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Biomedical subjects

M Bridget Zimmerman

Publications and source records attributed to M Bridget Zimmerman.

At least 37 records · Page 2Linked to original sources

Factors influencing survival following surgical treatment of obesity.

BACKGROUND: The prevalence of obesity in the United States and the surgical treatment of obesity have increased since 1999. An important measure of outcome following surgical treatment is survival. METHODS: This study began with data prospectively collected from Jan 1, 1986 to Dec 31, 1999 by 55 data collection sites, representing 77 surgeons who used standardized data collection software developed by the International Bariatric Surgery Registry (IBSR). A subset of 18,972 subjects was submitted to the National Death Index (NDI) for search of death occurring from Jan 1, 1986 to Dec 31, 2001. The univariate survival analysis included Kaplan-Meier plots and log-rank tests. Cox proportional-hazards (PH) frailty model was used to identify risk factors and estimate hazard ratios in a multi-factor survival analysis. Covariates included gender, operative age, body mass index, operation category (simple and complex), operation year, diabetes, smoking and hypertension as recorded prior to operation. RESULTS: Deaths were found for 3.45% of the patients (654/18,972). Average follow-up was 8.3 years. Age, gender, BMI, history of smoking, diabetes, and hypertension were significant predictors of survival. Operation category (P=0.13) and operation year (P=0.89) were not significant predictors of survival. CONCLUSION: Simple and complex operations were equally effective in keeping patients alive in this cohort of patients operated on for severe obesity from 1986 to 1999. Young, female, non-smoking patients with low BMI at operation and no history of diabetes or hypertension had the longest survival. Longer follow-up for death is needed before any recommendations can be made for operation category based on survival.

Adult↗

Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia.

OBJECTIVE: To examine the utility of red blood cell (RBC) zinc protoporphyrin/heme ratio (ZnPP/H) as an indicator of fetal iron status, because unfavorable neurodevelopmental outcomes have been associated with poor iron status at birth, as indicated by low serum ferritin, and because few reliable indicators of fetal and early neonatal iron status exist. METHODS: Consecutively studied preterm and term fetuses at delivery included the following groups: (1) control nonhypoxic, (2) fetuses with intrauterine growth retardation (IUGR), and (3) fetuses of insulin-treated mothers (FDM). We hypothesized (1) that rapid growth velocity associated with an accelerated erythropoiesis among normal fetuses will lead to reduced iron delivery to a rapidly expanding RBC mass and higher umbilical cord blood RBC ZnPP/H and (2) that fetuses that are exposed to pathologic hypoxemia will experience an additional increase in erythropoiesis and higher cord ZnPP/H. ZnPP/H was determined on saline-washed cord blood erythrocytes by hematofluorometry and was examined for its relationship with clinical factors and cord blood laboratory measurements indicative of tissue oxygenation (plasma erythropoietin [EPO] and reticulocyte count) and iron status (plasma ferritin and erythrocyte indices). Statistical testing included 1-way analysis of variance, 2-way analysis of variance with covariates, simple linear regression, and multiple regression analysis. RESULTS: Among control group subjects, gestational age at birth was inversely correlated with RBC ZnPP/H and reticulocyte count and positively correlated with ferritin and EPO. Relative to control subjects, IUGR and FDM fetuses at specified gestational age groupings had higher ZnPP/H, lower plasma ferritin, and higher plasma EPO. Statistical modeling of the relationship between ZnPP/H and plasma ferritin among all study groups demonstrated significant impacts of gestational age, plasma EPO, maternal hypertension, and maternal smoking. CONCLUSIONS: The inverse association of fetal ZnPP/H with gestational age at birth among control subjects is attributable to erythropoietic stimulation likely as a result of increasing growth velocity at the earliest gestational ages. The relatively higher ZnPP/H observed among fetuses in the IUGR and FDM groups likely is attributable to increased erythropoietic activity secondary to pathologic hypoxemia. Decreased placental iron transfer may also have limited iron availability and contributed to elevated ZnPP/H in the IUGR group. These data support the concept that increased erythropoietic activity and/or limited iron transport may place infants of diabetic mothers and infants with growth retardation at risk for developing systemic iron deficiency later in infancy and in early childhood.

