Evaluation of an independent prestin mouse model derived from the 129S1 strain.

Studies using the prestin knockout mouse indicate that removal of the outer hair cell (OHC) motor protein is associated with loss of sensitivity, frequency selectivity and somatic electromotility. Here we provide data obtained from another prestin mouse model that was produced commercially. In vivo electrical recordings from the round window indicate that the phenotype is similar to that of the original knockout generated by the Zuo group at St. Jude Children's Research Hospital. Hence, compound action potential (CAP) thresholds are shifted in a frequency-dependent manner and CAP tuning curves at 12 kHz are flat for masker frequencies between 3 and 18 kHz. Although CAP input-output functions at 6 kHz show a shift in sensitivity at low levels, responses approach wild-type magnitudes at high levels where the cochlear amplifier has less influence. In order to confirm that the loss of sensitivity and frequency selectivity is due to loss of prestin, we performed immunohistochemistry using a prestin antibody. Cochlear segments from homozygous mutant mice showed no fluorescence, while wild-type mice displayed a fluorescent signal targeted to the OHC's lateral membrane. Absence of prestin protein was confirmed using LDS-PAGE/Western blot analysis. These results indicate that the loss of function phenotype is associated with loss of prestin protein. Lack of prestin protein also results in a shortening of OHC length to approximately 60% of wild-type, similar to that reported previously by Liberman's group. The linkage shown between the loss of prestin protein and abnormal cochlear function validates the original knockout and attests to the importance of OHC motor function in the auditory periphery.

Perioperative transcranial Doppler US to evaluate intracranial compliance in young children undergoing craniosynostosis repair surgery.

PURPOSE: To determine whether measurements with transcranial Doppler ultrasonography (US) of resistive indexes (RIs) of basal cerebral arteries with pressure provocation can be used to identify infants and children with craniosynostosis who have abnormal intracranial compliance and to study the effects of surgery on compliance. MATERIALS AND METHODS: Transcranial Doppler US was performed through the temporal squama, fontanels, and existing skull defects prior to and immediately following cranioplasty. Twenty-four studies were performed in six patients with multisuture synostosis, and 61 studies were performed in 26 patients with single-suture synostosis. Study findings were compared with those of 23 control subjects and were characterized as normal or abnormal on the basis of age-specific normal criteria for RI. RESULTS: In multisuture synostosis, results of six of the nine preoperative transcranial Doppler US studies were abnormal. During postoperative follow-up, three recurrences requiring reoperation occurred, one of which was detected with abnormal transcranial Doppler US findings. In single-suture synostosis, results of seven of the 26 preoperative transcranial Doppler US studies were abnormal, and all occurred in young infants with sagittal and unicoronal synostosis. Immediate effects of surgery were variable. All patients with sagittal synostosis had a significant immediate postoperative increase in RI, which normalized during postoperative follow-up. There was no significant difference in RI between patients with successfully treated craniosynostosis and control subjects. CONCLUSION: Transcranial Doppler US can be used to identify patients with craniosynostosis with decreased intracranial compliance, and it is a suitable noninvasive test to monitor the effects of surgery on compliance.

Sleep structure following status epilepticus.

OBJECTIVES: To determine the effect of status epilepticus (SE) on sleep. BACKGROUND: SE has a high incidence of morbidity and mortality. The study of sleep structure following SE may have implications for recovery in these patients. METHODS: Twenty-four hour polysomnography was recorded in a 52-year-old patient following generalized convulsive SE not complicated by other medical or neurologic conditions. Another patient with no known history of seizures was recorded under similar conditions. RESULTS: The first day following SE was associated with markedly abnormal sleep structure, consisting largely of stage 1 with minimal slow wave or REM sleep. Over 4 days, slow wave and REM returned to normal values and no rebound was seen. The control patient demonstrated normal sleep parameters for their age, demonstrating that sleep disruption was not due to recording conditions alone. CONCLUSIONS: This case demonstrates that sleep structure is markedly abnormal following generalized convulsive SE. As sleep may serve a restorative function, improving sleep postictally may hasten or improve recovery. Larger studies will be required to determine whether this is a common finding in such patients, and whether outcome is associated with improved sleep quality.

Carbon dioxide kinetics and capnography during critical care.

Greater understanding of the pathophysiology of carbon dioxide kinetics during steady and nonsteady state should improve, we believe, clinical care during intensive care treatment. Capnography and the measurement of end-tidal partial pressure of carbon dioxide (PETCO2) will gradually be augmented by relatively new measurement methodology, including the volume of carbon dioxide exhaled per breath (VCO2,br) and average alveolar expired PCO2. Future directions include the study of oxygen kinetics.

