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Biomedical subjects

Mark W Johnson

Publications and source records attributed to Mark W Johnson.

At least 19 recordsLinked to original sources
PubMed2007

Terbinafine-induced hepatic failure requiring liver transplantation.

Drug-induced liver disease accounts for about 50% of acute or subacute liver failure in the United States. United Network of Organ Sharing (UNOS) data suggest 8%-20% of liver transplantation in this country per year is for fulminant liver failure due to drugs. Even though the most common medication implicated in acute liver injury is acetaminophen (75%), there are numerous other drugs that are responsible for acute and chronic liver injury. A variety of antifungal medications are known to cause a wide range of liver injury from a mild hepatocellular-cholestatic injury pattern to acute/subacute liver failure. Terbinafine is one of the antifungals that have been associated with such liver injuries. We report a case of terbinafine-induced severe liver failure requiring liver transplantation.

Acetaminophen↗
PubMed2006

Treatment of acute retinal necrosis syndrome with oral antiviral medications.

OBJECTIVE: Acute retinal necrosis (ARN) is a distinct ocular viral syndrome traditionally treated with intravenous acyclovir followed by oral acyclovir. We investigated the use of the oral antiviral medications valacyclovir and famciclovir as the sole treatment for patients with newly diagnosed ARN syndrome. DESIGN: Retrospective, uncontrolled, interventional case series. PARTICIPANTS: Eight consecutive patients with newly diagnosed ARN treated solely with oral antiviral medications. INTERVENTION: All patients received famciclovir or valacyclovir without antecedent intravenous therapy. One patient with bilateral ARN treated with famciclovir received a single intravitreal injection of foscarnet in the more severely involved eye. MAIN OUTCOME MEASURES: Clinically and photographically documented complete resolution of retinitis and best-corrected visual acuity on final follow-up. RESULTS: Active retinitis resolved completely in 10/10 (100%) affected eyes. Initial response to treatment was seen as early as 4 days (in 5 eyes), with a median time to complete resolution of 14 days. At the last examination, visual acuity was improved (> or = 2 Snellen lines) in 6 (60%) eyes, stable in 2 (20%) eyes, and worse in 2 (20%) eyes. Over a mean follow-up of 36 weeks (range, 7-72 weeks), 3 eyes developed rhegmatogenous retinal detachment that was successfully repaired with 1 vitrectomy surgery. No patient with initially unilateral involvement developed disease in the contralateral eye. CONCLUSIONS: In this pilot study, the use of the oral drugs valacyclovir and famciclovir resulted in complete regression of herpetic necrotizing retinitis. Additional studies are necessary to evaluate the role of these antiherpetic medications in the treatment of the ARN syndrome.

2-Aminopurine↗
PubMed2006

Neurophysiologic assessment of neonatal sleep organization: preliminary results of a randomized, controlled trial of skin contact with preterm infants.

BACKGROUND: Sleep is important to brain organization, but few strategies to promote sleep among premature infants have been tested. Behaviorally based measures of sleep have shown increased quiet sleep (QS) and decreased active sleep (AS) during skin-to-skin contact (SSC) with the mother, but these results have not been confirmed with objective electroencephalographic/polysomnographic measures of sleep organization. Important differences exist between behavioral and electroencephalographic/polysomnographic definitions of sleep state. METHODS: Data for the first 28 relatively healthy, preterm subjects of an ongoing randomized trial of one 2- to 3-hour session of SSC or incubator care between feedings are reported here. Infants were positioned prone, inclined, and nested in an incubator during the 2- to 3-hour pretest period, were fed, and then went into the test period of SSC or incubator care. Infants were left largely undisturbed throughout testing. A mixed-model regression analysis compared the test-pretest differences in outcome measures within and between groups. RESULTS: Results showed that arousals were significantly lower in the SSC group, compared with the control group, for the entire study period and for test-pretest matched segments of QS and AS. Rapid eye movement was significantly lower for the SSC group for the study period and AS segments. Indeterminate sleep was significantly lower for the SSC group when confounding environmental variables were included in the regression analysis. When 4 subjects who experienced excessive ambient light levels during SSC were removed from analysis, QS increased during SSC. CONCLUSIONS: The patterns demonstrated by the SSC group are analogous to more-mature sleep organization. SSC may be used as an intervention to improve sleep organization in this population of preterm infants.

