Concomitant hypertension, bradycardia, and loss of transcranial electric motor evoked potentials during pedicle hook removal: report of a case.

Neurophysiologic monitors in the form of transcranial electric motor evoked potentials (tceMEPs) and somatosensory evoked potentials (SSEPs) have become widely used modalities to monitor spinal cord function during major orthopedic spine procedures. In combination with invasive and non-invasive clinical monitoring and an anesthesia information management system (AIMS), we promptly recognized an acute change in hemodynamic and neurophysiologic parameters, managed intraoperative spinal cord contusion, and successfully minimized iatrogenic injury to the spinal cord during corrective spine surgery.

High density lipoprotein mediated lipid efflux from retinal pigment epithelial cells in culture.

BACKGROUND/AIM: [corrected] The transport of radiolabelled photoreceptor outer segments (POS) lipids was investigated by cultured retinal pigment epithelial cells (RPE). Phagocytosis of POS by the RPE is essential to maintain the health and function of the photoreceptors in vivo. POS are phagocytised at the apical cell surface of RPE cells. Phagocytised POS lipids may be either recycled to the photoreceptors for reincorporation into new POS or they may be transported to the basolateral surface for efflux into the circulation. RESULTS: The authors have demonstrated that high density lipoprotein (HDL) stimulates efflux of radiolabelled lipids, of POS origin, from the basal surface of RPE cells in culture. Effluxed lipids bind preferentially to HDL species of low and high molecular weight. Effluxed radiolabelled phosphotidyl choline was the major phospholipid bound to HDL, with lesser amounts of phosphatidyl ethanolamine, phosphatidyl inosotol. Effluxed radiolabelled triglycerides, cholesterol, and cholesterol esters also bound to HDL. Lipid free apolipoprotein A-I (apoA-I) and apoA-I containing vesicles also stimulate lipid efflux. CONCLUSION: The findings suggest a role for HDL and apoA-I in regulating lipid and cholesterol transport from RPE cells that may influence the pathological lipid accumulation associated with age related macular degeneration.

Sequential analysis of chemically induced hepatoma development in rats by two dimensional electrophoresis.

Using the Solt-Farber hepatocarcinogenesis model, a large population of preneoplastic and neoplastic nodules were induced in male Fischer 344 rats. Total cellular polypeptides from normal liver and individual preneoplastic and neoplastic nodules were analyzed for both qualitative and quantitative changes using computer assisted high resolution two-dimensional electrophoresis. Approximately 800-1000 cytosolic and 1200-1400 membrane associated polypeptides were readily separated and detected using an ultrasensitive silver stain. The polypeptide patterns were remarkably similar for each tissue and only four qualitative polypeptide differences were noted. One cytosolic polypeptide, 6.8/57 (designated pl/Mr X 10(-3), and three membrane associated polypeptides, 6.25/41, 6.75/24, and 6.05/21, were expressed in both preneoplastic and neoplastic nodules but not in normal liver. No qualitative polypeptide differences were detected among the individual preneoplastic or individual neoplastic nodules or between preneoplastic and neoplastic nodules. Numerous quantitative changes in both known markers for hepatocarcinogenesis and in as yet unidentified polypeptides were noted. In particular, the Ya subunit of glutathione S-transferase B, the Yb subunit of glutathione S-transferase A, as well as the three isoelectric point variants of the Yp subunit of glutathione S-transferase P were increased 2-, 4-, and 7-fold, respectively, in preneoplastic and neoplastic nodules. Whereas DT-diaphorase was increased 2-3-fold in hyperplastic nodules as compared to normal liver, no differences in the expression of albumin were noted. Although no differences were observed in the expression of aldehyde dehydrogenase in preneoplastic and neoplastic nodules, polypeptide b (6.9/54) was shifted slightly toward the basic region in normal liver. alpha-Fetoprotein was not detected in either preneoplastic or neoplastic nodules. In addition to these changes in known markers, comparison of 500-800 cytosolic and 750-1000 membrane associated polypeptides showed that roughly 4-10% of the polypeptides were undergoing quantitative changes of at least 4-fold during these stages of hepatocarcinogenesis. Thirty (10 cytosolic and 20 membrane) polypeptides were significantly down-regulated while 22 (7 cytosolic and 15 membrane) polypeptides were up-regulated in both preneoplastic and neoplastic nodules. In all cases the direction and magnitude of change were the same in both preneoplastic and neoplastic nodules with the exception of three polypeptides.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between oxidative metabolism of 2-acetylaminofluorene, debrisoquine, bufuralol, and aldrin in human liver microsomes.