Erythrocyte Indices↗

Reduction in red blood cell transfusions among preterm infants: results of a randomized trial with an in-line blood gas and chemistry monitor.

BACKGROUND: Critically ill, extremely premature infants develop anemia because of intensive laboratory blood testing and undergo multiple red blood cell (RBC) transfusions in the early weeks of life. To date, researchers have had only limited success in finding ways to reduce transfusions significantly in this patient population. OBJECTIVE: To reduce RBC transfusions for these infants by using a point-of-care bedside monitor that returns analyzed blood to the patient. DESIGN, SETTING, AND PATIENTS: This was a prospective, 2-center, randomized, open, controlled, clinical trial with a 1:1 assignment of extremely low birth weight infants (weighing 500-1000 g at birth) to control or monitor groups and analysis with the intention-to-treat approach. Predefined RBC transfusion criteria were applied uniformly in the 2 groups. INTERVENTIONS: Clinical treatment of study subjects with an in-line, ex vivo, bedside monitor that withdraws blood through an umbilical artery catheter, analyzes blood gases and sodium, potassium, and hematocrit levels, and returns the sample to the patient. MAIN OUTCOME MEASURES: The total volume and number of RBC transfusions during the first 2 weeks of life and the total volume of blood removed for laboratory testing. RESULTS: The trial was terminated prematurely when one center's NICU changed its standard method of laboratory testing. In the first 2 weeks of life, there was a nonsignificant 17% lower cumulative RBC transfusion volume in the monitor group (n = 46), compared with the control group (n = 47). However, data from the first week only (the period of greater catheter use) demonstrated a significant 33% lower cumulative RBC transfusion volume in the monitor group. Cumulative phlebotomy loss was approximately 25% less in the monitor group throughout the 2-week study period. There was no difference between groups in neonatal mortality, morbidity, and neurodevelopmental outcome rates at 18 to 24 months. This is the first randomized trial documenting that RBC transfusions administered to neonates can by reduced by decreasing laboratory phlebotomy loss. CONCLUSIONS: As long as an umbilical artery catheter is available for blood sampling with an in-line blood gas and chemistry monitor, significant reductions in neonatal RBC transfusions can be achieved. The patients most likely to benefit from monitor use are the smallest, most critically ill newborns.

Anemia, Neonatal↗

Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants.

OBJECTIVE: Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences. DESIGN, SETTING, AND PATIENTS: We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion. INTERVENTION: The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status. MAIN OUTCOME MEASURES: We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes. RESULTS: Infants in the liberal-transfusion group received more RBC transfusions (5.2 +/- 4.5 [mean +/- SD] vs 3.3 +/- 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 +/- 2.5 vs 2.2 +/- 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes. CONCLUSIONS: Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.

Anemia↗

Perineural and vascular invasion in oral cavity squamous carcinoma: increased incidence on re-review of slides and by using immunohistochemical enhancement.

CONTEXT: Perineural invasion and vascular invasion may be adverse prognostic factors in patients with oral cavity squamous cell carcinoma. However, the incidence of perineural and vascular invasion varies in the literature, and the use of immunohistochemistry to enhance their detection has not been evaluated in oral cavity squamous cell carcinomas. OBJECTIVE: To determine if the previously assessed incidence of perineural and vascular invasion in cases of oral cavity squamous cell carcinoma would be increased by re-review of the original routinely hematoxylin-eosin-stained sections as well as review of slides stained immunohistochemically with S100 and CD31 to enhance visualization of nerves and vessels. DESIGN: Forty cases of oral cavity squamous cell carcinoma in which the status of perineural and vascular invasion had been part of the original pathology report were reviewed. All original routinely stained slides were reviewed as well as S100- and CD31-stained sections of each case's tissue blocks that contained tumor. RESULTS: Perineural invasion was identified in 30% (12/ 40) of tumors in the original reports, 62% (25/40) of the authors' re-review of the same slides, and 82% (33/40) when cases were stained with S100. Vascular invasion was identified in 30% (12/40) of tumors in the original reports, 35% (14/40) of the authors' re-review of the same slides, and 42% (17/40) when cases were stained with CD31. False-positive and false-negative results were common in the original reports. The number of foci of both types of invasion was related to its discovery in the original reports. Vascular invasion, but not perineural invasion, was significantly associated with death at 5-year follow-up. CONCLUSIONS: Although careful re-review of routinely stained slides will detect a significant number of cases of perineural and vascular invasion, immunohistochemical enhancement further improves the accuracy of the determination.

