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Biomedical subjects

S A Reynolds

Publications and source records attributed to S A Reynolds.

At least 19 recordsLinked to original sources

Dying to be thin: a dinitrophenol related fatality.

2, 4-dinitrophenol (DNP) was originally used as an explosive and later introduced in the 1930's to stimulate metabolism and promote weight loss. It's also a component of pesticides still available globally. Concerns about hyperpyrexia lead to DNP being banned as a dietary aid in 1938. A 22-y-old male presented to the Emergency Department (ED) with a change in mental status 16 h after his last dose of DNP. On admission he was diaphoretic and febrile with an oral temperature of 102 F, but lucid and cooperative. He became agitated and delirious. Intravenous midazolam was initiated with mechanical cooling. Pancuronium was administered later and the patient was intubated. Over the next hour the patient became bradycardic, then asystolic, and despite resuscitative efforts, died. Advertisements claim DNP safe at the dose our patient ingested. It is widely available and with the potential to cause severe toxicity is an understudied public health concern.

2,4-Dinitrophenol↗

Analysis of preventable pediatric trauma deaths and inappropriate trauma care in Montana.

OBJECTIVE: To determine the rates of preventable mortality and inappropriate care, as well as the nature of treatment errors associated with pediatric traumatic deaths occurring in a rural state. METHODS: Retrospective multidisciplinary consensus panel review of deaths attributed to mechanical trauma in children aged 18 years or less, occurring in Montana between October 1, 1989, and September 30, 1992. The care rendered in both preventable and nonpreventable cases was evaluated for appropriateness according to nationally accepted guidelines. Rates of pediatric preventable death and inappropriate care, as well as the nature of inappropriate care, were compared with that of the adult population. RESULTS: One hundred thirty-eight cases were reviewed. One death (less than 1%) was judged frankly preventable, 11 deaths (8%) were judged possibly preventable, giving a total preventability rate of 9% for all cases reviewed. Considering only in-hospital deaths (n = 77), the total preventability rate was 16%. The rate of inappropriate care rendered for all deaths, regardless of preventability, was 36%. The rate of inappropriate care in the prehospital phase was 16%; for in-hospital deaths, it was 47%. In the emergency department (ED), the rate was 36%, and in post-ED care, 22%. In comparison to the adult population, the rates of preventable death (9% vs. 14%) and inappropriate care in the hospital phase (64% vs. 66%) were lower. Inappropriate care for the pediatric group was more prevalent in patients less than or equal to 14 years old. The nature of inappropriate care was most frequently associated with the management of respiratory problems, including airway control and management of chest trauma. CONCLUSION: Preventable mortality from traumatic injuries in children in a rural state appears to be low, and lower than that reported for adult trauma victims in the same state. A preponderance of these preventable deaths occur in the subgroup of children less than or equal to 14 years if age. Inappropriate trauma care in children occurs frequently, particularly in the ED phase of care, and is primarily associated with the management of the airway and chest injuries. Education of ED primary care providers in basic principles of stabilization and initial treatment of the injured child 14 years old or younger may be the most effective method of reducing preventable trauma deaths in the rural setting.

Adolescent↗

Staging of middle and late embryonic development in the medicinal leech, Hirudo medicinalis.

We present a description of the last half of embryonic development in the European medicinal leech, Hirudo medicinalis, based entirely on externally visible morphological features, and establish reliably observable stages during that development. Embryogenesis, from the time fertilized eggs are deposited in an eggcase (called a cocoon) to the emergence of juveniles from the cocoon, takes approximately 4 weeks at room temperature. The stages described in this paper extend from the completion of segmentation to the appearance of the final bands of pigmentation. Developmental stages are expressed as percentages of total embryonic developmental time. This staging table was constructed for embryos kept at 20 degrees C. In addition, the development of animals kept at 17 degrees C or at 24 degrees C was compared with those held at 20 degrees C. Development proceeds more quickly at higher temperatures. Because development in embryos held at higher or lower temperatures was linearly related to the stages determined for embryos held at 20 degrees C, the rate of development at any intermediate temperature can be predicted from the staging table at 20 degrees C by simple multiplication.

Animals↗

Development of spontaneous and evoked behaviors in the medicinal leech.

