Ketamine sedation in mentally disabled adults.
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Biomedical subjects
Publications and source records attributed to S M Green.
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OBJECTIVES: To identify factors predictive of patient load at major commercial concert first-aid stations, and to characterize the spectrum of presenting injuries and illnesses at such events. METHODS: This study was a retrospective case series of patients presenting to on-site first-aid stations at five major concert venues in southern California over a five-year period. The authors compared the number of patients per ten thousand attendees (PPTT) with four potential predictors (music type, overall attendance, temperature, and indoor vs outdoor location) using univariate techniques and negative binomial regression. The spectrum of chief complaints observed is described. RESULTS: There were 1,492 total patients out of 4,638,099 total attendees at 405 separate concerts. The median patient load per concert was 2.1 PPTT, ranging from 0 PPTT at 53 concerts to 71 PPTT at a punk rock festival that turned into a riot. Patient load varied significantly by music category (p = 0.0001) but not with overall attendance, temperature, or indoor vs outdoor location. Median PPTT by music category ranged from 1.3 PPTT for rhythm and blues to 12.6 PPTT for gospel/Christian, with negative binomial regression indicating that rock concerts had 2.5 times (95% CI = 2.0 to 3.0) the overall patient load of non-rock concerts. Music type, however, was able to account for only 4% of the variability observed in the regression model. Trauma-related complaints predominated overall, with similar rates at rock and non-rock concerts. Four cardiac arrests occurred at classical concerts. CONCLUSION: Rock concert first-aid stations evaluated 2.5 times the patient load of non-rock concerts overall, although there was substantial concert-to-concert variability. Trauma-related complaints predominate at both rock and non-rock events. These data may assist individuals and organizations planning support for such events.
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Nutritional status has been associated with the development and healing of pressure ulcers. This study aimed to examine the dietary intake of adults who had pressure ulcers (n = 75) and a control group with no pressure ulcers (n = 100), randomly selected from those receiving treatment from community nurses. All participants were considered to be at risk of developing pressure damage. Dietary intake was assessed using a 24-hour recall method (completed by 84 participants) and a nutritional questionnaire (completed by all 175 participants). The mean age of participants was 79 +/- 6 years and 70% were women. Patients who had pressure ulcers had a lower energy intake (mean difference -185 kcal, 95% confidence interval -413 to 43) and intake of protein (mean difference -6.73 g/day, 95% CI -16.20 to 2.74) but neither factor achieved a standard level of statistical significance. However, when protein was categorised into quartiles, a significantly higher proportion of participants with low intake had pressure ulcers on chi-squared analysis (p = 0.043). More participants who had pressure ulcers required assistance with eating (odds ratio 4.55, 95% CI 1.53 to 13.54) and more had experienced recent taste changes (odds ratio 3.28, 95% CI 1.19 to 9.10). While these differences were significant, there were few major differences between those who had pressure ulcers and the control group. A number of participants in both groups had poor nutritional intake and other risk factors for malnutrition were also found. Poor nutrition is a problem for all patients receiving community nursing care, not just those with pressure ulceration. Due to acknowledged difficulties in recording nutritional intake in elderly patients, further assessment of dietary intake in those receiving community nursing services should be undertaken to support these results.
Human cytomegalovirus (CMV) is a member of the Herpesviridae family of viruses that also includes herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), human herpes virus-6, 7, and 8 (HHV-6, HHV-7, and HHV-8), and Epstein-Barr virus (EBV). Each member of this family encodes a serine protease that is a potential target for antiviral therapeutic intervention. We recently reported the crystal structure of CMV proteases [Qiu, X., Culp, J. S., DiLella, A. G., Hellmig, B., Hoog, S. S., Janson, C. A., Smith, W. W., and Abdel-Meguid, S. S. (1996) Nature 383, 275-279] and proposed that the highly conserved Arg165 and Arg166 residues are involved in stabilizing the oxyanion intermediate in human herpes protease catalyzed reactions through the backbone NH and side chain, respectively. In the current study, site-directed mutagenesis was carried out to probe the catalytic function of these two amino acid residues. Substitution of Arg166 with an alanine has led to ablation of enzymatic activity without detectable change in CMV protease conformation, supporting suggestions from the crystal structure that Arg166 side chain plays a major role in catalysis. The wild-type has a Km = 138 +/- 17 microM and kcat = 19.9 +/- 1.1 min-1, while R166A has only residual activity, with a kcat = 0.012 +/- 0.001 min-1 and an unaltered Km = 145 +/- 18 microM. In the crystal structure, the side chain of Arg166 was shown previously to hold a water molecule that can act as a hydrogen-bond donor to the oxyanion and was thus proposed to stabilize the oxyanion intermediate. However, kinetic characterization of the mutant R165A only reveals a 2.7-fold lower activity than wild-type, with a Km = 166 +/- 19 microM and a kcat = 7.4 +/- 0.4 min-1. These results confirm that Arg165 side chain is not involved in the stabilization of the oxyanion. It is likely that Arg165 only utilizes the backbone NH for catalysis as suggested by the crystal structure.
