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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 109 records · Page 6Linked to original sources

Preliminary evaluation of a simple in vitro test for the diagnosis of type C botulism in wild birds.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of type C botulinum toxin (Clostridium botulinum) in wild birds. This simple, antigen-capture ELISA utilizes polystyrene immunosticks as the solid substrate, chicken antitoxin (IgY) as the coating antibody, rabbit antitoxin as the primary antibody, and peroxidase-labeled goat-anti-rabbit as the secondary antibody. To evaluate the immunostick ELISA as a diagnostic test for avian botulism, known concentrations of toxin were added to heparinized blood collected from healthy birds and tested by both the ELISA and mouse bioassay. Also, blood samples from 236 bird carcasses submitted to the National Wildlife Health Center (NWHC) for cause of death determinations were tested by both procedures. Using < or = 0.5 ml as the test volume for both procedures, the ELISA was less sensitive, detecting 0.25 ng/ml of toxin compared to 0.12 ng/ml for the mouse bioassay. Using the same volume of test sample for diagnostic submissions (< or = 0.5 ml), the ELISA was positive for 60% of the 149 clinically-diagnosed cases of botulism, whereas the mouse bioassay was positive for 79%. However, we demonstrated that with larger sample volumes (> or = 1.0 ml), the sensitivity of the ELISA may be equivalent or better than the mouse test due to the concentrating effect of the ELISA procedure. These preliminary results suggest that when adequate sample volumes are available, the immunostick ELISA can replace the mouse test for the diagnosis of botulism in wild birds.

Animals↗

State implementation of the AIDS drug assistance programs.

Acquired immunodeficiency syndrome (AIDS) drug assistance programs (ADAPs) provide access to medications for people who lack other health coverage. In this article, the authors present the results of a 1997 survey identifying how 48 States implemented ADAPs, focusing on the number of beneficiaries, medical and financial eligibility criteria, the administration of waiting lists, and the coverage of drugs including protease inhibitors. Increased funding for ADAPs is necessary to maintain this important part of the public sector safety net for human immunodeficiency virus (HIV) care.

Acquired Immunodeficiency Syndrome↗

Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia.

IL-10 protects mice from LPS-induced lethality. To determine the effects of IL-10 on LPS-induced inflammatory responses, six Papio anubis baboons were i.v. injected with a sublethal dose of LPS (Salmonella typhimurium; 500 microg/kg) directly preceded by either human rIL-10 (n = 3, 500 microg/kg) or diluent (n = 3). IL-10 strongly inhibited LPS-induced release of TNF, IL-6, IL-8, and IL-12 (all p < 0.05). By contrast, IL-10 did neither influence the activation of the coagulation system (plasma levels of thrombin/antithrombin III complexes), nor the activation of the fibrinolytic system (plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin/alpha 2-antiplasmin complexes). IL-10 modestly attenuated neutrophilic leukocytosis and neutrophil degranulation (plasma concentrations of elastase/alpha1-antitrypsin complexes) (both p < 0.05). Changes in surface TNF receptor expression on circulating granulocytes were not affected by IL-10. These results suggest that during sublethal endotoxemia the predominant anti-inflammatory effect of IL-10 treatment is inhibition of proinflammatory cytokine release.

Animals↗

Elevated levels of NO in both unchallenged and LPS-challenged C. parvum-primed mice are attributable to the activity of a cytokine-inducible isoform of iNOS.

Elevated levels of nitric oxide (NO2-/NO3-) were detected in the serum of mice 3-7 days after priming with Corynebacterium parvum (Propionibacterium acnes). The serum NO2-/NO3- response was completely inhibited when C. parvum-primed (C. parrum) mice were treated with N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited when the mice were treated with interleukin-10 (IL-10) and the cytokine was most effective when given in multiple doses beginning on the day of priming. In contrast to L-NMMA and AG, IL-10 had no effect on the serum NO2-/NO3- response when administered to the mice on days 6 and 7 post priming. The inducible isoform of NOS (iNOS) appeared to be responsible for the elevated NO2-/NO3- response in C. parvum mice because iNOS transcripts were readily detected in their livers. Moreover, these transcripts as well as the circulating levels of NO2-/NO3- were dramatically reduced when the mice were treated with anti-tumor necrosis factor alpha (anti-TNF-alpha) or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAbs) during the priming interval. There was a modest increase (less than twofold) in the serum NO2-/NO3- response following a lipopolysaccharide (LPS) challenge to C. parvum mice (C. parvum/LPS mice). LPS had a more dramatic stimulatory effect if the levels of NO2-/NO3- preexisting in C. parvum/LPS mice were reduced by treatment with L-NMMA, AG, or IL-10 before the challenge. Thus the levels of NO2-/NO3- that preexisted in C. parvum/LPS mice appeared to influence their ability to mount a NO2-/NO3- response subsequent to the LPS challenge. The NO2-/NO3- response did not contribute to lethality in C. parvum/LPS mice because anti-TNF-alpha and anti-IFN-gamma mAbs were protective but had no effect on serum NO2-/NO3- levels when administered to mice 24 h before the LPS challenge.

