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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 55 records · Page 3Linked to original sources

Corneal biopsy in the management of progressive microbial keratitis.

PURPOSE: To study the indications and role of diagnostic corneal biopsy in the management of patients with progressive microbial keratitis. METHODS: The records of 33 consecutive patients who underwent a diagnostic corneal biopsy from January 1, 1986, to December 31, 1998, were reviewed. The indication for corneal biopsy was progressive infectious keratitis despite intensive broad-spectrum topical antimicrobial therapy, or progressive stromal infiltration inaccessible to corneal scrapings. Microbiologic evaluation of all corneal biopsies was performed, and 11 of the 33 biopsies were also examined histopathologically. RESULTS: A microorganism was isolated from 27 (82%) of the 33 corneal biopsies. Of the six patients with a negative biopsy, a penetrating keratoplasty was performed in five patients and the pathogen was identified by examination of the corneal button. In one patient no microorganism was identified; however, the infection resolved with topical antimicrobial therapy. The most common risk factor for keratitis was foreign body exposure or corneal abrasion (14 patients). A solid stromal infiltrate was the most common pattern of corneal involvement. Corneal biopsy revealed previously unidentified microorganisms that led to a change in antimicrobial therapy in 24 (89%) of the 27 patients and confirmed prior culture results in the remaining 3 patients. Microbiologic evaluation of the corneal biopsy was more sensitive than histopathologic examination. Acanthamoeba was the most commonly isolated pathogen (five cases), followed by Propionibacterium acnes and Fusarium (four cases each). Gram-positive organisms were isolated in 16 patients. Only five of the 27 patients with a positive corneal biopsy required a penetrating keratoplasty, in contrast to five of the six patients with a negative corneal biopsy (P =.005). During the 13-year period of the study, only three corneal biopsies were performed in the last 6 years. CONCLUSIONS: Microbiologic evaluation of a diagnostic corneal biopsy contributed significantly to the diagnosis, treatment, and outcome of patients with progressive infectious keratitis.

Acanthamoeba↗

Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones.

OBJECTIVE: To study the distribution, current trends, and patterns of resistance to antimicrobial agents of bacterial keratitis isolates in South Florida. DESIGN: Retrospective, observational, case series. PARTICIPANTS: The microbiology records of all patients with bacterial keratitis seeking treatment at the Bascom Palmer Eye Institute from January 1, 1990 through December 31, 1998 were reviewed. MAIN OUTCOME MEASURES: In vitro laboratory minimum inhibitory concentration testing of the corneal isolates to the fluoroquinolones (ofloxacin and ciprofloxacin) and to the aminoglycosides (tobramycin and gentamicin) was performed using the Vitek (Automatic Microbial System Biomerieux Vitek, Inc., Hazelwood, Missouri) method. RESULTS: During this 9-year period, 2920 consecutive corneal cultures were obtained, and a pathogen was recovered in 1468 cultures (50%). The number of corneal ulcers scraped, positive cultures, recovered bacterial isolates, and ratio of gram-positive to gram-negative isolates per year remained approximately equal throughout the study period. Staphylococcus aureus and Pseudomonas aeruginosa represented 19.4% and 25.7%, respectively, of the total bacterial isolates during this period. However, we documented a gradual increase in the number of S. aureus keratitis isolates (29% of gram-positive organisms in 1990 versus 48% in 1998, P = 0.01) coupled with a decrease in the number of P. aeruginosa isolates (54% of gram-negative organisms in 1990 versus 46% in 1998). A decrease in the incidence of contact lens-associated keratitis and P. aeruginosa isolates in this group of patients was documented. Serratia marcescens and P. aeruginosa were most commonly isolated in contact lens-associated keratitis (18% each). There was increasing laboratory resistance of S. aureus keratitis isolates to the fluoroquinolones (11% in 1990 to 28% in 1998), but resistance patterns to the aminoglycosides remained unchanged. There was a three-fold increase in the percentage of resistant S. aureus isolates to fluoroquinolones between 1990 and 1994 and between 1995 and 1998. Both fluoroquinolones and aminoglycosides exhibited low in vitro effectiveness against P. aeruginosa throughout the study period. CONCLUSIONS: The increased recovery of S. aureus keratitis isolates and decreased laboratory effectiveness against fluoroquinolones to these pathogens present an important therapeutic challenge.

