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Biomedical subjects

S A Miller

Publications and source records attributed to S A Miller.

At least 19 recordsLinked to original sources
PubMed1992

Use of cholinesterases as pretreatment drugs for the protection of rhesus monkeys against soman toxicity.

Purified fetal bovine serum acetylcholinesterase (FBS AChE) and horse serum butyrylcholinesterase (BChE) were successfully used as single pretreatment drugs for the prevention of pinacolyl methylphosphonofluoridate (soman) toxicity in nonhuman primates. Eight rhesus monkeys, trained to perform Primate Equilibrium Platform (PEP) tasks, were pretreated with FBS AChE or BChE and challenged with a cumulative level of five median lethal doses (LD50) of soman. All ChE-pretreated monkeys survived the soman challenge and showed no symptoms of soman toxicity. A quantitative linear relation was observed between the soman dose and the neutralization of blood ChE. None of the four AChE-pretreated animals showed PEP task decrements, even though administration of soman irreversibly inhibited nearly all of the exogenously administered AChE. In two of four BChE-pretreated animals, a small transient PEP performance decrement occurred when the cumulative soman dose exceeded 4 LD50. Performance decrements observed under BChE protection were modest by the usual standards of organophosphorus compound toxicity. No residual or delayed performance decrements or other untoward effects were observed during 6 weeks of post-exposure testing with either ChE.

Acetylcholinesterase↗
PubMed1992

Photic maculopathy after extracapsular cataract surgery. A prospective study.

Photic retinal injuries have been described after surgical exposure to the intense illumination systems of operating microscopes. The overall incidence of such injuries has been postulated at less than 10%. The authors prospectively studied 43 consecutive patients to determine the incidence of photic macular injuries during cataract surgery. Patients underwent complete ophthalmic examinations, fundus photography, and oral fluorography before and after surgery. Photic macular injuries developed in 12 of 43 eyes (28%) as a result of intraocular surgery. This incidence is much higher than previous estimates. The association with possible risk factors, cystoid macular edema, and the effect of these injuries on final visual acuity are discussed.

Cataract Extraction↗
PubMed1992

Reliability problems associated with the modified Schöber technique for true lumbar flexion measurement.

The modified Schöber technique, a method for assessing lumbar spine flexion, was subjected to an analysis of reliability. Fifty normal subjects (21 men, 29 women) were evaluated for lumbar flexion mobility using a blind inter-rater "worst case" protocol. Simultaneously, other sources of error affecting test reliability, such as presence of dimples of Venus, relationship of skin distraction to movement of underlying structures, and upper level of Schöber skin landmarks were also considered. Analysis suggested that systematic error can be introduced that adversely affects inter-rater reliability (r = 0.71). Moreover, skin landmarks are inconsistently present, being completely absent in 26% of cases. Skin tends to distract even over completely immobile bony structures (eg, the sacrum), whereas, on average, only 3.5 of the 6 spinal segments (T12-S1) are included in the Schöber technique for purported measurement of "lumbar spine flexion." The utility of this method is questioned on both scientific and clinical grounds.

Adult↗
PubMed1992

Lipid status after combined pancreas-kidney transplantation and kidney transplantation alone in type I diabetes mellitus.

This study was designed to compare changes in lipid status following organ transplantation between type I diabetes mellitus (DM-I) patients receiving combined pancreas-kidney transplantation (PKT) with those receiving kidney transplantation alone (KTA). A retrospective chart review was used to identify pre- and posttransplantation fasting total cholesterol (TC) and triglycerides (TG) in three groups: DM-I patients receiving KTA (DM:KTA; n = 14), DM-I patients receiving PKT (DM:PKT; n = 20), and kidney transplant recipients without DM (NDM; n = 16). The groups were matched for age, gender, weight, duration of dialysis, smoking history, and duration of diabetes mellitus. Linear regression was used to analyze differences in lipid trends over time (up to 24 months posttransplantation) and the effects of prednisone dose, cyclosporine dose, and serum creatinine. Preoperative TC was significantly lower in the DM:KTA group (P < 0.05) compared with DM:PKT or NDM. There were no significant differences in preoperative TG between the three groups. TC and TG decreased over time only in DM:PKT (P = 0.0112, P = 0.0278, respectively). TC increased and TG was unchanged over time in DM:KTA (P = 0.0003, P = 0.1103, respectively). Neither TC nor TG changed over time in NDM. Trends of TC and TG for DM:PKT were significantly different from DM:KTA (P < 0.01 for both). Trend of TC for NDM was also significantly different from DM:PKT (P = 0.0061). Prednisone dose was significantly related to TC in DM:KTA and NDM (P < 0.01) while cyclosporine dose was significantly related to TC for DM:KTA only (P = 0.0013) in the presence of time. None of the variables tested (prednisone dose, cyclosporine dose, and serum creatinine) significantly affected TG in the presence of time. In summary, TC and TG decreased over time only in DM:PKT. In contrast, TC increased while TG was unchanged in DM:KTA over the same interval (0-24 months). If these trends continue, the beneficial change in lipids in the DM:PKT group may translate into a net improvement in atherosclerosis-mediated events for diabetic patients with chronic renal failure who receive PKT compared with those who do not.

