Biomedical subjects
J Bader
Publications and source records attributed to J Bader.
Prostate cancer: are new prognostic markers on the horizon?
Current diagnostic methods in prostate cancer are lacking in their ability to predict individual patient outcome which highlights the need for more sensitive prognostic markers. Biological markers are seen as attractive and relevant candidates in current efforts to improve prognostic methods. Since metastasis is the most important component of cancer progression and mortality, markers which are able to predict the likely acquisition of the metastatic phenotype, before the onset of metastases, would be extremely useful clinically. This review outlines various metastasis suppressor genes and metastasis promoters which might have potential prognostic use in prostate cancer. Prostate Cancer and Prostatic Diseases (2000) 3, 62-65
[Incidence of immunogenic hyperthyroidism after radioiodine therapy of focal thyroid gland autonomy. Results of a multicenter study].
BACKGROUND: There are case reports in the literature that patients occasionally develop immunogenic hyperthyroidism 2 to 14 months following iodine-131-therapy of focal, non-immunogenic, autonomous thyroid nodules with a prevalence between 0.05 and 2.5%. Purpose of this multicenter evaluation was to assess the appearance of this phenomenon in a larger patient population. PATIENTS AND METHODS: So far 2867 patients out of 4 university hospitals are included in our study focusing on the appearance of pathologically elevated levels of thyrotropin-receptor-antibodies (TRAb) combined with hyperthyroidism following iodine-therapy. Records of the patients were screened for pre- and post-therapeutic biochemical tests, scintigraphic uptake patterns and ultrasound findings of the thyroid. RESULTS: Nineteen of 2867 patients with pretherapeutically scintigraphic "hot nodules" developed recurrent hyperthyroidism suggestive for immunogenic genesis 2 to 12 months following iodine-131-therapy (elevated TRAb-levels, homogeneous uptake in Tc-99m-pertechnetate scans). Pretherapeutically, 9 of these patients presented with a strictly focal scintigraphic uptake-pattern, 10 cases with a mixed disseminated-focal pattern. Because of missing pretherapeutic TRAb-tests in 8/9 patients presenting with a strictly focal scintigraphic uptake pattern, postradiogenic immunogenic hyperthyroidism could be reliably assessed in 1 case only. CONCLUSION: One could speculate that iodine-131-therapy may stimulate immunogenic mechanisms finally leading to immunogenic hyperthyroidism. Posttherapeutically observed hyperthyroidism following iodine-treatment might be based on an exacerbation of a preexisting--clinically not relevant/detectable--immunothyropathia. Also pretherapeutic TRAb-negative immunogenic hyperthyroidism could not be definitely excluded. Our multicenter data collected in a large patient population show similar results to the case reports of immunogenic hyperthyroidism following iodine-131-treatment in smaller populations. Therfore, the occurrence of this phenomenon plays a minor role regarding to its prevalence. Therapeutical consequences in treatment of functional thyroid autonomy are not recommended.
Evidence-based dentistry and the dental research community.
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Immunogenicity and safety of a liquid combination of DTP-PRP-T [corrected] vs lyophilized PRP-T reconstituted with DTP.
The immunogenicity and safety of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b-tetanus conjugate vaccine (DTP-PRP-T) was compared to the same combination obtained by the reconstitution of H. influenzae type b-tetanus conjugate vaccine lyophilized (PRP-T) with liquid diphtheria-tetanus-pertussis vaccine (DTP). Two hundred and sixty-two healthy infants were randomized to receive a intramuscular injection of 0.5 ml of one of the above combination vaccines at 2, 4 and 6 months of age, and a subgroup of 134 infants received a booster dose at 12 months. Serum antibody levels to each vaccine component were measured at ages 2, 6, 7, 12 and 13 months. Systemic and local reactions were assessed during the first 3 days after each injection by diary cards distributed to the parents. After the third dose and booster administered at 12 months of age, significant equivalence between the groups was observed, and the geometric mean titer of anti H. influenzae type b capsular polysaccharide (Hib-CP) antibodies were 5.9 and 32.6 micrograms ml-1 for the liquid combination group and 5.8 and 19.4 for the lyophilized group, respectively. After the third dose, anti-Hib-PC antibody levels of > or = 1.0 microgram ml-1 and 0.15 microgram ml-1 were seen in 94% and 100%, respectively, of the liquid combination group and 90 and 99%, respectively of the lyophilized group. After the booster dose, levels of > or = 1.0 microgram ml-1 were observed in 100% and 93.5% of the liquid combination group and the lyophilized combination group, respectively. Systemic and local reactions to the vaccination were generally mild and did not differ significantly between the groups. We conclude that the liquid combination of DTP-PRP-T is safe and at least as immunogenic as the lyophilized preparation. This liquid preparation, like other combined vaccines may be helpful for planning vaccination programs with a reduced number of injections.