To elucidate the role of N-phenylhydroxylamine (PHA, N-hydroxylated metabolite of aniline) in the selective toxicity of aniline to the spleen, dose-dependent studies were conducted with PHA in rats. Male Sprague-Dawley rats were given four doses each (1 dose/day) of 0.025, 0.05, 0.1, or 0.2 mmol/kg PHA in 0.5 ml of aqueous agar (0.25%) by gavage. The control animals received an equal volume of vehicle only. The animals were euthanized 24 h following the last dose. PHA toxicity in the blood was evident from a dose-dependent increase of methemoglobin. The most affected organ was spleen, which appeared dark and enlarged (splenomegaly) and showed increased spleen-to-body weight ratios, which were 28, 40, 66, and 87% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. Splenic lipid peroxidation (malondialdehyde content) was higher in all PHA-treated groups, whereas splenic protein oxidation (carbonyl content) increased in only the 0.05, 0.1, and 0.2 mmol/kg groups. The total iron content in the spleen also showed increases of 88, 135, 168, and 209% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. These biochemical changes were accompanied by a dose-dependent vascular congestion in the spleen, a characteristic feature of aniline toxicity. Although the ratio of organ to body weight increased for both testes and heart at the highest dose, striking morphological changes were observed only in heart. The cardiac lesions consisted of a both acute and resolving multifocal subendocardial necrosis involving predominently the left ventricle. Our results suggest that PHA is a splenotoxin and thus contributes to the toxicity of aniline, while at a high dose, it is also cardiotoxic, perhaps due to anoxia associated with the marked methemoglobinemia. These results further support the involvement of oxidative stress in the splenotoxicity of aniline which may be caused by its reactive metabolite(s) such as PHA.
STUDY OBJECTIVE: To determine the safety of intramuscular ketamine when administered by emergency physicians for pediatric procedures in accordance with a defined protocol. METHODS: We assembled a consecutive case series of children aged 15 years or younger who were given ketamine in the emergency departments of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine use (4 mg/kg, intramuscularly) was followed. Treating physicians were instructed to complete data forms recording complications and adequacy of sedation concurrent with patient care. Subsequent chart review was used to determine indications, adjunctive drugs, time to discharge, and adverse reactions for all patients. RESULTS: Intramuscular ketamine was administered 1,022 times, mainly for laceration repair and fracture reduction. Physicians completed data forms for 431 of treated children (42%). Transient airway complications occurred in 1.4%: airway malalignment (n = 7), laryngospasm (n = 4), apnea (n = 2), and respiratory depression (n = 1). All were quickly identified and treated without intubation or sequelae. Emesis occurred in 6.7%, without evidence of aspiration. Mild recovery agitation occurred in 17.6%, moderate to severe agitation in 1.6%. No child required hospitalization for complications caused by ketamine. Ketamine produced acceptable sedation in 98% of patients. The median time from injection to emergency department discharge was 110 minutes for children given a single dose of ketamine. CONCLUSION: Intramuscular ketamine may be administered safely by emergency physicians to facilitate pediatric procedures in accordance with a defined protocol and with appropriate monitoring. Ketamine is highly effective, has a wide margin of safety, does not require intravenous access, and uniquely preserves protective airway reflexes.
