Human malignant hyperthermia associated with desflurane anesthesia.
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Adolescent↗
Biomedical subjects
G C Allen
Publications and source records attributed to G C Allen.
The sensitivity and specificity of the caffeine-halothane contracture test: a report from the North American Malignant Hyperthermia Registry. The North American Malignant Hyperthermia Registry of MHAUS.
BACKGROUND: The caffeine-halothane contracture test (CHCT) is the only recognized laboratory test to diagnose malignant hyperthermia (MH). The authors report the results of their analysis of pooled data from the North American Malignant Hyperthermia Registry database to determine the sensitivity and specificity of the CHCT. METHODS: The MH Clinical Grading Scale was used to identify 32 case subjects who were "almost certain" to be MH susceptible based on clinical criteria alone. Their CHCT results were compared with those of a group of 120 control subjects considered to be at low risk for MH. Diagnostic thresholds of the CHCT were adjusted, and its component tests were combined to generate receiver operating characteristic curves. The maximal Youden index for each component test was chosen as the diagnostic threshold indicative of MH susceptibility. RESULTS: The highest sensitivity (97%; 95% CI, 84-100%) was achieved with a two-component test with thresholds of > or = 0.5 g contracture for 3% halothane, > or = 0.3 g contracture at 2 mM caffeine, or both, considered positive for MH. The test specificity was 78% (95% CI, 69-85%). The addition of other CHCT component tests did not improve CHCT sensitivity or specificity. CONCLUSION: The CHCT achieves high sensitivity and acceptable specificity as a clinical laboratory diagnostic test when it is performed according to published standards. However, it cannot be used as a screening test because of the low prevalence of MH in the general population.
Adult↗
Time-dependent effects of melatonin on immune measurements in male Syrian hamsters.
Adult, male Syrian hamsters received daily subcutaneous melatonin (25 microg) injections or vehicle injections at 08:00 or 17:00 hr for 11 weeks. Body weights were measured weekly throughout the experiment and testes weights, spleen weights, and serum was collected at the end of the experiment. The spleens were sectioned and immunocytochemically analyzed for immunoglobulin G and serum levels of interferon-gamma, interleukin-2, and interleukin-4 were determined in heterologous mouse assays. Melatonin injections at 17:00 hr, but not at 08:00 hr, increased body weights, decreased testes weights and serum testosterone levels, and had no effect on immunoglobulin G content in the spleen. Likewise, melatonin injections at 17:00 hr, but not at 08:00 hr, increased serum interferon-gamma levels, had no effect on interleukin-2 levels, and appeared to increase interleukin-4 levels. Since melatonin injections at 08:00 hr were ineffective in altering immune measurements and correlations between reproductive measures and immune measures were high, the most parsimonious explanation for these results is that melatonin injections at 17:00 hr depressed reproductive hormone levels and these depressed levels altered immune measures.
Animals↗
Transient-evoked otoacoustic emissions in children after cisplatin chemotherapy.
Little is known about cisplatin ototoxicity in pediatric patients. Measurement of otoacoustic emissions is a rapid, reproducible, objective method of evaluating hearing. We examined whether transient-evoked otoacoustic emissions in pediatric patients exposed to cisplatin in the past correlated with audiographic findings. Twelve patients were entered into the study (mean age at treatment 7.8 years, mean cumulative dose 442.5 mg/mm2, mean 7.1 doses). Hearing at 3000 Hz was preserved in 82.6% of patients. In the higher frequencies significant sensorineural hearing loss was noted: 43.5% at 4 kHz; 81.0% at 6 kHz; and 90.5% at 8 kHz. Transient-evoked otoacoustic emissions were measurable in 11 of 12 patients. Middle ear disease accounted for abnormal otoacoustic emission seen in three patients (1 with effusion, 2 with significant negative middle ear pressure). When the middle ear was normal, a statistically significant correlation was seen between the transient-evoked otoacoustic emissions reproducibility and pure-tone threshold (correlation coefficient = -0.69, p = 0.008). Increased hearing loss was also associated with young age at first dose of cisplatin (p = 0.044), high number of chemotherapy cycles (p = 0.042), and high cumulative dose (p = 0.042).
Adolescent↗
Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies.