Anti-Bacterial Agents↗

Capnocytophaga keratitis.

PURPOSE: To review the clinical course, treatment, and visual outcomes of keratitis caused by the gram negative rod CAPNOCYTOPHAGA: DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Ten patients with culture-proven unilateral CAPNOCYTOPHAGA: keratitis examined at the Bascom Palmer Eye Institute between January 1, 1989, and December 31, 1998. INTERVENTION: All patients underwent standard diagnostic microbiologic evaluation, and topical antimicrobial therapy was instituted. A penetrating keratoplasty or enucleation was performed in some patients. MAIN OUTCOME MEASURES: The changes in visual acuity and clinical response to antimicrobial therapy. RESULTS: Predisposing factors were present in all patients. Cultures identified CAPNOCYTOPHAGA: species at a mean of 7.5 days. Initial topical treatment consisted of an aminoglycoside and vancomycin in four patients, a quinolone or aminoglycoside alone in two patients each, and ofloxacin with vancomycin or tobramycin with ceftazidime in one patient each. After the microbiologic identification of CAPNOCYTOPHAGA:, treatment in four patients was changed to intensive, topical clindamycin. Five of the 10 eyes were medically cured (3 of these eyes underwent penetrating keratoplasty for corneal scarring), and 5 eyes required enucleation. The indications for enucleation included persistent infection with development of endophthalmitis or blind, painful eye. Five of the 10 eyes achieved 20/80 or better final visual acuity. Four of these five eyes were treated with topical clindamycin. CONCLUSIONS: Important factors in achieving a good visual outcome in CAPNOCYTOPHAGA: keratitis include early microbiologic identification and intensive therapy with topical clindamycin. CAPNOCYTOPHAGA: should be included in the differential diagnosis of bacterial keratitis in patients with suggestive predisposing factors or with protracted keratitis unresponsive to treatment.

Adult↗

Endogenous endophthalmitis caused by Histoplasma capsulatum var. capsulatum: a case report and literature review.

OBJECTIVE: We report the first case of clinically diagnosed endogenous endophthalmitis caused by Histoplasma capsulatum var. capsulatum in a patient with the acquired immune deficiency syndrome. DESIGN: Interventional case report and literature review. INTERVENTION: Pars plana vitrectomy and scleral buckling procedure in the left eye with intravenous and intravitreal amphotericin in both eyes. MAIN OUTCOME MEASURES: The clinical features, culture results, visual outcome, and complications were studied. RESULTS: This case demonstrates a bilateral endophthalmitis with severe subretinal exudation, choroidal granulomas, and intraretinal hemorrhage leading to exudative bilateral retinal detachments. Vitreous cultures grew H. capsulatum var. capsulatum. Treatment consisted of intravenous amphotericin, intravitreal amphotericin (both eyes), pars plana vitrectomy (left eye), and scleral buckling procedure (left eye) with resulting counting fingers vision (right eye) and 20/300 (left eye). Four cases of Histoplasma endophthalmitis have been reported previously, all of which had a documented history of disseminated histoplasmosis and resulted in enucleation. CONCLUSIONS: H. capsulatum should be considered a possible etiologic agent of endophthalmitis, especially in patients with a history of disseminated histoplasmosis and/or immune deficiency.

AIDS-Related Opportunistic Infections↗

Origin of anterior patterning. How old is our head?

Most animals that display a bilateral symmetry (bilaterians) share homologous regulatory genes involved in head development. Recently, homologues of several of these genes have been cloned from animals that are radially organized, such as coral, sea anemones, jellyfish or hydra (cnidarians). Surprisingly, some of these are expressed apically and/or during apical patterning in hydrozoans, suggesting that head patterning is much older than previously thought.