STUDY OBJECTIVE: Although adjunctive intravenous bicarbonate therapy is commonly recommended for children with severe diabetic ketoacidosis (DKA), no studies assessing clinical outcome with this therapy have ever been performed. Our objective was to determine whether bicarbonate therapy influenced outcome for pediatric DKA. METHODS: The study was a retrospective consecutive case series of 147 admissions for severe DKA (initial pH < or = 7.15 and glucose concentration > or = 300 mg/dL [16.7 mmol/L]) in 106 children during a 16-year period at a tertiary university medical center. Descriptive statistics were applied to the 147 admissions. The first patient admitted with DKA was then selected for each of the 106 children, and clinical and laboratory data were compared between subjects who did and did not receive bicarbonate. Multivariate and matched pair analyses were performed to control potentially confounding variables. RESULTS: Fifty-seven of the 147 patients admitted with DKA (39%) were successfully treated without bicarbonate, including 9 with a pH of 7.00 or less and one with a pH of 6.73. The frequency of complications was comparable between bicarbonate and nonbicarbonate groups (4% versus 2%, P = 1.00). The mean duration of hospitalization for children receiving bicarbonate was 23% (16 hours) longer than children who did not receive bicarbonate in the multivariate analysis (P = .07) and 37% (22 hours) longer in the matched pair analysis (P = .01). The mean rate of metabolic recovery by three distinct measures was similar between groups, and the sample had 80% power to detect differences of 14% to 29% in these measures. CONCLUSION: We found no evidence that adjunctive bicarbonate improved clinical outcome in children with severe DKA. The rate of metabolic recovery and complications were similar in patients treated with and without bicarbonate, and prolonged hospitalizations were noted in the bicarbonate group. We conclude that adjunctive bicarbonate is unnecessary and potentially disadvantageous in severe pediatric DKA.
OBJECTIVE: To determine whether parenteral antibiotics are superior to oral antibiotics in preventing serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia. METHODS: Using the MEDLINE database, the English language literature was searched for all publications concerning bacteremia, fever, or Streptococcus pneumoniae from 1966 to January 1, 1997. All nonduplicative studies with a series of children with S. pneumoniae occult bacteremia having both orally treated and parenterally treated groups were reviewed. Children were excluded from individual studies if at the time of their initial evaluation they were immunocompromised, had a serious bacterial infection, underwent a lumbar puncture, or did not receive antibiotics. RESULTS: Only 4 studies met study criteria. From these studies, 511 total cases of S. pneumoniae occult bacteremia were identified. Ten of 290 (3.4%) in the oral group and 5 of 221 (2.3%) in the parenteral antibiotic group developed serious bacterial infections (pooled p-value = 0.467, pooled OR = 1.48; 95% CI, 0.5-4.3). Two patients in the oral group (0.7%) and 2 patients in the parenteral group (0.9%) developed meningitis (pooled p-value = 0.699, pooled OR = 0.67; 95% CI, 0.1-5.1). CONCLUSION: The rates of serious bacterial infections and meningitis did not differ between children who were treated with oral and parenteral antibiotics. The extremely low rate of complications observed in both groups suggests no clinically significant difference between therapies. A study with >7,500 bacteremic children (or >300,000 febrile children) would be needed to have 80% power to prove parenteral antibiotics are superior to oral antibiotics in preventing serious bacterial infections.
OBJECTIVES: To determine the safety of i.v. ketamine when administered by emergency physicians (EPs) for pediatric procedures, and to contrast the sedation characteristics of the i.v. and i.m. routes. METHODS: The study was a retrospective consecutive case series of children aged < or =15 years given i.v. ketamine in the EDs of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine was used by treating physicians. Records were reviewed for adverse effects, indication, dosing, adjunctive drugs, inadequate sedation, and time to release. Results were contrasted with previously reported data for the i.m. route. RESULTS: During the study period i.v. ketamine was administered 156 times, primarily for laceration repair and fracture reduction. Transient apnea and respiratory depression occurred in one patient each; both were quickly identified and were without sequelae. Laryngospasm or aspiration was not noted in any children. There were 6 children with emesis and 2 with mild agitation during recovery. The median time from initial dose to ED release was 103 minutes (25th to 75th percentiles 76 to 146 minutes). The i.v. and i.m. routes were comparable in terms of adverse effects, inadequate sedation, and time to release. CONCLUSION: I.v. ketamine can be administered safely by EPs to facilitate pediatric procedures when used in a defined protocol. The sedation characteristics of the i.v. and i.m. routes appear comparable.