Electroencephalography↗
PubMed2005

Cyclicity of neonatal sleep behaviors at 25 to 30 weeks' postconceptional age.

Previous sleep studies of preterm neonates describe the rudimentary expression of sleep state cyclicity after 30 wk postconceptional age (PCA), with stability over multiple cycles only after 36 wk PCA. The research objective for this study was to determine whether sleep state cyclicity was expressed in neonates of 25-30 wk PCA, using two criteria for state identification. Our neonatal sleep consortium includes a total cohort of 359 children who were healthy and medically ill neonates who were recruited from three obstetric-neonatal services and received multiple-hour EEG sleep studies. A subset of the 33 youngest preterm infants were selected to evaluate the first of serial 2- to 3-h EEG-sleep recordings to assess the presence of sleep state cyclicity. One neonatal neurophysiologist visually assigned EEG-sleep characteristics for each record. Rapid eye movement (REM) counts and EEG discontinuity were specifically chosen to assess whether sleep cyclicity was expressed. A combined measure of REM and EEG discontinuity were used in an autocovariance analysis to assess cycling and mean cycle duration. A mean cycle duration of 68 +/- 19 min with a range of 37-100 min was determined from the REM-EEG discontinuity state for 24 neonates. The remaining nine infants had absent or poor sleep cyclicity. Sleep state cyclicity is expressed for a majority of neonates between 25 and 30 wk PCA, reflecting an ultradian biologic rhythm during the early perinatal stage of brain development.

Activity Cycles↗
PubMed2005

Effect of intravitreal triamcinolone acetonide on susceptibility to experimental bacterial endophthalmitis and subsequent response to treatment.

OBJECTIVES: Recent reports of high endophthalmitis rates after intravitreal triamcinolone acetonide injection have raised concerns about the safety of this treatment. We sought to evaluate the effect of intravitreal triamcinolone injection on (1) the susceptibility to experimental bacterial endophthalmitis and (2) the subsequent therapeutic response to antibiotic treatment. DESIGN: For the susceptibility study, the right eye of 40 New Zealand white rabbits received an intravitreal injection of a known quantity of Staphylococcus epidermidis organisms. Half of the eyes received a simultaneous intravitreal injection of triamcinolone acetonide, 4 mg. All eyes were examined daily for signs of endophthalmitis (photophobia, conjunctival injection, and vitritis) using standardized grading protocols (scaled from 0 to 4 with increasing severity). On day 7, vitreous cultures were obtained. For the therapeutic response study, the right eye of 12 rabbits received an intravitreal injection of S epidermidis organisms sensitive to vancomycin. Half of the eyes received a simultaneous intravitreal injection of triamcinolone acetonide, 4 mg. All 12 eyes received an intravitreal injection of vancomycin hydrochloride, 1 mg, on development of the first signs of endophthalmitis. All eyes were examined daily for 7 additional days. On day 7 after treatment, vitreous cultures were obtained. RESULTS: In the susceptibility study, all 40 eyes developed signs of endophthalmitis. In eyes that received intravitreal bacteria plus triamcinolone, 17 (85%) of the 20 vitreous cultures were positive, whereas only 6 (30%) were positive in the 20 eyes receiving bacteria alone (P = .001). The vitritis was significantly increased in the bacteria plus triamcinolone group compared with the bacteria-only group (17 of 20 vs 7 of 20 with 4+ vitritis, respectively; P = .003). In the therapeutic response study, all 12 eyes developed clinical signs of endophthalmitis within 48 hours. All vitreous samples obtained 7 days after intravitreal vancomycin injection were culture negative. However, the severity of vitritis at the time of vitreous sampling was less in the eyes receiving triamcinolone plus bacteria compared with eyes receiving bacteria alone (0 of 6 vs 5 of 6 with 4+ vitritis, respectively; P = .02). CONCLUSIONS: In eyes with experimentally induced bacterial endophthalmitis, the presence of intravitreal triamcinolone results in a higher culture-positive rate and a higher degree of inflammation, suggesting an impaired ocular immune response and greater susceptibility to infection. However, in eyes with experimentally induced bacterial endophthalmitis receiving early treatment with intravitreal antibiotics, triamcinolone appears to suppress the ocular inflammatory response without impairing the therapeutic effect. CLINICAL RELEVANCE: These data suggest that caution must be exercised when combining intravitreal triamcinolone injection with intraocular surgery.

