Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 343 records · Page 19Linked to original sources

PubMed1997

Modulatory effects of human donor bone marrow cells on allogeneic cellular immune responses.

BACKGROUND: In order to evaluate whether immunoregulatory mechanisms are brought about by human donor bone marrow cell infusions accompanying organ transplantation, we established in vitro culture systems analogous to the transplant model. METHODS: Cell-mediated lympholysis (CML) and mixed lymphocyte culture (MLC) responses of peripheral blood lymphocytes or spleen cells stimulated with irradiated cadaver donor spleen cells in the presence of specific donor vertebral-body bone marrow cell (DBMC) modulators were tested. RESULTS: When compared with spleen cells as modulator controls, DBMC inhibited both the proliferative and cytotoxic responses in a dose-dependent manner. Use of unirradiated and T cell-depleted DBMC was required for detection of the inhibitory activity. Furthermore, DBMC had to be added within the first 2 days after the initiation of the cultures for the down-regulation of CML (MLC) to occur. The down-regulation of MLC responses could not be shown to be antigen (donor) specific. Physical separation of DBMC from the responder-stimulator cells using the transwell system abrogated modulation of the CML (and MLC) reactions, suggesting the requirement of cell-cell contact for modulatory effect. The inhibitory activity by DBMC could not be overcome by addition of up to 200 U/ml of exogenous recombinant interleukin 2 to the cultures. However, it could be abrogated by restimulation with donor spleen cells, indicating that donor reactive cells were not deleted by DBMC in short-term cultures. CONCLUSIONS: These results showed a regulatory role for DBMC in cellular immune responses against donor cell alloantigens, supporting the rationale for DBMC for facilitating clinical allograft acceptance.

Bone Marrow↗

PubMed1997

Use of intravenous FK506 to treat acute rejection in simultaneous pancreas-kidney transplant recipients on maintenance oral FK506.

Most recipients of simultaneous pancreas-kidney transplants experience acute rejection in the early postoperative course. We report our experience with four recipients of simultaneous pancreas-kidney transplants with acute rejection who were effectively treated with the combination of intravenous and oral FK506 therapy. This spared these patients an extra course of monoclonal or polyclonal antibody.

Administration, Oral↗

PubMed1997

[Maggot therapy for gangrene and osteomyelitis].

5 patients with diabetic-foot were treated by maggot therapy. The most serious case was in a 75-year-old man who had gangrene and osteomyelitis of the right foot. Proteus mirabilis, Enterococcus sp., Providencia stuartii and Staphylococcus spec. (coagulase positive) were isolated from lesions which did not respond to antibiotic therapy. The patient had twice refused amputation but agreed to maggot therapy. Larvae of the sheep blowfly Phoenicia (Lucilia) sericata were used for twice-weekly treatment over a period of 7 months. Sterile larvae were applied to the wound and replaced every 3-4 days. After 4 months of treatment, the necrotic tissue around the toes and on the sole of the foot detached from the healthy tissue. During the last 3 months of treatment the larvae removed the remaining infected tissue. As therapy progressed, new layers of healthy tissue covered the wound. The offensive odor associated with the necrotic tissue and the intense pain in the foot decreased significantly. At the end of therapy, during which there were no complaints of discomfort, he was able to walk. In the 4 other patients who had relatively superficial gangrene, the maggots debrided the wounds within 2-4 weeks. Thereafter treatment was continued with antibiotics. Maggot therapy can be recommended in cases of intractable gangrene and osteomyelitis, when treatment with antibiotics and surgical debridement have failed.

Aged↗

PubMed1997

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate (a) the stabilization of the donor CD3+ and CD34+ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; (b) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; (c) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; (d) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and (e) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls (P = 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively (P = < 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need to be defined.

Adolescent↗

PubMed1997

The tyrosine photophysics of a primase-derived peptide are sensitive to the peptide's zinc-bound state: proof that the bacterial primase hypothetical zinc finger sequence binds zinc.

A 35-amino acid peptide corresponding to the putative "zinc finger" sequence of primase was prepared to study its zinc binding properties. When zinc was added to the peptide, it was found that the fluorescence quantum yield of the single tyrosine increased by 46% and the average lifetime by 34%. The binding stoichiometry was one zinc per peptide. Below pH 6.0 and above pH 8.5, the zinc-peptide binding affinity was less than 1 microM and could be accurately determined. Interpolation from those binding constants suggested that the affinity at pH 7.5 was between 10 and 100 nM. The absorption spectrum of the cobalt(II)-peptide complex was consistent with tetrahedral metal coordination by three sulfur and one imidazole nitrogen ligands. The peptide affinity for cobalt was less than for zinc, indicating metal specificity. Analysis of the fluorescence intensity pH profile, circular dichroism spectra, the effect of extrinsic quenchers indicated that at neutral pH (1) the free peptide up into a structure to place the tyrosine in an environment protected from solvent, (2) the peptide bound zinc via its three cysteines and one of its histidines resulting in little change to the polypeptide secondary structure or to the tyrosine solvent accessibility, and (3) when the peptide bound zinc, it bound directly to or caused the immobilization of the groups that had been intramolecularly collisionally quenching the tyrosine which resulted in the observed increases in tyrosine quantum yield and lifetime.