Erwinia chrysanthemi strains cause death of human gastrointestinal cells in culture and express an intimin-like protein.

The bacterium Erwinia chrysanthemi is a model plant pathogen, responsible for causing cell death in plant tissue. Cell-wall depolymerizing enzymes and avirulence proteins essential for parasitism by this bacterium utilize dedicated type II and type III secretion systems, respectively. Although E. chrysanthemi is not recognized as a mammalian pathogen, we have observed that the bacterium can adhere to, cause an oxidative stress response in and kill cultured human adenocarcinoma cells. These bacteria express a surface protein that bears immunological identity to intimin, a protein required for full virulence of enterohemorrhagic and enteropathogenic Escherichia coli. A type III secretion mutant of E. chrysanthemi was observed to have a significantly lower capability of causing death than the wild-type strain in parallel cultures of human colon adenocarcinoma cells. These observations suggest that E. chrysanthemi has the potential to parasitize mammalian hosts as well as plants.

Positron emission tomography study of regional cerebral metabolism in humans during isoflurane anesthesia.

BACKGROUND: Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on human cerebral glucose metabolism using positron emission tomography (PET). METHODS: Five volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/- SD; expired = 0.5 +/- 0.1%). Scans were obtained with a GE2048 scanner (4.5-mm resolution-FWHM) using the 18fluorodeoxyglucose technique. RESULTS: Awake whole-brain glucose metabolism averaged 6.9 +/- 1.5 mg.100 g-1.min-1 (means +/- SD). Isoflurane reduced whole-brain metabolism 46 +/- 11% to 3.6 +/- 0.3 mg.100 g-1.min-1 (P < or = 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region-of-interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake. CONCLUSION: These data clarify that the anesthetic state evident in the living human brain during unresponsiveness induced with isoflurane is associated with a global, fairly uniform, whole-brain glucose metabolic reduction of 46 +/- 11%.

Factors associated with postoperative pulmonary complications in patients with severe chronic obstructive pulmonary disease.

The purpose of this study was to determine the incidence of different postoperative pulmonary complications (PPCs) and their associated risk factors in patients with severe chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 s [FEV1] < or = 1.2 L and FEV1/forced vital capacity (FVC) < 75%) undergoing noncardiothoracic operations. Thirty-nine of 105 patients (37%) had one or more PPCs (death, pneumonia, prolonged intubation, refractory bronchospasm, or prolonged intensive care unit (ICU) stay). Thirty-eight of 39 patients (97%) with a PPC had an anesthetic duration > 2 h. Our study patients had a 47% 2-yr mortality rate. We determined specific risk factors for each PPC by analyzing potential preoperative and intraoperative risk factors. Pulmonary factors alone do not predict the likelihood of PPCs in severe COPD patients. Multiple logistic regression identified composite scoring systems, such as the ASA physical status, as the best preoperative predictors of PPCs, probably because they include both pulmonary and nonpulmonary factors. During the intraoperative period, avoiding general anesthesia with tracheal intubation may decrease the risk of postoperative bronchospasm. Shortening the duration of surgery and anesthesia may decrease the risk of prolonged ICU stay.

The role of gravity in gentamicin-induced toxic effects in a rabbit model.

OBJECTIVE: To define the role of gravity in gentamicin sulfate-induced retinal toxic effects by injecting the drug into vitrectomized rabbit eyes oriented in one of two positions. METHODS: Ten right eyes of New Zealand white rabbits underwent a two-port pars plana vitrectomy and were positioned with traction scleral sutures to rotate the medullary ray superiorly (five eyes) or nasally (five eyes). Six eyes received a pars plana intravitreal injection of 400 micrograms (0.1 mL) of gentamicin, and four eyes received 0.1 mL of balanced salt solution only. All eyes were kept in position for 30 minutes after the injection. Unoperated-on fellow eyes served as controls. Three or 5 days later, the eyes were enucleated and histopathologic examination was performed. RESULTS: Light and electron microscopy of gentamicin-treated eyes showed inner-retinal edema and disruption of the nerve-fiber and ganglion-cell layers within the more dependent retina vs sparing of the less dependent half of the retina. Eyes that received balanced salt solution showed rare inflammatory cells along the inner-retinal surface but essentially no inner-layer disruption. Examination of unoperated-on control eyes showed no inflammatory cells, edema, or necrosis. CONCLUSION: Gravitational effects and positioning contribute to the location of gentamicin-induced retinal toxic effects in vitrectomized eyes.