Animals↗
PubMed2005

Tractional cystoid macular edema: a subtle variant of the vitreomacular traction syndrome.

PURPOSE: To describe clinical characteristics and treatment outcomes in a series of patients with tractional cystoid macular edema, a subtle variant of the vitreomacular traction syndrome. DESIGN: Retrospective, uncontrolled, observational, and interventional case series. METHODS PATIENT POPULATION: Ten consecutive patients (11 eyes) with multicystoid foveolar thickening caused by localized perifoveal vitreous detachment. EXPERIMENTAL PROCEDURES: Slit-lamp biomicroscopy and fluorescein angiography; confirmation of vitreomacular relationship with B-scan ultrasonography, optical coherence tomography (OCT), or both. Vitrectomy with peeling of posterior hyaloid in 8 eyes with pretreatment visual acuity <or=20/60. MAIN OUTCOME MEASURES: Visual acuity and resolution of cystoid macular edema at final follow-up. RESULTS: The median age of symptom onset was 71 years (range 48-81 years). Shallow perifoveal vitreous detachment was detectable on biomicroscopy in 8 of 11 eyes (73%) and with ultrasound and OCT in all eyes. Fluorescein angiography revealed no leakage from perifoveal capillaries in 8 eyes (73%). After a mean postoperative follow-up of 26.0 months (range 3-84 months), the final visual acuity had improved by 2 or more Snellen lines and measured 20/40 or better in 8 (100%) of 8 operated eyes. Cystoid foveal thickening resolved in all operated eyes. CONCLUSION: Subtle, localized perifoveal vitreous detachment may cause anterior traction on the foveola, resulting in multicystoid foveal thickening without macular hole formation or capillary leakage. OCT and ultrasound imaging are useful in detecting the detached posterior hyaloid when clinically invisible. Foveal thickening resolves and visual acuity typically improves after the relief of vitreofoveolar traction.

Aged↗
PubMed2005

The elusive nature of primary intraocular lymphoma.

A 58-year-old woman with an initial diagnosis of multiple evanescent white dot syndrome OU experienced deteriorating vision despite corticosteroid treatment. Reevaluation disclosed retinal and subretinal infiltrates and pigmentary alterations, prompting a suspicion of primary intraocular lymphoma (PIOL). Diagnostic vitrectomy yielded inconclusive cytology, but flow cytometry demonstrated small monoclonal B cells less suggestive of PIOL than of small lymphocytic lymphoma originating outside the eye or central nervous system. Brain magnetic resonance imaging, chest/abdomen/pelvis computed tomography, lumbar puncture, and laboratory studies failed to disclose lymphoma elsewhere. There was insufficient evidence to recommend radiation therapy. Vision deteriorated rapidly, prompting a diagnostic retinal biopsy and aspiration of the subretinal infiltrate, revealing unequivocal evidence of PIOL. After 40 Gy orbital x-irradiation, visual function improved dramatically. This case emphasizes the unusual ocular manifestations of PIOL and the difficulty of obtaining a definitive diagnosis by sampling vitreous, particularly after corticosteroid treatment. In such cases, subretinal aspiration or retinal biopsy may be necessary. Timely diagnosis is critical because treatment can reverse visual loss if it is not severe.

Biopsy↗
PubMed2005

Automated state analyses: proposed applications to neonatal neurointensive care.