Adult↗

Residual sleepiness after N2O sedation: a randomized control trial [ISRCTN88442975].

BACKGROUND: Nitrous oxide (N2O) provides sedation for procedures that result in constant low-intensity pain. How long do individuals remain sleepy after receiving N2O? We hypothesized that drug effects would be apparent for an hour or more. METHODS: This was a randomized, double blind controlled study. On three separate occasions, volunteers (N = 12) received 100% oxygen or 20% or 40% N2O for 30 min. Dependent measures included the multiple sleep latency test (MSLT), a Drug Effects/Liking questionnaire, visual analogue scales, and five psychomotor tests. Repeated measures analysis of variance was performed with drug and time as factors. RESULTS: During inhalation, drug effects were apparent based on the questionnaire, visual analogue scales, and psychomotor tests. Three hours after inhaling 100% oxygen or 20% N2O, subjects were sleepier than if they breathed 40% N2O. No other drug effects were apparent 1 hour after inhalation ceased. Patients did not demonstrate increased sleepiness after N2O inhalation. CONCLUSION: We found no evidence for increased sleepiness greater than 1 hour after N2O inhalation. Our study suggests that long-term effects of N2O are not significant.

Journal Article↗

Intraocular pressure abnormalities associated with central and hemicentral retinal vein occlusion.

OBJECTIVE: To evaluate the prevalence of ocular hypertension (OHT) and glaucoma in patients with central retinal vein occlusion (CRVO) and hemi-CRVO (HCRVO) and of the fall in intraocular pressure (IOP) secondary to CRVO/HCRVO. DESIGN: Nonrandomized comparative case series. PARTICIPANTS AND METHODS: We investigated 674 consecutive patients who were initially seen with unilateral CRVO (n = 548) and HCRVO (n = 126) at their onset, with a normal fellow eye. The fellow uninvolved eye in each patient acted as a control. Central retinal vein occlusion and HCRVO were categorized into nonischemic and ischemic. At all visits, patients had a detailed ocular history, as well as a thorough bilateral ocular evaluation, including IOP recording with a Goldmann applanation tonometer; when the diagnosis of OHT or glaucoma was initially uncertain, the 24-hour diurnal IOP was recorded. The observed prevalence rates of OHT and glaucoma among patients with CRVO and HCRVO were compared with those in the general population. MAIN OUTCOME MEASURES: The prevalence of OHT and glaucoma, and of ocular hypotension secondary to CRVO/HCRVO. RESULTS: The overall prevalence of glaucoma was 9.9% and of OHT 16.2%. The prevalence of glaucoma/OHT was found to be significantly (P<0.0001) higher in patients with CRVO and HCRVO than in the general population. There was no significant difference in the proportion of patients with glaucoma/OHT among the various types of CRVO/HCRVO (P = 0.156). Forty-eight percent of all patients had lower IOP (>/==" BORDER="0">2 mmHg) in the CRVO/HCRVO eye than in the fellow (uninvolved) eye at their initial evaluation. The prevalence of ocular hypotension was significantly (P<0.0001) higher in patients with glaucoma/OHT not on ocular hypotensive therapy than in patients without glaucoma. Among the patients without glaucoma, the prevalence of ocular hypotension differed significantly among the various types of CRVO/HCRVO (P = 0.007). CONCLUSIONS: Central retinal vein occlusion and HCRVO have a significant association with glaucoma and OHT and with a subsequent fall in IOP in the involved eye. Few patients with CRVO/HCRVO have high IOP in the involved eye, although many of them do have it in the fellow uninvolved eye. It is important to exclude glaucoma/OHT in the fellow eye of any patient with CRVO/HCRVO; if present, elevated IOP should be treated to reduce the risk of that eye developing (1) CRVO/HCRVO and (2) glaucomatous damage. There may be no benefit to prescribing IOP-lowering drops for involved eyes whose IOP is already normal.

