PubMed Health⌕ Search

Biomedical subjects

S Meehan

Publications and source records attributed to S Meehan.

At least 19 recordsLinked to original sources
PubMed2000

The use of SPECT bone scans to evaluate patients with idiopathic jaw pain.

OBJECTIVE: The purpose of this study was to investigate the potential usefulness of single photon emission computed tomography (SPECT) bone scanning with technetium-99m methylene diphosphonate (Tc-99m MDP) in the diagnosis of idiopathic jaw pain. Unlike planar bone scanning, SPECT uses tomographic technology to provide 3-dimensional images, which are more useful in localizing small lesions. STUDY DESIGN: Twenty patients, each with a diagnosis of chronic idiopathic jaw pain, were compared after SPECT bone scanning with 20 age-matched and gender-matched normal controls. Uptake was identified and compared in sites with previously detected jaw pathoses and jaw pain. RESULTS: Nineteen of 20 patients with jaw pain evaluated with SPECT had positive scans, in contrast with 12 of 20 control subjects (P <.04). Positive scans were correlated with painful sites in 15 of 20 patients, with the remaining 5 patients demonstrating no uptake in painful locations. Patients with jaw pain demonstrated 37 of 80 mouth quadrants with positive scans, in contrast with 21 of 80 mouth quadrants in the controls (P <.01). Nineteen of 24 painful mouth quadrants had uptake in the pain group. Of the 21 quadrants positive in the controls, 17 were correlated with previously detected jaw pathoses. The sensitivity and specificity for detecting painful sites were 0.79 and 0.68, respectively. The sensitivity and specificity for detecting previously identified pathoses in the jaws of normal controls were 0. 80 and 0.93, respectively. CONCLUSION: Patients with idiopathic jaw pain had a significantly greater frequency of positive SPECT bone scans when compared with normal controls. However, the sensitivity and specificity of SPECT bone scans in detecting painful sites were low. These findings suggest that SPECT bone scanning with Tc-99m MDP is not indicated as a routine imaging procedure for the detection of jaw pathoses, but may be considered as a potential research tool in the future study of chronic idiopathic jaw pain.

Adult↗
PubMed1999

Tolerance in a concordant nonhuman primate model.

BACKGROUND: We have previously demonstrated that induction of mixed lymphohematopoietic chimerism resulted in donor specific renal allograft tolerance without the need for chronic immunosuppression in nonhuman primates. Here we have tested whether tolerance can be similarly induced for baboon to cynomolgus renal xenografts. METHODS: After preconditioning with anti-thymocyte globulin (ATG), nonlethal total body irradiation, and thymic irradiation, cynomolgus monkeys underwent splenectomy, native nephrectomies, and baboon marrow and renal transplants. Postoperative cyclosporine was given for 28 days. RESULTS: In Group 1 (n=2, survival= 13, 14 days), both animals developed anti-donor immunoglobulin G, had biopsy findings consistent with humoral rejection, and showed rapidly progressive xenograft failure. In Group 2 (n=5, survival=1, 16, 33, 112, 190 days), 15-deoxyspergualine was added to the regimen (Day 0-13). In one long-term survivor, donor specific hyporesponsiveness was first observed (mixed lymphocyte culture [(MLR]) on Day 48. MLR reactivity returned on Day 64 together with the development of anti-donor antibody and subsequent xenograft failure on Day 112. Donor specific T-cell hyporesponsiveness was detected in the other long-term survivor for the first 133 days, after which a donor-specific skin xenograft was placed, (survival 24 days). Following the skin graft rejection, a rise in the MLR, development of anti-donor antibody and progressive rejection of the renal xenograft were observed. CONCLUSIONS: Antibody-mediated rejection seems to constitute the major difference between concordant xenografts and allografts. Addition of 15-deoxyspergualine for 2 weeks posttransplant extended concordant primate xenograft survival to 6 months without chronic immunosuppression. In contrast to the allogeneic model, renal transplant acceptance in this xenogeneic system was interrupted by placement of a donor-specific skin graft.

Animals↗
PubMed1998

Immunohistochemical study of actin binding protein (p55) in the human kidney.