The two principal challenges of neonatal physiologic monitoring device are: (1) the development of computational strategies that consider the rudimentary forms of neonatal sleep state especially for preterm infants and (2) any physiologic monitoring device for clinical applications in a neonatal intensive care setting must be small, portable, and user-friendly. Our multicenter neonatal sleep consortium has acquired more than 1,100 multihour EEG-sleep recordings on over 370 neonates, ranging from 24 to 44 weeks gestation. Each recording was visually-scored for state, arousals, movements, and rapid eye movements, which were used as templates when applying spectral analyses. The authors have defined a brain dysmaturity index to represent functional brain reorganization as the prenate matures to a full-term age; delayed or accelerated physiologic behaviors have been described for the preterm cohort when compared to the full-term group at the same postmenstrual age. Seven EEG-sleep measures comprise this index: quiet sleep percentage, sleep cycle length, rapid eye movements, arousals, spectral beta EEG energies, spectral EEG correlations, and a spectral measure of respiratory regularity. Linear and nonlinear computational algorithms are being developed to automate the computation of the dysmaturity index and to identify new feature types that correlate with dysmaturity. Automated neonatal sleep monitoring system can potentially improve neonatal neurointensive care by facilitating analyses of pervasive neonatal brain disorders expressed primarily as altered sleep state organization, and help predict altered developmental trajectories of children at higher risk for neurologic sequelae.

Brain↗
PubMed2005

The influence of norfloxacin and metronidazole on the disposition of mycophenolate mofetil.

The objective of this study was to investigate the effect of concurrent antibiotic administration on the disposition of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) after oral administration of mycophenolate mofetil (MMF) in healthy subjects. Eleven healthy subjects were enrolled. The study was divided into 4 treatment periods. Subjects received MMF as a single oral 1-g dose alone and were then randomized to 3 antibiotic treatment periods. The 3 periods included norfloxacin, metronidazole, and a combination of norfloxacin and metronidazole. Antibiotic treatment was started 3 days prior to each MMF pharmacokinetic study day and was given for a total of 5 days. On day 4 of each antibiotic phase, subjects received a single 1-g oral dose of MMF. Plasma and urine samples were obtained over 48 hours after the MMF dose in all treatment periods and were quantitatively measured for MPA and MPAG. Pharmacokinetic parameters for MPA and MPAG were determined for all periods. Compared to MMF alone, the area under the plasma concentration versus time curve (AUC) of MPA was reduced by an average of 10%, 19%, and 33% when given with norfloxacin, metronidazole, and norfloxacin plus metronidazole, respectively. The AUC of MPAG was also reduced on average by 10%, 27%, and 41% in the corresponding periods. The combination of norfloxacin and metronidazole significantly reduced the AUC of MPA and MPAG in healthy subjects. This likely occurs as a result of reduced enterohepatic recirculation.

Administration, Oral↗
PubMed2005

Prediction of neonatal state and maturational change using dimensional analysis.

Nonlinear time series analysis techniques have been used to analyze physiologic signals such as EEG and heart rate. The authors illustrate the application of dimensional analysis (DA) to assess neonatal sleep states at increasing gestational ages up to full-term age. One hundred and sixteen EEG-polygraphic recordings were performed on 55 neonatal subjects between 28 and 43 weeks gestational age from which state assignments were initially scored by visual analysis. A single channel of EEG (i.e., FP1-C3) was selected for dimensional analysis. Two-tailed t-tests were used to test for differences in the correlation dimension (CD) between active and quiet sleep states for both preterm and full-term neonates as a function of maturation. A significant difference in CD between active and quiet sleep states (P < 0.001) was noted for the full-term infant. A positive correlation between CD and increasing conceptional age was noted (P < 0.001). DA showed an increase in the complexity for both active and quiet sleep as the preterm infant matured toward a full-term corrected age. Lower dimensionality (CD), indicative of reduced complexity, was noted for the healthy preterm cohort at corrected full-term age when compared with the full-term group. Dimensional analysis demonstrated a positive correlation for both active and quiet sleep, as the infant matured toward corrected term age. Lower dimensionality was noted for the healthy preterm cohort at corrected full-term age. These findings support the concept of physiologic dysmaturity for the preterm neonate as a reflection of altered neural plasticity of the brain as a result of the conditions of prematurity.