PURPOSE: Acanthamoeba is an uncommon cause of corneal infection in which the best visual outcome follows prompt diagnosis and a long course of appropriate antimicrobial therapy. Because conventional detection techniques for Acanthamoeba have certain limitations, we investigated the ability of the polymerase chain reaction (PCR) to confirm the clinical diagnosis of Acanthamoeba keratitis, with the ultimate aim of achieving early diagnosis. METHODS: Using two different pairs of primers, PCR was performed on representative cultured Acanthamoeba isolates to confirm the assay's ability to amplify Acanthamoeba DNA from a wide range of acanthamoebae. Subsequently, corneal epithelial samples from 19 patients and tear samples from 12 patients with Acanthamoeba keratitis were analyzed by PCR for the presence of Acanthamoeba DNA. RESULTS: Acanthamoeba DNA was amplified by PCR from 16 (84%) of 19 corneal epithelial samples, whereas Acanthamoeba was cultured from 10 samples (53%), all of which were PCR positive. Tear samples from 8 (66%) of 12 patients were positive on PCR testing, and one tear sample was PCR positive, whereas the corresponding epithelial biopsy had yielded a negative PCR result. Samples from culture-positive patients were positive on PCR testing more frequently than those from culture-negative patients (10/10 culture-positive corneal epithelial and 5/7 [71%] culture-positive initial tear samples versus 6/9 [66%] culture-negative corneal epithelial and 2/5 [40%] culture-negative tear samples). All control epithelial (n = 15) and tear (n = 15) samples yielded negative results. CONCLUSIONS: PCR was a more sensitive diagnostic test than a culture for Acanthamoeba keratitis, and the use of two different primers achieved better sensitivity than a single set. A PCR of a tear sample also may be a useful complementary test and, in combination with PCR of epithelial samples, would prove particularly helpful in confirming the clinical diagnosis in culture-negative cases.
The complex kinetic behavior commonly observed in protein folding studies suggests that a heterogeneous population of molecules exists in solution and that a number of discrete steps are involved in the conversion of unfolded molecules to the fully native form. A central issue in protein folding is whether any of these kinetic events represent conformational steps important for efficient folding rather than side reactions caused by slow steps such as proline isomerization or misfolding of the polypeptide chain. In order to address this question, we used stopped-flow fluorescence techniques to characterize the kinetic mechanism of folding and unfolding for a Pro- variant of SNase in which all six proline residues were replaced by glycines or alanines. Compared to the wild-type protein, which exhibits a series of proline-dependent slow folding phases, the folding kinetics of Pro- SNase were much simpler, which made quantitative kinetic analysis possible. Despite the absence of prolines or other complicating factors, the folding kinetics still contain several phases and exhibit a complex denaturant dependence. The GuHCl dependence of the major observable folding phase and a distinct lag in the appearance of the native state provide clear evidence for an early folding intermediate. The fluorescence of Trp140 in the alpha-helical domain is insensitive to the formation of this early intermediate, which is consistent with a partially folded state with a stable beta-domain and a largely disordered alpha-helical region. A second intermediate is required to model the kinetics of unfolding for the Pro- variant, which shows evidence for a denaturant-induced change in the rate-limiting unfolding step. With the inclusion of these two intermediates, we are able to completely model the major phase(s) in both folding and unfolding across a wide range of denaturant concentrations using a sequential four-state folding mechanism. In order to model the minor slow phase observed for the Pro- mutant, a six-state scheme containing a parallel pathway originating from a distinct unfolded state was required. The properties of this alternate unfolded conformation are consistent with those expected due to the presence of a non-prolyl cis peptide bond. To test the kinetic model, we used simulations based on the six-state scheme and were able to completely reproduce the folding kinetics for Pro- SNase across a range of denaturant concentrations.
BACKGROUND: Previous animal and human studies have indicated that prenatal exposure to nicotine is associated with adverse reproductive outcomes, including altered neural structure and functioning, cognitive deficits, and behavior problems in the offspring. Our study extends previous research on humans by controlling a broad range of correlates of maternal smoking during pregnancy to determine if smoking is associated with behavior problems in the offspring severe enough to qualify for DSM-III-R diagnosis. METHODS: Subjects were 177 clinic-referred boys, ages 7 to 12 years at the time of the first assessment, who underwent longitudinal assessment for 6 years using annual structured diagnostic interviews. Correlates of maternal smoking during pregnancy and previously identified demographic, parental, perinatal, and family risk factors for the disruptive behavior disorders were controlled in logistic regression analyses. RESULTS: Mothers who smoked more than half a pack of cigarettes daily during pregnancy were significantly more likely to have a child with conduct disorder (odds ratio, 4.4; P = .001) than mothers who did not smoke during pregnancy. This association was statistically significant when controlling for socioeconomic status, maternal age, parental antisocial personality, substance abuse during pregnancy, and maladaptive parenting. CONCLUSIONS: Maternal smoking during pregnancy appears to be a robust independent risk factor for conduct disorder in male offspring. Maternal smoking during pregnancy may have direct adverse effects on the developing fetus or be a marker for a heretofore unmeasured characteristic of mothers that is of etiologic significance conduct disorder.