Adolescent↗

Central retinal artery occlusion. Retinal survival time.

PURPOSE: To investigate the retinal survival time following central retinal artery occlusion (CRAO). METHODS: In 38 elderly, atherosclerotic and hypertensive rhesus monkeys, transient CRAO (varying from 97 to 240 min) was produced by temporarily clamping the CRA at its site of entry into the optic nerve. Stereoscopic color fundus photography, fluorescein fundus angiography, electroretinography (ERG), and visual evoked potential (VEP) recording were performed before and during CRA clamping, after unclamping, and serially thereafter. After unclamping of the CRA, the animals were followed for variable lengths of time (median duration 8.14 weeks). Finally, the eyes and optic nerves were examined histologically. The data on ERG changes were analyzed in the following four time frames: (1) baseline before CRA clamping, (2) during CRA clamping, (3) immediately after unclamping, and (4) at the end of follow-up. Duration of CRAO was divided into four groups: 97, 105-120, 150-165, and > or = 180 min. RESULTS: A 'negative ERG' appeared during CRA clamping. With removal of the CRA clamp, there was b-wave recovery, with differential rates of recovery of ERG-eyes with shorter CRAO recovered sooner than those with longer occlusion. On removal of clamp, recovery was seen in scotopic 24 dB b-wave, photopic 0 dB single flash b-wave and 30 Hz flicker, with the b/a ratio of the combined rod and cone response and selective rod response showing statistically significant differences amongst the shorter and longer periods of CRAO. A delayed normalization of the depressed b/a ratio immediately after CRA reperfusion may indicate high-grade ischemic damage. At the final follow-up test session, no clear-cut derangement of any ERG parameter was seen for any group, with subtotal b-wave amplitude recovery for all groups. Longer CRAO produced incomplete VEP recovery. On histology, in the macular retina, eyes with CRAO for 97 min showed practically no damage, but duration of CRAO was found to be significantly associated with the amount of damage in the ganglion cell layer (p = 0.009) and inner nuclear layer (p = 0.017). Outer nuclear and plexiform layers and photoreceptors showed no damage at all with CRAO. There was no significant association of the ERG measures and histologic changes with any of the residual retinal circulation variables. CONCLUSIONS: Our electrophysiologic, histopathologic and morphometric studies showed that the retina of old, atherosclerotic, hypertensive rhesus monkeys suffers no detectable damage with CRAO of 97 min but above that level, the longer the CRAO, the more extensive the irreversible damage. The study suggests that CRAO lasting for about 240 min results in massive irreversible retinal damage.

Animals↗

Autonomic response to stress in interstitial cystitis.

PURPOSE: Previous studies have documented elevations in indices of sympathetic activity in cats and humans with interstitial cystitis (IC). To examine potential autonomic dysregulation in IC we examined the effects of a laboratory mental stress challenge on blood pressure and heart rate (HR) in patients with IC and healthy controls. MATERIALS AND METHODS: A total of 14 female patients with IC and 14 age matched controls participated in a laboratory session, including a 25-minute mental stress challenge. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured at intervals before, during and following the stressor. The level of chronic stress, symptom severity and pain at voiding were assessed. RESULTS: Mean age was 49 years (range 32 to 66). The resting HR of patients with IC (82.02 bpm) was significantly higher than that of controls (63.31 bpm, p = 0.0001). There was also suggested evidence of elevated resting DBP in patients with IC (p = 0.07) but no significant difference in mean resting SBP. Autonomic arousal elicited by the laboratory stressor did not differ between the groups and subjects in each group perceived the task as equally stressful. Patients with IC had significantly elevated HR at each time point compared with controls (p <0.0001) with an average mean difference +/- SD between the groups of 19.5 +/- 4.0 (main effect for group p <0.0001). Although consistent increases in SBP and DBP were observed in patients after baseline, these differences were not significant. CONCLUSIONS: Patients with IC had an increased HR at baseline and throughout a laboratory mental stress challenge compared to healthy age matched women. No differences in HR or blood pressure reactivity were observed between the 2 groups.

Adult↗

Effect of initial weight-bearing in a total contact cast on healing of diabetic foot ulcers.