Adult↗
PubMed1992

Photoaging effects on spectral transmittance of plastic filters.

We examined the effects of ultraviolet (UV) radiation in combination with high levels of infrared (IR) radiation on the spectral transmittance of plastic filters. The biological action spectrum for damage to the human eye and skin changes dramatically in the 300-400 nm wavelength range. Cut-off filters used in this region to shape the spectrum of exposure sources are thus critical to the design of experiments which use broadband light sources. The changes in transmittance of three types of plastic filters were observed over an exposure period of 1000 h. One set of three filters was exposed mainly to UV radiation, while the other set was exposed to UV radiation plus IR radiation. Filters exposed to both UV and IR radiation showed spectral changes in their transmittance, while the filters exposed to UV only showed no measurable changes.

Eye↗
PubMed1992

Lipid status after pancreas-kidney transplantation.

OBJECTIVE: This study was performed to determine the net effects of euglycemia, resolution of renal failure, immunosuppressant drugs, and hyperinsulinemia on fasting lipid profiles of patients with renal failure and insulin-dependent diabetes mellitus (IDDM) after combined pancreas-kidney transplantation (PKT). RESEARCH DESIGN AND METHODS: Thirty subjects with IDDM received PKT between April 1989 and October 1990, and all were studied. Mean +/- SE age was 35.2 +/- 1.3 yr; 19 recipients were men, and 11 were women. All had a functioning pancreatic allograft post-PKT. Fasting lipid profiles including total cholesterol (C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-chol), and C/HDL-chol were compared before and after PKT (38-555 days divided into groups: preoperation and 0-2, 3-8, and 9-19 mo). RESULTS: Significant hyperlipidemia was observed preoperatively (means +/- SE): C, 5.92 +/- 0.27 mM; HDL-chol, 1.07 +/- 0.09 mM; TG, 5.85 +/- 0.56 mM; and C/HDL-chol, 6.49 +/- 0.83. All lipids and C/HDL-chol dropped immediately after PKT (0-2 mo vs. preoperation, all P less than 0.01, except HDL-chol). After this immediate postoperative period, C, HDL-chol, and TG stabilized at new concentrations. C (5.44 +/- 0.22 mM) and TG (4.54 +/- 0.48 mM) levels were less than preoperation (not statistically significant and P less than 0.05, respectively). HDL-chol was greater than preoperative values (1.29 +/- 0.06 mM, P less than 0.05). C/HDL-chol dropped after PKT (0-2 mo, 4.85 +/- 0.18, P less than 0.01) and continued to decrease throughout the observation period (3-8 mo, 4.42 +/- 0.23; 9-19 mo, 4.23 +/- 0.23; both P less than 0.01 vs. preoperation). There was no statistical difference between lipid concentrations in male and female subjects. CONCLUSIONS: The lipid status of subjects with IDDM and renal failure was abnormal before PKT and once lipid concentrations stabilized after PKT (greater than 2 mo), HDL-chol was higher and TG and C/HDL-chol levels were significantly lower than preoperative values. If these changes are sustained, risk of future cardiovascular disease in this group of patients might be significantly reduced.

Adult↗
PubMed1991

Liver warning.

Explore the source record for details and available documents.

Humans↗
PubMed1991

Differential sensitivity of CNS regions to acetylcholinesterase inhibition following chronic low-dose soman treatment in the rat.