Animals↗

Long-term induction of Fos-related antigen-2 after methamphetamine-, methylenedioxymethamphetamine-, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine- and trimethyltin-induced brain injury.

A long-term induction of Fos-related antigens has been shown in neurons after brain injury, suggesting that Fos-related antigens are involved in enhancing the transcription of genes related to the process of regeneration and repair. In the present study, we report that levels of Fos-related antigen-2 are elevated in several models of chemically induced brain injury. Trimethyltin, which causes degeneration of neurons primarily in the hippocampus and other limbic regions, results in a five-fold induction of Fos-related antigen-2 immunoreactivity in neurons in the pyramidal and dentate layers of the hippocampus starting at seven days post-treatment and persisting for 60days. Methamphetamine and methylenedioxymethamphetamine, agents which cause degeneration of dopaminergic nerve terminals in the striatum of the mouse, cause an increase in Fos-related antigen-2 immunoreactivity which begins at three days post-treatment and returns to basal levels by days 5 and 15, respectively. Treatment with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine elevated levels of Fos-related antigen-2 in the mouse striatum at three days post-treatment. This abbreviated time-course of Fos-related antigen-2 induction is consistent with less severe insult (terminal damage) relative to trimethyltin (cell death), but induction occurs during the period of regeneration and repair in both models. Dexfenfluramine, a non-neurotoxic amphetamine, does not induce Fos-related antigen-2 expression. Decreasing core temperature of the mouse, which blocks amphetamine-induced neurotoxicity, also blocks Fos-related antigen-2 induction. In summary, Fos-related antigen-2 is induced in models of both cell death and terminal degeneration, suggesting that this transcription factor may serve as a universal signal transduction molecule involved in the regulation of genes related to regeneration and repair in the CNS.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Relationship between fetal monitoring and resuscitative needs: fetal distress versus routine cesarean deliveries.

BACKGROUND: There is debate as to whether pediatricians should be present at all cesarean deliveries. Little published data exist regarding the differences in resuscitative needs of infants delivered by cesarean section for "fetal distress" versus those without this diagnosis. OBJECTIVE: To describe the differences in resuscitative and immediate postnatal intervention needs for neonates with fetal distress delivered by cesarean section and those without fetal distress delivered in the same manner. Also, to devise an evaluation tool to assess and compare levels of neonatal resuscitation between infants and groups of infants. METHODS: The delivery records of 1411 term infants delivered by cesarean section after uncomplicated pregnancies at Los Angeles County/University of Southern California Medical Center from March 3, 1995 through March 8, 1997 were examined retrospectively. Apgar scores and resuscitative needs were assigned to a newly devised, weighted scoring system. Resuscitation subscores and total resuscitation scores were compared using non-parametric methods. RESULTS: The fetal distress group (n = 80) had a significantly greater resuscitative needs mean score (p < 0.001) and subscores (p < 0.001 to p = 0.004) than did the non-fetal distress group (n = 419). Of the non-fetal distress group, 48.7% still received some active form of intervention. CONCLUSION: In our study group, infants with fetal distress had significantly greater intervention needs than infants without fetal distress.

Cesarean Section↗

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism.

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.

Aged↗

Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors.

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this hypodopaminergic trait under the rubric of a reward deficiency syndrome.

Behavior, Addictive↗

Pharmacological characterization of phospholipid growth-factor receptors.

The phospholipid growth-factor (PLGE) terminology is proposed to describe a group of endogenous glycerol- and sphingolipid mediators that regulate cell proliferation through plasma membrane receptors. In addition to LPA and SPP, multiple PLGFs are present in blood plasma and serum. PLGF activity is regulated by its stimulus-coupled production and by endogenous inhibitors. In addition to LPA and SPP, alkenyl-glycerophosphate, cyclic-phosphatidic acid, and sphingosylphosphorylcholine were detected in biological fluids using mass spectrometry. Heterologous desensitization studies indicate the expression of multiple LPA-activated receptors in a variety of cell types, which are differentially activated by the different PLGFs. Northern blot and RT-PCR results reinforce the coexpression of PSP24 alpha and different members of the EDG1-7 receptors in the same cell. Stable heterologous expression of the PSP24 alpha, EDG2, and EDG4 receptors in HEK293 cells show distinct PLGF specificities and dose-response properties for each receptor subtype. Thus, both the controlled availability of the different agonists/inhibitors and the regulated expression of their receptors regulate the biological effects of PLGFs.