In 1992, the Malignant Hyperthermia Association of the United States and The North American Malignant Hyperthermia Registry received reports of cardiac arrest in apparently healthy children given succinylcholine. Using data from 1990 to 1993, this study analyzes: (1) etiology of all reported pediatric arrests and (2) whether survival was associated with certain patient or treatment variables. We reviewed retrospectively all reports of pediatric (age < 18 years) arrests occurring within 24 hours of anesthesia. Etiology of arrests and presence of myopathy were determined. Twenty-five patients (92% male, median 45 months old) arrested; 23/25 (92%) were scheduled for minor surgery. Before receiving a potent inhalational anesthetic (92%) and/or succinylcholine (72%), these patients were evaluated by the anesthesiologist as being healthy with no personal or family history of myopathy. Serum potassium during arrest was measured in 18/25 (72%) patients; hyperkalemia (mean [K+] = 7.4 +/- 2.8, median 7.5 mmol/L) was detected in 13/18 (72%) patients. Postarrest resuscitations lasted a median of 42 minutes (range 10-296). Ten (40%) patients died, 1 (4%) is vegetative, and 14 (56%) returned to baseline neurologic function. A previously unrecognized Duchenne dystrophy (n = 8) or unspecified myopathy (n = 4) was diagnosed in 12 (48%) patients. Eight of these 12 patients' arrests were associated with hyperkalemia. Ten (40%) patients had no postarrest evaluation to exclude occult myopathy. No patient or treatment variables were statistically associated with survival. We conclude that, whenever possible, pediatricians should evaluate their patients (especially male infants and children) preoperatively for the presence of occult myopathy. During perianesthetic resuscitations, the pediatric advanced life support protocol should be modified to detect and treat hyperkalemia, a potentially reversible state even after prolonged resuscitation efforts. Following anesthetic deaths, pathologists should examine body fluid electrolytes and skeletal muscle for myopathy and dystrophin. If a preanesthetic creatine kinase screen for myopathy in male patients and restrictions on succinylcholine had been used, 64% of arrests and 60% of deaths might have been prevented. A formal prospective risk/benefit analysis for preventive measures is needed.
Adolescent↗
X-ray photoelectron spectroscopic investigation of conducting polymer blends.
Electrochemically prepared films of conducting polymers of polypyrrole and polythiophene and their blends with polyamide have been investigated by X-ray photoelectron spectroscopy. In the N1s region of the spectra of films containing polypyrrole the peak corresponding to N(+) at 402.0 eV is separated from that of neutral N. The intensity of the N(+) peak can be correlated with the electrical conductivity of the films and the spectroscopically derived ratio of F/N(+) is close to 4 indicating that one BF(-)(4) dopant ion is incorporated for every oxidized nitrogen center. In the spectra of films of polythiophene and its blends peaks corresponding to S and S(+) can not be resolved but again the F/C ratio correlates with the electrical conductivity.
Journal Article↗
Electron spectroscopic investigation of Sn coatings on glasses.
Float glasses of different thicknesses and a conducting tin oxide glass have been investigated using Photo and Auger Electron Spectroscopy induced by AlKalpha X-rays. On the basis of measured chemical XPS shifts in the binding energies the chemical state of Sn (+2 or +4) incorporated on the float glasses could not be assigned. The use of the Auger parameter allows to separate relaxation and chemical contributions. The derived true chemical shifts of Sn on float-glasses are larger than those of SnO and/or SnO(2) due to the larger ionic environment of the glass matrix. Ar(+) or HF etching reveals that the concentration of Sn decreases exponentially as a function of depth from the surface.
Journal Article↗
Epidermal growth factor regulates topoisomerase II activity and drug sensitivity in human KB cells.