BACKGROUND: In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with DC morphology for identification of DCs. METHODS: The distribution of the p55 antigen (fascin), which is selectively expressed by human blood and lymphoid DCs, was investigated by immunohistochemistry. RESULTS: Our study demonstrates that p55-positive DCs are absent from the normal human kidney and CD1a- and S100-positive cells are absent or very rare. Furthermore, HLA-DR and factor VIII-related antigen show almost complete colocalization in capillaries. In contrast, all 16 kidney biopsies from patients with inflammatory processes demonstrated p55-positive DCs in the cellular infiltrates. CONCLUSIONS: These results suggest that DCs are not present or are very rare in normal renal tissues but may migrate into the renal interstitium with inflammatory changes.

Adult↗
PubMed1997

Nephrotic syndrome after liver transplantation in a patient with hepatitis C virus-associated glomerulonephritis.

In recent years, hepatitis C virus infection has been reported to be typically associated with membranoproliferative glomerulonephritis and less frequently with membranous nephropathy. Treatment of hepatitis C with interferon-alpha can reduce viremia and improve renal disease. After liver transplantation for hepatitis C virus-associated liver failure, standard immunosuppressive protocols result in a significant increase in hepatitis C viremia. In this report we describe a patient with end-stage liver disease and biopsy-proven hepatitis C-associated glomerulonephritis who underwent liver transplantation. Within 1 month after transplantation, he developed a severe nephrotic syndrome that paralleled a marked increase in viremia. We discuss the possible pathogenic relationship between hepatitis C virus infection and the nephrotic syndrome that followed liver transplantation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Role of the thymus in transplantation tolerance in miniature swine. I. Requirement of the thymus for rapid and stable induction of tolerance to class I-mismatched renal allografts.

The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance.

Animals↗
PubMed1997

Pig to monkey bone marrow and kidney xenotransplantation.

BACKGROUND: The intensity of discordant xenograft cellular rejection makes it unlikely that safe doses of immunosuppressive drugs will alone be sufficient to permit long-term survival. We have therefore concentrated our efforts on establishing tolerance to xenogeneic organs through lymphohematopoietic chimerism and the elimination of preformed natural antibodies (nAbs). METHODS: Here we report the most recent series of 11 technically successful porcine to nonhuman primate transplantation procedures. In eight experimental animals induction therapy consisted of (1) 3 x 100 cGy nonlethal whole body irradiation (day -6 and day -5) to all animals, (2) horse anti-human thymocyte globulin (day -2, day -1, and day 0) to seven of the animals, (3) 700 cGy thymic irradiation (day -1) to five of the animals, and (4) pig bone marrow infused on day 0 (2-9 x 10(8)/cells/kg). On day 0, just before the renal xenograft, the recipient was splenectomized, and antipig nAbs were removed by means of perfusion of the monkey's blood through either a pig liver (n = 6) or a Gal-alpha (1,3)-Gal adsorption column (n = 5). There control animals did not receive this pretransplantation induction therapy but did undergo hemoperfusion and posttransplantation immunosuppression identical to the experimental animals. All 11 recipients were treated after transplantation with cyclosporin A and 15-deoxyspergualin. Recombinant pig-specific growth factors (interleukin-3 and stem cell factor) were given to six experimental animals from day 0 until the termination of the experiment. RESULTS: Analysis of recipients' sera by means of flow cytometry indicated the effective removal of immunoglobulin M and immunoglobulin G nAbs by either liver perfusion or column adsorption. In the eight experimental animals, nAb titers remained low until death (up to 15 days), but in the three control animals nAb titers increased substantially with time. The longest surviving recipient maintained excellent kidney function with creatinine levels at 0.8 to 1.3 mg/dl throughout its course. Death occurred at day 15 from complications caused by a urinary leak and pancytopenia. Histologic examination of the xenograft revealed only focal tubular necrosis and cytoplasmic vacuolization, with trace amounts of fibrin and C3 in peritubular capillaries. In this animal a fraction of the peripheral blood cells (3%) at day 7 were of pig origin as detected by pig-specific monoclonal antibodies. In addition, colony-forming assays performed on a bone marrow biopsy specimen taken at day 14 indicated that approximately 30% of the relatively few myeloid progenitors detected were of swine origin. CONCLUSIONS: We have demonstrated that our protocol is effective in the prevention of hyperacute rejection and in the maintenance of excellent function of the renal xenograft for up to 15 days. These results also indicate that at least short-term engraftment of the xenogeneic donor bone marrow cells is possible to achieve in this discordant large animal combination. Longer survivals will be required to assess the possible effect of this engraftment on induction of tolerance.

Animals↗
PubMed1997

Interferon-gamma induces a decrease in the intracellular calcium pump in a human salivary gland cell line.

