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Biomedical subjects

M V Smith

Publications and source records attributed to M V Smith.

At least 19 recordsLinked to original sources

Dose response for UV-induced immune suppression in people of color: differences based on erythemal reactivity rather than skin pigmentation.

Ultraviolet radiation (UVR) is known to suppress immune responses in human subjects. The purpose of this study was to develop dose responses across a broad range of skin pigmentation in order to facilitate risk assessment. UVR was administered using FS 20 bulbs. Skin pigmentation and UVR sensitivity were evaluated using Fitzpatrick classifications, minimal erythemal dose (MED), slope of the erythemal dose response curve (sED), baseline pigmentation and tanning response. To assess immune responses dinitrochlorobenzene (DNCB) was applied to irradiated buttock skin 72 h after irradiation. Two weeks later DNCB was applied to the inside upper arm. Skin thickness was measured before and after challenge. Dose response was modeled (to obtain a regression line) for the entire group of 185 subjects. With the exception of sED none of the above-mentioned pigmentation indicators contributed significantly to variability around the regression line. Thus, differences in sensitivity for multiple skin types based on Fitzpatrick classification or MED were not observed. However, differences in immune sensitivity to UVR were detected between subjects with steep erythemal dose response curves and those with moderate or flat responses. For subjects with steep erythemal responses the dose calculated to suppress the immune response by 50% was 114 mJ/cm2. This group included individuals with Fitzpatrick skin types I-V, MED for these subjects ranged from 30 to 80 mJ/cm2. The 50% suppression dose for subjects with weak or no erythemal response could not be computed (the dose response was flat). This resistant group included subjects with skin types IV-VI and MED for these subjects ranged from 41 to > 105 mJ/cm2. This study provides a human dose response for UVR suppression of contact sensitivity that will be useful in risk assessment. It is the first study to provide this information using the FS sun lamp and is the first study to include people of color. The sED appears to be a new variable for identifying sensitive subjects at risk of UVR-induced immune suppression.

Adolescent↗

Incorporating observability thresholds of tumors into the two-stage carcinogenesis model.

This paper discusses a general way of incorporating the growth kinetics of malignant tumors with the two-stage carcinogenesis model. The model is presented using time-homogeneous rate parameters. In that case, the differential equations comprising the model are straightforward to solve using standard numerical techniques and software. An extension of the method to time-dependent rate parameters is included in Appendix A. Allowing the rate parameters to be time-dependent does incur computational cost. An expression is given for the expected time without visible tumor, a generalization of the expected time to an observable tumor that includes the possibility of tumor regression. The model is illustrated using incidental liver tumor data in control rats from NTP rodent carcinogenicity studies, using linear birth-death kinetics of tumors combined with a non-absorbing detection limit. The approach is also shown to be potentially useful with tumor observability thresholds having more complicated features.

Animals↗

Endoscopic colloid cyst surgery.

OBJECTIVE: The purpose of this report is to discuss the technical aspects of operating on colloid cysts through a transventricular approach, with rigid endoscopes. METHODS: Twelve patients underwent 14 endoscopic operations in attempts to treat their colloid cysts. All patients were symptomatic, with headache being the most common complaint (8 of 12 patients). Six patients in this series exhibited enlarged ventricles associated with their colloid cysts. Using rigid endoscopes of < or =3.5-mm diameter, the cysts were inspected and fenestrated. Both hard and soft cyst contents were evacuated, and then the walls of the cysts were coagulated inside and outside. External ventriculostomy tubes were usually placed. Technical obstacles to successful completion of endoscopic colloid cyst surgery are discussed. RESULTS: For 11 of the 12 patients, the colloid cysts could be treated via an endoscopic approach. The mean follow-up time was 173 weeks, and the median follow-up time was 125 weeks. For the 12th patient, bilateral scarring of the foramina of Monro precluded direct surgery; therefore, a septostomy was performed and a ventriculoperitoneal shunt was placed. CONCLUSION: Endoscopic transventricular surgery should be considered for the treatment of colloid cysts.

Adult↗

Ozone-induced respiratory symptoms: exposure-response models and association with lung function.

