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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 73 records · Page 4Linked to original sources
PubMed2000

A comparison of laparoscopic supracervical hysterectomy vs laparoscopically assisted vaginal hysterectomy.

BACKGROUND: We set out to compare the length of stay, costs, and morbidity associated with laparoscopic supracervical hysterectomy (LSH) with laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: We performed a cohort analysis of consecutive patients at a university-based medical center from April 1997 through October 1999. RESULTS: A total of 145 patients were identified initially; however, 13 cases were excluded because of concomitant procedures (retropubic urethropexy, lymphadenectomy, paravaginal repair). Of the 132 patients included in the study, 27 underwent LSH and 105 underwent LAVH. The two groups were similar with respect to gravidity, parity, uterine weight, and preoperative diagnosis. Patients undergoing LSH had significantly shorter operating times (median, 181 vs 220 min, p = 0.007), briefer hospital stays (median, 1.0 vs 2.0 days, p = 0.0001), and less blood loss (median, 125 vs 400 ml, p = 0.0001). None of the patients submitted to LSH experienced morbidity, as compared with a 13% morbidity rate for LAVH (bladder injury, n = 3; blood loss >1000 ml, n = 7; vaginal cuff hematoma, n = 4; 0% vs 13%; p = 0.04). CONCLUSIONS: Patients undergoing laparoscopic supracervical hysterectomy had shorter operating times, shorter hospital stays, and less morbidity than those who underwent laparoscopically assisted vaginal hysterectomy. The practice of routine cervicectomy at laparoscopic hysterectomy should be reconsidered.

Case-Control Studies↗
PubMed2000

Conformational analysis of alkylated biuret and triuret: evidence for helicity and helical inversion in oligoisocyanates

The conformations of several oligoisocyanates have been investigated by NMR in order to study the onset and dynamics of helicity in polyisocyanates. Pentaethylbiuret and hexaethyltriuret were found to adopt turns and helices in solution. For hexaethyltriuret, symmetric and asymmetric helices are present. Not only is an interconversion of these forms observed (DeltaG(SA)(double dagger) = 9.3 +/- 0.4 kcal/mol) but also a reversal of helicity (DeltaG(PM)(double dagger) = 9.0 +/- 0.4 kcal/mol). The coalescence pattern for the latter process provides direct evidence for a concerted, conrotatory helical inversion.

Journal Article↗
PubMed2000

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Adjuvants, Immunologic↗
PubMed2000

Noninvasive strategies for the estimation of cardiac risk in stable chest pain patients. The Economics of Noninvasive Diagnosis (END) Study Group.

Effective allocation of medical resources in stable chest pain patients requires the accurate diagnosis of coronary artery disease and the stratification of future cardiac risk. We studied the relative predictive value for cardiac death of 3 commonly applied noninvasive strategies, clinical assessment, stress electrocardiography, and myocardial perfusion tomography, in a large, multicenter population of stable angina patients. The multicenter observational series comprised 7 community and academic medical centers and 8,411 stable chest pain patients. All patients underwent pretest clinical screening followed by stress (exercise 84% or pharmacologic 16%) electrocardiography and myocardial perfusion tomography. Risk-adjusted multivariable Cox proportional hazards models were developed to predict cardiac death. Kaplan-Meier rates of time to cardiac catheterization were also computed. Cardiac mortality was 3% during the 2.5 +/- 1.5 years of follow-up. The number of infarcted vascular territories and pretest clinical risk factors were strong predictors of cardiac mortality, whereas the number of ischemic vascular territories gained increasing importance when determining post-test resource use requirements (i.e., the decision to perform cardiac catheterization). Exertional ST-segment depression in a population with a high frequency of electrocardiographic abnormalities at rest was not a significant differentiator of cardiac death risk. Stable chest pain patients are accurately identified as being at high risk for near-term cardiac events by both physicians' screening clinical evaluation and by the results of stress myocardial perfusion imaging. Disease management strategies for stable chest pain patients aimed at risk reduction should incorporate knowledge of relevant end points in treatment and guideline development.

Aged↗
PubMed2000

In vivo DNA damage in gastric epithelial cells.

A number of risk factors have been linked epidemiologically with gastric cancer, but studies of DNA damage in gastric epithelial cells are limited. The comet assay is a simple technique for determining levels of DNA damage in individual cells. In this study, we have validated the comet assay for use in epithelial cells derived directly from human gastric biopsies, determined optimal conditions for biopsy digestion and investigated the effects of oxidative stress and digestion time on DNA damage. Biopsies taken at endoscopy were digested using combinations of pronase and collagenase, ethylenediaminetetra-acetic acid (EDTA) and vigorous shaking. The resultant cell suspension was assessed for cell concentration and epithelial cell and leukocyte content. A score for DNA damage, the comet %, was derived from the cell suspension, and the effect of various digestion conditions was studied. Cells were incubated with H(2)O(2) and DNA damage was assessed. Pronase and collagenase provided optimum digestion conditions, releasing 1. 12x10(5) cells per biopsy, predominantly epithelial. Of the 23 suspensions examined, all but three had leukocyte concentrations of less than 20%. The comet assay had high inter-observer (6.1%) and inter-assay (4.5%) reproducibility. Overnight storage of the biopsy at 4 degrees C had no significant effect on DNA migration. Comet % increased from a median of 46% in untreated cells to 88% in cells incubated for 45 min in H(2)O(2) (p=0.005). Serial 25-min digestions were performed on biopsies from 13 patients to release cells from successively deeper levels in the crypt. Levels of DNA migration were significantly lower with each digestion (r=-0.94, p<0.001), suggesting that DNA damage is lower in younger cells released from low in the gastric crypt. The comet assay is a reproducible measure of DNA damage in gastric epithelial cells. Damage accumulates in older, more superficial cells, and can be induced by oxidative stress.