The capacity of human liver microsomes from 28 individuals to metabolize debrisoquine and bufuralol, two drugs oxidized polymorphically in humans, as well as the carcinogen 2-acetylaminofluorene (AAF), was determined. In addition, the cytochrome P-450 content and the capacity of these microsomes to carry out the epoxidation of aldrin were measured. Interindividual differences in debrisoquine 4-hydroxylation, bufuralol 1-hydroxylation, and aldrin epoxidation were 12-, 20-, and 2.4-fold, respectively. The metabolism of debrisoquine was not correlated with cytochrome P-450 content (r = 0.26), whereas both the metabolism of bufuralol (r = 0.45; r2 = 0.20) and the epoxidation of aldrin (r = 0.72; r2 = 0.52) were correlated. Rates of debrisoquine and bufuralol metabolism were significantly correlated (r = 0.73), whereas only weak correlations existed between debrisoquine:aldrin (r = 0.49) and bufuralol:aldrin (r = 0.51). Because biphasic kinetics have been observed in human liver microsomes for the 7- and 5-hydroxylation of AAF, two concentrations of this substrate were used. The disappearance of AAF at either 0.37 or 50 microM was not correlated with debrisoquine, bufuralol, or aldrin metabolism. Similarly, at 0.37 microM AAF, no correlation existed between the formation of N-, 1-, 3-, 5-, 7-, and 9-hydroxylation products of AAF and debrisoquine, bufuralol, or aldrin metabolism. At 50 microM AAF, only the 7-hydroxylation of this substrate correlated with bufuralol metabolism (r = 0.47). This lack of, or weak correlation between pathways leading to metabolic activation (N-hydroxylation) or detoxication (C-hydroxylation) of the carcinogen AAF and debrisoquine, bufuralol, and aldrin metabolism strongly suggests that different forms of cytochrome P-450 are involved in these pathways. In contrast, exceptionally high correlations (r greater than 0.94) existed between N-OH-AAF:1-OH-AAF. N-OH-AAF:7-OH-AAF, and 7-OH-AAF:1-OH-AAF at the low concentration of AAF, and imply that similar forms of cytochrome P-450 produce these metabolites. However, at 50 microM AAF, these correlations are considerably weaker and explain less than 35% of the variance in the data. It is concluded, based on these multiple cross-correlations, that common cytochrome P-450 isoenzymes are involved in the formation of AAF metabolites, while the metabolism of debrisoquine, bufuralol, and aldrin is unrelated to the metabolism of this carcinogen in human liver microsomes.

An economic analysis of interventions for diabetes.

The objective of this article is to stratify interventions for diabetes according to their economic impact. We conducted a review of the literature to select articles that performed a cost-benefit analysis for 17 widely practiced interventions for diabetes. A scale for categorizing interventions according to their economic impact was defined. The 17 interventions were classified as follows: 1) clearly cost-saving, 2) clearly cost-effective, 3) possibly cost-effective, 4) non-cost-effective, or 5) unclear. Clearly cost-saving interventions included eye care and pre-conception care. Clearly cost-effective interventions included nephropathy prevention in type 1 diabetes and improved glycemic control. Possibly cost-effective interventions included nephropathy prevention in type 2 diabetes and self-management training. Non-cost-effective interventions were not identified. Interventions with unclear economic impact included case management, medical nutrition therapy, self-monitoring of blood glucose, foot care, blood pressure control, blood lipid control, smoking cessation, exercise, weight loss, HbA1c measurement, influenza vaccination, and pneumococcus vaccination. Widely practiced interventions for patients with diabetes can be clearly cost-saving and clearly cost-effective. These practices are attractive from both a medical and an economic perspective.

Do anorectics get well? Current research and future needs.

The authors review data from 12 major outcome studies of anorexia nervosa published in the 15 years since the last review article of Ziolko (1966). Across the 12 studies the mortality rate from self-starvation was 6%. On follow-up, well over half of the subjects continued to have eating difficulties, and close to half showed other signs of psychiatric impairment. In nonsymptomatic areas of adjustment there was a striking contrast between the 90% who were successfully employed and the 54% who made some minimal form of marital or social adjustment. The authors present a series of recommendations about the form and content of future research in the field.

Early abnormalities of brainstem auditory evoked potentials in Friedreich's ataxia: evidence of primary brainstem dysfunction.

We studied five children with classic Friedreich's ataxia, using an audiologic test battery to determine the primary site of auditory dysfunction. None of the children had any hearing complaints, and all were tested soon after onset of symptoms. The audiologic test battery consisted of brainstem auditory evoked potential test, tympanometry, and acoustic reflex measurements. The results indicated that the brainstem was the primary site of auditory dysfunction.

