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Biomedical subjects

S A Miller

Publications and source records attributed to S A Miller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Therapeutic implications of interleukin-10 in surgical disease.

Pharmacological therapy of surgical disease often involves manipulating the physiologic balance between pro- and anti-inflammatory responses. Many agents target only one aspect of the inflammatory cascade. Originally identified as a protein elaborated by T-lymphocytes, IL-10 appears to globally inhibit cytokine production. The purpose of this manuscript is to examine the immunomodulatory and anti-inflammatory effects of interleukin-10 (IL-10) in an attempt to define the clinical utility of IL-10, both as a marker of and as a therapeutic strategy for intervention in inflammatory and immune-mediated diseases. IL-10 is elaborated from multiple sources and has diverse cellular effects to regulate immune and inflammatory responses. Accumulating evidence suggests that the anti-inflammatory influence of IL-10 observed at the cellular level may be manipulated to impact the immune and inflammatory-mediated responses associated with injury and sepsis, gastrointestinal and cardiovascular disease, and transplantation. In conclusion, IL-10 is an important mediator of immune and anti-inflammatory responses in surgical disease and, as such, has therapeutic promise as an immunomodulator and as an anti-inflammatory agent.

Animals↗
PubMed1998

Clinical relevance of in vitro propagation of activated lymphocytes from endomyocardial biopsy samples of pediatric heart transplant recipients.

In vivo activated T-lymphocytes can be cultured from endomyocardial biopsy samples of human cardiac allografts, sometimes even in the absence of histological rejection. We investigated the clinical relevance of this "lymphocyte growth assay" in pediatric heart transplant recipients. Specifically, we wished to determine if: (i) positive lymphocyte growth from EMB samples in the absence of significant rejection identifies a patient as being at increased risk for the development of acute rejection; (ii) withdrawal or major dose reduction of corticosteroids in the presence of lymphocyte growth results in high risk of rebound rejection; and (iii) presence of lymphocyte growth during acute rejection helps predict the response to treatment. Cultures were performed on 789 consecutive EMB samples from 65 pediatric heart transplant recipients in media containing 30 U/ml of recombinant IL-2. T-lymphocytes were cultured from 16% of EMB samples with low grade rejection (grade 0-1b) and from 34% of EMB samples with grade 2-4 rejection. EMB samples obtained early post-transplant (<180 days) were significantly more likely to yield positive lymphocyte growth compared to biopsies obtained late for any given rejection grade. Lymphocyte growth was comparable between patients managed with cyclosporine or tacrolimus based immunosuppression. For 227 EMB samples without rejection, a subsequent EMB sample was obtained within 12 weeks. Lymphocyte cultures were positive in 47 of these 227 EMB samples (21%), and in 19 out of 47 (40%) cases acute rejection (grade 2-4) was present on the follow-up EMB sample. By contrast, of 180 biopsies without growth, only 29 (16%) showed rejection at the next EMB (p<0.0001). When a follow-up biopsy was performed within 12 weeks of corticosteroid withdrawal, "rebound rejection" was observed in 3 out of 10 (30%) cases where the previous EMB sample yielded positive lymphocyte growth and in 4 out of 38 (11%) cases when it did not (p=0.29). The presence of lymphocyte growth in association with rejection was also predictive of whether rejection would resolve following high dose intravenous corticosteroid therapy (persistent rejection in 33 out of 50 (66%) cases with positive growth, versus 25 out of 80 (31%) cases without growth (p<0.0001)). Thus, positive lymphocyte growth is strongly associated with higher grade of rejection and earlier time from transplantation. Lymphocyte growth in the absence of rejection indicates high risk for rejection within the next 12 weeks. Growth in association with acute rejection indicates high probability of persistence of rejection following treatment with high dose corticosteroids.

Adolescent↗
PubMed1998

An analysis of UVA emissions from sunlamps and the potential importance for melanoma.

Exposure to solar UV radiation is a risk factor for cutaneous malignant melanoma (CMM). Epidemiologic studies have also considered the use of sunlamps as a possible contributor to CMM. We measured and analyzed the emission spectra of six different currently marketed sunlamps and a historical sunlamp, the UVB-emitting FS lamp, and compared the results to solar exposure. For a typical tanner (20 sessions @ 2 minimal erythema doses (MED)/session), the annual UVA doses from commonly used fluorescent sunlamps were 0.3-1.2 times that received from the sun. For a frequent tanner (100 sessions @ 4 MED/session), the annual UVA doses from fluorescent sunlamps were 1.2-4.7 times that received from the sun and 12 times for recently available, high-pressure sunlamps. To determine biologically effective doses, action spectra for squamous cell carcinoma (SCC) in humans and for melanoma in the Xiphophorus fish (XFM) were applied to the sunlamps' emission spectra. The results for the effective doses using the SCC action spectrum tracked the UVB doses, while the results using the XFM action spectrum tracked the UVA doses. When combined with UV exposure received from the sun, typical sunlamp use results in an approximate doubling of annual effective dose, if the XFM action spectrum is applied. Frequent use, however, can increase the annual effective XFM dose by as much as 6 times what would be received from the sun alone for fluorescent sunlamps and as much as 12 times for newer, high-pressure sunlamps.