Several discrete brain regions were analyzed for regional brain sensitivity to acetylcholinesterase (AChE) inhibition following administration of repeated low-dose soman (39 micrograms/kg, SC; once daily for 5 days). The same brain regions were also assayed on days 3 through 7 after the last injection of soman, to examine possible recovery of AChE. The observed regional brain sensitivity to AChE inhibition can be described in the following order: frontal cortex = piriform cortex greater than hippocampus = cerebellum = thalamus greater than striatum = hypothalamus. Most brain areas showed only a small recovery from this inhibition through the seventh day following the last soman injection. The progressive nature of the AChE inhibition during the week of soman administration and the failure to find a significant interaction between injection and day indicates that tolerance to soman exposure did not develop in this paradigm. The protocol described here appears to provide a useful method to study prophylactic measures for low-dose repeated soman exposure and evaluation of differential CNS inhibition and recovery from AChE inhibition.

Acetylcholinesterase↗
PubMed1991

Generally recognized as safe (GRAS) evaluation of 4-hexylresorcinol for use as a processing aid for prevention of melanosis in shrimp.

4-Hexylresorcinol (C12H18O2) is proposed for use as a processing aid for prevention of melanosis ("black spot") in shrimp and as an alternative to the currently approved sulfites. A safety evaluation was conducted to affirm, based upon scientific procedures, the generally recognized as safe ("GRAS") status of 4-hexylresorcinol for proposed use. The GRAS safety evaluation compiled, reviewed, and analyzed data on the following areas: chemical identity, analytical methodology, historical and proposed uses, functionality, and safety. The publicly available safety data on 4-hexylresorcinol cover a broad range of potential toxicity concerns including acute and subacute toxicity, subchronic toxicity, carcinogenicity, mutagenicity, and allergenicity. These studies, along with the aforementioned data, demonstrate that 4-hexylresorcinol presents no risk of toxicity at the levels proposed for treatment of shrimp, and the use of 4-hexylresorcinol as a processing aid to prevent melanosis in shrimp is GRAS.

Animals↗
PubMed1991

Differential inactivation of surrogate viruses with merocyanine 540.

Bacteriophages may be useful as surrogates for animal viruses when the virucidal properties of different photosensitizing compounds are initially investigated. We studied photoinactivation of four bacteriophages, phi X174, T7, PRD1, and phi 6, by the dye merocyanine 540 (MC540) (15 micrograms/mL). Merocyanine 540 (MC540) should be most effective with lipid-containing viruses, since it is primarily lipophilic (but also binds to proteins). Two of the phages, PRD1 and phi 6 contain lipid, with only phi 6 having an external lipoprotein envelope. Filtered radiation (450-600 nm) from a 750 W projector was used at 16-100 W/m2. The survival curves of the different viruses clearly demonstrated different levels of sensitivity to photoinactivation by MC540, with phi 6 (Do = 1.5 kJ/m2) being the most sensitive, followed by T7 (21-fold less sensitive). While both PRD1 and phi 6 have lipid components, only phi 6 was photoinactivated by MC540. Thus the internal lipid components of PRD1 were not sufficient to allow photoinactivation by this dye, at fluences up to 300 kJ/m2. For comparison, we also photoinactivated Herpes simplex virus (Do = 0.053 kJ/m2) and found it to be 28-fold more sensitive than phi 6 to photoinactivation by the same concentration of MC540. Thus phi 6 may be used as a surrogate for enveloped human viruses for photoinactivation by lipophilic dyes, but the results may only be useful qualitatively.

Animals↗
PubMed1990

Acid-induced esophagobronchial-cardiac reflexes in humans.

Esophagobronchial reflexes have been demonstrated in both the cat and dog models. In order to determine if these reflexes are present in humans and if they are vagally mediated, a prospective sequential study was initiated. One hundred thirty-six individuals referred for esophageal manometric measurements were studied. Measurements of airway flow, arterial oxygen saturation, and pulse rate were performed before and after intraesophageal infusion of sterile water, normal saline solution, and 0.1 N hydrochloric acid. Highly significant reductions in heart rate, airway flow, and arterial oxygen saturation were noted after infusion of normal saline and 0.1 N hydrochloric acid compared with baseline water infusion (P less than 0.001). Graded responses were noted with heart rate: the more acidic the solution infused, the larger the decrement of heart rate. Atropine abolished postsaline/acid decrements of airway flow, arterial oxygen saturation, and heart rate. It is concluded that acid-induced, vagally mediated esophagobronchial reflexes are present in humans.

Atropine↗
PubMed1990

Retinal injury induced by near-ultraviolet radiation in aphakic and pseudophakic monkey eyes. A preliminary report.