Interferon-gamma (IFN-gamma) +/- tumor necrosis factor-alpha (TNF-alpha) induces antiproliferation and intracellular Ca2+ store depletion in a human submandibular ductal cell line (HSG), which can be reversed on cytokine removal [A. J. Wu, G. C. Chen, B. J. Baum, and I. S. Ambudkar. Am. J. Physiol. 270 (Cell Physiol. 39): C514-C521, 1996]. Here we have examined a possible mechanism for the IFN-gamma-induced intracellular Ca2+ store depletion. There was a time-dependent decrease in thapsigargin-dependent internal Ca2+ release after exposure of the cells to the cytokines. The intracellular Ca2+ pump [sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] protein in lysates and membranes of cells treated with IFN-gamma +/- TNF-alpha, but not with TNF-alpha alone, showed a similar time-dependent decrease (examined using a SERCA2 antibody). Removal of the cytokines, which resulted in recovery of cell growth and refill of internal Ca2+ stores, also increased the level of SERCA protein. The decrease in SERCA is not a result of decreased cell proliferation, since thapsigargin, 2,5-di-(t-butyl)-1,4-hydroquinone, or serum-free growth conditions induced antiproliferative effects on HSG cells without any corresponding decrease in SERCA. We suggest that the IFN-gamma-induced decrease in the level of SERCA accounts for the depleted state of internal Ca2+ stores in cytokine-treated HSG cells. These data suggest a novel mechanism for the inhibition of HSG cell growth by IFN-gamma.

Calcium↗
PubMed1996

Radiotherapy for high grade clinically localized adenocarcinoma of the prostate.

PURPOSE: We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy. RESULTS: Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46% of the cases and stage T3 or T4 in 54%. The overall actuarial probability of freedom from biochemical failure at 4 years was 23%. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64% free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16% at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83% of those treated to more than 71 Gy. were free of progression compared to 0% for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome. CONCLUSIONS: At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.

Actuarial Analysis↗
PubMed1995

Orofacial pain resulting from ill-fitting dentures.

The patient who presents to the physician with a history of facial pain can be a diagnostic challenge. The etiology can be elusive, and this problem is compounded by the subjective nature and the often multi-factorial causes of facial pain. The differential diagnoses to be considered include both local and systemic disorders such as neuropathy, myofascial pain, dentoalveolar pathoses, and psychological disturbances, among others. This paper presents the case of a patient with a history of left auricular pain that was managed for over 12 years with drug therapy with only limited success. A thorough head and neck evaluation revealed probable myofascial pain with a poorly occluding set of complete dentures as a potential etiology. Fabrication of a new set of dentures and modification of the patient's denture-wearing habits has produced an almost complete remission of the pain. This case demonstrates the importance of a dental consultation to rule out a possible oral-musculoskeletal and/or dental etiology in the management of the patient with facial pain.

Denture, Complete↗
PubMed1994

Embryonal rhabdomyosarcoma of the floor of the mouth. A case report.

Rhabdomyosarcoma is a neoplasm composed of striated muscle. One of the most common types of soft tissue mesenchymal tumors in infants, children, and adolescents, rhabdomyosarcoma was considered an almost uniformly fatal cancer as recently as 30 years ago. Presently a multimodal approach consisting of surgery, radiation, and chemotherapy has significantly improved the outlook for the patient with rhabdomyosarcoma. This article presents a case of intraoral rhabdomyosarcoma that was initially poorly controlled because of a lack of patient compliance. After proper treatment, the cancer went into remission. The patient remained cancer-free for 7 years, albeit with significant morbidity. This case demonstrates the significantly improved prognosis achieved with multimodal therapy.

Adult↗
PubMed1991

Reduction of proteinuria with captopril therapy in patients with focal segmental glomerulosclerosis and IgA nephropathy.

Angiotensin-1 converting enzyme inhibitors (ACEI) have been shown to reduce proteinuria in azotaemic diabetics and in other glomerulopathies, and such treatment has also slowed the development of experimentally-induced glomerulosclerosis in animals. We have treated 13 patients with focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN) with Captopril 12.5 mg twice daily for six months and assessed their response in terms of 24 hour urinary protein excretion, blood pressure, glomerular filtration rate, effective renal plasma flow and derived values for filtration fraction and renal vascular resistance. A mean fall of 29 per cent in urinary protein excretion was observed over the six months treatment schedule. No significant changes were observed in other parameters of renal haemodynamics measured. We conclude that Captopril therapy in patients with FSGS and IgAN reduces urinary protein excretion consistently over a six month period, and that this may in the longer term retard the progression of their renal failure.