ABSTRACT The ontogeny of behavior in an organism must reflect developmental events in the nervous system, and it thus provides a noninvasive measure of neuronal development. This approach may be particularly fruitful in the medicinal leech because the neuronal basis of several behaviors has been characterized in adult leeches, providing a rich background against which behavioral development can be interpreted. We have investigated the order in which behaviors arise during the period of embryonic development and have determined the time at which each behavior is first expressed. Some behaviors, such as lateral ridge formation, germinal plate bending, spiral twisting, and sidewinding, were produced spontaneously by embryos. Others, such as shortening, circumferential indentation, local bending, and elongation, occurred only when they were elicited by weak mechanical stimulation. Such stimulation rarely evoked a behavioral response in young embryos (at 45% of the time required for complete embryonic development, 45% ED), but by 80% ED embryos responded to nearly 100% of the stimuli presented. In embryos older than 50% ED, the behavior most frequently evoked by stimulation of the anterior end, the posterior end, or the rear sucker was shortening. Stimulation of the midbody usually evoked behavior other than shortening, illustrating that the body was behaviorally compartmentalized, at least in part. Some behaviors observed during embryogenesis are never seen in adult leeches. For example, in response to stimulation of the midbody, young embryos produced a behavior that we have called "circumferential indentation," whereas older embryos produced local bending, a response previously described for adults. The switch from circumferential indentation to local bending may signal the formation of new synaptic connections.

Animals↗

In vitro incubation of low-density lipoproteins with inflammatory cells causes enhanced degradation by macrophages in culture.

Utilizing the polyvinyl sponge-implant model, we have reported in vivo modification of low-density lipoproteins (LDL) isolated from interstitial inflammatory fluid (IF) of the rabbit. Further studies on the metabolism of IF-LDL by resident mouse peritoneal macrophages (MPM), demonstrated enhanced uptake and degradation of these modified lipoproteins by scavenger mechanisms. Based upon these studies, we attempted to examine the mechanisms of these observed in vivo modifications in IF-LDL by in vitro incubation of plasma LDL with inflammatory fluid subfractions. Incubation of LDL with inflammatory cells at 37 degrees C resulted in an increased anodal electrophoretic mobility and alteration in apolipoprotein (APO) composition. Subsequent incubation of this modified plasma LDL with MPM resulted in a significant increase in cell surface binding and an increase in the appearance of degradation products in the medium. The formation of lipid peroxides, measured as thiobarbituric acid-reacting substances (T Bars), increased with the time of LDL incubation with inflammatory cells. Conversely, incubation of LDL with cell-free, lipoprotein-deficient IF (LPDIF, d greater than 1.210 g/ml) significantly inhibited LDL degradation by MPM. LPDIF did not alter the electrophoretic mobility of LDL or result in the appearance of T Bars in the medium. These results implicate peroxidative reactions associated with an inflammatory response as mediators of the in vivo modifications in IF-LDL which facilitates enhanced uptake via the scavenger receptor in MPM.

Animals↗

The effect of oral l-carnitine on lipoprotein composition in the Watanabe Heritable Hyperlipidemic Rabbit (Oryctolagus cuniculus).

1. We have recently reported the ability of orally administered l-carnitine to lower plasma triglyceride in the Watanabe Heritable Hyperlipidemic Rabbit (WHHL), an animal model of familial hyperlipoproteinemia. 2. In the present studies we examined the effect of l-carnitine administration upon individual lipoprotein subfractions in this animal model. 3. Carnitine feeding resulted in a reduction in very low density lipoproteins (VLDL) and high density lipoprotein (HDL). 4. Compositional analysis revealed a reduction in core triglyceride content with a concomitant increase in protein and phospholipid in VLDL and low density lipoproteins (LDL). 5. Conversely, electrophoretic mobility and apolipoprotein composition were unchanged with l-carnitine. 6. These results further demonstrate the ability of l-carnitine to modulate lipoprotein lipid composition in this animal model of familial hyperlipoproteinemia.

Animals↗

Turnover of low-density lipoprotein isolated from interstitial inflammatory fluid of the rabbit.