BACKGROUND: Although total contact casts are highly effective in the treatment of plantar ulcerations in patients with diabetes mellitus, they are not widely used. One reason for this lack of acceptance may be the difficulty in complying with an initial period of non-weight-bearing, as is generally recommended by physicians. We performed this study to assess the effects of early weight-bearing on the healing rates of plantar ulcers in patients with diabetes who were wearing a total contact cast. METHODS: Forty patients with diabetes mellitus who had a noninfected forefoot or midfoot ulcer were treated with total contact casts until healing or for thirteen weeks. The patients were instructed to bear no weight on the cast for forty-eight hours after it was applied. Using an embedded step counter, we measured the number of steps taken during the first twenty-four and forty-eight hours, the first week, and each subsequent two-week period after application of the cast. We removed the cast, measured the radius of the ulcer, and then reapplied the cast at the end of the first week and of each subsequent two-week period after cast application until the ulcer healed or for thirteen weeks. We then determined the effect of the number of steps during various time intervals on the rate of ulcer healing (defined as a change in the ulcer radius). RESULTS: Most patients walked on the cast in the immediate postoperative period. The effects of modest amounts of early weight-bearing on ulcer healing rates appear negligible. Only excessive walking during the first twenty-four or forty-eight hours after cast application is likely to prolong the duration of cast treatment. CONCLUSIONS: Moderate early weight-bearing retards healing of plantar ulcers only minimally in patients with diabetes mellitus treated with total contact casts. Allowing patients to walk immediately after placement of a total contact cast may improve their acceptance of this form of therapy. LEVEL OF EVIDENCE: Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

Adult↗

Plantar foot surface temperatures with use of insoles.

PURPOSE: Patients with diabetes are often prescribed foot orthoses to help prevent foot ulcer formation. Orthotics are used to redistribute normal and shear stress. Shear stresses are not easily measurable and considered to be responsible for skin breakdown. Local elevation of skin temperature has been implicated as an early sign of impending ulceration especially in regions of high shear stress. The purpose of this study was to measure the effects of commonly prescribed insole materials on local changes in plantar foot temperature during normal gait. METHODS: Six commonly used foot orthosis materials were tested using the Thermo Trace infrared thermometer to measure foot temperature. Ten healthy adult volunteers without any history of diabetes or abnormal sensation participated in the study. During each trial the subject walked on a treadmill with the test material in the dominant foot's shoe, for six minutes at a speed of four miles per hour and rested for six minutes between trials. Four locations on the foot (hallux, first and fifth metatarsal heads, and heel) and the contralateral bicep temperatures were measured at 0, 1, 3, 5 minutes during the rest period. The order of material and skin location testing was randomized. RESULTS: Significant differences were found between baseline temperatures and foot temperatures for all materials. However, no differences were found between materials for any location on the foot. CONCLUSION: Previous studies have attempted to characterize materials based on laboratory and clinical testing, while other studies have attempted to characterize the effect of pressure on skin temperature. However, no study has previously attempted to characterize foot orthosis materials based on foot temperatures. This study compared foot temperatures of healthy adults based on the material tested. Although this study was unable to distinguish between materials based on foot temperatures, it was able to show a rise in foot temperature with any material used. This study demonstrates a need to a larger study on a population with diabetes.

Adult↗

Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation: experimental studies.