DNA Primase↗

PubMed1997

High-dose donor bone marrow infusions to enhance allograft survival: the effect of timing.

BACKGROUND: The development of strategies to enhance survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advance in posttransplant patient care. The aim of this clinical trial was to determine the effect of timing and dose of peripheral donor bone marrow cell (DBMC) infusion on graft and patient survival after liver transplantation. METHODS: DBMC, obtained from vertebral bodies, were administered in 101 recipients of liver allografts (OLTX). There were 107 patients for whom DBMC could not be obtained; they received OLTX alone (controls). A total of 5 x 10(8)/kg DBMC were infused at day 0 (group 1; n=9); at days 0 and 11 (group 2; n=26); or at days 5 and 11 (group 3; n=26). In group 4 (n=40), patients received up to five infusions of 2 x 10(8)/kg DBMC at days 5, 14, 21, 28, and 90 after OLTX. RESULTS: When the results from patients receiving two or more DBMC infusions (groups 2, 3, and 4) are considered, both patient and graft survival were significantly improved compared with the control group (P=0.02 and P=0.01, respectively). In groups 3 and 4, 88.5% and 95% of patients were alive with mean follow-up of 536 and 265 days, respectively, compared with 77.6% of patients in the control group (average follow-up of 452 days) (P=0.02). Graft survival was also significantly improved in groups 3 (88.5%) and 4 (92.5%), compared with the controls (72%) (P=0.007). CONCLUSIONS: The results suggest that dose and timing of DBMC infusions may be important variables affecting allograft survival. A randomized prospective trial is now in progress to compare group 3 DBMC infusion protocol with controls receiving OLTX alone.

Adult↗

PubMed1997

Tests of Race Models for Reaction Time in Experiments with Asynchronous Redundant Signals

Predictions of race models are derived for divided attention experiments in which redundant signals are presented at slightly different times. The models place constraints on the change in mean reaction time (RT) as a function of the time interval between signal onsets, and these constraints can be used to test race models within the redundant signals paradigm. Copyright 1997 Academic Press. Copyright 1997 Academic Press

Journal Article↗

PubMed1997

The development of strains, forces and nociceptor activity in retrodiscal tissues of the temporomandibular joint of male and female goats.

Chronic pain in the temporomandibular (TM) joint is predominantly manifested in women. We examined biomechanical and neural factors that could contribute to this differential representation. Relationships between jaw rotation, soft tissue strains and soft tissue forces were examined in the goat TM joint. Strains were minimal until the jaw was rotated beyond the normal range of motion (7.25 deg). There were no significant differences in rotation-strain patterns in males and females. Stress developed as strains were introduced by jaw rotation. Gender differences were observed. Males manifested higher failure loads (15.94 +/- 1.98 and 11.37 +/- 2.02 N, for males and females respectively) and higher elastic stiffness than females (5.62 +/- 1.19 N/mm and 1.64 +/- 0.31 N/mm, for males and females respectively). Recordings were made from cell bodies in the trigeminal ganglion whose distal processes innervated the retrodiscal tissue of the temporomandibular joint of the goat (n = 48). Nociceptor reactivity was characterized with respect to the capacity to transduce mandibular rotation (rotation-interval functions; n = 29). On the basis of established relationships between rotation, strain and tissue forces, rotation-interval functions were transformed into strain-interval and force-interval functions. Comparisons were made between nociceptor properties grouped by gender. No differences in properties were observed when nociceptors were characterized with respect to jaw rotation; however, gender differences were obtained when nociceptor reactivity was characterized with respect to retrodiscal strains or forces. Consistent with smaller failure loads, nociceptors of retrodiscal tissues of females manifested a smaller range (1.12 vs 4.33 N), force to average (1.51 vs 4.64 N), force to minimum (0.95 vs 2.48 N) and force to asymptotic discharge (2.07 vs 6.81 N). Consistent with lower elastic stiffness, nociceptors of female tissues manifested higher average strain (54.4% vs 41.9%) and peak strain (74.0% vs 58.1%) to asymptotic discharge relative to those sampled from male tissues. The implications of these findings for TM joint injury and chronic pain are considered.

Animals↗

PubMed1997

[Urologic tumors in Germany. Initial data of 56,013 cases from clinical cancer registers].