Utilizing the polyvinyl sponge-implant model in the rabbit, we have described in vivo modification of low-density lipoproteins (LDL) in interstitial inflammatory fluid (IF). In the present studies, plasma clearance rates of IF-LDL were determined and compared with normal whole plasma LDL (WP-LDL) as well as plasma LDL modified by chemical reaction with acetic anhydride (Ac-LDL). Lipoproteins were labeled with 125I and injected into the lateral ear vein of recipient rabbits. At 10 min after injection, only 51.5% of IF-LDL could be accounted for in recipient plasma, as compared to 91.9% for WP-LDL, and 2.4% of Ac-LDL. Subsequent log-linear decay rates were similar for IF-LDL and WP-LDL (t 1/2 = 9.5 vs. 11.0 h). Autoradiography of plasma obtained from recipient animals at 15 min and 1 h after injection revealed a return to normal electrophoretic mobility of [125I]IF-LDL. These results indicate that IF-LDL is a mixture of both modified and essentially unmodified particles. We propose that the modified particles may be removed from the circulation by mechanisms described for Ac-LDL.

Animals↗

Lipoproteins of the extravascular space: enhanced macrophage degradation of low density lipoproteins from interstitial inflammatory fluid.

Current evidence has demonstrated that cholesteryl ester-loaded macrophages are important components of the atherosclerotic lesion. Additional studies have implicated low density lipoproteins (LDL) and circulating monocytes as central to the origin of lipid-laden foam cells found in the arterial wall. This is a result of the finding of accelerated macrophage uptake of LDL chemically modified by reaction with malondialdehyde (MDA-LDL), acetic anhydride (Ac-LDL), or incubation with arterial cells in vitro. In concert with these chemical modifications, we have previously demonstrated selective in vivo modification of LDL isolated from interstitial inflammatory fluid (IF) of the rabbit. Utilizing the polyvinyl sponge implant model, we reported that IF-LDL had an altered chemical composition, electrophoretic mobility, and particle size distribution when compared to LDL isolated from homologous plasma (WP-LDL). In this study reported herein, we examined the metabolism of IF-LDL by resident mouse peritoneal macrophages (MPM) in culture. IF-LDL was degraded substantially faster by MPM, and resulted in a substantial increase in cellular cholesteryl ester when compared to cells incubated with WP-LDL. IF-LDL binding to MPM was inhibited by Ac-LDL derived from WP-LDL, but only minimally by unmodified WP-LDL. Transmission electron microscopy of MPM revealed extensive lipid deposition in cells incubated with Ac-LDL and IF-LDL. These results implicate LDL from interstitial inflammatory fluid as an in vivo modified lipoprotein that can enhance uptake via the acetyl LDL receptor pathway in resident macrophages.

Acetic Anhydrides↗

Direct modification of plasma low-density lipoproteins in interstitial inflammatory fluid of the rabbit.

Utilizing the polyvinyl sponge-implant model in the rabbit, we have previously demonstrated modification in low-density lipoproteins (LDL) in the extravascular space in association with a cellular inflammatory response. In an attempt to isolate the source of these modifications, plasma LDL was labeled with 125I, and introduced directly into the extravascular space at the time of sponge implantation. [125I] plasma LDL recovered from interstitial inflammatory fluid (IF) at 24 h after implantation demonstrated increased electrophoretic mobility as well as heterogeneity in particle size and hydrated density. These results are in agreement with our previous observations and indicate that modification in IF-LDL probably occurs after it has entered the extravascular space across the vascular wall.

Animals↗

Effect of cholesterol feeding on lipoprotein distribution in interstitial inflammatory fluid of the rabbit.

Utilizing the polyvinyl sponge-implant model in the rabbit we have previously demonstrated modification in low density lipoproteins (LDL) of interstitial tissue fluid obtained in association with a cellular inflammatory response. In order to examine the interaction between the inflammatory response and lipoproteins from hypercholesterolemic rabbits, 30 male, New Zealand White rabbits were fed standard chow supplemented with 0.5% cholesterol for 4 weeks prior to sponge implantation. Lipoproteins were prepared from interstitial inflammatory fluid (IF) as well as homologous whole plasma (WP). Total IF cholesterol was positively correlated with plasma cholesterol (459 +/- 43 vs. 1485 +/- 130 mg/dl, means +/- SEM, r = 0.81, P less than 0.01). Distribution of lipoproteins in IF was similar to WP in both particle size and density. Beta-migrating VLDL were the predominant particles in both WP and IF, containing 43.7 +/- 3.4 and 42.2 +/- 5.1% of WP and IF cholesterol, respectively. IF-VLDL were similar to WP-VLDL in lipid and apoprotein composition, morphology and particle size distribution. We conclude from these data that the observed dramatic alterations in lipoprotein distribution in response to a dietary cholesterol challenge in rabbit plasma is essentially unaltered in interstitial inflammatory fluid obtained from these animals.