Animals↗

Utility of tissue culture for detection of Toxoplasma gondii in vitreous humor of patients diagnosed with toxoplasmic retinochoroiditis.

Laboratory recovery and confirmation of the etiologic agent in necrotizing retinochoroiditis are problematic. Tissue culture and intraocular antibody titers were compared as adjuncts to clinical diagnosis for toxoplasmic retinochoroiditis: the correlations were 91 and 67%, respectively. Isolation of Toxoplasma gondii may establish a definitive diagnosis in patients with toxoplasmic retinochoroiditis.

Animals↗

Corneal ulceration in the elderly in Hyderabad, south India.

AIMS: To report demographic, microbiological, therapeutic, anatomical, and visual results of corneal ulceration in the elderly patients seen at a tertiary eye care centre in south India. METHODS: 102 consecutive cases of microbial keratitis in patients 65 years and older were studied. Inclusion criteria were: (i) presence of corneal stromal infiltrate upon slit lamp examination; and (ii) microbiological evaluation of corneal scrapings for suspected microbial keratitis. RESULTS: The principal predisposing factors identified in this study were ocular disease (38.2%), previous ocular surgery in the same eye (29.4%), trauma (17.6%), and severe systemic disease (16.7%). Contact lens wear was associated with only two cases (2.0%). 99 organisms were isolated in cultures of corneal scrapings from 74 (72.5%) of the 102 cases. Staphylococcus epidermidis (31.1%), filamentous fungi (25.7%), and Streptococcus pneumoniae (13.5%) were the most common isolates. 12 eyes (11.8%) required surgery, 15 (14.7%) eventually required evisceration, and nine (9.6%) of the 94 followed patients achieved an unaided vision of 20/60 or better at last follow up. CONCLUSIONS: This work represents the largest recent single centre study on (non-viral) microbial keratitis in the elderly, its management, and outcomes of therapy. While the predisposing factors differ from those of general population, the spectrum of microbes responsible for keratitis in the elderly appears to reflect the local microbial flora rather than a predilection for elderly patients. Delay in diagnosis and systemic conditions associated with advancing age probably contribute to poorer outcome from therapeutic measures.

Acanthamoeba Keratitis↗

Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia.

OBJECTIVE: Previous studies have suggested that there may be an association between longer duration of untreated psychosis and poor outcome in schizophrenia. These studies have been interpreted as providing evidence that untreated psychosis may constitute an "active morbid process" that is "toxic" to the brain. If untreated psychosis is neurotoxic, this would form a strong basis for early intervention in schizophrenia. METHOD: Seventy-four neuroleptic-naive patients with DSM-IV schizophrenia were evaluated 6 months after their first inpatient hospitalization. The authors examined the relationship between untreated initial psychosis duration (measured from onset of first symptom as well as from onset of full positive syndrome) and quality of life, symptom severity, and time to remission of positive symptoms. RESULTS: Earlier age at illness onset was associated with longer duration of untreated prodromal psychotic symptoms. There were no significant gender differences in duration of untreated initial psychosis, nor were there any significant associations between untreated initial psychosis duration and premorbid functioning. After controlling for the effects of age at onset, the duration of untreated initial psychosis did not significantly impair subsequent quality of life, symptom severity, or remission of positive symptoms. CONCLUSIONS: Duration of untreated initial psychosis was not prognostic of poor outcome early in the course of schizophrenia. Biological measures of neurotoxicity are needed to examine the "toxic psychosis" hypothesis more directly.

Adult↗

Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients.

Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow-up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNbeta-1a (Avonex) in relapsing- remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing--remitting MS.

Adjuvants, Immunologic↗