Animals↗

Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men.

Although triiodothyronine (T3) exerts major regulatory actions in both animals and humans, most clinical studies of T3 administration have been relatively short-term. The present study examined the effects of more than 2 months (63 days) of low-dose T3 treatment on overnight pulsatile growth hormone (GH) secretion, short-term insulin secretion, and of sex steroid levels in seven healthy, lean men studied at an inpatient metabolic unit. At baseline, there were strong correlations between sex hormone-binding globulin (SHBG) and several measures of GH production, including total GH production (r = .99), GH interburst interval (r = -.75), and GH mass (r = .82). SHBG was also inversely correlated with basal insulin secretion (r = -.74). There was a 42% increase in serum levels of total testosterone (18.5 +/- 1.3 to 26.3 +/- 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 +/- 2.2 to 44.9 +/- 7.0 nmol/L, P = .008) following T3 treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L. T3 treatment significantly reduced the GH interburst interval (P < .05) and produced slight increases in the measures of GH secretion. There were no statistically significant effects of T3 treatment on insulin secretion, although insulin peak amplitude, mass secreted per burst, and total production all decreased. We conclude that experimentally induced T3 excess in healthy men produces significant and sustained changes in sex hormone levels and GH secretion. Furthermore, there are strong associations between SHBG and both GH and insulin secretion independent of thyroid hormone excess that require additional study.

Adult↗

Development and validation of a measure of adolescent dissociation: the Adolescent Dissociative Experiences Scale.

This study describes the initial reliability and validity data on the Adolescent Dissociative Experiences Scale (A-DES), a screening measure for pathological dissociation during adolescence. The A-DES showed good scale and subscale reliability, and, as hypothesized, increased scores were associated with reported trauma in a patient population. A-DES scores were able to distinguish dissociative disordered adolescents from a normal sample and from a patient sample with a variety of diagnoses.

Adolescent↗

Case report of metallic mercury injury.

OBJECTIVE: Injury and poisoning from metallic mercury has become a rare event. Review of the literature and a case report of pediatric metallic mercury injury are presented. DESIGN: A case report. SETTING: The Emergency Department at St. Louis Children's Hospital. PATIENTS OR PARTICIPANTS: A 15-year-old boy. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: The 15-year-old boy fell on a broken mercury thermometer. A subcutaneous abscess formed on his left forearm during the next five days. He had no signs or symptoms of mercury toxicity. His wound was debrided in the operating room and healed completely after several months. CONCLUSIONS: This case shows elemental mercury from a thermometer as a potential, if unusual, source of mercury toxicity.

Abscess↗

Infections complicating pulsed carbon dioxide laser resurfacing for photoaged facial skin.