Because of its unique DNA-cleaving and strand-passing activities, topoisomerase II is involved in many aspects of DNA metabolism, including replication, transcription, recombination, and repair. The cytotoxic potential of topoisomerase II-targeted drugs, such as etoposide, is related to their ability to stabilize covalently linked enzyme-DNA complexes, which are intermediates in the enzyme's catalytic cycle. Epidermal growth factor receptor is expressed on the cell surface of the majority of squamous cell carcinomas, and epidermal growth factor binding is known to stimulate a number of cellular transduction pathways, including tyrosine kinase, protein kinase C, and phospholipase C. Because topoisomerase II is a proliferation-dependent protein and has been shown to be a high-affinity substrate for many of these cellular transduction pathways, the effects of epidermal growth factor on cellular regulation and sensitivity to etoposide were studied with the human oral cavity squamous cell line, KB. Topoisomerase II catalytic activity was rapidly and transiently inhibited after the addition of epidermal growth factor to the cellular growth media. Western blot on nuclear extracts did not demonstrate alterations in topoisomerase II polypeptide levels to account for changes in catalytic activity. Epidermal growth factor treatment also led to the formation of stabilized, covalently linked enzyme-DNA complexes. Furthermore, epidermal growth factor-induced, topoisomerase II-mediated DNA strand breaks were additive to those induced by etoposide. This study indicates that epidermal growth factor specifically regulates the catalytic and DNA-cleaving activities of topoisomerase II in KB cells. This may direct clinical strategies for circumventing the intrinsic cellular resistance to chemotherapy commonly observed in squamous cell carcinomas of the head and neck.
Antineoplastic Agents, Phytogenic↗
High-level transgene expression in plant cells: effects of a strong scaffold attachment region from tobacco.
We have previously shown that yeast scaffold attachment regions (SARs) flanking a chimeric beta-glucuronidase (GUS) reporter gene increased per-copy expression levels by 24-fold in tobacco suspension cell lines stably transformed by microprojectile bombardment. In this study, we examined the effect of a DNA fragment originally identified in a tobacco genomic clone by its activity in an in vitro binding assay. The tobacco SAR has much greater scaffold binding affinity than does the yeast SAR, and tobacco cell lines stably transformed with constructs containing the tobacco SAR accumulated greater than fivefold more GUS enzyme activity than did lines transformed with the yeast SAR construct. Relative to the control construct, flanking the GUS gene with plant SARs increased overall expression per transgene copy by almost 140-fold. In transient expression assays, the same construct increased expression only approximately threefold relative to a control without SARs, indicating that the full SAR effect requires integration into chromosomal DNA. GUS activity in individual stable transformants was not simply proportional to transgene copy number, and the SAR effect was maximal in cell lines with fewer than approximately 10 transgene copies per tobacco genome. Lines with significantly higher copy numbers showed greatly greatly reduced expression relative to the low-copy-number lines. Our results indicate that strong SARs flanking a transgene greatly increases expression without eliminating variation between transformants. We propose that SARs dramatically reduce the severity or likelihood of homology-dependent gene silencing in cells with small numbers of transgenes but do not prevent silencing of transgenes present in many copies.
Amino Acid Oxidoreductases↗
Complications of endoscopic sinus surgery in a residency training program.
Endoscopic sinus surgery has emerged in the last decade as the treatment of choice for chronic sinusitis. Reports of complications of the procedure from different centers vary depending on the technique used and the experience of the surgeon. Between August 1990 and August 1993, 337 patients underwent endoscopic sinus surgery at West Virginia University. Most of the cases were performed by senior residents under faculty supervision. Minor complications were encountered in 15.1% of the cases and major complications in 1.5% of the patients. The most common major complication was cerebrospinal fluid leak. All patients with cerebrospinal fluid leaks were diagnosed and treated successfully at the time of surgery. Middle turbinate adhesions and orbital penetration were the most common minor complications. Routine partial middle turbinectomy did not decrease the adhesion rate. Endoscopic sinus surgery is a relatively safe procedure, even when performed by residents under adequate supervision.
Adolescent↗
Cylindrical cell papilloma of the nasal septum.
Papillomas of the sinonasal tract are uncommon tumors. They can be subdivided into different histopathological entities including inverting papilloma, fungiform papilloma and cylindrical cell papilloma. Cylindrical cell papilloma is one of the rarest with only twenty-three cases reported. This rare histologically distinct variant of papillomas of the sinonasal tract behaves clinically like inverting papillomas. We present what we believe to be the first reported case of a cylindrical cell papilloma isolated to the nasal septum. The patient's pathology and a literature review of cylindrical cell papillomas of the sinonasal tract are presented.
Adult↗
A clinical grading scale to predict malignant hyperthermia susceptibility.
BACKGROUND: The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. METHODS: Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. RESULTS: This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. CONCLUSIONS: The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. It use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.