Biopsy↗
PubMed2000

In vitro selection of RNA molecules that inhibit the activity of ricin A-chain.

The cytotoxin ricin disables translation by depurinating a conserved site in eukaryotic rRNA. In vitro selection has been used to generate RNA ligands (aptamers) specific for the catalytic ricin A-chain (RTA). The anti-RTA aptamers bear no resemblance to the normal RTA substrate, the sarcin-ricin loop (SRL), and were not depurinated by RTA. An initial 80-nucleotide RNA ligand was minimized to a 31-nucleotide aptamer that contained all sequences and structures necessary for interacting with RTA. This minimal RNA formed high affinity complexes with RTA (K(d) = 7.3 nM) which could compete directly with the SRL for binding to RTA. The aptamer inhibited RTA depurination of the SRL and could partially protect translation from RTA inhibition. The IC(50) of the aptamer for RTA in an in vitro translation assay is 100 nM, roughly 3 orders of magnitude lower than a small molecule inhibitor of ricin, pteroic acid, and 2 orders of magnitude lower than the best known RNA inhibitor. The novel anti-RTA aptamers may find application as diagnostic reagents for a potential biological warfare agent and hold promise as scaffolds for the development of strong ricin inhibitors.

Base Sequence↗
PubMed2000

Analysis and significance of messenger RNA in human ejaculated spermatozoa.

Human ejaculate spermatozoa contain multiple mRNA species carried over from earlier stages in spermatogenesis. To date, gene-specific RT-PCR or in situ hybridization has detected transcripts for beta-actin, heat shock proteins (HSP) 70 and 90, protamines (PRM) 1 and 2, transition protein (TNp) 2, HLA II, beta-integrins, and, most recently, phosphodiesterase subtypes. We have further evidence for a complex population of transcripts based on screening a human testis cDNA library with a heterologous spermatozoal probe. High levels of transcribed repetitive sequences are present in human spermatozoa, including medium reiteration repeats (MERs) and short and long nuclear interspersed repeats (SINES and LINES). Both SINES and LINES belong to the retroposon class of repeat elements, which are thought to proliferate via an intermediate RNA that is converted to DNA by an RNA-dependent DNA polymerase (reverse transcriptase). We have circumstantial evidence for the presence of an RT in ejaculate sperm based on the detection of transcripts for ORF2 of LINE 1 encoding such an enzyme. Our data suggests the following: 1. Ejaculate spermatozoa may be a very useful tool in the identification of genes linked to an infertile phenotype. 2. Spermatozoa (or spermatids) may express a reverse transcriptase, the role of which is unknown. 3. RNA isolated from spermatozoa or washed semen samples may facilitate the detection of mutations and deletions in testis-expressed AZF-linked genes.

Ejaculation↗
PubMed2000

Functional significance of parasitism-induced suppression of juvenile hormone esterase activity in developmentally delayed Choristoneura fumiferana larvae.

The parasitic wasp Tranosema rostrale transmits a polydnavirus (PDV) to its host, Choristoneura fumiferana, during oviposition. Last-instar C. fumiferana larvae parasitized by T. rostrale early in the stadium fail to undergo metamorphosis, and injection of the wasp's calyx fluid (CxF; contains PDV) into healthy caterpillars induces a dose-dependent delay in initiation of metamorphosis (D. Doucet and M. Cusson, 1996, Entomol. Exp. Appl. 81, 21-30). In the present work, parasitization and injection of CxF (0.5 female equivalent) on the first day of the last stadium both prevented the rise in hemolymph 20-hydroxyecdysone (20HE) titer observed between day 4 and day 7 in control and saline-injected larvae. Similarly, juvenile hormone esterase (JHE) activity was depressed following parasitization or CxF injection, whereas control larvae displayed a peak on day 4. However, neither parasitism nor injection of CxF on day 1 prevented the JH-producing glands from turning off during the first half of the last stadium. Likewise, low but clearly detectable JH titers were observed in the first hours following the molt but very low titers, at or near the detection limit of our radioimmunoassay, were seen in both control and parasitized larvae on day 4. Prothoracic glands showed no apparent sign of degeneration 4 days after injection of CxF but had significantly smaller cells than saline-injected larvae 7 days postinjection. It is not clear whether this was a direct effect of T. rostrale PDV. Thus, disruption of spruce budworm metamorphosis by T. rostrale CxF involves depression of 20HE titers but is not associated with a measurable increase in the level of JH, as shown for some other host-parasitoid systems. In view of the latter observation, we put forward three hypotheses regarding the functional significance of the observed suppression of JHE activity in developmentally arrested C. fumiferana larvae.

Animals↗
PubMed2000

Effects of ENU dosage on mouse strains.

The germline supermutagen, N-ethyl-N-nitrosourea (ENU), has a variety of effects on mice. ENU is a toxin and carcinogen as well as a mutagen, and strains differ in their susceptibility to its effects. Therefore, it is necessary to determine an appropriate mutagenic, non-toxic dose of ENU for strains that are to be used in experiments. In order to provide some guidance, we have compiled data from a number of laboratories that have exposed male mice from inbred and non-inbred strains or their F(1) hybrids to ENU. The results show that most F(1) hybrid animals tolerate ENU well, but that inbred strains of mice vary in their longevity and in their ability to recover fertility after treatment with ENU.

Animals↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