Ozone-induced respiratory symptoms are known to be functions of concentration, minute ventilation, and duration of exposure. The purposes of this study were to identify an exposure-response model for symptoms, to determine whether response was related to age, and to assess the relationships between symptom and lung function responses to ozone. Four hundred and eighty-five healthy male volunteers (ages 18-35 yrs) were exposed to one of six ozone concentrations at one of three activity levels for 2 h. Symptoms and forced expiratory volume in one second (FEV1) were assessed at the end of 1 and 2 h. The exposure and response data were fitted by a nonlinear exposure-response model previously found to describe FEV1 response. The proportion of individuals experiencing moderate or severe cough, shortness of breath, and pain on deep inspiration were accurately described as functions of concentration, minute ventilation, and time. Response was inversely related to age for shortness of breath (p=0.0001), pain on deep inspiration (p=0.0002), and cough (p=0.0013). Controlling for exposure differences, symptom responses were significantly but weakly (correlation coefficient 0.30-0.41) related to the FEV1 response. In conclusion, the exposure-response model did accurately predict symptoms, response was inversely related to age.

Adolescent↗

A statistical model for FEV1 response to arbitrary dynamic ozone exposure conditions.

Lung function response to inhaled ozone at ambient air pollution levels is known to be a function of ozone concentration, exposure duration, and minute ventilation. Most data-driven exposure-response models address exposures under static condition (i.e., with a constant ozone concentration and exercise pattern). Such models are simplifications, as both ambient ozone concentrations and normal human activity patterns change with time. The purpose of this study was to develop a dynamic model of response with the advantages of a statistical model (a relatively simple structure with few parameters). A previously proposed mechanistic model for changes in specific airways resistance was adapted to describe the percent change in forced expiratory volume in one second (FEV1). This model was then reduced using the fit to three existing exposure-response data sets as criterion. The resulting model consists of a single linear differential equation together with an algebraic logistic equation. Under restricted static conditions the model reduces to a logistic model presented earlier by the authors.

Computer Simulation↗

Chronic pulmonary artery balloon counterpulsation in sheep via percutaneous route.

BACKGROUND: In clinical practice pulmonary artery balloon counterpulsation (PABC) has been utilized only in the operative setting with the balloon housed in a graft attached to the pulmonary artery. Clearly, percutaneous insertion of a dedicated pulmonary artery balloon is a desirable goal for patients requiring temporary assist for right ventricular failure. METHODS: To address the question of right sided cardiopulmonary tolerance for a chronic indwelling pulmonary artery balloon, six adult ewes underwent percutaneous placement of an 11 ml pulmonary artery balloon, via the femoral vein. Effective pumping and timing were monitored for 48 hours at which time the animals were sacrificed. At autopsy gross and microscopic study of all right heart structures, the pulmonary arteries and the lungs were studied for adverse effects. RESULTS: There were inconsequential minor abrasions to right heart structures in most animals. The pulmonary artery in five of six animals revealed ecchymoses and some transmural hemorrhage, but no necrosis or perforation. There was no pulmonary injury that could not be ascribed to postoperative atelectasis. CONCLUSIONS: This study demonstrates that chronic pulmonary artery balloon counterpulsation can be carried out for a period of 48 hours without significant injury to right heart and pulmonary structures in the ovine model

Adult↗

Giant cervical epidural veins after craniectomy for head trauma.

Markedly dilated cervical epidural veins and right upper extremity weakness developed in a 43-year-old man 4 months after contralateral craniectomy for head trauma. After cranioplasty, his symptoms improved markedly and the size of the veins returned to normal. These findings suggest that enlarged cervical epidural veins may occur without an underlying vascular lesion and that upper extremity weakness may occasionally be attributable to spinal cord venous stasis.

Adult↗

Prediction of ozone-induced FEV1 changes. Effects of concentration, duration, and ventilation.

The purpose of this analysis of previously published data was to identify a model that accurately predicts the mean ozone-induced FEV1 response of humans as a function of concentration (C), minute ventilation (VE), duration of exposure (T), and age. Healthy young adults (n = 485) were exposed for 2 h to one of six ozone concentrations while exercising at one of three levels. Candidate models were fitted to portions of the data and evaluated on the basis of their ability to predict the mean response of independent samples. A sigmoid-shaped model that is consistent with previous observations of ozone exposure-response (E-R) characteristics was identified and found to accurately predict the mean response with independent data. This model in a more general form may allow the prediction of responses under conditions of changing C and VE. We did not find that response was more sensitive to changes in C than in VE, nor did we find convincing evidence of an effect of body size upon response. We did find that response to ozone decreases with age. In summary, we have identified a biologically plausible, predictive model that quantifies the relationship between the ozone-induced change in FEV1, and C, VE, T, and age.

Adolescent↗

Transnasal endoscopic surgery of the pituitary gland: technical note.