Animals↗
PubMed1997

Analysis of hospital charges after simultaneous pancreas-kidney transplantation in the era of managed care.

BACKGROUND: The purpose of this study was to analyze and compare hospital charges in simultaneous pancreas-kidney transplant (SPKT) recipients before and after implementation of managed care principles. METHODS: Two groups were compared: 14 consecutive SPKT patients transplanted in 1991 vs. 15 consecutive SPKT patients transplanted in 1995. All patients underwent whole organ pancreas transplantation with bladder drainage and received quadruple immunosuppression with OKT3 induction. The two groups were well-matched; outliers were excluded (four in 1991 and five in 1995), and no attempt was made to convert 1991 to 1995 dollars. Patient and graft survival rates were 100%, and no major early complications occurred. All SPKTs were performed in a single hospital setting, and all inpatient charges for the initial hospitalization were analyzed retrospectively and itemized by service. RESULTS: Pharmacy, organ acquisition, and clinical laboratory services accounted for nearly 80% of charges in each group. For the initial transplant hospitalization, the 1995 group experienced significant reductions in: (1) length of stay (16.3+/-1.4-135+/-3.5 days, P=0.03); (2) total number of laboratory tests (392+/-15-224+/-60, P<10(-3)); (3) clinical laboratory charges ($23,623+/-$1,780-$11,165+/-$3,091, P<10(-6)); and (4) total inpatient charges with organ acquisition charges excluded ($87,815+/-$8,678-$75,152+/-$16,871, P=0.049). However, these potential savings were offset by a nearly 47% increase in organ acquisition charges and a 38% increase in medical/surgical supplies. Consequently, total hospital charges for SPKT were no different in 1991 and 1995. CONCLUSIONS: Despite the rising costs of medical care, we have implemented managed care principles after SPKT that were successful in stabilizing hospital charges by decreasing length of stay and clinical laboratory tests during the study period. However, escalating charges related to organ acquisition and medical/surgical supplies remain a problem.

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

Blockade of hippocampal long-term potentiation following soman pretreatment in the rat.

One of the most potent toxins known is the cholinesterase inhibitor, soman, which produces severe convulsions and cell loss in the central nervous system. In these experiments the effect of multiple low doses of soman on the acquisition and maintenance of long-term potentiation (LTP) was determined in rats. LTP is a form of synaptic plasticity that has been studied as a cellular substrate for learning and memory mechanisms. Under urethane anesthesia, electrodes were positioned in the dentate gyrus for recording evoked potentials before and after tetanic stimulation of the perforant path. LTP levels were greatly reduced in rats recovering from convulsion-inducing soman treatment. Rats exposed to similar amounts of soman, but not displaying convulsions, also displayed reduced levels of LTP. The responses recorded from these animals were highly variable, ranging from control levels of potentiation to no LTP. The variability could be attributed to some animals having convulsions that were not detected before surgery or to other interanimal differences in the degree of soman-induced toxicity. The long range goal of the experiments presented here is to develop a better rodent model for studying soman-induced functional changes in the CNS that can be detected prior to the gross morphological changes.

Analysis of Variance↗
PubMed1997

Young children's understanding of conflicting mental representation predicts suggestibility.

This study examined the relation between developmental suggestibility effects and preschoolers' emerging ability to reason about conflicting mental representations (CMRs). Three- to 5-year-olds listened to a story accompanied by pictures. Following a 4-min delay, children answered straightforward and misleading questions about the story. One week later, their memory for the story was assessed. Children also completed tasks indexing their ability to reason about CMRs. Stepwise regression analyses revealed that suggestibility was negatively related to performance on CMR tasks. This finding remained significant after controlling for age, children's level of initial encoding of the event, and their ability to retrieve event details when not misled. An integration is proposed between children's theory of mind and source monitoring that may help to explain early developmental changes in suggestibility.

Age Factors↗
PubMed1997

Are chest radiographs and electrocardiograms still valuable in evaluating new pediatric patients with heart murmurs or chest pain?