OBJECTIVES: Our objective was to evaluate the efficacy of triphasic waveforms for transthoracic defibrillation in a swine model. BACKGROUND: Triphasic shocks have been found to cause less post-shock dysfunction than biphasic shocks in chick embryo studies. METHODS: After 30 s of electrically induced ventricular fibrillation (VF), each pig in part I (n = 32) received truncated exponential biphasic (7.2/7.2 ms) and triphasic (4.8/4.8/4.8 ms) transthoracic shocks. Each pig in part II (n = 14) received biphasic (5/5 ms) and triphasic shocks (5/5/5 ms). Three selected energy levels (50, 100, and 150 J) were tested for parts I and II. Pigs in part III (n = 13) received biphasic (5/5 ms) and triphasic (5/5/5 ms) shocks at a higher energy (200 and 300 J). Although the individual pulse durations of these shocks were equal, the energy of each pulse varied. Nine pigs in part I also received shocks where each individual pulse contained equal energy but was of a different duration (biphasic 3.3/11.1 ms; triphasic 2.0/3.2/9.2 ms). RESULTS: Triphasic shocks of equal duration pulses achieved higher success than biphasic shocks at delivered low energies: <40 J: 38 +/- 5% triphasic vs. 19 +/- 4% biphasic (p < 0.01); 40 to <50 J: 66 +/- 7% vs. 42 +/- 7% (p < 0.01); and 50 to <65 J: 78 +/- 4% vs. 54 +/- 5% (p < 0.05). Shocks of equal energy but different duration pulses achieved relatively poor success for both triphasic and biphasic waveforms. Shock-induced ventricular tachycardia (VT) and asystole occurred less often after triphasic shocks. CONCLUSIONS: Triphasic transthoracic shocks composed of equal duration pulses were superior to biphasic shocks for VF termination at low energies and caused less VT and asystole.

Animals↗

Vitreous amino acid concentrations in patients with glaucoma undergoing vitrectomy.

OBJECTIVE: To measure vitreous concentrations of glutamate and other amino acids in patients with glaucoma undergoing vitrectomy. METHODS: Undiluted vitreous samples were collected from patients undergoing vitrectomy at the University of Iowa (Iowa City) between 1997 and 1998 (n = 69). Vitreous concentrations of 16 amino acids, including glutamate, were determined using high-pressure liquid chromatography. Patients with a history of diabetes mellitus were excluded from the analysis. The study group consisted of those with a history of glaucoma (n = 8), and the control group included those with an epiretinal membrane and/or macular hole with no history of glaucoma (n = 17). Comparison of amino acid concentrations between the 2 groups was performed using a multifactor main effects model that adjusted for the effect of 10 selected covariates. Power analysis was done to determine the level of significant difference in amino acid concentrations. RESULTS: The glaucoma group comprised vitreal specimens from patients with primary open-angle (n = 3) and angle-closure glaucomas that included aqueous misdirection (n = 2), uveitis with secondary angle-closure (n = 2), and Axenfeld Rieger syndrome (n = 1). Indications for vitrectomy in this group included epiretinal membrane, retinal detachment, aqueous misdirection, and uveitis. The control group included specimens from patients with a macular hole (n = 11) and epiretinal membrane (n = 7), with 1 eye having both. Surgical indications in controls were macular hole, retinal detachment, and epiretinal membrane. The mean +/- SD levels of vitreous glutamate, glycine, gamma-aminobutyric acid, and alanine were 6.1 +/- 2.4, 16.3 +/- 7.5, 0.8 +/- 0.3, and 260.5 +/- 101.9 microM, respectively, in glaucoma and 5.2 +/- 2.3, 8.5 +/- 2.5, 0.6 +/- 0.2, and 159.5 +/- 54.9 microM in controls (P >.05 for all). None of the 16 amino acid concentrations measured showed a statistically significant difference between glaucoma and controls (P values between.06 and >.99). A power analysis indicated that a 1.8-fold elevation in the glutamate level was needed to reach significance. MAIN OUTCOME MEASURES: Vitreous amino acid concentrations. CONCLUSIONS: None of the 16 amino acids measured, including glutamate, were significantly elevated in the vitreous of glaucomatous eyes compared with controls. Our results are not consistent with the simple hypothesis of glutamate excitotoxicity in glaucoma. Instead, our findings indicate the dynamic nature of extracellular glutamate, whose concentration is dependent on complex mechanisms not yet fully understood. Further studies are needed to fully elucidate the role of glutamate in the pathogenesis of glaucoma.

Aged↗

Prospective polysomnographic analysis of obstructive sleep apnea in down syndrome.

