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Biomedical subjects

J Herman

Publications and source records attributed to J Herman.

At least 19 recordsLinked to original sources

Specifics on the refinement and application of two serological assays for the detection of antibodies to HHV-8.

BACKGROUND: Serologic assays for the detection of antibodies to human herpesvirus type 8 (HHV-8) are important for epidemiological studies and to further investigate the proposed pathogenesis of the virus in cancer. Although a variety of assays are available, a lack of optimization and standardization makes their usefulness uncertain, and may be responsible for the controversy concerning the prevalence of infection. OBJECTIVES: To refine an indirect immunofluorescent assay (IFA) for the detection of latent antibodies and a recombinant ORF 65 ELISA for the detection of lytic antibodies in order to increase their ability to differentiate individuals at higher and lower risk for HHV-8 infection. STUDY DESIGN: Sera from Kaposi's sarcoma (KS) patients and blood donors (BDs) were used to modify assay parameters in an attempt to better discriminate between the two populations. Modifications included methods of substrate fixation, incubation times, sample dilution, and antigen/conjugate concentrations. RESULTS: Optimal modifications to the latent IFA included acetone fixation of substrate, and dilution of sera to 1:64 which enhanced detection of HHV-8 antibodies from 68 to 92% in the KS population. Similarly, successful refinement of the ORF 65 ELISA to increase the signal-to-noise ratio included the use of 88 ng of ORF 65 antigen per well and serum dilutions of 1:50. Optical density-to-cut-off ratios directly correlated with titers, thereby introducing a strategy to predict antibody concentrations. The ORF 65 ELISA and the latent IFA were both able to discriminate between the two populations but with different efficiencies. CONCLUSIONS: Although neither the latent IFA nor the ORF 65 ELISA produced perfect test indices, improvement in their performances was noted following the optimization strategies. The ELISA produced better detection of antibodies to the virus than the IFA and permitted prediction of sample titers, thus improving cost and time effectiveness.

Antibodies, Viral↗

Evaluation of anti-human leukocyte antigen allo-immunization in pediatric cadaveric kidney transplantation.

Forty-eight pediatric cadaveric renal transplantations, performed between May 1986 and February 1997, were retrospectively screened, pre- and post-transplant, for antibodies to human leukocyte antigen (anti-HLA) using complement-dependent cytotoxicity (CDC) assay and enzyme immunoassay (EIA). The correlation between anti-HLA immunization and graft outcome was investigated. The combined analysis of CDC and EIA enabled the differentiation between complement-fixing and non-complement-fixing, anti-HLA class I and anti-HLA class II antibodies. The median post-transplant follow-up for all patients with a functioning graft was 86 months (range 10-138 months). In the whole population, 16 grafts were lost: six following a non-immunologic complication; and 10 as a result of rejection. Of these 10 grafts lost, eight were in patients with pre- and/or post-transplant donor antigen specific (DAS) anti-HLA class I or class I + II antibodies; and two were in patients with DAS anti-HLA class II antibodies only. Three of these grafts were lost in patients with weak pre-existing DAS anti-HLA class I antibodies. Immunological graft loss appeared at a median post-transplant time of 38 months (range 2-68 months). All patients without DAS anti-HLA antibodies had a good graft outcome. The presence of pre- and post-transplant DAS anti-HLA antibodies, especially if directed against HLA class I, were associated with a poor graft outcome. A systematic search for, and identification of, anti-HLA antibodies should therefore be part of a pretransplant evaluation to allow the identification of 'unacceptable' donor HLA antigens, following which the impact of the HLA-cross-match on graft outcome will improve. Screening for DAS anti-HLA antibodies post-transplant could be helpful for detecting patients with an increased risk for graft loss following rejection episodes.

Cadaver↗

Reading for empathy.

As our preoccupation with empathy grows, we cast about for means of inculcating it. Literature has been proposed as an enabling factor for physicians in developing a creative imagination. This essay, using a number of examples, points out that reading for pleasure in areas not necessarily related to medicine, can yield insights into its practice. Thus, sensitizing students and young physicians to the nuances of human interaction described by great writers could constitute part of basic and continuing medical education and might be one way of instilling empathy.

Education, Medical↗

A course for teaching patient-centered medicine to family medicine residents.