Validity of acoustic reflectometry in detecting middle ear effusion.

Pneumootoscopy, tympanometry, and acoustic reflectometry were performed in 256 middle-class children seen in a surburban pediatric office. The results demonstrated that relectometry, when validated by otoscopic findings, detected middle ear effusion with 88% sensitivity and 83% specificity when a cut-off of 5 linear units was used. Corresponding values for tympanometry were 87% and 77.5%. These results are in keeping with those of earlier studies on acoustic reflectometry and demonstrate the usefulness of this simple technique in detecting chronic and acute otitis media with effusion.

Acupuncture and transdermal electrostimulation in the treatment of deafness.

A review and critique of the research on acupuncture and transdermal electrostimulation therapy in treating sensorineural hearing loss is presented. Of 111 subjects in these studies were noted to exhibit a decrease in hearing sensitivity. Additional data collected at our clinics on four preschool hearing-impaired children failed to provide evidence of improvement following acupuncture. Similar results are reported with transdermal therapy, suggesting that both procedures are inappropriate for the treatment of sensorineural hearing loss.

Acute otitis media: diagnosis and drug therapy.

Diagnostic criteria for acute otitis media have become more precise with recent improvements in the otoscope and emphasis on meticulous aural toilet and careful observation of the ossicular landmarks, contour and mobility of the tympanic membrane. The treatment of the acute phase of the disease poses few therapeutic difficulties. There are many alternative antibacterial agents which have proven effective against the common middle ear pathogens. However, each drug or combination has indications and associated problems. Middle ear effusion is the most frequent sequelae of acute otitis media occurring after approximately 50% of cases in younger children. Between 5 to 10% of these effusions persist in excess of 3 months. There is intense interest in the prevention of recurrent acute otitis media (in otitis-prone children) by chemoprophylaxis, immunisation or assuring continuous middle ear ventilation by tympanostomy tube insertion. Several major projects are underway to evaluate the role of decongestants in acute middle ear disease.

Guarded microvitreoretinal blade.

During vitreoretinal surgery, the microvitreoretinal blade may be misdirected and injure operating room personnel. A sheated, retractable blade has been developed to reduce the likelihood of such injuries. In the blade's retracted position, a safety feature prevents inadvertent exposure of the sharp blade. This device may have its greatest utility in operating on patients with cytomegalovirus retinitis who require either retinal reattachment surgery or placement of a ganciclovir implant.

Management of traumatic hemorrhagic retinal detachment with pars plana vitrectomy.

Traumatic hemorrhagic retinal detachment may prevent successful visual rehabilitation of eyes with severe posterior segment injury. We managed 19 consecutive cases of traumatic hemorrhagic retinal detachment with pars plana vitrectomy, scleral buckling, and fluid-gas exchange, with or without internal drainage of subretinal hemorrhage. We based our approach on the amount of subretinal hemorrhage present and the location of associated retinal breaks. Internal drainage of subretinal hemorrhage was performed in 16 eyes to allow adequate retinopexy to hemorrhagically elevated retinal breaks (9 eyes), to remove massive subretinal hemorrhage (4 eyes), and to allow intraoperative reattachment when the retina exhibited bullous retinal detachment (3 eyes). Overall, with a minimum of 6 months of follow-up, anatomic reattachment was achieved in 13 (68%) of 19 eyes, and functional success (visual acuity 5/200 or better) was achieved in 6 (32%) of 19 eyes. Anatomic failure resulted from proliferative vitreoretinopathy (4 eyes) and globe atrophy (2 eyes). Drainage of subretinal blood appeared to be beneficial for hemorrhagically elevated retinal tears to allow adequate retinopexy and may help to accomplish long-term anatomic attachment in eyes with massive subretinal hemorrhage or bullous retinal detachment.

Experimental study of tetrodotoxin, a long-acting topical anesthetic.