Developmental Disabilities↗
PubMed2005

Perifoveal vitreous detachment and its macular complications.

PURPOSE: To evaluate the vitreoretinal relationship in eyes with idiopathic macular disorders putatively caused by vitreomacular traction associated with early stages of age-related posterior vitreous detachment (PVD). METHODS: Retrospective observational case series of 43 eyes of 40 patients diagnosed with one of several idiopathic vitreomacular conditions. Included patients had no biomicroscopic evidence for complete PVD on presentation and underwent a specific clinical assessment of the vitreoretinal relationship. Affected eyes were evaluated with slit-lamp biomicroscopy, B-scan ultrasonography, optical coherence tomography, and/or intraoperative examination of the posterior hyaloid. RESULTS: By one or more examination techniques, 41 (95.3%) of the 43 study eyes had evidence of vitreous detachment from the perifoveal macular region and the remaining two eyes had complete PVD. When measurable, the size of the vitreomacular adhesion varied by diagnosis. Of 31 eyes with perifoveal vitreous detachment seen in follow-up, only three (9.7%) showed progression to complete PVD over an average preoperative or total follow-up period of 30.0 months (range, 2 to 237 months). Surgical or spontaneous separation of the residual vitreomacular adhesion in 16 eyes was followed in 15 (93.8%) by partial or complete resolution of the symptoms and signs of macular traction. CONCLUSIONS: Age-related PVD appears to be an insidious, chronic event that begins in the perifoveal macula and evolves over a prolonged period of time prior to vitreopapillary separation. Though usually asymptomatic, its early (perifoveal) stages may be complicated by one of several macular pathologies, determined in part by the size of the residual vitreomacular adhesion.

Adult↗
PubMed2004

Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease.

Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the central region of the retina. AMD is clinically heterogeneous, leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at advanced stages. Considerable data exists in support of a genetic predisposition for AMD. Recent linkage studies have provided evidence in favor of several AMD susceptibility loci. We have performed a high-resolution (5-cM) genome scan of 412 affected relative pairs that were enriched for late-stage disease (GA and/or CNV). Nonparametric linkage analysis was performed using two different diagnostic criteria and also by dividing the affected individuals according to GA or CNV phenotype. Our results demonstrate evidence of linkage in regions that were suggested in at least one previous study at chromosomes 1q (236-240 cM in the Marshfield genetic map), 5p (40-50 cM), and 9q (111 cM). Multipoint analysis of affected relatives with CNV provided evidence of additional susceptibility loci on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected members in the restricted group with AMD, 346 additional patients with AMD, and 237 unaffected controls. Our results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants.

Aging↗
PubMed2004

Pathogenic implications of subretinal gas migration through pits and atypical colobomas of the optic nerve.

OBJECTIVE: To describe subretinal migration of gas and silicone oil in a series of patients with congenital cavitary optic disc anomalies and to further clarify the pathogenesis of the associated maculopathy. METHODS: Medical records of 4 female patients, aged 8 to 34 years, who developed subretinal gas migration after vitreous surgery for macular detachment associated with cavitary optic disc anomalies were reviewed. A theoretical model was used to calculate the pressure differential required to induce subretinal gas migration through an optic pit. RESULTS: The 4 patients had bilateral atypical optic nerve colobomas or a unilateral large optic pit. A definite defect in the tissue overlying the disc excavation could be seen in one eye, and intraoperative drainage of subretinal fluid through the disc anomaly was possible in all cases. Subretinal migration of gas or silicone oil was seen intraoperatively in one case and first appeared between 1 and 17 days postoperatively in the remaining cases. Theoretical calculations suggest that the pressure differential required for migration of gas through a small defect in the roof of a cavitary disc lesion is within the range of expected fluctuations in cerebrospinal fluid pressure. CONCLUSIONS: These observations provide clinical confirmation of a defect in tissue overlying cavitary optic disc anomalies and imply interconnections between the vitreous cavity, subarachnoid space, and subretinal space. We theorize that intermittent pressure gradients resulting from normal variations in intracranial pressure play a critical role in the pathogenesis of retinopathy associated with cavitary disc anomalies.

Adult↗