In 1988 the Department of Family Medicine at Ben Gurion University of the Negev in Israel developed a course that helps residents to acquire the attitudes and skills required for practicing patient-centered medicine. In the patient-centered approach, the physician relates to patients according to their needs rather than the doctor's own agenda, moving from professional control to patient empowerment. Though there are many elements to this method, certain basic orientations and skills are essential and must be taught, modeled, and reinforced in trainees. To accomplish these aims, a three-year course was developed, which is largely based on directed reading, open discussion, case presentations, role-plays, and Balint groups. It is composed of four levels, each of which must be mastered before residents can move to the next. The levels are (1) doctor-patient communication; (2) family-systems theory-concepts; (3) family-systems theory-practical applications; and (4) multidimensional approaches to simulated patients. In this article, the authors describe the course's concepts and content, and some indicators as to its influence on graduates.

Curriculum↗

[Quo vadis laparoscopic appendectomy?].

The authors evaluated a group of 282 patients subjected between January 1993 and December 1998 to appendectomy, either by the open or laparoscopic route. They compared the period of work incapacity in the two groups to confirm or rule out the fact that after laparoscopic appendectomy the return to work is faster. The results are more favourable in the group of patients operated by the mini-invasive procedure, but even then the period of work incapacity is twice as long, as compared with other countries.

Adult↗

Erythropoietin treatment in children with renal failure.

Erythropoietin (EPO) treatment dramatically changes the life of a child with end-stage renal disease. The administration of recombinant human (rHu)EPO is beneficial and safe in the predialysis period, during hemodialysis or peritoneal dialysis, and after renal transplantation. The goal of hemoglobin correction should be the level at which normal quality of life is possible without adverse events: in children this is usually 10-11 g/dl. rHuEPO is administered once to twice a week subcutaneously to children before dialysis, during peritoneal dialysis, and after transplantation. There is no real benefit of intraperitoneal administration. In children on hemodialysis two to three times a week IV administration is preferred. Among the many reasons for non-response to rHuEPO, iron deficiency (absolute or functional), infections, and hyperparathyroidism are the most common in the pediatric renal patient. Hypertension is the most-frequent side effect of rHuEPO treatment and needs careful monitoring. Iron should be supplemented orally or IV. No significant beneficial effect of rHuEPO on growth has been demonstrated. However, the association with recombinant human growth hormone therapy is not detrimental in children.

Anemia↗

Differences in the recognition by CTL of peptides presented by the HLA-B*4402 and the HLA-B*4403 molecules which differ by a single amino acid.

The HLA-B*4402 and B*4403 molecules differ only at residue 156, which borders the peptide binding site. Strong in vivo allogeneic reactions mediated by cytolytic T lymphocytes (CTLs) were reported in patients who received a bone marrow graft mismatched for these B44 subtypes, indicating that HLA-B*4402 and B*4403 molecules present distinct antigens. This could be due either to the presentation of different sets of antigenic peptides or to the recognition by CTLs of conformational epitopes formed by the MHC molecules alone or in association with antigenic peptides. To address this question, we compared the two B44 subtypes in their presentation to tumor-specific CTLs of three peptides, encoded by genes MAGE-3, MUM-1 and Tyrosinase. The peptides bound with similar affinities to B*4402 or B*4403 molecules, as assessed by lytic competition assays. One HLA-B*4402-restricted and one HLA-B*4403-restricted CTL clone were derived against each peptide. When tested for lysis of B*4402 and B*4403 cells incubated with the antigenic peptides, most CTLs showed a marked preference for one of the two B44 subtypes. Using variant peptides incorporating single alanine substitutions, we compared a given CTLs' recognition of its antigenic peptide presented by both B44 subtypes. Some substitutions, which had no effect on the binding of the peptide, affected its recognition by the same CTL differently on B*4402 and B*4403 molecules. These results imply that the conformations adopted by the same peptide on the two HLA-B44 subtypes are different. We conclude that the B44 subtype specificity of T cells results mostly from distinct conformations adopted by the same peptides in the two B44 molecules. This does not exclude the possibility that in some cases the B44 subtype specificity results from the selective binding of a peptide to one subtype. We found several peptides, different from the three mentioned above, that contain the canonical HLA-B44 binding motif and bind to B*4403 but not to B*4402 molecules.

Amino Acid Substitution↗

Sandimmune to Neoral conversion and value of abbreviated AUC monitoring in stable pediatric kidney transplant recipients.