PURPOSE: To determine the effectiveness and toxicity of tetrodotoxin for use as a long-acting topical anesthetic. METHODS: Four groups of six rabbits each received a 40-microl aliquot of either tetrodotoxin in one of three concentrations (10 mM, 1 mM, or 0.1 mM) or proparacaine 0.5% into the inferior conjunctival cul-de-sac of one eye, with the fellow eye of each rabbit receiving 40 microl of a 60-mM, pH 4.3 sodium citrate vehicle as a control. Corneal sensation was tested for up to 8 hours after administration of drugs, and response was noted by no blink, partial blink without full eyelid closure, and full blink. Slit-lamp examination at 12 and 24 hours after administration and pachymetry before and 24 hours after administration were performed to detect corneal toxicity. RESULTS: Rabbits receiving all three concentrations of tetrodotoxin did not demonstrate any ocular irritation, corneal thickening, or signs of systemic toxicity. At a dose of 10 mM, tetrodotoxin produced an anesthetic effect lasting up to 8 hours. At 1 mM, tetrodotoxin was an effective but shorter-acting anesthetic. At 0.1 mM, tetrodotoxin had no significant anesthetic effect. Proparacaine-treated rabbits initially were anesthetic, but this effect was largely gone by 1 hour and completely gone by 3 hours. CONCLUSIONS: Tetrodotoxin is a long-acting topical anesthetic in the rabbit cornea. Although additional toxicity studies are required, tetrodotoxin may provide an effective, long-lasting topical anesthetic for use in pain control after corneal procedures such as photorefractive keratectomy.

A sensitive and specific polymerase chain reaction-based assay for the diagnosis of cytomegalovirus retinitis.

PURPOSE: To develop a sensitive and specific laboratory assay for the diagnosis of cytomegalovirus retinitis. METHOD: We used a polymerase chain reaction-based assay for detection of cytomegalovirus DNA in vitreous samples. We attempted to detect cytomegalovirus DNA in 19 vitreous samples from patients with the acquired immunodeficiency syndrome (AIDS) who had untreated cytomegalovirus retinitis and in 40 vitreous samples from patients with AIDS who had been treated with systemic ganciclovir or foscarnet, or both. We also attempted to detect cytomegalovirus DNA in vitreous samples from 54 immunocompetent patients, including 32 with retinal detachment or macular hole, 11 with vitreous inflammation, and 11 with vitreous hemorrhage. Additionally, we attempted to detect cytomegalovirus DNA in 15 vitreous samples from patients with AIDS who had vitreoretinal inflammation not caused by cytomegalovirus. RESULTS: Cytomegalovirus DNA was detected in 18 of 19 eyes with untreated cytomegalovirus retinitis. We detected cytomegalovirus DNA in 19 of 40 vitreous samples from patients with previously treated cytomegalovirus retinitis. Cytomegalovirus DNA was not detected in any of 69 patients who did not have a clinical diagnosis of cytomegalovirus retinitis. Thus, the assay had an estimated sensitivity of 95% in detecting untreated cytomegalovirus retinitis and a sensitivity of 48% in detecting cytomegalovirus retinitis that had been treated with systemic ganciclovir or foscarnet, or both. The assay did not give false-positive results in patients with vitreous hemorrhage or vitreous inflammation. Most important, the assay did not give false-positive results in AIDS patients with vitreous inflammation from causes other than cytomegalovirus retinitis. CONCLUSION: We have developed a sensitive and specific diagnostic assay that will assist in the diagnosis of cytomegalovirus retinitis.

Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis.

PURPOSE: To determine anatomic and visual acuity outcomes of posterior segment complications after ganciclovir implant surgery. METHODS: We reviewed the medical records of 63 patients with acquired immunodeficiency syndrome who had active cytomegalovirus retinitis in 82 eyes and who underwent 110 consecutive ganciclovir implant procedures. Preoperative and postoperative visual acuity, type of postoperative complication, treatment, and lines of visual acuity change were determined. RESULTS: Thirty-eight eyes of 19 patients had bilateral ganciclovir implant procedures, and 25 eyes of 19 patients underwent two or more ganciclovir implant procedures. Thirteen (12%) of 110 ganciclovir implant procedures developed posterior segment complications: rhegmatogenous retinal detachment in six, vitreous hemorrhage in four, endophthalmitis in two, and cystoid macular edema with epiretinal membrane in one. Treatment included pars plana vitrectomy with silicone oil in two cases and without silicone oil in three cases, scleral buckling in one, intravitreal antibiotic injection in two, and laser photocoagulation in two. Overall, median visual acuity was 20/25 preoperatively. Median follow-up was 6 months for all eyes and 7 months for eyes with complications. Postoperative median visual acuity was 20/25 for eyes without complications vs 20/40 at 1 month, 20/60 at 3 and 6 months, and 20/100 at 12 months in eyes with complications (P < .001). More eyes with than without complications lost 2 or more lines of visual acuity (P < .001). CONCLUSION: Postoperative complications occurred in 12% of the ganciclovir implant procedures and were associated with decreased visual acuity despite treatment.

Saxitoxin: an anesthetic of the deepithelialized rabbit cornea.