OBJECTIVES: To investigate obstructive sleep apnea (OSA) in a consecutively encountered, nonselected population of young patients with Down syndrome using standard overnight polysomnography and to determine the effects of therapy. METHODS: In a population of patients seen for routine developmental evaluations, 9 boys and 10 girls were studied using standard overnight polysomnography. RESULTS: Using pediatric standards, OSA was found in 79% of the subjects (95% confidence interval, 54%-94%), with a median apnea index of 3 events per hour (interquartile range, 2-5), a median apnea-hypopnea index of 6 events per hour (interquartile range, 3-8), and a median arterial oxygen saturation (SaO2) low point of 88% (interquartile range, 84%-90%). Higher body mass index was significantly associated with a higher apnea index and a lower SaO2 level, and there was a significant inverse relationship between age and the lowest SaO2 value as well as a possible association between sleep-related symptoms at the time of diagnosis and the lowest SaO2 value. In addition, patients with OSA had a significantly higher movement arousal index than those without OSA. CONCLUSIONS: Using rigid polysomnographic standards, this pilot study revealed OSA in a high percentage of young subjects with Down syndrome and an association between OSA and obesity, age, and poor sleep quality. These findings justify larger and more detailed population studies to further define clinical factors that are concomitant with OSA in Down syndrome and to improve therapy.

Adenoidectomy↗

Pupil light reflex in normal and diseased eyes: diagnosis of visual dysfunction using waveform partitioning.

OBJECTIVE: To evaluate changes in pupil size (corresponding to neuronal firing) within different time windows of the pupil light reflex in patients and normal subjects to understand which segments of the pupil waveform are best able to differentiate normal from abnormal subjects. DESIGN: Comparative, observational case series. PARTICIPANTS: Forty-nine normal subjects and 25 patients with known unilateral or asymmetric visual field damage were tested. METHODS: A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz. Each eye was stimulated alternately (30 degrees full-field, 200 milliseconds duration every 3 seconds) over 10 different stimulus intensities. The recorded waveform of the pupil light reflex was subdivided into six time windows based on landmarks corresponding to contraction onset, maximum contraction velocity, peak contraction, and maximum dilation velocity to assess which portion was most affected by disease. MAIN OUTCOME MEASURES: The linear correlation between pupil contractions elicited by right versus left full-field stimulation at different light intensities provided diagnostic parameters (slope, intercept, and correlation coefficient R(2)) that were useful for differentiating normal subjects from patients and for categorizing disease. Sensitivity and specificity of the time windows were evaluated with receiver-operator curve analysis. RESULTS: The diagnosis of asymmetric disease was greatest at time windows that included pupil contraction but not dilation. When the contraction phase was subdivided into an early phase and into a late phase, the late phase was the most diagnostic compared with the entire phase of contraction amplitude (onset to peak contraction). CONCLUSIONS: By use of a range of light intensity, the change in pupil size measured between the time at which maximum contraction velocity occurs and the time to peak contraction provided the best response parameter for objective diagnosis of asymmetric disease of the anterior visual pathway. The waveform of the pupil light reflex may be an expression of the firing of retinal ganglion cells. Therefore, understanding which segment of the pupil light reflex provides maximal diagnostic power may give insight into how disease affects the pattern of neuronal firing rate.

Diagnostic Techniques, Ophthalmological↗

Open-chest epicardial "surgical" defibrillation: biphasic versus monophasic waveform shocks.

The aim of the study was to compare biphasic versus monophasic shocks for open-chest epicardial defibrillation. Transthoracic biphasic waveform shocks require less energy to terminate ventricular fibrillation compared to monophasic waveform shocks. However, if biphasic shocks are effective for open-chest epicardial ("surgical") defibrillation has not been established. Twenty-eight anesthetized adult swine (15-25 kg) underwent a midline sternotomy. Ventricular fibrillation was electrically induced. After 15 seconds of ventricular fibrillation, each pig in group 1 (n = 16) randomly received damped sinusoidal monophasic epicardial shocks and truncated exponential biphasic epicardial shocks from large (44.2 cm2) paddle electrodes at eight energy levels (2-50 J). Pigs in group 2 (n = 12) received monophasic and truncated exponential biphasic shocks from small (15.9 cm2) paddle electrodes. In group 1 (large paddle electrodes), the overall percent shock success rose from 15 +/- 9% at 2 J to 97 +/- 3% at 50 J. In this group there was no significant difference in percent of shock success between damped sinusoidal monophasic and biphasic waveform shocks. In group 2 (small paddle electrodes), biphasic shocks yielded a significantly higher percent of shock success than monophasic shocks at mid-energy levels from 7 to 20 J (all P < 0.01). With small surgical paddle electrodes, biphasic waveform shocks demonstrated a significantly higher percent of shock success rate compared to monophasic waveform shocks. With large paddle electrodes, the two waveforms were equally effective.