OBJECTIVE: An approach to transnasal transsphenoidal debulking of pituitary tumors using endoscopic guidance is presented. METHODS: Technical details of this approach using an endoscope inserted through one nostril and operating instruments inserted through a submucosal tunnel created via the other nostril are discussed. RESULTS: Ten patients who had operations are tabulated. Illustrative cases are presented. CONCLUSION: Endoscopic debulking of pituitary tumors can provide good results with minimal operative morbidity.

Adenoma↗

Proportion of moderately exercising individuals responding to low-level, multi-hour ozone exposure.

The purpose of this study was to describe the proportion of moderately exercising individuals experiencing significant respiratory responses to low-level, multi-hour ozone exposure as a function of ozone concentration and exposure duration. Sixty-eight healthy, nonsmoking adults, ages 18 to 34 yr, underwent two or more 6.6-h exposures to 0.0, 0.08, 0.10, or 0.12 ppm ozone. Five hours of exercise was performed during exposure, and lung function was measured before exposure and following each hour of exposure. For each combination of concentration and duration, each individual was determined to either have or not have experienced a 10% or greater decrement in FEV1. A logistic function was used to model the proportion of individuals experiencing such a decrement as a function of concentration and exposure duration. Bootstrap 90% confidence intervals (CIs) were calculated around the predictions. The model was found to give predictions that were in good agreement with observed data. The lowest level of exposure (C x T) for which the 90% CI excluded zero was approximately 0.2 ppm-h. For exposure to 0.12 ppm ozone for 6.6 h, 47% (90% CI = 30 to 65%) of exposed individuals were predicted to experience a 10% decrement in FEV1. A greater proportion of younger adults than of older adults were found to experience a given effect for a given exposure.

Adolescent↗

Concurrent comparison of the safety of paid cytapheresis and volunteer whole-blood donors.

BACKGROUND: Historically, paid blood donors were found to transmit hepatitis at higher rates than volunteers. In those older studies, paid donors frequently were recruited from prisons or slum areas--a finding consistent with the belief that monetary payment in itself did not necessarily lead to the high-risk status of commercial blood. Instead, it was the population base from which the donors were recruited that was important. STUDY DESIGN AND METHODS: Today, cytapheresis donors are in great demand. Because payment is one incentive that might entice donors to undertake the increased commitment of repeated cytapheresis donation, the results were studied of infectious disease history and laboratory testing performed concurrently in 917 volunteer whole-blood donors and 1240 paid cytapheresis donors, who were enrolled in distinct programs at the DeGowin Blood Center from October 7, 1987, through November 30, 1990. RESULTS: When first, repeat, and overall donations made by these donors were evaluated separately, paid cytapheresis donors were found to exhibit no increase in infectious disease history or test results beyond those of volunteer whole-blood donors. CONCLUSION: Thus, paid cytapheresis donors, when managed within a formal program, should not necessarily be presumed to be more dangerous than volunteers, from an infectious disease aspect. However, definitive proof of safety (comparison of transfusion-transmitted infection rates in two groups of patients receiving blood components exclusively from either paid cytapheresis or volunteer donors) was not pursued by long-term follow-up studies.

Blood Donors↗

Prediction of carboxyhemoglobin formation due to transient exposure to carbon monoxide.

Fifteen men were exposed to 6,683 ppm C18O for 3.09-6.65 min. Arterial and antecubital vein blood samples were drawn at 1-min intervals beginning at the start of C18O inhalation and ending 10 min later. Simultaneously, alveolar ventilation was calculated from the measured values of minute ventilation and dead space. All other parameters of the Coburn-Forster-Kane equation (CFKE), except the Haldane affinity ratio, were measured separately in each subject. Means of CFKE predictions of increases in venous HbCO (delta HbCO) in samples collected approximately 2 min after cessation of exposure were accurate, but the range in errors of prediction for individual subjects was +/- 3.8% HbCO, depending on the time after exposure cessation. Increases in venous and arterial HbCO were inaccurately predicted during and immediately after HbCO formation, however. Venous blood was overestimated during CO uptake because of a delayed appearance of HbCO. Individual subjects differed markedly in the degree of delay of HbCO appearance in venous blood. Arterial delta HbCO was consistently underestimated either by the CFKE or by predictions based on venous blood samples. Thus, exposure of such organs as brain or heart to HbCO may be substantially higher than expected during transient high-level CO exposure.

Adolescent↗

Description of acute ozone response as a function of exposure rate and total inhaled dose.