LDL stimulates chemotaxis of human monocytes through a cyclooxygenase-dependent pathway.
Monocyte migration into the vessel wall is an early step in atherogenesis. Even though a number of chemotactic factors have been identified, the regulation of the chemotactic response is not clearly understood. As the release of arachidonic acid has been implicated in monocyte chemotaxis, we studied the influence of LDL, which can supply this fatty acid to cells, on the chemotactic mobility of monocytes. Migration of human monocytic U937 cells was abolished by a 30-hour incubation in medium containing lipoprotein-depleted 10% fetal calf serum. Thereafter, human VLDL, LDL, acetyl LDL, methyl LDL, HDL, free cholesterol, linoleic acid, oleic acid, or arachidonic acid was added. At the end of varying incubation periods (0.5 to 8 hours), chemotaxis, viability, and cellular cholesterol content were measured. In the same experimental setting we also studied the effects of the pharmacological agents chloroquine, indomethacin, and acetylsalicylic acid on LDL-mediated chemotaxis. Chemotaxis was restored by LDL in a dose- and time-dependent manner starting at concentrations as low as 5 micrograms/mL and at incubations as brief as 30 minutes. The other lipoproteins tested (VLDL, HDL, acetyl LDL, and methyl LDL) as well as free cholesterol had no comparable effect on chemotaxis. Viability and total cholesterol content did not differ among the groups. Simultaneous incubation of cells with chloroquine, indomethacin, and acetylsalicylic acid reduced restitution of chemotaxis by LDL by 71%, 82%, and 68%, respectively. In contrast, the agents had only slight inhibitory effects on the chemotactic mobility of serum-fed control cells. Incubation with linoleic acid showed a 60% restoration of chemotaxis, whereas arachidonic acid stimulated chemotaxis by 140% compared with the positive control. Preincubation of LDL with the monoclonal antibody MB47 directed against LDL resulted in a significantly reduced migratory response. The data suggest a novel cyclooxygenase-dependent regulatory mechanism of chemotaxis by LDL.
[54-year-old patient with anemia, jaundice, hepatosplenomegaly and paravertebral space-occupying lesions].
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Theory of correlated hops in surface diffusion.
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Risks of the "big three": what dentists and patients believe about dental amalgam, fluoride and HIV.
Dental professionals have seriously considered the risks to the public from dental amalgam, fluoridated water and HIV transmission in the dental office. These issues are important to the public, who typically rely on practicing dentists for information about just how serious the risks are.
How dentists see themselves, their profession, the public.
The public traditionally has held dentistry in high regard as a profession. But some recent evidence suggests a decline in public confidence--a fact that may be affecting the way dentists view themselves. What should and can be done?
Chemotaxis of the monocyte cell line U937: dependence on cholesterol and early mevalonate pathway products.
In the present study we investigated the influence of cholesterol depletion and hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibition on chemotaxis of the human monocytic cell line U937. Chemotaxis was nearly completely depressed after incubation for 24 h in the absence of lipoproteins. This was accompanied by a significant decrease in cellular cholesterol. Addition of 10 micrograms/ml low density lipoprotein (LDL) for 2 h to the cholesterol-depleted cells restored chemotaxis. Free cholesterol had no effect under these conditions. Inhibition of HMG-CoA reductase by pravastatin (0.01-1.0 mM) for 20 or 72 h also reduced chemotaxis. However, this effect was not accompanied by a decrease in cellular cholesterol when cells were grown in the presence of lipoproteins. The effect of pravastatin could be reversed by the addition of mevalonate. Addition of LDL did not change the response to pravastatin. We propose that the availability of cholesterol plays an important role in cellular chemotaxis. Furthermore, it can be suggested that other products of the mevalonate pathway apart from cholesterol may contribute to the regulation of chemotaxis.
Health services research in dental public health.
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The effect of crown receipt on measures of gingival status.