OBJECTIVES: To determine the usefulness of electrocardiography (ECG) and chest radiography (CXR) in evaluation of patients referred to the pediatric cardiologist for the evaluation of heart murmur or chest pain. DESIGN: In this prospective study, 106 consecutive outpatients were categorized with no heart disease, possible heart disease, or definite heart disease based on history and physical examination; they then underwent ECG and CXR. Studies were reviewed and the examining cardiologist could change the diagnosis and order an echocardiogram. SETTING: Academic pediatric cardiology practice. RESULTS: In patients thought to have no heart disease, the diagnosis was changed to definite heart disease in four solely on the basis of abnormal CXR or ECG. In 25 patients thought to have possible heart disease, the diagnosis was changed to no heart disease (7) or definite heart disease (5) after review of the CXR and ECG. All 25 patients diagnosed with definite heart disease had this confirmed by abnormal CXR (2), ECG (3), both abnormal CXR and ECG, or echocardiogram (18). CONCLUSIONS: ECG and CXR helped diagnose heart disease in four patients thought to have no heart disease, helped to rule out lesions in seven patients with possible heart disease, helped diagnose heart disease in five patients thought to have possible heart disease, and helped confirm heart disease in nine patients. In these days of cost containment, routine ECG and CXR continue to be valuable tools for the pediatric cardiologist in evaluation of patients with heart murmurs or chest pain.

Adolescent↗
PubMed1997

New-onset diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression.

BACKGROUND: Tacrolimus has a negative effect on the pancreatic beta islet cell, and both glucose intolerance and diabetes mellitus are well-recognized complications of tacrolimus-based immunosuppression among adult solid organ transplant recipients. METHODS: To determine the association between tacrolimus and new-onset diabetes mellitus in childhood, we reviewed data on 78 pediatric heart and heart-lung/lung recipients receiving tacrolimus-based immunosuppression. Trough tacrolimus levels, fasting and random blood glucose levels, and corticosteroid requirements were reviewed. Diabetes was defined as glucose intolerance requiring long-term insulin treatment more than 30 days after transplantation. RESULTS: No patient had diabetes before introduction of tacrolimus. In heart-lung/lung recipients, 12 of 28 (43%) had development of diabetes at a median follow-up of 7 months (range 1 to 39). In this group diabetes developed in three of eight (38%) patients with cystic fibrosis and nine of 20 (45%) without (p = NS). In contrast, only two of 50 (4%) heart transplant recipients had development of diabetes. Of the 14 patients with diabetes, 10 had development of diabetes during augmentation of immunosuppression with pulsed corticosteroids. Tacrolimus trough levels were significantly lower in heart compared with heart-lung/lung transplant recipients (9.4 +/- 3.3 versus 15.3 +/- 0.9 ng/ml) (p < 0.01), and at latest follow-up significantly fewer heart transplant recipients were treated with maintenance corticosteroids (28% versus 75%; p < 0.01). In the heart-lung/lung group, no significant difference in tacrolimus levels was found between patients with and without diabetes, nor was there a significant difference in the average corticosteroid dose or number of pulses of corticosteroids per patient. CONCLUSIONS: New-onset diabetes mellitus is rare in pediatric heart transplant recipients receiving tacrolimus-based immunosuppression, but it occurs with a high incidence after pediatric heart-lung/lung transplantation and usually develops during pulsed corticosteroid therapy. However, it is currently not possible to predict which heart-lung/ lung transplant recipients will have development of this serious complication.

Adolescent↗
PubMed1996

Kinematics of four methods of stabbing: a preliminary study.

Despite considerable research and development into stab-resistant clothing, no data exists which provides valid data for knife-body contact speeds which may be used to ensure that an appropriate and standard protection level is provided. Such data can only be obtained by a quantitative kinematic analysis of the stabbing movement. Two-dimensional video techniques (50 Hz) were used to record images of subjects (n = 10) performing each of four stabbing actions; Long Over (LO), Long Under (LU), Short Over (SO), Short Under (SU). Images were digitised from a minimum of ten frames pre-, to at least six frames post-blade entry. A two-way analysis of variance applied to selected kinematic parameters revealed significantly higher (P < 0.01) blade entry speeds for LO and LU as compared to SO and SU, respectively. This was due to the extra distance over which knife speed could be increased in the former conditions. Significantly greater shoulder joint angular velocities were found for LU and SU conditions, whilst for the elbow joint, conditions LO and SO were significantly greater (P = 0.000008). This suggests that the entry speeds during LO and SO are derived from a greater contribution from elbow extensor muscles, whilst those for LU and SU are derived from a greater contribution from the shoulder flexors. It was concluded that two separate kinematic strategies were employed by subjects, and that the maximum speed which may be generated during stabbing is influenced by the manner in which the knife is held.

Adult↗
PubMed1996

Apoptosis removes chick embryo tail gut and remnant of the primitive streak.