Neoral is a new microemulsion formulation of cyclosporin A (CsA) that has been reported to have better absorption characteristics than sandimmune. We converted 25 long-term pediatric renal transplant recipients with a mean age of 14.1 yr and a mean follow-up period of 6.4 yr from sandimmune (SIM) to neoral (NEO) on a 1:1 basis. The mean dosage of SIM or NEO required to maintain 'therapeutic range' steady-state trough levels between 100 and 200 ng/mL was similar. We compared 6-h CsA pharmacokinetic profiles taken approximately 6 months after the conversion to NEO with the previous SIM profiles of the same patients. Generally, in the NEO profiles the time to reach the maximum concentration was shorter and the maximum concentration was higher, showing a rapid decline towards the trough-level when compared to the previous SIM profiles. During intake of NEO the AUC0-12 h in the 12-h profiles correlates strongly with the AUC0-6 h in the 6-h profiles (r = 0.98), a similar finding to that which we reported previously for SIM. The median AUC0-6 h for NEO demonstrates a 70% increase compared to the median AUC0-6 h for SIM. Despite the increased drug exposure NEO was well tolerated and did not cause any apparent toxicity within the first 6 months after conversion. The CsA blood level 2 h after intake of NEO showed a higher correlation with the AUC0-12 h (r = 0.91) than the trough level (r = 0.64). The abbreviated profile based on three early sampling points and calculated by AUCPRED = 335.9 + 1.1*(C1) + 1.1*(C2) + 5.4*(C4) correlated well with the full AUC (r2 = 0.98, p < 0.0001). Mean prediction error (+/- SD) was 0.16% (+/- 4.32), and in no patients did the calculated values fall outside the 10% prediction error limit. We therefore conclude that NEO exhibits a higher bioavailability in children compared to SIM without causing apparent toxicity. Monitoring of the C2 might be a better alternative for trough level monitoring in daily clinical practice. A strategy of three early sampling points (C1, C2 and C4) allows a reliable AUC0-12 h prediction and can reduce the length of observation, making it a useful and cost-effective tool in clinical practice.

Administration, Oral↗

Practice standards: the need for a personal element.

With rare exceptions, guidelines for clinical practice lack a personal element that allows for physicians' varying goals and patients' differing preferences. The importance of this element is illustrated by means of four examples: 1, hormone replacement therapy for the menopause; 2, early detection of breast cancer; 3, the treatment of acute streptococcal pharyngitis and 4, the diagnosis of symptoms that do not implicate any specific organ system. The advantages and disadvantages of guidelines are pointed out. Among the advantages are their usefulness as standards for audit and the fact that, in the process of reaching consensus, personal experience is taken into consideration. Chief among the disadvantages is their possible misuse by people outside of the profession. It is concluded that guidelines can be improved if their recommendations consider individual goals and preferences. They can become more influential if attention is paid to their proper dissemination.

Breast Neoplasms↗

Collaborative practice agreements for advanced practice nurses: what you should know.

Advanced practice nurses (APNs) seeking employment are often presented with employment practice agreements. A collaborative practice agreement is a written statement that defines the joint practice of a physician and an APN in a collaborative and complementary working relationship. It provides a mechanism for the legal protection of the APN and sets out the rights and responsibilities of each party involved. All APNs, regardless of practice setting, should be knowledgeable about aspects of a collaborative practice agreement before they sign one. The purposes of this article are to delineate basic guidelines for evaluating and developing a collaborative practice agreement and to identify areas of special concern for APNs.

Cooperative Behavior↗

[Endoscopic mobilization of the proximal portion of the great saphenous vein].

The authors describe a mini-invasive procedure in surgery of varicosities of the lower extremities. The objective is to reduce surgical trauma and improve the resulting cosmetic effect after extirpation of the great saphenous vein. The method was used in 9 patients of 35 operated between September and December 1998. The initial experience with endoscopic dissection of the proximal portion of the saphenous vein is favourable. The tissue traumatization is smaller, haematoma of the thigh is less common.

Adult↗

Miniinvasive approaches in varicose vein surgery.

Authors present their own experience with the treatment of chronic venous insufficiency. Between August 1995 and November 1998 they operated on 318 patients for the disease of venous system. In 28 patients (i.e. 9%) they performed 30 miniinvasive interventions--8x retroperitoneoscopic lumbar sympathectomy and 22x endoscopic subfascial dissection of vein perforators. The rest of patients (91%) were treated by means of classical operations on superficial venous system.

Adult↗