The effect of repeated exposures to low-intensity, near-ultraviolet (UV) radiation on the retinas of phakic, aphakic, and pseudophakic monkey eyes was studied. Ten eyes (4 aphakic eyes, 3 pseudophakic eyes, and 3 normal phakic eyes) of five rhesus monkeys were used. The near-UV radiation was generated by a high-pressure mercury vapor lamp with a total radiance of 14.43 mW/cm2/sr. Exposure regimens were 5 minutes a day for 10 days, 15 minutes a day for 5 days, or 60 minutes a day for 5 days. The retinas of aphakic and pseudophakic eyes were exposed to a daily dose of more than 0.97 J/cm2, or a total dose of more than 4.9 J/cm2 in 5 days at a retinal irradiance of more than 1.0 mW/cm2. Three of four aphakic eyes and one of three pseudophakic eyes showed clinical and pathologic retinal lesions after radiation. None of the three phakic eyes was damaged. The retinal lesions showed mild opalescent thickening ophthalmoscopically and retinal pigment epithelial staining by fluorescein angiography. Histopathologically, the retinal pigment epithelium was the site of primary injury by near-UV radiation.

Animals↗
PubMed1990

Simultaneous assay of felbamate plus carbamazepine, phenytoin, and their metabolites by liquid chromatography with mobile phase optimization.

Felbamate is an investigational antiepileptic drug (AED) in clinical trials. A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin, carbamazepine (CBZ), carbamazepine-10,11-epoxide, and carbamazepine-10,11-diol in serum was developed by a mobile phase optimization technique. Capacity factors for the compounds of interest and 12 other AEDs and metabolites were determined with mixtures of methanol, acetonitrile, or tetrahydrofuran and a 0.01 M ammonium phosphate buffer, pH 6.5, on a reversed-phase C8 column. An optimized mobile phase composition was determined that could separate the compounds of interest and three internal standards in less than 15 min. Serum was extracted with CH2Cl2/ethyl acetate (2:1) after addition of three internal standards. The method was validated for within-day and between-day precision and accuracy for the six compounds. Coefficients of variation were generally less than 10% at all concentrations and less than 5% in the typical therapeutic range for each compound. The lower limit of detection was estimated at 0.2 micrograms/ml for CBZ and its metabolites and 0.5 micrograms/ml for felbamate and PHT. For felbamate, the lowest point on the standard curve was 1.88 micrograms/ml with a between-day variability of 10.3%. The assay was used to determine the serum concentrations of PHT and CBZ and its metabolites in a subject before, during, and after felbamate therapy.

Carbamazepine↗
PubMed1990

The role of platelets in the reflex tachypnoeic response to miliary pulmonary embolism in anaesthetized rabbits.

Experiments were performed upon twenty-eight male Californian rabbits anaesthetized with sodium pentobarbitone and breathing room air. Successive injections of glass bead emboli (diameter 125 microns) caused an increase in respiratory rate, and decreases in tidal volume (tachypnoeic response) and platelet count. The tachypnoeic response was not observed in rabbits that had been rendered thrombocytopaenic by platelet antiserum. Induction of thrombocytopaenia by antiserum was accompanied by tachypnoea which was not significantly different (P greater than 0.05) from the response to emboli. The tachypnoeic response to antiserum, like that to emboli, was prevented by bilateral cervical vagotomy. Pre-treatment with aspirin (5 mg/kg), which inhibits the platelet-release reaction, also prevented the tachypnoeic response to both emboli and antiserum, although it did not prevent the fall in platelet count which following injection of antiserum. These data support the hypothesis that the post-embolic reflex tachypnoea is platelet dependent and may be secondary to the platelet-release reaction.

Animals↗
PubMed1989

Cell proliferation in chick oral membrane lags behind that of adjacent epithelia at the time of rupture.

Radioautographic analysis showed that ectoderm and endoderm cells in chick oral membrane continued to label with tritiated thymidine through the period of rupture, but their frequency of labeling was significantly lower than those of adjacent epithelia. Frequency of labeling increased in adjacent ectoderm and endoderm, while oral membrane rates remained relatively low, suggesting that growth in the membrane lags relative to adjacent epithelia. Relatively greater proliferation in adjacent epithelia could generate tension and pull apart the thinned oral membrane. Differentials in rates of cell proliferation, when considered along with knowledge of cellular rearrangements following changes in basal lamina and matrical components, suggest that differential growth is an important force in rupture of the avian oral membrane.

Animals↗