The magnitude of respiratory responses to short-term ozone exposure is known to be a function of the exposure variables concentration (C), duration of exposure (T), and minute ventilation (VE) during exposure. The purpose of this study was to identify a mathematical model that described ozone-induced mean decrements in forced expiratory volume in 1 s (FEV1) as a function of exposure rate (C x VE) and total inhaled dose (C x VE x T). Three hundred seventy-four young male nonsmokers participated in 504 exposures to several concentrations of ozone for 2 or 6.6 h. Mean percent change in FEV1 was calculated for each hour of exposure and was fit to the exposure variables by use of nonlinear models. We identified a general sigmoid-shaped model that well described the observed mean response in terms of exposure rate and total inhaled dose over a wide range of C and T. By fixing the value of a single parameter, this model reduces to a simpler form, which was adequate for description of responses over narrower ranges of exposure conditions. We concluded that the observed mean responses to short-term ozone exposure were adequately described by the nonlinear models identified in this study and that models of this form may be useful for description of responses over a wide range of C and T.

Administration, Inhalation↗

Effect of regional circulation patterns on observed HbCO levels.

In an earlier experiment, we briefly exposed 15 young men to high levels of CO while simultaneously monitoring arterial and peripheral venous HbCO levels. The arterial HbCO levels were considerably higher than the venous levels during the CO exposure. Furthermore, great variation in the difference between arterial and venous HbCO levels was observed, with the maximal difference for each subject ranging from 2.3 to 12.1% HbCO. In the present paper, we suggest an explanation for the observed differences between arterial and venous HbCO on the basis of the regional circulation of the forearm, where both samples were taken. Because regional circulation patterns are known to vary with physical training, the differences in physical training between subjects may account for the observed variation. An expanded model was derived from the Coburn-Forster-Kane equation, which reflects the above hypothesis. Most of the parameter values for the expanded model were measured on individual subjects. Literature values were used for other parameters. Two parameters were estimated using five of the subjects and were then used in the predictions of the expanded model for the remaining subjects.

Arteries↗

Magnetic resonance imaging measurements of pituitary stalk compression and deviation in patients with nonprolactin-secreting intrasellar and parasellar tumors: lack of correlation with serum prolactin levels.

Prolactin (PRL) Levels are frequently elevated in patients with non-PRL-secreting adenomas or other intrasellar and parasellar diseases ("pseudoprolactinomas"). This phenomenon is believed to result from a loss of dopaminergic inhibition on pituitary lactotrophs and is known as the "stalk-section effect." Using magnetic resonance imaging scans and a high-magnification sella technique, we measured a number of parameters indicative of the disruption of normal sellar structures. The investigator was blind to the patient's diagnosis and PRL level while collecting the data. Parameters measured were the tumor size, the angular deviation of the pituitary stalk, and the degree of compression of the pituitary stalk. Measurements were obtained from 44 patients with pathologically confirmed tumors that had no immunohistochemical reactivity to PRL. PRL levels were often higher than expected. Four patients (9%) had a PRL level of more than 150 ng/ml, and three patients (7%) had a PRL level of 200 ng/ml or more. One patient with a plasmacytoma eroding the sella floor had a PRL level as high as 504 ng/ml. There was no significant correlation of PRL level and the degree of pituitary stalk compression, stalk deviation, or tumor size. PRL levels were found to be markedly elevated in some patients with a tumor causing little distortion of the pituitary stalk. Conversely, PRL levels were often normal despite evidence of massive distortion of the stalk. Therefore, magnetic resonance imaging evidence of pituitary stalk distortion cannot be used to determine the diagnosis of prolactinoma versus pseudoprolactinoma in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Retrograde coronary sinus perfusion provides non-homogeneous myocardial blood flow.

The ability of retrograde cardioplegia to protect the right ventricle has been questioned. Canine myocardial circulation was assessed by infusing colored microspheres through the coronary sinus. The relative flow index (RFI), a normalized measure of tissue blood flow, was determined for 76 sections of myocardium. Three distinct flow regions were evident from these measurements. A paucity of blood flow through some basal sections of the right ventricle (RFI = 0.23 +/- 0.19) was found to be significantly different (p < 0.005) from regions of the heart with normal flow (RFI = 1.12 +/- 0.06). Sections from the right ventricular apex demonstrated augmented flow (RFI = 3.72 +/- 1.18). These data indicate that retrograde coronary perfusion provides nonuniform flow and under some conditions may provide inadequate perfusion to portions of the right ventricle.

Animals↗