Subglottic plasmacytoma: the use of jet ventilation and contact Nd:YAG laser for tissue diagnosis.

Extramedullary plasmacytomas (EMP) constitute only 1% of all head and neck malignancies, with the vast majority occurring in the upper respiratory tract. The diagnosis of laryngeal EMP can be difficult since the symptoms are non-specific and the tumor usually mucosally covered. This paper discusses the successful combination of jet Venturi ventilation technique with suspension microlaryngoscopy and contact Nd:YAG laser for tissue diagnosis in a patient presenting with a large subglottic mass. Previous attempts using standard endotracheal intubation and forceps technique for biopsy failed to reach the diagnosis and resulted in significant bleeding from the biopsy site. A review of the disease and technique is presented.

What methods of pediatric pain management can be incorporated into a generalist's anesthesia practice?

Historically, pain in ill and injured pediatric patients has not been recognized or attended to. Subsequently, children often suffer in silence. Caretakers are often fearful to intervene aggressively to alleviate pain. A critical evaluation and integrative approach to the treatment of pediatric pain has only recently emerged, and curricula addressing the physiologic, behavioral, and biochemical differences related to pain has only recently been instituted in some medical schools and pediatric training programs. Children deserve special consideration in pain management since they may not be capable of comprehending the need for painful procedures and may not have learned strategies to cope with them. The importance of a comprehensive evaluation can not be overstated. The anesthetist can be of great assistance in pain management of the pediatric surgical patient by assessing his patient's postoperative pain needs and planning his/her anesthetic technique and recovery room course accordingly. Research in pediatric pain is still in its infancy, with crucial issues yet to be addressed. One of the most important is how to individualize the treatment of pain. We also need to learn more about children's natural coping styles and how parents and health care providers can enhance their effectiveness in contributing to the therapeutic team. It is hoped that readers will notice their patient's behaviors a little more closely, think about the extent of their private suffering, and become willing to offer a more studied, justifiable, and aggressive approach to pediatric pain management.

Cholecystectomy during pregnancy without fetal loss.

Cholecystectomy in the pregnant patient has been generally avoided because of the reported high incidence of associated fetal loss that has been linked to spontaneous and elective abortion during the first trimester and premature labor during the third trimester. Recent developments relating to diagnostic and anesthetic management and the use of tocolytic agents have altered the over-all approach to patients. We have, therefore, retrospectively reviewed the medical records of all women discharged from four area hospitals during 1982 to 1987 with a concurrent diagnosis of cholelithiasis and pregnancy. Twenty-two patients met the review criteria. The incidence of biliary stone disease among gravid patients during the time interval was 0.05 per cent. Of 22 patients, none underwent radiation for diagnosis. Nine patients underwent cholecystectomy while pregnant; two were operated upon during the first trimester, four during the second and three during the third. Three required common bile duct exploration and three had intraoperative cholangiograms. Elective abortion was not recommended to the six patients because of radiation exposure. Two of nine had premature contractions develop that were controlled with tocolytic agents. There were no spontaneous abortions. The mean Apgar scores for neonates born subsequent to cholecystectomy was virtually identical to neonates born to patients in whom cholecystectomy was deferred. It is concluded that the diagnosis and surgical treatment of cholelithiasis can be safely undertaken in the pregnant patient without fetal loss. Delaying appropriate surgical therapy no longer seems warranted.

The literature and perspectives on muscle relaxants for rapid sequence induction.

Since the advent of surgical anesthesia, one of the single greatest challenges to providers and researchers has been to develop, test, and promote drugs and techniques to facilitate rapid intubation and security of the airway to diminish risk of regurgitation and gastric aspiration. This article provides a comprehensive, historical perspective of such efforts, including the efficacy of various techniques and muscle relaxant drugs that have been used to further the ideal situation in which airway control would obviate the all-too-common morbidity statistics of gastric aspiration. Special emphasis is given to the review of succinylcholine and vecuronium relative to their roles in rapid sequence induction.

Premedication for the pediatric patient: new and old drugs.

Over the last 15 years a rapid growth has occurred in the number of pediatric patients that are encountered in the operating room. A developing sophistication on the part of both children and parents, coupled with a rapidly expanding recognition of the need to minimize the amount of physical and psychological trauma that a child has to experience, has led to a growing use of premedication agents for children. A review of the premedication agents currently in use, their various routes of administration, as well as their associated benefits and risks, is presented.