BACKGROUND: With proper technique and instrumentation, laser resurfacing for facial wrinkles has been found to be highly effective and relatively safe. Most, if not all, of the noninfectious complications such as pigmentary changes, scarring, and persistent erythema can either be avoided or managed with appropriate therapy. Postoperative infections, on the other hand, may develop despite proper technique and instrumentation. Without proper management, they may cause significant physical morbidity and psychological distress defying the expected benefit of the procedure. OBJECTIVE: To quantify the incidence and to study the characteristics of infections arising after laser resurfacing for facial wrinkles with pulsed carbon dioxide laser treatment. METHOD: A retrospective study was carried out by reviewing the records of all patients undergoing laser resurfacing for facial wrinkles from January 1, 1995 to April 30, 1996. An infection is defined as a positive culture in the presence of signs or symptoms of an infection. RESULTS: Over 16 months, 395 procedures were performed and 17 cases of culture-proven infection recorded, an incidence of 4.3%. All patients had symptoms starting between days 2 and 10 after the operation. Over half of the patients had multiple infections with two to three microorganisms. Pseudomonas aeruginosa was the most common causative agent, found in 41% of all infected cases, followed by Staphylococcus aureus (35%), S. epidermidis (35%), and Candida species (24%). Multiple drug-resistant, gram-negative bacteria were found in four cases, implicating the possibility of hospital-acquired infections. Almost all isolates of gram-positive bacteria were resistant to both erythromycin and penicillin, but not oxacillin. With proper treatment, most patients healed normally. Only one patient had persistent, multiple atrophic scars due to locally disseminated herpes simplex infection despite proper prophylaxis and treatment. CONCLUSIONS: Postoperative infection is uncommon and manageable with early recognition and proper treatment. The types of infectious agents being found are very similar to those reported in burn patients. This complication has been found to be much more common in patients undergoing full face resurfacing and those using a bio-occlusive dressing postoperatively. With comprehensive preventive and management measures, it is likely that this type of uncommon, yet distressful, complication can be avoided and more successfully treated. Recommendations are made for prevention and management of suspected postoperative infections.

Candidiasis↗

A paradigm of experimentally induced mild hyperthyroidism: effects on nitrogen balance, body composition, and energy expenditure in healthy young men.

Although T3 exerts major regulatory actions in both animals and humans, most clinical studies of T3 administration have been relatively short term. The present study examined the effects of more than 2 months (63 days) of low dose T3 treatment on nitrogen balance, body composition, 24-h energy expenditure (EE), and protein turnover in seven healthy men studied at an in-patient metabolic unit. Subjects were also randomly assigned to either high or low fat diets to determine the effects of diet composition. T3 treatment produced significant losses in both lean mass (1.5 +/- 0.3 kg) and fat mass (2.7 +/- 0.4 kg) by 6 weeks, with similar reductions in both at 9 weeks. The high fat diet somewhat attenuated the loss of body fat. Nitrogen balance was significantly negative for the first 3 weeks of T3 treatment, but tended to return to baseline thereafter. There were no significant effects of treatment on protein turnover at 9 weeks, although there was a slight increase in leucine oxidation (P = 0.07). Despite the apparent adaptation in nitrogen balance, total 24-h EE and sleeping EE were significantly increased at 9 weeks. We conclude that although healthy men are able to adapt to mild hyperthyroidism in terms of nitrogen balance, they exhibit significant and persistent changes in fat and fat-free mass as well as energy balance.

Adult↗

Medial gastrocnemius transposition flap for the treatment of disruption of the extensor mechanism after total knee arthroplasty.

We describe a modified technique for the salvage of a total knee arthroplasty after disruption of the extensor mechanism. Between January and December 1992, seven patients had reconstruction of the extensor mechanism with use of a medial or an extended medial gastrocnemius flap. Six of the seven patients were followed for a mean of thirty-three months (range, twenty-six to forty-one months) and were evaluated both preoperatively and postoperatively with regard to the knee and functional scores of The Knee Society as well as the range of motion, extensor lag, walking status, and patellar height. The seventh patient was lost to follow-up six months postoperatively and was excluded from the analysis of the results. Preoperatively, the knee and functional scores were 16 +/- 12.3 points and 12 +/- 12.1 points (mean and standard deviation), respectively; the mean range of motion was 70 +/- 44.0 degrees; and the mean extensor lag was 53 +/- 33.4 degrees. Postoperatively, the mean knee and functional scores improved to 82 +/- 12.4 points and 51 +/- 23.0 points, respectively; the mean range of motion improved to 100 +/- 21.8 degrees; and the mean extensor lag decreased to 24 +/- 18.8 degrees. After the procedure, all patients who previously had been dependent on a walker were able to walk about the community with or without a cane, and those who had been dependent on a wheelchair were able to walk with the assistance of a walker. Patellar height was measured according to the method of Insall and Salvati for the four patients who had a patella. Preoperatively, the patellar heights were grossly abnormal; postoperatively, they more closely approached accepted normal values for three of the four patients. Reconstruction of a complicated rupture of the extensor mechanism with use of a medial gastrocnemius transposition flap after total knee arthroplasty is a reliable option for treatment.