Although the association between crown margins and increased inflammation and probing depth is well-established, studies examining these effects have been largely post hoc. Change in gingival status measures due to receipt of crowns may affect longitudinal evaluations in clinical trials and epidemiological studies. This study examined the effects of receipt of crowns on the periodontal health of the Ramfjord index teeth. Gingival status descriptors included measures of plaque, gingival inflammation, calculus, probing depth, and gingival recession. Changes in periodontal status scores (1987-89) for teeth receiving crowns among 67 patients were compared with change in scores for teeth not receiving crowns. Teeth that were crowned showed small, but significant, differences. These teeth had greater decreases in calculus scores for both surfaces, increases in inflammation compared with decreases for teeth not receiving crowns, and increased facial probing depths. Change in gingival recession was markedly decreased on facial surfaces among teeth receiving crowns. The results suggest that crown status should be recorded routinely in clinical trials involving gingival status, and that teeth receiving crowns during the course of the study should be eliminated from the analyses.
[Dental care of the handicapped in intubation anesthesia. The outpatient dental care of handicapped patients in intubation anesthesia at a rehabilitation center].
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Effect of preoperative chemotherapy on mastectomy for locally advanced breast cancer.
Mastectomy is frequently performed after intensive chemotherapy for locally advanced breast cancer. The effects of preoperative chemotherapy on the postoperative course and the timing of subsequent adjuvant therapy, however, have not been defined. We therefore reviewed the perioperative course of 54 patients undergoing mastectomy after combination (CAMFPT) chemotherapy for stage IIIA,B (IIIA - 25 pts; IIIB noninflammatory - 5 pts; IIIB inflammatory-24 patients) breast cancer. A median of 7 cycles (6 months) of chemotherapy was administered preoperatively. Mastectomy was performed a median of 20 days after last chemotherapy; white blood cell count (WBC) and platelet counts returned to normal limits preoperatively. Total mastectomy with or without axillary node dissection was performed in 53 patients, and a Halsted radical mastectomy in 1 patient. Negative margins on breast and/or axillary tissue were achieved in 47 patients (87.0%). Postoperative complications included skin flap necrosis in 8 patients (14.8%), seroma formation in 5 patients (9.3%), and wound infection in 1 patient (1.9%). Median operative blood loss (550 cc), hospital stay (8 days), and duration of wound catheter drainage (6 days) were comparable to published reports for modified radical mastectomy without preoperative chemotherapy. Systemic chemotherapy was resumed a median of 16 days after mastectomy, and radiotherapy started a median of 33 days after mastectomy. These findings indicate that intensive preoperative chemotherapy does not increase the hospital course or the postoperative complications of mastectomy for locally advanced breast cancer. In view of the current interest in treatment of stage I and II breast cancer with preoperative chemotherapy, this information may be useful in their management as well.
New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS-antiviral activity.
We have developed an effective and optimally safe microculture method for rapid and convenient assay of the in vitro cytopathic effects of human immunodeficiency virus (HIV-1) on human lymphoblastoid or other suitable host cells. The assay procedure is applicable to the evaluation of drug effects on in vitro infections induced directly in cultured host cells by cell-free HIV-1 or by coculture with H9 cells chronically infected with HIV-1. The assay uses a newly developed tetrazolium reagent that is metabolically reduced by viable cells to yield a soluble, colored formazan product measurable by conventional colorimetric techniques. This simple microassay minimizes the number of plate manipulations typically required with other assay methods and, coupled with computerized data collection and analysis, facilitates large-scale screening of agents for potential antiviral activity. To support and enhance the discovery of new anti-HIV-1 agents, the National Cancer Institute is offering investigators worldwide the opportunity to submit new candidate agents for anti-HIV-1 screening with this method.
Locally advanced breast cancer current status and future directions.
Patients described as having locally advanced breast cancer comprise a heterogeneous group of patients with variable clinical presentations. Systematic evaluation of patients with these presentations has been limited, with much of our current understanding based on retrospective reviews. Prospective pilot studies have demonstrated the feasibility of multimodality therapy. However, there have been few well-conducted randomized trials in this setting. Comparison of results among studies is made difficult by the varying eligibility criteria and the way in which the data are reported. The use of common and consistent definitions of operable and inoperable disease is necessary for a more uniform understanding of the therapeutic interventions necessary for a given patient within this broad category of Stage III or locally advanced breast cancer. There are a variety of opportunities for clinical research activities in this group of patients including tests of hormonal recruitment or synchronization, high dose chemotherapy requiring autologous bone marrow transplantation, perioperative or preoperative chemotherapy, and alternating chemotherapy with short course radiotherapy. The integration of clinical information with biological characteristics of the tumor such as cytokinetics, oncogene amplification, and hormone receptors will be an important and necessary focus of future investigation in this disease.
Task force on innovation in dental hygiene curricula.
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