Removal of transient features in morphogenesis of chick embryo tail is by programmed cell death. We used ApopTagTM (Oncor, Gaithersburg, MD) with the peroxidase/diaminobenzidine (DAB) procedure to correlate apoptosis with earlier reports of patterns of cell death in stage HH17-25 embryos, and our results suggest that the cell death inferred with supravital staining and appearance of cells in morphogenesis of the tail bud is programmed cell death called apoptosis. Apoptosis markers in tail bud are most abundant in the median cell cord of occluded degenerating tail gut. Tail bud mesenchyme marks for apoptosis most frequently in the ventrum of older stages, where cell death has been reported. Cells of the remnant of the primitive streak (Hensen's node) mark for apoptosis, suggesting that programmed cell death is a stop signal for axial organization at the caudal terminus. Apoptosis markers in postmembrane cloacal endoderm anticipate the transient cloacal fenestra. Lack of apoptosis markers in neural tube, notochord, and somites supports the suggestion of Schoenwolf ([1981] Anat, Embryol. (Beri.) 162:183-197) that cells of those areas in the tail bud are assimilated into the growing rump of the chick embryo. Lack of markers in neural tube of tail bud formed by secondary neurulation suggests that apoptosis is not involved in cavitation of medullary cord, but further investigation is necessary. A limited investigation of pharyngeal membranes and midgut, where cell death has not been reported to be as important in morphogenesis, did not show apoptosis markers in those tissues (Miller and Briglin [1994] "Cell Death in Development and Cancer," Houston: University of Texas MD Anderson Cancer Center, pp, 82-83). Absence of apoptosis markers in roof of gut tube suggests that the lower frequency of thymidine labeling reported for those cells (Miller [1986] Anat. Rec. 214: 87A) is not a result of apoptosis. Clearly marked cells correlated with expected locations of migrating neural crest and primordial germ cells in these stages, but distribution of apoptosis markers was not abundant or general for either cell type.

Animals↗
PubMed1996

Medical UV exposures and HIV activation.

This paper presents the first attempt to evaluate the potential of clinical UV exposures to induce the human immunodeficiency (HIV) promoter and, thus, to upregulate HIV growth in those skin cells that are directly affected by the exposure. Using the data for HIV promoter activation in vitro, we computed UVB and psoralen plus UVA (PUVA) doses that produce 50% of the maximal promoter activation (AD50). Then, using (a) literature data for UV transmittance in the human skin, (b) a composite action spectrum for HIV promoter and pyrimidine dimer induction by UVB and (c) an action spectrum for DNA synthesis inhibition by PUVA, we estimated the distribution of medical UVB and PUVA doses in the skin. This allowed us to estimate how deep into the skin the HIV-activating doses might penetrate in an initial and an advanced stage of UVB or PUVA therapy. Such analysis was done for normal type II skin and for single exposures. The results allow us to predict where in the skin the HIV promoter may be induced by selected small and large therapeutic UVB or PUVA doses. To accommodate changes in skin topography due to disease and UV therapy, our considerations would require further refinements. For UVB we found that, when the incident dose on the surface of the skin is 500 J/m2 (290-320 nm) (initial stage of the therapy), the dose producing 50% of the maximal HIV promoter activation (ADUVB50) is limited to the stratum corneum. However, with an incident dose of 5000 J/m2 (an advanced stage of the therapy), ADUVB50) may be delivered as far as the living cells of the epidermis and even to some parts of the upper dermis. For PUVA we found that, when the incident UVA doses are 25 or 100 kJ/m2 (320-400 nm) (an initial and an advanced stage of therapy, respectively), and the 8-methoxypsoralen concentration in the blood is 0.1 microgram/mL (the desired level), the combined doses to the mid epidermis (and some areas of the upper dermis) are well below the 50% HIV promoter-activating PUVA dose (ADPUVA50). Only under the worst scenario conditions, i.e. an exceptionally high drug concentration in the patient's tissues and localization of HIV in the nearest proximity to the skin surface, would the combined PUVA dose expected during photochemotherapy exceed ADPUVA50. These results suggest that the probability of HIV activation in the epidermis by direct mechanisms is higher for UVB than for PUVA treatment. However, complexities of the UV-inducible HIV activation and immunomodulatory phenomena are such that our results by themselves should not be taken as an indication that UVB therapy carries a higher risk than PUVA therapy when administered to HIV-infected patients.

HIV↗
PubMed1996

Prevalence of modifiable risk factors for sudden infant death syndrome in British Forces Germany.

A questionnaire survey was conducted amongst parents in the military community in British Forces Germany to investigate the prevalence of known and suspected risk factors for Sudden Infant Death Syndrome. Over a thousand questionnaires were returned (response rate 58%) and these showed that the prevalence of babies being placed in the prone position to sleep is now extremely low and the use of room thermometers to help control ambient temperature is widespread. However 29% of the mothers had smoked in pregnancy and 44% of households with a new-born baby had at least one parent who smoked. Additional health promotion activity aimed at reducing the prevalence of smoking in pregnancy and amongst the parents of new-born babies is recommended.

Age Distribution↗