Achilles Tendon↗

Voluntary wheel running decreases adipose tissue mass and expression of leptin mRNA in Osborne-Mendel rats.

The purpose of this study was to assess the effects of voluntary wheel running on the expression of leptin mRNA in rats that are either sensitive (OM) or resistant (S5B/Pl) to diet-induced obesity. Male OM and S5B/Pl rats had ad libitum access to standard rodent diet and water. At 3-5 weeks of age, animals of both strains were randomly assigned to either an exercise or sedentary control group. The exercise groups had 24-h access to a running wheel, and they trained for 7 weeks. During weeks 1-4, animals in both OM and S5B/Pl exercise groups progressively increased their running. During weeks 5-7, S5B/Pl exercisers tended to run more than did OM (approximately 60 vs. 45 km/week), but by the end of the study both groups had an equally greater heart weight (mg/g body weight) and planteris citrate synthase activity than their sedentary controls. Oral glucose tolerance tests performed during the last week of training revealed that compared with their appropriate controls, insulin sensitivity was enhanced (P < 0.05) in OM but not in the S5B/Pl wheel-running groups. Inguinal, epididymal, and retroperitoneal fat pads weighed less in the running than in the nonrunning groups of both strains (P < 0.01). Additionally, exercised animals had an increased percentage of smaller cells (40-60 microm; P < 0.05) and a decreased percentage of larger cells (120-160 microm; P < 0.05) in the epididymal fat depot. Epididymal leptin mRNA measured by Northern blot analysis was reduced in the exercise-trained rats of both strains (P < 0.05). Furthermore, serum leptin was reduced in exercise-trained compared with the control animals of both strains. In comparison to S5B/Pl, control OM animals exhibited both a higher expression and higher circulating levels of leptin (P < 0.05). While serum leptin levels were decreased and food intake was increased in the exercise-trained animals of both strains (P < 0.05), the exact relationship between exercise, leptin, and food intake in this rat model of dietary obesity remains to be determined. Nonetheless, these results suggest that the expression and secretion of leptin can be influenced by exercise training and that these changes (i.e., reduced expression and secretion of protein) can occur independently of changes in whole-body insulin sensitivity and susceptibility to diet-induced obesity.

Adipose Tissue↗

Soluble IL-6R in plasma cell dyscrasias.

The understanding of the biology of multiple myeloma has advanced significantly in the past few years. The identification of the pivotal role of Interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), and how the ligand receptor complex interacts with the signal transducer gp130 has provided new biological insights into plasma cell disorders. Some studies have suggested that sIL-6R levels may have prognostic significance in MM, however this is not a consistent finding. Here the biology and function of IL-6 and sIL-6R are reviewed and the clinical significance of sIL-6R discussed.

Humans↗

Administration of interleukin-10 at the time of priming protects Corynebacterium parvum-primed mice against LPS- and TNF-alpha-induced lethality.

Several laboratories have described the protective effects of interleukin-10 (IL-10) in mouse models of lethal endotoxemia. In most of these experiments, protection was observed in normal mice that were given a lethal dose of LPS. However, we failed to observe protection with IL-10 in LPS-challenged mice that had been primed with Corynebacterium parvum (Proprionibacterium acnes). We have extended our studies with IL-10 in C. parvum-primed mice and in some cases have observed protection that appears to depend on the strength of the sensitization to C. parvum. When IL-10 was administered to mice at the time of priming, it was particularly effective in blocking sensitization, as evidenced by the inability of treated mice to mount a strong inflammatory cytokine response when subsequently challenged with LPS. Following such treatment with IL-10, C. parvum-primed mice were also protected from a subsequent lethal challenge with rMuTNF-alpha. In addition, the mice were protected against LPS- and TNF-alpha-induced lethality with a single dose of an anti-TNF-alpha or anti-IFN-gamma mAb given at the time of priming. Our results suggest that TNF-alpha and IFN-gamma are produced early after priming with C. parvum and are at least partly responsible for the enhanced sensitivity of the mice to LPS and TNF-alpha. IL-10 affords protection to the mice because of its ability to block the C. parvum-induced TNF-alpha and IFN-gamma responses.

Animals↗