Animals↗

Lipoprotein metabolism in the extravascular space. Cyclophosphamide inhibits modification of low-density lipoproteins in interstitial inflammatory fluid of the rabbit.

We have recently reported preferential modification and reduction in low-density lipoproteins (LDL) of inflammatory exudates in the rabbit. In an attempt to establish the role of inflammatory cells in these specific alterations, using the sponge-implanted rabbit model we characterized extravascular lipoproteins in animals with severely induced leukopenia. Under these conditions we were unable to demonstrate alterations in the distribution of lipoproteins in inflammatory fluid as compared to homologous plasma. Characterization of LDL from both plasma and inflammatory fluids revealed close similarity in molecular composition and electrophoretic mobility. These studies further implicate the role of scavenger cell systems as a significant component of daily lipoprotein homeostasis.

Animals↗

Lipoproteins of the extravascular space: alterations in low density lipoproteins of interstitial inflammatory fluid.

Although extrahepatic degradation of low density lipoproteins (LDL) by peripheral cells is considered to be a significant component of daily cholesterol homeostasis, the nature of lipoproteins in the extravascular space has not been well described. Using a sponge implantation model in the rabbit, we examined lipoproteins prepared from interstitial inflammatory fluid. Inflammatory fluid cholesterol is correlated with plasma values, (r = 0.735, P less than 0.01), but triglyceride values are not. Examination of inflammatory fluid lipoproteins by agarose gel electrophoresis, column chromatography, and density gradient centrifugation revealed a marked reduction in LDL concentration as compared to plasma LDL. Inflammatory fluid low density lipoproteins prepared by sequential density flotation had a larger mean diameter, they were erratic in shape, and contained more triglyceride and less cholesterol and cholesteryl ester than plasma LDL. Total cholesterol to protein ratio was significantly reduced in inflammatory fluid LDL (0.73 vs. 1.10, P less than 0.05). Inflammatory fluid LDL migrated further than plasma LDL on agarose electrophoresis, despite similar apoprotein patterns. These data concur with findings of altered composition and electrophoretic mobility of plasma LDL modified in vitro by exposure to acetylating agents, malondialdehyde, or aortic cells in culture, and they may represent the actual form of LDL in the extravascular space.

Animals↗

Circulating phospholipids in interstitial inflammatory fluid of the rabbit.

Using a sponge implantation model in the rabbit, we have examined the distribution and fatty acid composition of extravascular phospholipids in interstitial inflammatory fluid. Inflammatory fluid contained less phosphatidylserine and -inositol and a complete absence of phosphatidylethanolamine as compared to autologous plasma. Inflammatory fluid phospholipids contained an increased amount of oleic acid, decreased linoleic acid, and undetectable levels of arachidonic acid, despite unaltered levels of these fatty acids in other extravascular lipid classes as compared to plasma. Potential metabolic consequences of these findings are discussed.

Animals↗

Comparative results of postmastectomy rehabilitation in a specialized and a community hospital.

This article describes results of postmastectomy rehabilitation program as operating at Mt. Sinai Hospital of Cleveland, a general community facility. Common physical and emotional problems following mastectomy are documented, as well as barriers to effective rehabilitation--particularly the fact that such programs are usually associated with specialized oncology settings and not seen as feasible in the community hospital. An analysis of outcomes of a program operated at both Mt. Sinai and Memorial Sloan-Kettering Cancer Center demonstrates that comparable and positive patient outcomes can be achieved in terms of range of motion, resumption of prior activities, and emotional stress. Recommendations are made regarding ways to overcome common problems in implementing such programs in an inexpensive and effective manner.

Activities of Daily Living↗

Postmastectomy rehabilitation in a community hospital.

The need for, operation, and outcomes of an in-hospital postmastectomy rehabilitation program are described as operating at a general community hospital, the Mt. Sinai Hospital of Cleveland. Patient outcomes in terms of range of motion (94 and 98 percent normal 90 days after discharge, right and left arm respectively); resumption of normal activities and return to work (94 percent had resumed normal activities within 90 days and 85 percent had returned to work); and emotional stress (fewer than one in ten reported moderate to severe emotional stress) are demonstrated to be indicative of good rehabilitation. These results are comparable to those reported achieved in a specialized oncology setting. This type of program can be successfully conducted in a community hospital with the limited use of regular hospital personnel, although problems related to physician resistance and assuring the regular availability of appropriate staff members for even a short time each day must be overcome.

Activities of Daily Living↗