Adolescent↗
PubMed1991

Pleural granulocytic sarcoma: CT characteristics.

The CT findings in a case of granulocytic sarcoma of the pleura are presented and correlated with pathology sections. CT features included diffuse, circumferential pleural thickening, multiple pleural fluid locules and mediastinal adenopathy. Similarities with the appearance of mesothelioma and metastatic pleural disease are discussed and the literature reviewed.

Humans↗
PubMed1991

Geriatric evaluation and management: current status and future research directions.

In the last decade the concept of geriatric evaluation and management (GEM) has been widely discussed in the literature. Studies of GEM have occurred primarily in three settings: inpatient units, outpatient clinics, and specialized types of home care. We have reviewed the literature, focusing on randomized trials, to determine the strength of the evidence for the efficacy of these interventions. Two single-site randomized controlled trials of inpatient GEM units have been conducted and indicate that such units that provide care to targeted disabled older patients probably have a favorable impact on subsequent physical function, rates of institutionalization, and mortality. Two randomized trials of inpatient GEM consultation teams have been conducted. The trial that did not target high-risk individuals showed no benefit while the trial that did target an at-risk group showed that those receiving the service had improvements in mental status and short-term mortality. The results of randomized trials of outpatient GEM clinics to date have been unimpressive. Two trials of in-home GEM by a trained observer tended to show that the service resulted in a reduction in mortality. To date randomized trials of GEM have been very heterogeneous in terms of the type of assessment and subsequent care, the site in which services are delivered, and the manner in which patients are selected for the studies. This limits the ability to compare and extrapolate across studies. In the future there is a need to better clarify the selection of study participants, the exact structure of the assessment intervention provided, and the elements of successful interventions that may be most critical to insuring a good outcome.

Aged↗
PubMed1991

Research strategies for geriatric evaluation and management: conference summary and recommendations.

In this paper, we present the consensus statement from a national conference on research priorities and methodologies for studying geriatric evaluation and management (GEM) programs. These conclusions, discussion points, and recommendations resulted from discussions of plenary papers, working group deliberations, and a final session in which findings were synthesized by the conference co-chairmen and presented to conference participants for final review. Major conclusions included: (1) The importance of linking geriatric evaluation with care management in future studies; (2) The need for multi-center trials of inpatient units to establish efficacy; (3) The importance of studying criteria for targeting GEM care on patients who are most likely to benefit; (4) The need for further developmental studies of outpatient GEM clinics; (5) The importance of assessing a range of outcomes including mortality, patient function, satisfaction, caregiver burden, and cost; and (6) The need to define more carefully the nature of the intervention that is being studied to aid in comparing and extrapolating findings. The following research priorities for GEMS were formulated based on the conference: (1) Within the VA health care system, a multi-site randomized trial of inpatient GEM units should be initiated; (2) Multi-site studies of inpatient GEM units and consultation teams linked to outpatient care should be initiated in non-VA settings; (3) Studies should identify the components of GEM that are most critical to outcome; (4) Studies should explore efficacy of GEM in settings that have not been well studied to date such as nursing homes; and (5) Studies are needed to test screening methods and targeting criteria for GEM in all settings.

Geriatric Assessment↗
PubMed1975

Effect of induced locus of control on change in field independence.

Three groups, alike in Rod and Frame Test (RFT) scores on pretesting, were given different instructions for Rotter's Locus of Control scale. Thirty-two Ss were told to fake internal or external answers. Another 16 Ss were instructed to answer the scale according to their own actual beliefs. Analysis of RFT pretest-posttest changes revealed that in both experimental conditions initially field-dependent Ss changed in the direction of higher field independence, and field-independent Ss shifted toward higher field dependence. The total amount of change manifested by field-dependent Ss in both conditions was in excess of the change by field-independent Ss. Standard test-taking instructions raised the level of field independence for field-dependent and field-independent Ss, with the magnitude of change greater among field-independent Ss. When Ss given internal and external instructions filled out the Locus of Control scale again at the end of the experiment, field-independent Ss professed to hold significantly more beliefs than field-dependent Ss that were coincident with beliefs of their previously simulated role. The findings were discussed primarily in terms of the relationship between role-playing and development of identity.

Female↗