This paper introduces a satiety quotient (SQ) to assess the satiating effect of an eating episode. This procedure constitutes an improvement on previous measures by considering the satiating effects of the eating episode over time. A satiety quotient was calculated from data obtained from several studies involving the presentation of a preload/meal to young lean male and female subjects. Subjects were presented with preloads/meals of varying composition, and motivation to eat immediately prior to, and periodically following, the eating episode were measured. Food and fluids were not consumed whilst motivation to eat was measured in the post preload/meal period. The SQ was calculated by dividing the difference between ratings of motivation to eat before and after the eating episode (pre minus post) by the weight or energy content of intake during the episode. This quotient relates intake to the rate of return of motivation to eat in the post-ingestive period, a relationship which is not apparent on separate examination of the amount consumed or ratings of motivation to eat. Development of this satiety quotient is a further contribution to the evolution of the concept of quantifying satiating effects of foods, and provides additional information on the effects of food attributes on short-term appetite control.
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The authors tested free-ranging New World monkeys (nocturnal owl monkeys [Aotus nancymai] and diurnal capuchin monkeys [Cebus apella]) to determine the extent to which they use olfactory cues to locate food hidden in containers at 2 of 6 feeding sites within a 1 1/2-ha forested enclosure. These 2 sites were selected randomly for each trial and then were baited with banana and banana peel residue. The 4 other sites were unbaited and unscented. In trials in which the food was not visible to the monkeys, Aotus monkeys located the baited sites at a level greater than expected by chance, whereas Cebus monkeys did not. Use of olfactory information by Aotus monkeys in foraging may be an adaptation for nocturnal foraging because olfactory cues are more salient than visual cues at low light levels.
OBJECTIVE: To prospectively derive high-yield criteria for the detection of clinically significant electrolyte abnormalities (CSEAs) in children presenting to the ED. METHODS: A prospective, multicenter, observational study was performed at the EDs of 2 urban teaching hospitals, a university medical center, and a children's hospital with a combined census of > 275,000 patient visits/year (100,000 visits for children < 13 years old). All children < 13 years old who had electrolyte panels obtained were eligible for analysis. A data form containing potential predictor variables for a CSEA was completed by the clinician prior to receipt of electrolyte results. A CSEA was any abnormal electrolyte value that 1) stimulated constructive assessment of the patient's condition (monitoring, reevaluation of nonspurious laboratory values, or admission), 2) led to further diagnostic studies, 3) led to a new diagnosis, or 4) affected therapy. chi 2 recursive partitioning was used to derive a decision rule for ordering electrolytes. RESULTS: Of 715 eligible patient visits, 488 (68%) electrolyte panels contained a laboratory abnormality, with 182 (25%) CSEAs. A decision rule requiring 1 of 6 clinical criteria was 100% sensitive (95% CI 98-100%) and 24% specific (95% CI 21-28%) in detecting CSEAs with positive and negative predictive-values of 31% (95% CI 28-34%) and 100% (95% CI 97-100%), respectively. If these criteria had been used to screen patients for whom electrolyte panels were ordered, 128 patients (18%) would not have had electrolyte panels obtained and no CSEAs would have been missed. CONCLUSION: A set of clinical criteria was derived that may be useful for limiting electrolyte panels ordering in children. This criterion set requires prospective validation in a separate patient population.
OBJECTIVES: To examine the pattern of nontrauma cranial CT use in an urban ED, to identify the rate of significant CT abnormalities in this setting, and to develop criteria for restricting the ordering of CT scans. METHODS: A prospective, observational study of a case series of adults who underwent cranial CT scanning for nontraumatic cases was performed at the EDs of an urban teaching hospital and an affiliated community hospital with a combined annual census of 110,000. Clinically significant CT scans were defined as: 1) acute stroke, 2) CNS malignancy, 3) acute hydrocephalus, 4) intracranial bleeding, or 5) intracranial infection. X2 recursive partitioning was used to derive a decision rule to restrict ordering of CT scans. RESULTS: Only 61 (8%) of 806 CT scans revealed clinically significant abnormalities. The presence of any of the following: age > or = 60 years, focal neurologic deficit, headache with vomiting, or altered mental status, was 100% sensitive (95% CI: 94-100%) and 31% specific (95% CI: 28-33%) in detecting clinically significant CT scans. This set of features had positive and negative predictive values of 11% (95% CI: 8-13%) and 100% (95% CI: 98-100%), respectively. If these criteria had been used to restrict cranial CT use, 229 fewer patients (28%) would have had CT scans obtained and no clinically significant abnormalities would have been missed. CONCLUSION: Clinically significant CT abnormalities were uncommon in this study population, suggesting that current criteria for ordering nontrauma cranial CT scans may be too liberal. In this study, a set of clinical criteria was derived that may be useful at separating patients into high- and low-risk categories for clinically significant cranial CT abnormalities. Before these results are applied clinically, these criteria should be validated in larger, prospective studies.