Since 1985 a special work group involved in the coordination of hospital cancer registries in Germany (AKKK) has been collecting, storing and analysing data on tumour patients, received from cancer centres, oncological departments and specialised practices. The documentation of tumour patients is based, among other things, on information concerning localisation, histological findings and tumour spread. The data are stored in a central database administered by the work group. At present it contains data on approximately 500,000 oncological patients. In the period from 1987 to 1992, 56,013 initial entries were made concerning patients with urological tumours. Of these cases, tumours of the kidney (n = 11,424) constituted 20.4%. In 94.6% of the cases, histological investigation revealed a renal cell carcinoma-pT1: 5.8%; pT2: 53.6%, pT3: 37.2% and pT4: 3.4%. Tumours of the urinary bladder (n = 16,246) constituted 29.0% of all urological tumours. In 93.8% of the cases a transitional cell carcinoma was detected-pTis: 1.0%; pTa: 36.9%; pT1: 29.6%; pT2: 16.9%; pT3: 11.4%; pT4: 4.4%. Transitional cell carcinomas of the ureter or of the collecting system (n = 1,846) constituted 3.3% of the cases. The proportion of testicular tumours (n = 6,594) amounted to 11.8%; 53.6% of these germ-cell tumours (n = 6,281) were seminomas and 46.6% were non-seminomas. In all, 66.3% of the cases were lymph-node negative. Tumours of the prostate (n = 19,903) constituted 35.5% of the cases. In the period from 1987 to 1992, the proportion of lymph-node-positive prostate carcinomas decreased from 39.8% to 16.2%. The detailed analysis of these data shows how the hospital cancer registries can support the discussion regarding diagnosis and therapy of urological tumours.

Adult↗

PubMed1997

[Transurethral laser ablation of the prostate in high risk patients with obstructive benign prostatic hyperplasia. Perioperative morbidity and 6 month outcome in 72 patients].

Between November 1993 and September 1995, we carried out visual laser ablation of the prostate (VLAP) in 72 high-risk patients (ASA 3-4; severe cardiovascular and/or pulmonary diseases) aged 60-88 years (mean 76.7 years); the prostate volume was 22-136 ml (mean 56 ml). The urinary peak flow rates (Qmax.) ranged from 2 to 15 ml/s (mean 4.4 ml/s) preoperatively; 42 patients (58.3%) suffered from acute urinary retention for up to 2 weeks and had an indwelling catheter. The residual urinary volume (RUV) was 0-320 ml (mean 142.3 ml) in those 30 patients with spontaneous micturition. The International Prostate Symptom Score (IPSS) ranged from 10 to 33 (mean 21.8). In the first 37 patients, pressure-flow studies were carried out only in cases of doubt to verify obstruction. In the last 35 patients, pressure-flow studies were carried out in every case. Perioperatively, there was no appearance of blood loss of absorption of irrigation fluid. None of our patients needed transfusions or intensive care perioperatively. Further complications were not severe and could be handled without problems. In two patients with large benign prostate hypertrophy (BPH) a second operation (VLAP, no conventional transurethral prostatectomy) was necessary. After 6 weeks, 29.4% of the patients suffered from symptomatic urinary tract infections (UTI). After 6 months, only 7.1% of the patients had symptomatic UTI. After 6 weeks (n = 61), Qmax. was 6-34 ml/s (mean 15.3 ml/s), RUV was 0-230 ml (mean 51.5 ml), and the IPSS was 12.3 (8-28). After 3 months (n = 54), Qmax. was 9-45 ml/s (mean 19.8 ml/s), RUV was 0-96 ml (mean 31.6 ml), and the IPSS was 1-23 (mean 7.4). After 6 months (n = 52) Qmax. was 12-33 ml/s (mean 20.4 ml), RUV was 0-53 ml (mean 26.4 ml), and the IPSS was 1-12 (mean 4.1). VLAP provided no further risks for our high-risk patients, while Qmax., RUV, and IPSS were improved noticeably (improvement of more than 75%). It represents a step forward in the treatment of obstructive BPH in high-risk patients. Particularly in high-risk patients with cardiac diseases, this procedure lessens the perioperative risk. Despite the minimal appearance of UTI after 6 months, UTI seemed to be the most important complication during the first few weeks after VLAP by virtue of the bothersome symptoms.

Aged↗

PubMed1997

A comparison of the postures assumed when using laptop computers and desktop computers.

This study evaluated the postural implications of using a laptop computer. Laptop computer screens and keyboards are joined, and are therefore unable to be adjusted separately in terms of screen height and distance, and keyboard height and distance. The posture required for their use is likely to be constrained, as little adjustment can be made for the anthropometric differences of users. In addition to the postural constraints, the study looked at discomfort levels and performance when using laptops as compared with desktops. Statistical analysis showed significantly greater neck flexion and head tilt with laptop use. The other body angles measured (trunk, shoulder, elbow, wrist, and scapula and neck protraction/retraction) showed no statistical differences. The average discomfort experienced after using the laptop for 20 min, although appearing greater than the discomfort experienced after using the desktop, was not significantly greater. When using the laptop, subjects tended to perform better than when using the desktop, though not significantly so. Possible reasons for the results are discussed and implications of the findings outlined.

Adult↗

PubMed1997

Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years.

OBJECTIVE: Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood. METHODS: Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed. RESULTS: Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1. CONCLUSIONS: Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.

Adolescent↗

PubMed1997