Animals↗

Hemorrhage after coronary artery bypass graft procedures.

OBJECTIVES: To identify risk factors for excessive bleeding after coronary artery bypass graft (CABG) procedures and to quantify the outcomes related to this complication. DESIGN: We conducted a case-control study to identify risk factors for hemorrhage following CABG surgery and a historical cohort study to quantify outcomes of hemorrhage. SETTING: The cardiothoracic surgery service of a university hospital. RESULTS: Factors associated with excessive blood loss were recent catheterization (odds ratio [OR] = 0.44; 95% confidence interval [CI95], 0.21 to 0.91); age older than 65 years (OR = 1.94; CI95, 0.96 to 3.93); bypass time of 150 minutes or more (OR = 2.91; CI95, 1.09 to 7.81); and postoperative platelet count of 160,000/mm3 or less (OR = 2.36; CI95, 1.06 to 5.22). The attributable cost of a postoperative hemorrhage was $3,866 (P = .0002) overall, $9,912 (P = .0001) for patients who required reoperation, and $3,316 (P = .03) for those treated medically. The median attributable postoperative length of stay was 1 day longer for cases than for controls (P = .011). Postoperatively, patients who hemorrhaged received significantly larger volumes of packed red blood cells (P < .0001), fresh frozen plasma (P < .0001), platelets (P < .0001), plasminate (P = .007), protamine sulfate (P < .0001), desmopressin acetate (P < .0001), and epsilon-aminocaproic acid (P < .0001) than did controls. CONCLUSIONS: Age, duration of bypass, and postoperative platelet count were associated with excessive bleeding. Hemorrhage after CABG surgery significantly increased the length of stay and cost of care.

Age Factors↗

Rate of optic disc cup progression in treated primary open-angle glaucoma.

PURPOSE: To quantitatively evaluate the rate of cup-to-disc ratio progression in treated patients with primary open-angle glaucoma and to identify clinical factors associated with cup progression. PATIENTS AND METHODS: Fifty one eyes of 51 treated primary open-angle glaucoma patients with a minimum of 9-year longitudinal series of stereoscopic optic disc photographs were studied. Eyes with any other ocular disease except for mild cataract were excluded. Each set of stereoscopic photographs was digitized and viewed stereoscopically on a computer screen using a hand-held stereoscope. Computer-aided planimetry was performed on each set of photographs with examiner-defined cup and disc margins using custom-made software. The software computed linear cup-to-disc ratios as well as peripapillary atrophy area. Both inter-observer and intra-observer reliabilities were evaluated in a masked, random fashion using intra-class correlation. Changes in linear cup-to-disc ratios and peripapillary atrophy were estimated using linear regression over time. All available clinical factors were evaluated for association with the rate of cup progression using a multiple regression model. RESULTS: All patients studied were Caucasian; 31(61%) were females. The mean age at the beginning of the study was 61.6 +/- 7.8 years (range 46-81). The mean follow-up period was 14.3 +/- 3.5 years (median 14.0, range 9.6-22.3). A total of 173 sets of stereo disc photographs were analyzed (3.4 +/- 1.3 per patient). The initial and final linear cup-to-disc ratios were 0.64 +/- 0.15 and 0.73 +/- 0.14 respectively. The inter-rater and intra-rater intraclass correlations were 0.76 (95% CI 0.61-0.87) and 0.97 (95% CI 0.93-0.98) respectively. Using linear regression the rate of linear cup-to-disc ratio change was 0.0068 +/- 0.0062 per year (range -0.0025- 0.0269). Three eyes had an increase in the peripapillary atrophy area. The higher yearly average intraocular pressure was significantly associated with faster rate of linear cup-to-disc ratios progression (P = 0.03). CONCLUSIONS: In treated patients with primary open-angle glaucoma, the rate of progressive optic disc cupping was slow (LCDR progression of 0.0068 per year). The higher yearly average intraocular pressure was significantly associated with a faster rate of cup progression.

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