Adult↗
Light modulation of ferredoxin mRNA abundance requires an open reading frame.
Ferredoxin I (Fed-1) mRNA abundance is modulated by an internal light regulatory element that includes sequences both 5' and 3' of the translational initiation site. To test the hypothesis that the light response mediated by this element might be coupled to translation, we transformed tobacco plants with gene constructs blocked in translational initiation or elongation. Here, we report that such mutations abolish the light response in vivo. A nonsense mutation could be rescued by restoring the open reading frame with a different sequence, even when the new codon caused an amino acid substitution. Our data establish that the light response requires a translatable reading frame and thus provide strong circumstantial evidence for post-transcriptional modulation of Fed-1 mRNA levels. The Fed-1 system is presently the only higher plant example of a developmentally regulated change in mRNA abundance that requires translation of the affected mRNA.
Ferredoxins↗
Assembly of the primosome of DNA replication in Escherichia coli.
Assembly of the Escherichia coli primosome requires six proteins, PriA, PriB, PriC, DnaB, DnaC, and DnaT, acting at a primosome assembly site (pas) on an SSB-coated single-stranded (ss) DNA. Assembly is initiated by interactions of PriA and PriB with ssDNA and the pas. PriC, DnaB, DnaC, and DnaT then act on the PriA-PriB-DNA complex to yield the primosome. In the primosome, the dATPase (ATPase) of PriA becomes hyper-activated. In addition, the assembled primosome appears to block the pas, preventing it from activating additional PriA molecules. Either ATP alone or dATP in combination with GTP is sufficient for primosome assembly, while ATP or GTP provides for its maintenance during isolation. These nucleotide requirements can be reconciled with the need for ATP or dATP for DnaB-DnaC complex formation and hydrolysis of ATP or GTP by DnaB when it binds ssDNA. Such isolated primosomes contain a dATPase, the hallmark of PriA, and a GTPase indicative of DnaB. Further studies indicate that the isolated primosome contains the PriB replication activity in addition to PriA and DnaB.
Bacterial Proteins↗
Strand switching of a replicative DNA helicase promoted by the E. coli primosome.
The E. coli primosome assembles at an origin on a single-stranded DNA, like that of phi X174, to promote replication of that template. Upon conversion to the duplex form, the primosome can generate a rolling circle product from this template. Rolling circle synthesis implies the transfer of the DnaB helicase from its initial loading site on the viral strand to a displaced complementary strand. Isolated primosomes promote only unit-length synthesis; supplementation with PriC, DnaC, and DnaT is necessary to reconstitute rolling circle synthesis. Rolling circle replication is sensitive to salts, whereas primosome assembly and unit-length synthesis are not. Thus, the primosome promotes two distinct reactions: assembly for first-round synthesis and strand switching for rolling circle synthesis.
Ammonium Sulfate↗
Anterior mediastinal mass in a patient susceptible to malignant hyperthermia.
We report a malignant hyperthermia-susceptible patient who required investigation for a large, symptomatic anterior mediastinal mass. Multiple attempts at tissue diagnosis under local anaesthesia were unsuccessful. Following awake fibreoptic tracheal intubation, general anaesthesia was administered using ketamine, midazolam, and nitrous oxide, maintaining spontaneous ventilation. Prophylactic dantrolene was not used, to avoid potential muscle weakness and respiratory compromise. Diagnostic mediastinotomy was performed without incident. We conclude that ketamine anaesthesia is appropriate for patients with anterior mediastinal masses, and is considered safe in malignant hyperthermia-susceptible patients.
Adult↗
Surface analysis of titanium implants.
Medical grade titanium samples were examined using X-ray photoelectron spectroscopy before and after immersion in various proteins. Additionally, an implant removed from a patient following clinical failure was examined using scanning ion and electron microscopy. The surface of the as-received samples was found to be mainly TiO2, with contaminants of H2O/OH-, calcium and nitrogen which remained after autoclaving. The immersed proteins adhered to the titanium surface, possibly via a Ca-O link. The failed clinical sample was found to be partially fibrously encapsulated with evidence of calcification. Small amounts of TiOOH were detected at the fibrous periphery, supporting the theory of Tengvall and co-workers that in vivo titanium implants are covered in a gel of this material.
Bone and Bones↗