dentures. The cumulative success rates for implants and for overdentures supported by two implants in the edentulous mandible were 94.5% and 100%, respectively. The corresponding cumulative success rates for implants and for overdentures supported by an optimal number of implants in the maxilla were 72.4% and 77.9%, respectively. Significantly better jawbone characteristics at the time of implant surgery were considered to contribute to the better cumulative success rates in the mandibles. Mean marginal bone loss was 0.8 mm (SD 0.8) and 0.5 mm (SD 0.8) for loaded implants during a 5-year period of time in the maxillae and mandibles, respectively. Measurements of the clinical height of the abutment cylinders indicated a mean recession (0.2 mm) of peri-implant mucosa during the follow-up period in the mandibles. Conversely, hyperplasia was observed in the maxillae.

Adult↗
PubMedDate not supplied

Prosthodontic treatment, patient response, and the need for maintenance of complete implant-supported overdentures: an appraisal of 5 years of prospective study.

The prosthodontic methods and outcomes of treating 127 patients in nine centres over a period of 5 years is described. The benefits perceived by patients and the changes induced in the denture-bearing tissues and temporomandibular joints are reported. To sustain effective treatment outcomes, the levels of maintenance needed by the overdentures are contrasted for restoration of the edentulous mandibles and maxillae.

Alveolar Bone Loss↗