PURPOSE: The aim of the current study was to define the efficacy of saxitoxin as a corneal anesthetic in rabbits after mechanical corneal abrasion and photorefractive keratectomy (PRK). METHODS: Twelve Dutch belted rabbits were given a single 1.2-microg dose of saxitoxin or vehicle after mechanical abrasion of the cornea. Corneal sensation was evaluated hourly for 6 hours. A second group of 12 Dutch belted rabbits was given a 1.2-microg dose of saxitoxin or vehicle every 5 hours for 30 hours after PRK. Corneal sensation was evaluated after 5, 10, 15, 20, 25, and 30 hours. Pachometry was performed before PRK and again after the epithelial defects had healed. The rate of epithelial defect closure was assessed by measuring the epithelial defect size 25, 42, 65, 88, and 113 hours after PRK. RESULTS: A dose of 1.2 microg of saxitoxin given every 5 hours produced continuous corneal anesthesia after PRK. There was no difference in the rate of wound healing between eyes treated with saxitoxin and vehicle. There was no difference in the degree of wound healing, as measured by pachometry, between eyes treated with saxitoxin and vehicle. There were no apparent ocular or systemic toxic effects from saxitoxin administration. CONCLUSION: At a dose of 1.2 microg, saxitoxin is a safe, effective, long-acting corneal anesthetic in rabbits after PRK.

Experimental use of tetrodotoxin for corneal pain after excimer laser keratectomy.

PURPOSE: To determine the duration of anesthesia, effect on corneal reepithelialization, and systemic toxicity of topical tetrodotoxin (TTX) administered after excimer laser keratectomy. METHODS: Two groups of six rabbits each underwent excimer laser keratectomy in the right eye to create a 5-mm-diameter wound, 75 mm in depth. One group then received a 40-microl aliquot of topical 1 mM TTX into the injured eye, whereas the other group received 40 microl of the sodium citrate vehicle as a control. The rabbits were treated with TTX or vehicle again at 6, 12, 18, and 24 h. Corneal sensation was tested at 3, 6, 9, 12, 15, 18, 21, 24, 30, 32, and 40 h. To determine whether TTX inhibited corneal reepithelialization, compared with vehicle-treated control eyes, the healing rate of the epithelial defect was measured. RESULTS: Administration of TTX every 6 h for 24 h produced nearly complete anesthesia for > or = 30 h. At 32 h, 8 h after the final application of TTX, there was still significant anesthesia of the TTX-treated corneas (p = 0.0325, Wilcoxon test). Normal corneal sensation in all TTX-treated animals returned at 40 h, or 16 h after the final dose. In contrast, vehicle-treated eyes all had normal sensation for nearly the entire duration of the experiment. At 40 h, the TTX-treated eyes had slightly larger defects than vehicle-treated eyes, 7.85+/-1.74 versus 4.54+/-1.31 mm2 (p < 0.025, t test). However, at 49 h and thereafter, both groups were equally healed (p > 0.05, t test). No systemic toxicity was observed in any of the rabbits. CONCLUSION: Topical TTX is a long-acting and nontoxic local anesthetic in a rabbit model of excimer laser keratectomy.

Corneal endothelial hyaluronidase: a role in anterior chamber hyaluronic acid catabolism.

The possible role of the human corneal endothelium in the turnover of anterior chamber hyaluronic acid (HA) was investigated. Hyaluronidase, an endoglycosidase that degrades HA and other glycosaminoglycans, is thought to play a role in HA homeostasis. The presence of hyaluronidase in the corneal endothelium was demonstrated immunohistochemically in sections from normal adult human cornea. Additionally, by using a modified enzyme-linked immunosorbent assay-like assay, active hyaluronidase was detected in the supernatant from primary culture human corneal endothelial cells. The optimal activity for the corneal endothelial hyaluronidase was in the acid range (pH 4.0), similar to previously isolated lysosomal hyaluronidase. Further immunohistochemistry showed that the corneal endothelial cells also express CD44, the receptor for HA, which would allow endocytosis of HA. Human corneal endothelial hyaluronidase may play a role in normal anterior segment HA metabolism and in the degradation of highly concentrated HA used as a visco-elastic.

Office myringotomy for acute otitis media: its value in preventing middle ear effusion.

Middle ear effusion (MEE) as a residual of treated acute otitis media was found in 49% of 776 children studied. No antibiotic singly or in combination, demonstrated superiority in reducing the incidence of MEE. Simple myringotomy, as a therapeutic modality in 415 children who presented with an acutely bulging painful eardrum, did not facilitate adequate drainage as 51% of such children, treated with simple myringotomy in addition to antibiotics, had MEE detected 10 days later. The incidence of MEE also occurred independently of the middle ear pathogen. Within six weeks, spontaneous resolution of the effusion occurred in 85% of the 382 children with MEE that was detected 10 days after acute otitis media.